Liver Disease

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.

Non-Hispanic Black and Hispanic patients are underrepresented on many liver transplant waiting lists, whereas non-Hispanic White patients are often overrepresented, according to data from 109 centers.

pixelheadphoto/Thinkstock

While racial disparities “greatly diminished” after placement on a waiting list, which suggests recent progress in the field, pre–wait-listing disparities may be more challenging to overcome, reported lead author Curtis Warren, MPH, CPH, of the University of Florida, Gainesville, and colleagues.

“In 2020, the Organ Procurement and Transplantation Network implemented a new allocation system for liver transplantation based on concentric circles of geographic proximity rather than somewhat arbitrarily delineated Donor Service Areas (DSAs),” the investigators wrote in Journal of the American College of Surgeons. “Although this was a step toward improving and equalizing access to lifesaving organs for those on the liver transplant wait list, the listing process determining which patients will be considered for transplantation has continued to be a significant hurdle.”

The process is “rife with impediments to equal access to listing,” according to Dr. Warren and colleagues; getting on a waiting list can be affected by factors such as inequitable access to primary care, lack of private health insurance, and subjective selection by transplant centers.

To better characterize these impediments, the investigators gathered center-specific data from the Scientific Registry of Transplant Recipients and the U.S. Census Bureau. The final dataset included 30,353 patients from treated at 109 transplant centers, each of which performed more than 250 transplants between January 2013 and December 2018. The investigators compared waiting list data for each center with demographics from its DSA. Primary variables included race/ethnicity, education level, poverty, and insurance coverage.

Multiple logistic regression analysis was used to compare expected waiting list demographics with observed waiting list demographics with the aid of observed/expected ratios for each race/ethnicity. Univariate and multivariate analyses were used to identify significant predictors, including covariates such as age at listing, distance traveled to transplant center, and center type.

On an adjusted basis, the observed/expected ratios showed that non-Hispanic Black patients were underrepresented on waiting lists at 88 out of 109 centers (81%) and Hispanic patients were underrepresented at 68 centers (62%). In contrast, non-Hispanic White patients were overrepresented on waiting lists at 65 centers (58%). Non-Hispanic White patients were underrepresented on waiting lists at 49 centers, or 45%. Minority underrepresentation was further supported by mean MELD (Model for End-Stage Liver Disease) scores, which were significantly higher among non-Hispanic Black patients (20.2) and Hispanic patients (19.4), compared with non-Hispanic White patients (18.7) (P < .0001 for all) at the time of wait-listing.

Based on the multivariate model, underrepresentation among Black patients was most common in areas with a higher proportion of Black individuals in the population, longer travel distances to transplant centers, and a higher rate of private insurance among transplant recipients. For Hispanic patients, rates of private insurance alone predicted underrepresentation.

Once patients were listed, however, these disparities faded. Non-Hispanic Black patients accounted for 9.8% of all transplants across all hospitals, compared with 7.9% of wait-listed individuals (P < .0001). At approximately two out of three hospitals (65%), the transplanted percentage of Black patients exceeded the wait-listed percentage (P = .002).

“Data from this study show that the wait lists at many transplant centers in the United States underrepresent minority populations, compared with what would be expected based on their service areas,” the investigators concluded. “Future work will need to be devoted to increasing awareness of these trends to promote equitable access to listing for liver transplantation.”

Looking at social determinants of health

According to Lauren D. Nephew, MD, MSc, MAE, of Indiana University, Indianapolis, “The question of access to care is particularly important at this juncture as we examine the inequities that COVID-19 exposed in access to care for racial minorities, and as we prepare for potential changes to health insurance coverage with the new administration.”

Dr. Nephew noted that the reported racial disparities stem from social determinants of health, such as proximity to transplant centers and type of insurance coverage.

“Another striking finding was that the disparity in wait-listing non-Hispanic Black patients increased with the percentage of non-Hispanic Black patients living in the area, further highlighting barriers in access to care in majority Black neighborhoods,” she said. “Inequities such as these are unacceptable, given our mandate to distribute organs in a fair and equitable fashion, and they require prospective studies for further examination.”
 

Identifying discrimination

Lanla Conteh, MD, MPH, of the Ohio State University Wexner Medical Center, Columbus, described how these inequities are magnified through bias in patient selection.

“Often times two very similar patients may present with the same medical profile and social circumstances; however, one is turned down,” she said. “Often the patient turned down is the non-Hispanic Black patient while the non-Hispanic White patient is given a pass.”

Dr. Conteh suggested that the first step in fixing this bias is recognizing that it is a problem and calling it by its proper name.

“As transplant centers, in order to address and change these significant disparities, we must first be willing to acknowledge that they do exist,” she said. “Only then can we move to the next step of developing awareness and methods to actively combat what we should label as systemic discrimination in medicine. Transplantation is a lifesaving treatment for many patients with decompensated liver disease or liver cancer. Ensuring equitable access for all patients and populations is of paramount importance.”

The study was supported by a Health Resources and Services Administration contract, as well as grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. The investigators and interviewees reported no conflicts of interest.

AGA applauds researchers who are working to raise our awareness of health disparities in digestive diseases. AGA is committed to addressing this important societal issue head on. Learn more about AGA’s commitment through the AGA Equity Project.

This article was updated Mar. 12, 2021.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

A novel minimal monitoring (MINMON) approach to hepatitis C virus (HCV) treatment was safe and achieved sustained virology response (SVR) compared to current clinical standards in treatment-naive patients without evidence of decompensated cirrhosis, according to a recent study.

©Jezperklauzen/ThinkStock

“This model may allow for HCV elimination, while minimizing resource use and face-to-face contact,” said investigator Sunil S. Solomon, MBBS, PhD, of Johns Hopkins University in Baltimore. “The COVID-19 pandemic has highlighted the urgent need for simple and safe models of HCV [care] delivery.”

Dr. Solomon described the new approach to HCV treatment during a presentation at this year’s Conference on Retroviruses and Opportunistic Infections virtual meeting.
 

Study design

ACTG A5360 was an international, single-arm, open-label, phase 4 trial that enrolled 400 patients across 38 treatment sites.

The researchers evaluated the efficacy and safety of the MINMON approach in treatment-naive individuals who had no evidence of decompensated cirrhosis. Study participants received a fixed-dose, single-tablet regimen of sofosbuvir 400 mg/velpatasvir 100 mg once daily for 12 weeks.

The MINMON approach comprised four key elements: no pretreatment genotyping, all tablets dispensed at study entry, no scheduled on-treatment clinic visits/labs, and two remote contacts at weeks 4 (adherence evaluation) and 22 (scheduled SVR visit). Unplanned visits for patients concerns were permitted.

Key eligibility criteria included active HCV infection (HCV RNA > 1,000 IU/mL) and no prior HCV treatment history. Persons with HIV coinfection (50% or less of sample) and compensated cirrhosis (20% or less of sample) were also eligible. Persons with chronic hepatitis B virus (HBV) infection and decompensated cirrhosis were excluded.

The primary efficacy endpoint was SVR, defined as HCV RNA less than the lower limit of quantification in the first sample at least 22 weeks post treatment initiation. The primary safety endpoint was any serious adverse events (AEs) occurring between treatment initiation and week 28.
 

Results

Among 400 patients enrolled, 399 (99.8%) were included in the primary efficacy analysis and 397 (99.3%) were included in the safety analysis. The median age of participants was 47 years, and 35% were female sex at birth. At baseline, 166 (42%) patients had HIV coinfection and 34 (9%) had compensated cirrhosis.

After analysis, the researchers found that remote contact was successful at weeks 4 and 22 for 394 (98.7%) and 335 (84.0%) participants, respectively.

In total, 15 (3.8%) participants recorded 21 unplanned visits, 3 (14.3%) of which were due to AEs, none of which were treatment related. Three participants reported losing study medications and one participant prematurely discontinued therapy due to an AE.

HCV RNA data at SVR were available for 396 participants. Overall, 379 patients (95.0%) achieved SVR (95% confidence interval [CI], 92.4%-96.7%).

“The study was not powered for SVR by subgroups, which explains why we observed wide confidence intervals in our forest plot,” Dr. Solomon said.

With respect to safety, serious AEs were reported in 14 (3.5%) participants through week 24 visit, none of which were treatment related or resulted in death.

Dr. Solomon acknowledged that a key limitation of the study was the single-arm design. As a result, there was no direct comparison to standard monitoring practices. In addition, these results may not be generalizable to all nonresearch treatment sites.

“The COVID-19 pandemic has required us to pivot clinical programs to minimize in-person contact, and promote more remote approaches, which is really the essence of the MINMON approach,” Dr. Solomon explained.

“There are really wonderful results in the population that was studied, but may reflect a more adherent patient population,” said moderator Robert T. Schooley, MD, of the University of California, San Diego.

During a discussion, Dr. Solomon noted that the MINMON approach may be further explored in patients who are actively injecting drugs, as these patients were not well represented in the present study.

Dr. Solomon disclosed financial relationships with Gilead Sciences and Abbott Diagnostics. The study was funded by the National Institutes of Health and Gilead Sciences.

Clinicians who manage patients with cirrhosis should incorporate palliative care “irrespective of transplant candidacy,” according to a clinical practice update from the American Gastroenterological Association.

“[T]his care should be based on needs assessment instead of prognosis alone, delivered concurrently with curative or life-prolonging treatments, and tailored to the stage of disease,” wrote Puneeta Tandon, MD, of University of Alberta in Edmonton, Alta., and associates. Their report is in Clinical Gastroenterology and Hepatology.

Cirrhosis has a median survival ranging from 2 years for decompensated disease to 12 years for compensated disease, according to one systemic review. Moreover, even compensated cirrhosis incurs “a high burden of physical and psychological symptoms,” which increases as cirrhosis progresses, the update authors noted.

According to another review, there is established evidence outside cirrhosis that palliative care – including comprehensive symptom management, advance care planning, and timely referrals to specialty palliative care and hospice support – has the potential to significantly improve quality of life, end-of-life care, health care costs, coordination among providers, and caregiver outcomes.

However, the update authors noted that there remain few guidelines or guidance statements regarding palliative care in cirrhosis. Hence, the clinical practice update reviews 10 best practices to help clinicians fill this gap.

Providers “from any specialty, within any healthcare setting” can help provide palliative care for patients with cirrhosis, the experts emphasized. This is, in part, because of the growing population with cirrhosis being met with a limited number of palliative care specialists; dealing with this reality can be helped by inviting other providers to learn about and engage in palliative care.

Another best practice statement addressed assessing symptoms “within physical, psychological, social, and spiritual domains related to [patients’] liver disease, its treatment, and prognosis.” This approach is needed because of the complex effects that a life-threatening illness and its symptoms can have on many variables, including loss of independence/identity, financial stress, and impact on personal relationships. A systematic review of symptom prevalence in end-stage liver disease revealed a complex milieu, including pain, muscle cramps, sexual dysfunction, insomnia, and anxiety.

High-quality communication is important in palliative care, including discussion of prognosis and goals of care. Providers specializing in gastroenterology/hepatology should reevaluate prognosis and clarify prognosis and goals of care with patients and caregivers during routine visits and sentinel events, such as new complications, a hospital or intensive care admission, and when transplant eligibility is determined. However, prognostication in cirrhosis can be challenging, the experts noted. The update authors also acknowledged that, while more research is needed to inform practice regarding communicating with patients with serious illness about palliative care and goals of care, there are courses and resources meant to help improve those skills, including those provided by Vital Talk, Respecting Choices, and the Serious Illness Conversation Guide.

Cirrhosis “has physical, mental, and financial consequences” for caregivers, especially when patients have decompensated disease. To support caregivers, clinicians can routinely evaluate their burdens and needs. Tools such as the Caregiver Strain Index are useful and can be administered by ancillary staff. Clinicians also can reach out to primary care and palliative care providers to identify local resources for caregiver support.

“Because lack of time is one of the major barriers to administering palliative care, healthcare providers should consider how they can optimize efficiencies in palliative care delivery,” the experts wrote. Examples include identifying local billing codes, arranging for ancillary staff to screen patients on their palliative care needs, and setting up multidisciplinary teams that work together to deliver palliative care. If access to specialty palliative care is limited, providers can collaborate with local specialist teams to set “clear triggers and pathways for referral.”

Finally, hospice referrals are often delayed for patients with cirrhosis. “Find out your local referral criteria for hospice and what would be required to refer a cirrhosis patient there,” the experts advised. “Healthcare providers caring for patients with cirrhosis should provide timely referral to hospice for patients who have comfort-oriented goals and prognosis of 6 months or less.”

The authors of the clinical practice update received no funding support. They reported having no relevant conflicts of interest.

Clinicians who manage patients with cirrhosis should incorporate palliative care “irrespective of transplant candidacy,” according to a clinical practice update from the American Gastroenterological Association.

“[T]his care should be based on needs assessment instead of prognosis alone, delivered concurrently with curative or life-prolonging treatments, and tailored to the stage of disease,” wrote Puneeta Tandon, MD, of University of Alberta in Edmonton, Alta., and associates. Their report is in Clinical Gastroenterology and Hepatology.

Cirrhosis has a median survival ranging from 2 years for decompensated disease to 12 years for compensated disease, according to one systemic review. Moreover, even compensated cirrhosis incurs “a high burden of physical and psychological symptoms,” which increases as cirrhosis progresses, the update authors noted.

According to another review, there is established evidence outside cirrhosis that palliative care – including comprehensive symptom management, advance care planning, and timely referrals to specialty palliative care and hospice support – has the potential to significantly improve quality of life, end-of-life care, health care costs, coordination among providers, and caregiver outcomes.

However, the update authors noted that there remain few guidelines or guidance statements regarding palliative care in cirrhosis. Hence, the clinical practice update reviews 10 best practices to help clinicians fill this gap.

Providers “from any specialty, within any healthcare setting” can help provide palliative care for patients with cirrhosis, the experts emphasized. This is, in part, because of the growing population with cirrhosis being met with a limited number of palliative care specialists; dealing with this reality can be helped by inviting other providers to learn about and engage in palliative care.

Another best practice statement addressed assessing symptoms “within physical, psychological, social, and spiritual domains related to [patients’] liver disease, its treatment, and prognosis.” This approach is needed because of the complex effects that a life-threatening illness and its symptoms can have on many variables, including loss of independence/identity, financial stress, and impact on personal relationships. A systematic review of symptom prevalence in end-stage liver disease revealed a complex milieu, including pain, muscle cramps, sexual dysfunction, insomnia, and anxiety.

High-quality communication is important in palliative care, including discussion of prognosis and goals of care. Providers specializing in gastroenterology/hepatology should reevaluate prognosis and clarify prognosis and goals of care with patients and caregivers during routine visits and sentinel events, such as new complications, a hospital or intensive care admission, and when transplant eligibility is determined. However, prognostication in cirrhosis can be challenging, the experts noted. The update authors also acknowledged that, while more research is needed to inform practice regarding communicating with patients with serious illness about palliative care and goals of care, there are courses and resources meant to help improve those skills, including those provided by Vital Talk, Respecting Choices, and the Serious Illness Conversation Guide.

Cirrhosis “has physical, mental, and financial consequences” for caregivers, especially when patients have decompensated disease. To support caregivers, clinicians can routinely evaluate their burdens and needs. Tools such as the Caregiver Strain Index are useful and can be administered by ancillary staff. Clinicians also can reach out to primary care and palliative care providers to identify local resources for caregiver support.

“Because lack of time is one of the major barriers to administering palliative care, healthcare providers should consider how they can optimize efficiencies in palliative care delivery,” the experts wrote. Examples include identifying local billing codes, arranging for ancillary staff to screen patients on their palliative care needs, and setting up multidisciplinary teams that work together to deliver palliative care. If access to specialty palliative care is limited, providers can collaborate with local specialist teams to set “clear triggers and pathways for referral.”

Finally, hospice referrals are often delayed for patients with cirrhosis. “Find out your local referral criteria for hospice and what would be required to refer a cirrhosis patient there,” the experts advised. “Healthcare providers caring for patients with cirrhosis should provide timely referral to hospice for patients who have comfort-oriented goals and prognosis of 6 months or less.”

The authors of the clinical practice update received no funding support. They reported having no relevant conflicts of interest.

Clinicians who manage patients with cirrhosis should incorporate palliative care “irrespective of transplant candidacy,” according to a clinical practice update from the American Gastroenterological Association.

“[T]his care should be based on needs assessment instead of prognosis alone, delivered concurrently with curative or life-prolonging treatments, and tailored to the stage of disease,” wrote Puneeta Tandon, MD, of University of Alberta in Edmonton, Alta., and associates. Their report is in Clinical Gastroenterology and Hepatology.

Cirrhosis has a median survival ranging from 2 years for decompensated disease to 12 years for compensated disease, according to one systemic review. Moreover, even compensated cirrhosis incurs “a high burden of physical and psychological symptoms,” which increases as cirrhosis progresses, the update authors noted.

According to another review, there is established evidence outside cirrhosis that palliative care – including comprehensive symptom management, advance care planning, and timely referrals to specialty palliative care and hospice support – has the potential to significantly improve quality of life, end-of-life care, health care costs, coordination among providers, and caregiver outcomes.

However, the update authors noted that there remain few guidelines or guidance statements regarding palliative care in cirrhosis. Hence, the clinical practice update reviews 10 best practices to help clinicians fill this gap.

Providers “from any specialty, within any healthcare setting” can help provide palliative care for patients with cirrhosis, the experts emphasized. This is, in part, because of the growing population with cirrhosis being met with a limited number of palliative care specialists; dealing with this reality can be helped by inviting other providers to learn about and engage in palliative care.

Another best practice statement addressed assessing symptoms “within physical, psychological, social, and spiritual domains related to [patients’] liver disease, its treatment, and prognosis.” This approach is needed because of the complex effects that a life-threatening illness and its symptoms can have on many variables, including loss of independence/identity, financial stress, and impact on personal relationships. A systematic review of symptom prevalence in end-stage liver disease revealed a complex milieu, including pain, muscle cramps, sexual dysfunction, insomnia, and anxiety.

High-quality communication is important in palliative care, including discussion of prognosis and goals of care. Providers specializing in gastroenterology/hepatology should reevaluate prognosis and clarify prognosis and goals of care with patients and caregivers during routine visits and sentinel events, such as new complications, a hospital or intensive care admission, and when transplant eligibility is determined. However, prognostication in cirrhosis can be challenging, the experts noted. The update authors also acknowledged that, while more research is needed to inform practice regarding communicating with patients with serious illness about palliative care and goals of care, there are courses and resources meant to help improve those skills, including those provided by Vital Talk, Respecting Choices, and the Serious Illness Conversation Guide.

Cirrhosis “has physical, mental, and financial consequences” for caregivers, especially when patients have decompensated disease. To support caregivers, clinicians can routinely evaluate their burdens and needs. Tools such as the Caregiver Strain Index are useful and can be administered by ancillary staff. Clinicians also can reach out to primary care and palliative care providers to identify local resources for caregiver support.

“Because lack of time is one of the major barriers to administering palliative care, healthcare providers should consider how they can optimize efficiencies in palliative care delivery,” the experts wrote. Examples include identifying local billing codes, arranging for ancillary staff to screen patients on their palliative care needs, and setting up multidisciplinary teams that work together to deliver palliative care. If access to specialty palliative care is limited, providers can collaborate with local specialist teams to set “clear triggers and pathways for referral.”

Finally, hospice referrals are often delayed for patients with cirrhosis. “Find out your local referral criteria for hospice and what would be required to refer a cirrhosis patient there,” the experts advised. “Healthcare providers caring for patients with cirrhosis should provide timely referral to hospice for patients who have comfort-oriented goals and prognosis of 6 months or less.”

The authors of the clinical practice update received no funding support. They reported having no relevant conflicts of interest.

Patients taking methotrexate for psoriasis or psoriatic arthritis (PsA) were at a higher risk of developing liver disease than were patients with rheumatoid arthritis (RA) on methotrexate, in a large population-based study published in the Journal of the American Academy of Dermatology.

Wavebreakmedia Ltd/ThinkStockPhotos.com

“These findings suggest that conservative liver monitoring is warranted in patients receiving methotrexate for psoriatic disease,” particularly psoriasis, the investigators concluded.

• Mild liver disease: The IR per 1,000 person-years for patients with psoriasis was 4.22 per 1,000 person-years (95% confidence interval, 3.61-4.91), compared with 2.39 per 1,000 person-years (95% CI, 1.95-2.91) for patients with PsA, and 1.39 per 1,000 person-years (95% CI, 1.25-1.55) for patients with RA.
• Moderate to severe liver disease: The IR for patients with psoriasis was 0.98 per 1,000 person years (95% CI, 0.70-1.33), compared with 0.51 (95% CI, 0.32-0.77) for patients with PsA, and 0.46 (95% CI, 0.37-0.55) for patients with RA.
• Cirrhosis: The IR for patients with psoriasis was 1.89 per 1,000 person years (95% CI, 1.49-2.37), compared with 0.84 (95% CI, 0.59-1.16) for patients with PsA, and 0.42 (95% CI, 0.34-0.51) for patients with RA.
• Cirrhosis-related hospitalization: This was the least common outcome, with an IR per 1,000 person years of 0.73 (95% CI, 0.49-1.05) for patients with psoriasis, 0.32 (95% CI, 0.18-0.54) for patients with PsA, and 0.22 (95% CI, 0.17-0.29) for patients with RA.

When results were adjusted with Cox regression analyses, the psoriasis group had a significantly increased risk compared with the RA group with regard to mild liver disease (hazard ratio, 2.22; 95% CI, 1.81-2.72), moderate to-severe liver disease (HR, 1.56; 95% CI, 1.05-2.31), cirrhosis (HR, 3.38; 95% CI, 2.44-4.68), and cirrhosis-related hospitalization (HR, 2.25; 95% CI, 1.37-3.69). Compared with patients with RA, patients with PsA had a significantly increased risk of mild liver disease (HR, 1.27; 95% CI, 1.01-1.60) and cirrhosis (HR, 1.63; 95% CI, 1.10-2.42), but not moderate to severe liver disease or hospitalizations related to cirrhosis.

The researchers noted it is unclear why there was a difference in risk between the three groups of patients.

“While such differences in hepatotoxicity risk were previously attributed to differences in rates of alcoholism, obesity, diabetes, and other comorbidities between the disease populations, our study finds that the underlying disease influences liver disease risk independent of age, sex, smoking, alcohol use, diabetes, hyperlipidemia, overall comorbidity, and weekly methotrexate dose,” wrote Dr. Gelfand and colleagues.

As far as they know, their study “ is one of the first and largest population-based studies to directly compare” liver disease in these three groups of patients on methotrexate, they wrote, noting that earlier studies were smaller and frequently used indirect hepatic injury measures.

Limitations of the study included the inability to account for disease severity as well as the potential for disease misclassification, surveillance bias, and confounding by unmeasured variables such as body mass index. Further, the results do not show whether “liver disease is attributed to methotrexate use, the underlying disease, or a combination of both,” the researchers noted.

Four authors report relationships in the form of consultancies, continuing medical information payments, deputy editor positions, fellowship support, individual or spousal honoraria, patents, research grants, and/or speaker positions with various pharmaceutical companies, medical journals, societies, and other organizations; two authors had no disclosures. There was no funding source.

Patients taking methotrexate for psoriasis or psoriatic arthritis (PsA) were at a higher risk of developing liver disease than were patients with rheumatoid arthritis (RA) on methotrexate, in a large population-based study published in the Journal of the American Academy of Dermatology.

Wavebreakmedia Ltd/ThinkStockPhotos.com

“These findings suggest that conservative liver monitoring is warranted in patients receiving methotrexate for psoriatic disease,” particularly psoriasis, the investigators concluded.

• Mild liver disease: The IR per 1,000 person-years for patients with psoriasis was 4.22 per 1,000 person-years (95% confidence interval, 3.61-4.91), compared with 2.39 per 1,000 person-years (95% CI, 1.95-2.91) for patients with PsA, and 1.39 per 1,000 person-years (95% CI, 1.25-1.55) for patients with RA.
• Moderate to severe liver disease: The IR for patients with psoriasis was 0.98 per 1,000 person years (95% CI, 0.70-1.33), compared with 0.51 (95% CI, 0.32-0.77) for patients with PsA, and 0.46 (95% CI, 0.37-0.55) for patients with RA.
• Cirrhosis: The IR for patients with psoriasis was 1.89 per 1,000 person years (95% CI, 1.49-2.37), compared with 0.84 (95% CI, 0.59-1.16) for patients with PsA, and 0.42 (95% CI, 0.34-0.51) for patients with RA.
• Cirrhosis-related hospitalization: This was the least common outcome, with an IR per 1,000 person years of 0.73 (95% CI, 0.49-1.05) for patients with psoriasis, 0.32 (95% CI, 0.18-0.54) for patients with PsA, and 0.22 (95% CI, 0.17-0.29) for patients with RA.

When results were adjusted with Cox regression analyses, the psoriasis group had a significantly increased risk compared with the RA group with regard to mild liver disease (hazard ratio, 2.22; 95% CI, 1.81-2.72), moderate to-severe liver disease (HR, 1.56; 95% CI, 1.05-2.31), cirrhosis (HR, 3.38; 95% CI, 2.44-4.68), and cirrhosis-related hospitalization (HR, 2.25; 95% CI, 1.37-3.69). Compared with patients with RA, patients with PsA had a significantly increased risk of mild liver disease (HR, 1.27; 95% CI, 1.01-1.60) and cirrhosis (HR, 1.63; 95% CI, 1.10-2.42), but not moderate to severe liver disease or hospitalizations related to cirrhosis.

The researchers noted it is unclear why there was a difference in risk between the three groups of patients.

“While such differences in hepatotoxicity risk were previously attributed to differences in rates of alcoholism, obesity, diabetes, and other comorbidities between the disease populations, our study finds that the underlying disease influences liver disease risk independent of age, sex, smoking, alcohol use, diabetes, hyperlipidemia, overall comorbidity, and weekly methotrexate dose,” wrote Dr. Gelfand and colleagues.

As far as they know, their study “ is one of the first and largest population-based studies to directly compare” liver disease in these three groups of patients on methotrexate, they wrote, noting that earlier studies were smaller and frequently used indirect hepatic injury measures.

Limitations of the study included the inability to account for disease severity as well as the potential for disease misclassification, surveillance bias, and confounding by unmeasured variables such as body mass index. Further, the results do not show whether “liver disease is attributed to methotrexate use, the underlying disease, or a combination of both,” the researchers noted.

Four authors report relationships in the form of consultancies, continuing medical information payments, deputy editor positions, fellowship support, individual or spousal honoraria, patents, research grants, and/or speaker positions with various pharmaceutical companies, medical journals, societies, and other organizations; two authors had no disclosures. There was no funding source.

Patients taking methotrexate for psoriasis or psoriatic arthritis (PsA) were at a higher risk of developing liver disease than were patients with rheumatoid arthritis (RA) on methotrexate, in a large population-based study published in the Journal of the American Academy of Dermatology.

Wavebreakmedia Ltd/ThinkStockPhotos.com

“These findings suggest that conservative liver monitoring is warranted in patients receiving methotrexate for psoriatic disease,” particularly psoriasis, the investigators concluded.

• Mild liver disease: The IR per 1,000 person-years for patients with psoriasis was 4.22 per 1,000 person-years (95% confidence interval, 3.61-4.91), compared with 2.39 per 1,000 person-years (95% CI, 1.95-2.91) for patients with PsA, and 1.39 per 1,000 person-years (95% CI, 1.25-1.55) for patients with RA.
• Moderate to severe liver disease: The IR for patients with psoriasis was 0.98 per 1,000 person years (95% CI, 0.70-1.33), compared with 0.51 (95% CI, 0.32-0.77) for patients with PsA, and 0.46 (95% CI, 0.37-0.55) for patients with RA.
• Cirrhosis: The IR for patients with psoriasis was 1.89 per 1,000 person years (95% CI, 1.49-2.37), compared with 0.84 (95% CI, 0.59-1.16) for patients with PsA, and 0.42 (95% CI, 0.34-0.51) for patients with RA.
• Cirrhosis-related hospitalization: This was the least common outcome, with an IR per 1,000 person years of 0.73 (95% CI, 0.49-1.05) for patients with psoriasis, 0.32 (95% CI, 0.18-0.54) for patients with PsA, and 0.22 (95% CI, 0.17-0.29) for patients with RA.

When results were adjusted with Cox regression analyses, the psoriasis group had a significantly increased risk compared with the RA group with regard to mild liver disease (hazard ratio, 2.22; 95% CI, 1.81-2.72), moderate to-severe liver disease (HR, 1.56; 95% CI, 1.05-2.31), cirrhosis (HR, 3.38; 95% CI, 2.44-4.68), and cirrhosis-related hospitalization (HR, 2.25; 95% CI, 1.37-3.69). Compared with patients with RA, patients with PsA had a significantly increased risk of mild liver disease (HR, 1.27; 95% CI, 1.01-1.60) and cirrhosis (HR, 1.63; 95% CI, 1.10-2.42), but not moderate to severe liver disease or hospitalizations related to cirrhosis.

The researchers noted it is unclear why there was a difference in risk between the three groups of patients.

“While such differences in hepatotoxicity risk were previously attributed to differences in rates of alcoholism, obesity, diabetes, and other comorbidities between the disease populations, our study finds that the underlying disease influences liver disease risk independent of age, sex, smoking, alcohol use, diabetes, hyperlipidemia, overall comorbidity, and weekly methotrexate dose,” wrote Dr. Gelfand and colleagues.

As far as they know, their study “ is one of the first and largest population-based studies to directly compare” liver disease in these three groups of patients on methotrexate, they wrote, noting that earlier studies were smaller and frequently used indirect hepatic injury measures.

Limitations of the study included the inability to account for disease severity as well as the potential for disease misclassification, surveillance bias, and confounding by unmeasured variables such as body mass index. Further, the results do not show whether “liver disease is attributed to methotrexate use, the underlying disease, or a combination of both,” the researchers noted.

Four authors report relationships in the form of consultancies, continuing medical information payments, deputy editor positions, fellowship support, individual or spousal honoraria, patents, research grants, and/or speaker positions with various pharmaceutical companies, medical journals, societies, and other organizations; two authors had no disclosures. There was no funding source.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.

Endoscopy with biopsies is best for diagnosing immune-mediated enterocolitis in patients receiving immune checkpoint inhibitors (ICIs), but another option is to first test the stool for lactoferrin or calprotectin to identify patients with mild diarrhea who could benefit from endoscopy, according to a clinical practice update from the American Gastroenterological Association.

Writing in Gastroenterology, Michael Dougan, MD, PhD, of Harvard Medical School, Boston, and colleagues noted that stool lactoferrin had been found in one study to be 90% sensitive for detecting histologic inflammation, while another study found that mucosal inflammation is absent in 20%-30% of patients with suspected ICI enterocolitis. Nonetheless, clinicians should consider diagnostic endoscopy before starting high-dose corticosteroids for ICI enterocolitis, especially because “colonic ulceration identified by endoscopy is the only established factor that predicts how ICI enterocolitis will respond to treatment,” Dr. Dougan and colleagues wrote. If performed, endoscopy must be prompt because ICI colitis can progress within days, especially if patients are receiving ipilimumab.

ICIs can induce autoimmune inflammation in almost any organ system because they target pathways that play “key roles in regulating autoimmunity,” the experts wrote. The gastrointestinal tract is one of the most common sites of toxicity: One study from 2006 and another from 2019 suggested that colitis, with or without enteritis, affects up to 40% of patients depending on the pathway targeted by the treatment. Oncologists manage most gastrointestinal ICI toxicities, but gastroenterologists and hepatologists often help with diagnosis, risk assessment, and managing complex, atypical, or treatment-refractory cases; to help guide this process, the experts reviewed the literature and made 15 relevant recommendations.

The authors noted that the differential diagnosis is broad, but suggested that Clostridioides difficile testing and stool culture (or stool pathogen testing, where available) should be performed in all patients to rule out infectious causes prior to any immunosuppressive treatments, such as corticosteroids. Abdominal imaging is not recommended if a patient only has diarrhea but can help rule out complications if fever, bleeding, or abdominal pain are also present. Laboratory blood tests are rarely informative.

High-dose glucocorticoids are usually effective, often being started at 0.5-2.0 mg/kg prednisone or equivalent daily and tapered over 4-6 weeks after clinical improvement, but these doses and schedules have not been rigorously examined. For glucocorticoid-refractory ICI enterocolitis, infliximab and vedolizumab “are reasonable options” for second line immunosuppression and should be individualized based on the underlying cancer and other risk factors; patients usually respond to these immunomodulators in less than a week, “an important contrast with IBD,” the experts wrote. Most cases of ICI enterocolitis do not recur unless the ICI is restarted, but “many patients require the full loading dose for infliximab or vedolizumab, and maintenance therapy may still be required for certain cases.”

ICI-induced hepatitis is less common, affecting less than 5% of patients in clinical trials according to the authors, but incidence rises if patients are on ICI combinations or an ICI plus chemotherapy. Before starting any ICI, patients’ total bilirubin, alkaline phosphatase, AST, and ALT levels should be checked, as should testing for hepatitis B. Liver chemistries should be repeated before each ICI cycle, and rising chemistries should trigger an assessment for other causes of liver injury.

Patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 1 hepatitis – defined as AST or ALT 1-3 times the upper limit of normal or total bilirubin 1-1.5 times upper limit of normal – should receive liver function tests once or twice weekly. For CTCAE grade 2 hepatitis, (AST/ALT more than 3-5 times upper limit of normal or total bilirubin more than 1.5-3 times upper limit of normal), ICI should be held until resolution to grade 1, and corticosteroids (prednisone or its equivalent dosed at 0.5-1.0 mg/kg daily) should be considered if there are clinical symptoms of liver toxicity. For grade 3 hepatitis (AST/ALT greater than 5-20 times upper limit of normal or total bilirubin more than 3-10 times upper limit of normal), ICI therapy should be halted, “and urgent consultation with a gastroenterologist/hepatologist is appropriate.” In this context, methylprednisone (1-2 mg/kg) is suggested, and azathioprine or mycophenolate mofetil can be considered if clinical hepatitis does not improve in 3-5 days. For CTCAE grade 4 hepatitis, hospitalization is recommended, and patients should permanently stop the ICI and receive 2 mg/kg per day of methylprednisolone or its equivalent.

The authors received no funding support. Dr. Dougan reported consulting or advisory relationships with Neoleukin Therapeutics, Genentech, Tillotts Pharma, and Partner Therapeutics and grant support from Novartis and Genentech. Two coauthors also reported ties to several pharmaceutical companies.
 

Endoscopy with biopsies is best for diagnosing immune-mediated enterocolitis in patients receiving immune checkpoint inhibitors (ICIs), but another option is to first test the stool for lactoferrin or calprotectin to identify patients with mild diarrhea who could benefit from endoscopy, according to a clinical practice update from the American Gastroenterological Association.

Writing in Gastroenterology, Michael Dougan, MD, PhD, of Harvard Medical School, Boston, and colleagues noted that stool lactoferrin had been found in one study to be 90% sensitive for detecting histologic inflammation, while another study found that mucosal inflammation is absent in 20%-30% of patients with suspected ICI enterocolitis. Nonetheless, clinicians should consider diagnostic endoscopy before starting high-dose corticosteroids for ICI enterocolitis, especially because “colonic ulceration identified by endoscopy is the only established factor that predicts how ICI enterocolitis will respond to treatment,” Dr. Dougan and colleagues wrote. If performed, endoscopy must be prompt because ICI colitis can progress within days, especially if patients are receiving ipilimumab.

ICIs can induce autoimmune inflammation in almost any organ system because they target pathways that play “key roles in regulating autoimmunity,” the experts wrote. The gastrointestinal tract is one of the most common sites of toxicity: One study from 2006 and another from 2019 suggested that colitis, with or without enteritis, affects up to 40% of patients depending on the pathway targeted by the treatment. Oncologists manage most gastrointestinal ICI toxicities, but gastroenterologists and hepatologists often help with diagnosis, risk assessment, and managing complex, atypical, or treatment-refractory cases; to help guide this process, the experts reviewed the literature and made 15 relevant recommendations.

The authors noted that the differential diagnosis is broad, but suggested that Clostridioides difficile testing and stool culture (or stool pathogen testing, where available) should be performed in all patients to rule out infectious causes prior to any immunosuppressive treatments, such as corticosteroids. Abdominal imaging is not recommended if a patient only has diarrhea but can help rule out complications if fever, bleeding, or abdominal pain are also present. Laboratory blood tests are rarely informative.

High-dose glucocorticoids are usually effective, often being started at 0.5-2.0 mg/kg prednisone or equivalent daily and tapered over 4-6 weeks after clinical improvement, but these doses and schedules have not been rigorously examined. For glucocorticoid-refractory ICI enterocolitis, infliximab and vedolizumab “are reasonable options” for second line immunosuppression and should be individualized based on the underlying cancer and other risk factors; patients usually respond to these immunomodulators in less than a week, “an important contrast with IBD,” the experts wrote. Most cases of ICI enterocolitis do not recur unless the ICI is restarted, but “many patients require the full loading dose for infliximab or vedolizumab, and maintenance therapy may still be required for certain cases.”

ICI-induced hepatitis is less common, affecting less than 5% of patients in clinical trials according to the authors, but incidence rises if patients are on ICI combinations or an ICI plus chemotherapy. Before starting any ICI, patients’ total bilirubin, alkaline phosphatase, AST, and ALT levels should be checked, as should testing for hepatitis B. Liver chemistries should be repeated before each ICI cycle, and rising chemistries should trigger an assessment for other causes of liver injury.

Patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 1 hepatitis – defined as AST or ALT 1-3 times the upper limit of normal or total bilirubin 1-1.5 times upper limit of normal – should receive liver function tests once or twice weekly. For CTCAE grade 2 hepatitis, (AST/ALT more than 3-5 times upper limit of normal or total bilirubin more than 1.5-3 times upper limit of normal), ICI should be held until resolution to grade 1, and corticosteroids (prednisone or its equivalent dosed at 0.5-1.0 mg/kg daily) should be considered if there are clinical symptoms of liver toxicity. For grade 3 hepatitis (AST/ALT greater than 5-20 times upper limit of normal or total bilirubin more than 3-10 times upper limit of normal), ICI therapy should be halted, “and urgent consultation with a gastroenterologist/hepatologist is appropriate.” In this context, methylprednisone (1-2 mg/kg) is suggested, and azathioprine or mycophenolate mofetil can be considered if clinical hepatitis does not improve in 3-5 days. For CTCAE grade 4 hepatitis, hospitalization is recommended, and patients should permanently stop the ICI and receive 2 mg/kg per day of methylprednisolone or its equivalent.

The authors received no funding support. Dr. Dougan reported consulting or advisory relationships with Neoleukin Therapeutics, Genentech, Tillotts Pharma, and Partner Therapeutics and grant support from Novartis and Genentech. Two coauthors also reported ties to several pharmaceutical companies.
 

Endoscopy with biopsies is best for diagnosing immune-mediated enterocolitis in patients receiving immune checkpoint inhibitors (ICIs), but another option is to first test the stool for lactoferrin or calprotectin to identify patients with mild diarrhea who could benefit from endoscopy, according to a clinical practice update from the American Gastroenterological Association.

Writing in Gastroenterology, Michael Dougan, MD, PhD, of Harvard Medical School, Boston, and colleagues noted that stool lactoferrin had been found in one study to be 90% sensitive for detecting histologic inflammation, while another study found that mucosal inflammation is absent in 20%-30% of patients with suspected ICI enterocolitis. Nonetheless, clinicians should consider diagnostic endoscopy before starting high-dose corticosteroids for ICI enterocolitis, especially because “colonic ulceration identified by endoscopy is the only established factor that predicts how ICI enterocolitis will respond to treatment,” Dr. Dougan and colleagues wrote. If performed, endoscopy must be prompt because ICI colitis can progress within days, especially if patients are receiving ipilimumab.

ICIs can induce autoimmune inflammation in almost any organ system because they target pathways that play “key roles in regulating autoimmunity,” the experts wrote. The gastrointestinal tract is one of the most common sites of toxicity: One study from 2006 and another from 2019 suggested that colitis, with or without enteritis, affects up to 40% of patients depending on the pathway targeted by the treatment. Oncologists manage most gastrointestinal ICI toxicities, but gastroenterologists and hepatologists often help with diagnosis, risk assessment, and managing complex, atypical, or treatment-refractory cases; to help guide this process, the experts reviewed the literature and made 15 relevant recommendations.

The authors noted that the differential diagnosis is broad, but suggested that Clostridioides difficile testing and stool culture (or stool pathogen testing, where available) should be performed in all patients to rule out infectious causes prior to any immunosuppressive treatments, such as corticosteroids. Abdominal imaging is not recommended if a patient only has diarrhea but can help rule out complications if fever, bleeding, or abdominal pain are also present. Laboratory blood tests are rarely informative.

High-dose glucocorticoids are usually effective, often being started at 0.5-2.0 mg/kg prednisone or equivalent daily and tapered over 4-6 weeks after clinical improvement, but these doses and schedules have not been rigorously examined. For glucocorticoid-refractory ICI enterocolitis, infliximab and vedolizumab “are reasonable options” for second line immunosuppression and should be individualized based on the underlying cancer and other risk factors; patients usually respond to these immunomodulators in less than a week, “an important contrast with IBD,” the experts wrote. Most cases of ICI enterocolitis do not recur unless the ICI is restarted, but “many patients require the full loading dose for infliximab or vedolizumab, and maintenance therapy may still be required for certain cases.”

ICI-induced hepatitis is less common, affecting less than 5% of patients in clinical trials according to the authors, but incidence rises if patients are on ICI combinations or an ICI plus chemotherapy. Before starting any ICI, patients’ total bilirubin, alkaline phosphatase, AST, and ALT levels should be checked, as should testing for hepatitis B. Liver chemistries should be repeated before each ICI cycle, and rising chemistries should trigger an assessment for other causes of liver injury.

Patients with Common Terminology Criteria for Adverse Events (CTCAE) grade 1 hepatitis – defined as AST or ALT 1-3 times the upper limit of normal or total bilirubin 1-1.5 times upper limit of normal – should receive liver function tests once or twice weekly. For CTCAE grade 2 hepatitis, (AST/ALT more than 3-5 times upper limit of normal or total bilirubin more than 1.5-3 times upper limit of normal), ICI should be held until resolution to grade 1, and corticosteroids (prednisone or its equivalent dosed at 0.5-1.0 mg/kg daily) should be considered if there are clinical symptoms of liver toxicity. For grade 3 hepatitis (AST/ALT greater than 5-20 times upper limit of normal or total bilirubin more than 3-10 times upper limit of normal), ICI therapy should be halted, “and urgent consultation with a gastroenterologist/hepatologist is appropriate.” In this context, methylprednisone (1-2 mg/kg) is suggested, and azathioprine or mycophenolate mofetil can be considered if clinical hepatitis does not improve in 3-5 days. For CTCAE grade 4 hepatitis, hospitalization is recommended, and patients should permanently stop the ICI and receive 2 mg/kg per day of methylprednisolone or its equivalent.

The authors received no funding support. Dr. Dougan reported consulting or advisory relationships with Neoleukin Therapeutics, Genentech, Tillotts Pharma, and Partner Therapeutics and grant support from Novartis and Genentech. Two coauthors also reported ties to several pharmaceutical companies.
 

The incidence of autoimmune hepatitis (AIH) may be rising, according to a prospective population-based study conducted in New Zealand.

From 2008 to 2016, the rising incidence of AIH led to a 40% increase in point prevalence, reported lead author Mehul Lamba, MD, of Christchurch (New Zealand) Hospital and colleagues.

The incidence of autoimmune hepatitis (AIH) may be rising, according to a prospective population-based study conducted in New Zealand.

From 2008 to 2016, the rising incidence of AIH led to a 40% increase in point prevalence, reported lead author Mehul Lamba, MD, of Christchurch (New Zealand) Hospital and colleagues.

The incidence of autoimmune hepatitis (AIH) may be rising, according to a prospective population-based study conducted in New Zealand.

From 2008 to 2016, the rising incidence of AIH led to a 40% increase in point prevalence, reported lead author Mehul Lamba, MD, of Christchurch (New Zealand) Hospital and colleagues.

Mounting evidence of strikingly high prevalence rates of fatty liver disease, advanced fibrosis, and cirrhosis among patients with type 2 diabetes has led to calls for heightened awareness and screening to identify these patients and target treatments to reduce their risk for irreversible liver damage.

Courtesy Dr. Christos S. Mantzoros

Among these calls is a pending statement from the Endocrine Society, the American Association of Clinical Endocrinologists, the American Gastroenterology Association, and other groups on what the growing appreciation of highly prevalent liver disease in patients with type 2 diabetes (T2D) means for assessing and managing patients. Publication of the statement is expected by spring 2021, said Christos S. Mantzoros, MD, DSc, PhD, chief of endocrinology for the Veterans Affairs Boston Healthcare System and a representative from the Endocrine Society to the statement-writing panel.

This upcoming “Call to Action” from these groups argues for a “need to collaborate across disciplines, and work together on establishing clinical guidelines, and creating new diagnostics and therapeutics,” said Dr. Mantzoros in an interview.

“Over time, it is becoming clearer that management of NAFLD [nonalcoholic fatty liver disease]/NASH [nonalcoholic steatohepatitis] requires a multidisciplinary panel of doctors ranging from primary care practitioners, to endocrinologists, and hepatologists. Given that the nature of the disease crosses scientific discipline boundaries, and that the number of patients is so large (it is estimated that about one in four U.S. adults have NAFLD), not all patients can be treated at the limited number of hepatology centers.

“However, not all stakeholders have fully realized this fact, and no effort had been undertaken so far by any professional society to develop a coordinated approach and clinical care pathway for NAFLD/NASH. The ‘Call to Action’ meeting can be considered as a starting point for such an important effort,” said Dr. Mantzoros, who is also a professor of medicine at Harvard Medical School and director of the human nutrition unit at Beth Israel Deaconess Medical Center, both in Boston.
 

Dramatic prevalence rates in patients with T2D

Results from two independent epidemiology reports, published in December 2020, documented steatosis (the fatty liver of NAFLD) in 70%-74% of unselected U.S. patients with T2D, advanced liver fibrosis accompanying this disease in 6%-15%, and previously unrecognized cirrhosis in 3%-8%.

One of these reports analyzed 825 patients with T2D included in the National Health and Nutritional Examination Survey of 2017-2018 run by the Centers for Disease Control and Prevention. All these patients, selected to be representative of the overall U.S. adult population with T2D, underwent transient elastography to identify steatosis and fibrosis, the first U.S. National Health Survey to run this type of population-based survey. The results showed an overall steatosis prevalence of 74% with grade 3 steatosis in 58%, advanced liver fibrosis in 15%, and cirrhosis in 8%, reported the team of Italian researchers who analyzed the data .

The second study focused on a single-center series of 561 patients with T2D who also underwent screening by transient elastography during 2018-2020 and had no history of NAFLD or other liver disease, or alcohol abuse. The imaging results showed a NAFLD prevalence of 70%, with 54% of the entire group diagnosed with severe steatosis, severe fibrosis in 6%, and cirrhosis in 3%. Among the 54% of patients with severe steatosis, 30% also had severe liver fibrosis. About 70% of the 561 patients assessed came from either the family medicine or general internal medicine clinics of the University of Florida, Gainesville, with the remaining 30% enrolled from the center’s endocrinology/diabetes outpatient clinic.

Neither report documented a NASH prevalence, which cannot receive definitive diagnosis by imaging alone. “This is the first study of its kind in the U.S. to establish the magnitude of [liver] disease burden in random patients with T2D seeking regular outpatient care,” wrote the University of Florida research team, led by Kenneth Cusi, MD, professor and chief of the university’s division of endocrinology, diabetes, and metabolism. Their finding that patients with T2D and previously unknown to have NAFLD had a 15% prevalence of moderate or advanced liver fibrosis “should trigger a call to action by all clinicians taking care of patients with T2D. Patient and physician awareness of the hepatic and extrahepatic complications of NASH, and reversing current diagnosis and treatment inertia will be the only way to avert the looming epidemic of cirrhosis in patients with diabetes.”

“Endocrinologists don’t ‘see’ NAFLD and NASH” in their patients with T2D “ because they don’t think about it,” Dr. Mantzoros declared.

Doug Brunk/Frontline Medical News

“Why is NASH underdiagnosed and undertreated? Because many physicians aren’t aware of it,” agreed Dr. Cusi during a talk in December 2020 at the 18th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease (WCIRDC). “You never find what you don’t look for.”

“Endocrinologists should do the tests for NASH [in patients with T2D], but we’re all guilty of not doing it enough,” Tracey McLaughlin, MD, an endocrinologist and professor of medicine at Stanford (Calif.) University, commented during the WCIRDC.

These prevalence numbers demand that clinicians suspect liver disease “in any patient with diabetes, especially patients with obesity who are older and have components of metabolic syndrome,” said Dr. Mantzoros. “We need to screen, refer the most advanced cases, and treat the early- and mid-stage cases.”
 

How to find NASH

Both the American Diabetes Association and the European Association for the Study of Diabetes call for routine screening of patients with T2D, starting with a check of liver enzymes, such as ALT, but no clear consensus exists for the specifics of screening beyond that. Dr. Mantzoros, Dr. Cusi, and other experts agree that the scheme for assessing liver disease in patients with T2D starts with regular monitoring of elevations in liver enzymes including ALT. Next is noninvasive ultrasound assessment of the extent of liver fibrosis inferred from the organ’s stiffness using transient elastography. Another frequently cited initial screening tool is the Fibrosis-4 (FIB-4) score, which incorporates a patient’s age, platelet count, and levels of ALT and a second liver enzyme, AST.

“There is more consensus about FIB-4 and then elastography, but some people use tests other than FIB-4. Unfortunately there is no perfect diagnostic test today. A top priority is to define the best diagnostic test,” said Dr. Mantzoros, who is leading an effort to try to refine screening using artificial intelligence.

“FIB-4 is simple, easy, and well validated,” commented Dr. Cusi during the WCIRDC last December. “FIB-4 and elastography should get you pretty close” to identifying patients with T2D and significant liver disease.

But in a recent editorial, Dr. Cusi agreed on the need for “more reliable tests for the diagnosis of NASH and advanced fibrosis in patients with T2D. Significant work is being done in the field to validate novel and more sophisticated fibrosis biomarkers. Future studies will help us enter a new era of precision medicine where biomarkers will identify and target therapy to those with more active disease at risk for cirrhosis,” he wrote.

“The ultimate goal is to diagnose fibrosis at an early stage to prevent people from developing cirrhosis,” Dr. Cusi said in a recent written statement. “We’re trying to identify these problems before they’re unfixable. Once someone has cirrhosis, there isn’t a whole lot you can do.”
 

Pioglitazone remains the best-documented treatment

Perhaps some of the inertia in diagnosing NAFLD, NASH, and liver fibrosis in patients with T2D is dissatisfaction with current treatment options, although several proven options exist, notably weight loss and diet, and thiazolidinedione (TZD) pioglitazone. But weight loss and diet pose issues for patient compliance and durability of the intervention, and many clinicians consider pioglitazone flawed by its potential adverse effects.

“When we don’t have an established treatment for something, we tend to not measure it or go after it. That’s been true of liver disease” in patients with T2D, said Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif., during the WCIRDC.

Treatment with pioglitazone has resolved NASH in about a third of patients compared with placebo, prevented fibrosis progression, and cut cardiovascular disease events, noted Dr. Cusi during the WCIRDC.

“Pioglitazone is used in only 8% of patients with T2D, or less, but we need to use it more often because of its proven efficacy in patients with T2D and NASH” said Dr. Mantzoros. “The problem is that pioglitazone has side effects, including weight gain and fluid retention, that makes it less attractive unless one thinks about the diagnosis of NASH.”

Others highlight that the adverse effects of pioglitazone have been either misunderstood, or can be effectively minimized with careful dosing.

“The data with the TZDs are much stronger than the data from anything else. TZDs have gotten a bad name because they also work in the kidney and enhance fluid reabsorption. We use modest dosages of pioglitazone, 15 mg or 30 mg a day, to avoid excess fluid retention,” Ralph A. DeFronzo, MD, chief of the diabetes division and professor of medicine at the University of Texas Health Science Center, San Antonio, said during the WCIRDC. “The best drug for NASH is pioglitazone. No other drug beats it” based on current data, Dr. DeFronzo asserted.

Other strategies include the potential to pair pioglitazone with other interventions that can blunt a weight-gain effect. One intriguing combination would combine pioglitazone with a GLP-1 receptor agonist, a drug class that can produce significant weight loss. Results from a phase 2 study showed promise for semaglutide (Rybelsus) in treating patients with NASH.
 

Getting the name right

Another factor that may be keeping NAFLD and NASH from achieving a higher profile for patients with T2D are those names, which focus on what the diseases are not – nonalcoholic – rather than what they are.

A series of recent publications in both the endocrinology and hepatology literature have called for renaming these disorders either “metabolic (dysfunction)–associated fatty liver disease (MALFD)”, or “dysmetabolism-associated fatty liver disease (DALFD)”.

“The names NAFLD and NASH indicate absence of alcohol as a cause, but the disease is also characterized by the absence of other causes, such as autoimmune disorders or hepatitis. The names were coined when we did not know much about these diseases. We now know that it is dysmetabolism that causes these conditions, and so we need to adopt a new, more accurate name,” explained Dr. Mantzoros, who has published support for a name change.

While many agree, some have raised concerns as to whether a name change now is premature. A group of hepatologists recently published a rebuttal to an immediate name change , saying that, “although we are in agreement that metabolic fatty liver disease may more accurately and positively reflect the relevant risk factors better than the age-old term nonalcoholic fatty liver disease, the term still leaves a great deal of ambiguity. A name change will be appropriate when informed by a new understanding of the molecular basis of the disease entity, insights that fundamentally change risk stratification, or other important aspects of the disease. We may be on the cusp of this, but we are not there yet.”

Dr. Mantzoros agreed, but for somewhat different reasons.

“We need to be careful and deliberate, because there is a significant body of knowledge and a lot of data from clinical trials collected using the old definitions. We need to find an appropriate time frame for a [name] transition. We need to find a nice and robust way to productively bridge the old to the new,” he said. “We also need new diagnostic criteria, and new therapies. A new name and definition will facilitate progress.”

Dr. Mantzoros been a shareholder of and consultant to Coherus and Pangea, he has been a consultant to AstraZeneca, Eisai, Genfit, Intercept, Novo Nordisk, P.E.S., and Regeneron, and has received travel support from the Metabolic Institute of America and the California Walnut Commission. Dr. Cusi has been a consultant to and has received research funding from numerous drug companies. Dr. McLaughlin is a consultant to January AI. Dr. Handelsman has been a consultant to numerous drug companies. Dr. DeFronzo received research grants from AstraZeneca, Janssen, and Merck; he has been an adviser to AstraZeneca, Boehringer Ingelheim, Intarcia, Janssen, and Novo Nordisk; and he has been a speaker on behalf of AstraZeneca and Novo Nordisk.

[email protected]

Mounting evidence of strikingly high prevalence rates of fatty liver disease, advanced fibrosis, and cirrhosis among patients with type 2 diabetes has led to calls for heightened awareness and screening to identify these patients and target treatments to reduce their risk for irreversible liver damage.

Courtesy Dr. Christos S. Mantzoros

Among these calls is a pending statement from the Endocrine Society, the American Association of Clinical Endocrinologists, the American Gastroenterology Association, and other groups on what the growing appreciation of highly prevalent liver disease in patients with type 2 diabetes (T2D) means for assessing and managing patients. Publication of the statement is expected by spring 2021, said Christos S. Mantzoros, MD, DSc, PhD, chief of endocrinology for the Veterans Affairs Boston Healthcare System and a representative from the Endocrine Society to the statement-writing panel.

This upcoming “Call to Action” from these groups argues for a “need to collaborate across disciplines, and work together on establishing clinical guidelines, and creating new diagnostics and therapeutics,” said Dr. Mantzoros in an interview.

“Over time, it is becoming clearer that management of NAFLD [nonalcoholic fatty liver disease]/NASH [nonalcoholic steatohepatitis] requires a multidisciplinary panel of doctors ranging from primary care practitioners, to endocrinologists, and hepatologists. Given that the nature of the disease crosses scientific discipline boundaries, and that the number of patients is so large (it is estimated that about one in four U.S. adults have NAFLD), not all patients can be treated at the limited number of hepatology centers.

“However, not all stakeholders have fully realized this fact, and no effort had been undertaken so far by any professional society to develop a coordinated approach and clinical care pathway for NAFLD/NASH. The ‘Call to Action’ meeting can be considered as a starting point for such an important effort,” said Dr. Mantzoros, who is also a professor of medicine at Harvard Medical School and director of the human nutrition unit at Beth Israel Deaconess Medical Center, both in Boston.
 

Dramatic prevalence rates in patients with T2D

Results from two independent epidemiology reports, published in December 2020, documented steatosis (the fatty liver of NAFLD) in 70%-74% of unselected U.S. patients with T2D, advanced liver fibrosis accompanying this disease in 6%-15%, and previously unrecognized cirrhosis in 3%-8%.

One of these reports analyzed 825 patients with T2D included in the National Health and Nutritional Examination Survey of 2017-2018 run by the Centers for Disease Control and Prevention. All these patients, selected to be representative of the overall U.S. adult population with T2D, underwent transient elastography to identify steatosis and fibrosis, the first U.S. National Health Survey to run this type of population-based survey. The results showed an overall steatosis prevalence of 74% with grade 3 steatosis in 58%, advanced liver fibrosis in 15%, and cirrhosis in 8%, reported the team of Italian researchers who analyzed the data .

The second study focused on a single-center series of 561 patients with T2D who also underwent screening by transient elastography during 2018-2020 and had no history of NAFLD or other liver disease, or alcohol abuse. The imaging results showed a NAFLD prevalence of 70%, with 54% of the entire group diagnosed with severe steatosis, severe fibrosis in 6%, and cirrhosis in 3%. Among the 54% of patients with severe steatosis, 30% also had severe liver fibrosis. About 70% of the 561 patients assessed came from either the family medicine or general internal medicine clinics of the University of Florida, Gainesville, with the remaining 30% enrolled from the center’s endocrinology/diabetes outpatient clinic.

Neither report documented a NASH prevalence, which cannot receive definitive diagnosis by imaging alone. “This is the first study of its kind in the U.S. to establish the magnitude of [liver] disease burden in random patients with T2D seeking regular outpatient care,” wrote the University of Florida research team, led by Kenneth Cusi, MD, professor and chief of the university’s division of endocrinology, diabetes, and metabolism. Their finding that patients with T2D and previously unknown to have NAFLD had a 15% prevalence of moderate or advanced liver fibrosis “should trigger a call to action by all clinicians taking care of patients with T2D. Patient and physician awareness of the hepatic and extrahepatic complications of NASH, and reversing current diagnosis and treatment inertia will be the only way to avert the looming epidemic of cirrhosis in patients with diabetes.”

“Endocrinologists don’t ‘see’ NAFLD and NASH” in their patients with T2D “ because they don’t think about it,” Dr. Mantzoros declared.

Doug Brunk/Frontline Medical News

“Why is NASH underdiagnosed and undertreated? Because many physicians aren’t aware of it,” agreed Dr. Cusi during a talk in December 2020 at the 18th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease (WCIRDC). “You never find what you don’t look for.”

“Endocrinologists should do the tests for NASH [in patients with T2D], but we’re all guilty of not doing it enough,” Tracey McLaughlin, MD, an endocrinologist and professor of medicine at Stanford (Calif.) University, commented during the WCIRDC.

These prevalence numbers demand that clinicians suspect liver disease “in any patient with diabetes, especially patients with obesity who are older and have components of metabolic syndrome,” said Dr. Mantzoros. “We need to screen, refer the most advanced cases, and treat the early- and mid-stage cases.”
 

How to find NASH

Both the American Diabetes Association and the European Association for the Study of Diabetes call for routine screening of patients with T2D, starting with a check of liver enzymes, such as ALT, but no clear consensus exists for the specifics of screening beyond that. Dr. Mantzoros, Dr. Cusi, and other experts agree that the scheme for assessing liver disease in patients with T2D starts with regular monitoring of elevations in liver enzymes including ALT. Next is noninvasive ultrasound assessment of the extent of liver fibrosis inferred from the organ’s stiffness using transient elastography. Another frequently cited initial screening tool is the Fibrosis-4 (FIB-4) score, which incorporates a patient’s age, platelet count, and levels of ALT and a second liver enzyme, AST.

“There is more consensus about FIB-4 and then elastography, but some people use tests other than FIB-4. Unfortunately there is no perfect diagnostic test today. A top priority is to define the best diagnostic test,” said Dr. Mantzoros, who is leading an effort to try to refine screening using artificial intelligence.

“FIB-4 is simple, easy, and well validated,” commented Dr. Cusi during the WCIRDC last December. “FIB-4 and elastography should get you pretty close” to identifying patients with T2D and significant liver disease.

But in a recent editorial, Dr. Cusi agreed on the need for “more reliable tests for the diagnosis of NASH and advanced fibrosis in patients with T2D. Significant work is being done in the field to validate novel and more sophisticated fibrosis biomarkers. Future studies will help us enter a new era of precision medicine where biomarkers will identify and target therapy to those with more active disease at risk for cirrhosis,” he wrote.

“The ultimate goal is to diagnose fibrosis at an early stage to prevent people from developing cirrhosis,” Dr. Cusi said in a recent written statement. “We’re trying to identify these problems before they’re unfixable. Once someone has cirrhosis, there isn’t a whole lot you can do.”
 

Pioglitazone remains the best-documented treatment

Perhaps some of the inertia in diagnosing NAFLD, NASH, and liver fibrosis in patients with T2D is dissatisfaction with current treatment options, although several proven options exist, notably weight loss and diet, and thiazolidinedione (TZD) pioglitazone. But weight loss and diet pose issues for patient compliance and durability of the intervention, and many clinicians consider pioglitazone flawed by its potential adverse effects.

“When we don’t have an established treatment for something, we tend to not measure it or go after it. That’s been true of liver disease” in patients with T2D, said Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif., during the WCIRDC.

Treatment with pioglitazone has resolved NASH in about a third of patients compared with placebo, prevented fibrosis progression, and cut cardiovascular disease events, noted Dr. Cusi during the WCIRDC.

“Pioglitazone is used in only 8% of patients with T2D, or less, but we need to use it more often because of its proven efficacy in patients with T2D and NASH” said Dr. Mantzoros. “The problem is that pioglitazone has side effects, including weight gain and fluid retention, that makes it less attractive unless one thinks about the diagnosis of NASH.”

Others highlight that the adverse effects of pioglitazone have been either misunderstood, or can be effectively minimized with careful dosing.

“The data with the TZDs are much stronger than the data from anything else. TZDs have gotten a bad name because they also work in the kidney and enhance fluid reabsorption. We use modest dosages of pioglitazone, 15 mg or 30 mg a day, to avoid excess fluid retention,” Ralph A. DeFronzo, MD, chief of the diabetes division and professor of medicine at the University of Texas Health Science Center, San Antonio, said during the WCIRDC. “The best drug for NASH is pioglitazone. No other drug beats it” based on current data, Dr. DeFronzo asserted.

Other strategies include the potential to pair pioglitazone with other interventions that can blunt a weight-gain effect. One intriguing combination would combine pioglitazone with a GLP-1 receptor agonist, a drug class that can produce significant weight loss. Results from a phase 2 study showed promise for semaglutide (Rybelsus) in treating patients with NASH.
 

Getting the name right

Another factor that may be keeping NAFLD and NASH from achieving a higher profile for patients with T2D are those names, which focus on what the diseases are not – nonalcoholic – rather than what they are.

A series of recent publications in both the endocrinology and hepatology literature have called for renaming these disorders either “metabolic (dysfunction)–associated fatty liver disease (MALFD)”, or “dysmetabolism-associated fatty liver disease (DALFD)”.

“The names NAFLD and NASH indicate absence of alcohol as a cause, but the disease is also characterized by the absence of other causes, such as autoimmune disorders or hepatitis. The names were coined when we did not know much about these diseases. We now know that it is dysmetabolism that causes these conditions, and so we need to adopt a new, more accurate name,” explained Dr. Mantzoros, who has published support for a name change.

While many agree, some have raised concerns as to whether a name change now is premature. A group of hepatologists recently published a rebuttal to an immediate name change , saying that, “although we are in agreement that metabolic fatty liver disease may more accurately and positively reflect the relevant risk factors better than the age-old term nonalcoholic fatty liver disease, the term still leaves a great deal of ambiguity. A name change will be appropriate when informed by a new understanding of the molecular basis of the disease entity, insights that fundamentally change risk stratification, or other important aspects of the disease. We may be on the cusp of this, but we are not there yet.”

Dr. Mantzoros agreed, but for somewhat different reasons.

“We need to be careful and deliberate, because there is a significant body of knowledge and a lot of data from clinical trials collected using the old definitions. We need to find an appropriate time frame for a [name] transition. We need to find a nice and robust way to productively bridge the old to the new,” he said. “We also need new diagnostic criteria, and new therapies. A new name and definition will facilitate progress.”

Dr. Mantzoros been a shareholder of and consultant to Coherus and Pangea, he has been a consultant to AstraZeneca, Eisai, Genfit, Intercept, Novo Nordisk, P.E.S., and Regeneron, and has received travel support from the Metabolic Institute of America and the California Walnut Commission. Dr. Cusi has been a consultant to and has received research funding from numerous drug companies. Dr. McLaughlin is a consultant to January AI. Dr. Handelsman has been a consultant to numerous drug companies. Dr. DeFronzo received research grants from AstraZeneca, Janssen, and Merck; he has been an adviser to AstraZeneca, Boehringer Ingelheim, Intarcia, Janssen, and Novo Nordisk; and he has been a speaker on behalf of AstraZeneca and Novo Nordisk.

[email protected]

Mounting evidence of strikingly high prevalence rates of fatty liver disease, advanced fibrosis, and cirrhosis among patients with type 2 diabetes has led to calls for heightened awareness and screening to identify these patients and target treatments to reduce their risk for irreversible liver damage.

Courtesy Dr. Christos S. Mantzoros

Among these calls is a pending statement from the Endocrine Society, the American Association of Clinical Endocrinologists, the American Gastroenterology Association, and other groups on what the growing appreciation of highly prevalent liver disease in patients with type 2 diabetes (T2D) means for assessing and managing patients. Publication of the statement is expected by spring 2021, said Christos S. Mantzoros, MD, DSc, PhD, chief of endocrinology for the Veterans Affairs Boston Healthcare System and a representative from the Endocrine Society to the statement-writing panel.

This upcoming “Call to Action” from these groups argues for a “need to collaborate across disciplines, and work together on establishing clinical guidelines, and creating new diagnostics and therapeutics,” said Dr. Mantzoros in an interview.

“Over time, it is becoming clearer that management of NAFLD [nonalcoholic fatty liver disease]/NASH [nonalcoholic steatohepatitis] requires a multidisciplinary panel of doctors ranging from primary care practitioners, to endocrinologists, and hepatologists. Given that the nature of the disease crosses scientific discipline boundaries, and that the number of patients is so large (it is estimated that about one in four U.S. adults have NAFLD), not all patients can be treated at the limited number of hepatology centers.

“However, not all stakeholders have fully realized this fact, and no effort had been undertaken so far by any professional society to develop a coordinated approach and clinical care pathway for NAFLD/NASH. The ‘Call to Action’ meeting can be considered as a starting point for such an important effort,” said Dr. Mantzoros, who is also a professor of medicine at Harvard Medical School and director of the human nutrition unit at Beth Israel Deaconess Medical Center, both in Boston.
 

Dramatic prevalence rates in patients with T2D

Results from two independent epidemiology reports, published in December 2020, documented steatosis (the fatty liver of NAFLD) in 70%-74% of unselected U.S. patients with T2D, advanced liver fibrosis accompanying this disease in 6%-15%, and previously unrecognized cirrhosis in 3%-8%.

One of these reports analyzed 825 patients with T2D included in the National Health and Nutritional Examination Survey of 2017-2018 run by the Centers for Disease Control and Prevention. All these patients, selected to be representative of the overall U.S. adult population with T2D, underwent transient elastography to identify steatosis and fibrosis, the first U.S. National Health Survey to run this type of population-based survey. The results showed an overall steatosis prevalence of 74% with grade 3 steatosis in 58%, advanced liver fibrosis in 15%, and cirrhosis in 8%, reported the team of Italian researchers who analyzed the data .

The second study focused on a single-center series of 561 patients with T2D who also underwent screening by transient elastography during 2018-2020 and had no history of NAFLD or other liver disease, or alcohol abuse. The imaging results showed a NAFLD prevalence of 70%, with 54% of the entire group diagnosed with severe steatosis, severe fibrosis in 6%, and cirrhosis in 3%. Among the 54% of patients with severe steatosis, 30% also had severe liver fibrosis. About 70% of the 561 patients assessed came from either the family medicine or general internal medicine clinics of the University of Florida, Gainesville, with the remaining 30% enrolled from the center’s endocrinology/diabetes outpatient clinic.

Neither report documented a NASH prevalence, which cannot receive definitive diagnosis by imaging alone. “This is the first study of its kind in the U.S. to establish the magnitude of [liver] disease burden in random patients with T2D seeking regular outpatient care,” wrote the University of Florida research team, led by Kenneth Cusi, MD, professor and chief of the university’s division of endocrinology, diabetes, and metabolism. Their finding that patients with T2D and previously unknown to have NAFLD had a 15% prevalence of moderate or advanced liver fibrosis “should trigger a call to action by all clinicians taking care of patients with T2D. Patient and physician awareness of the hepatic and extrahepatic complications of NASH, and reversing current diagnosis and treatment inertia will be the only way to avert the looming epidemic of cirrhosis in patients with diabetes.”

“Endocrinologists don’t ‘see’ NAFLD and NASH” in their patients with T2D “ because they don’t think about it,” Dr. Mantzoros declared.

Doug Brunk/Frontline Medical News

“Why is NASH underdiagnosed and undertreated? Because many physicians aren’t aware of it,” agreed Dr. Cusi during a talk in December 2020 at the 18th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease (WCIRDC). “You never find what you don’t look for.”

“Endocrinologists should do the tests for NASH [in patients with T2D], but we’re all guilty of not doing it enough,” Tracey McLaughlin, MD, an endocrinologist and professor of medicine at Stanford (Calif.) University, commented during the WCIRDC.

These prevalence numbers demand that clinicians suspect liver disease “in any patient with diabetes, especially patients with obesity who are older and have components of metabolic syndrome,” said Dr. Mantzoros. “We need to screen, refer the most advanced cases, and treat the early- and mid-stage cases.”
 

How to find NASH

Both the American Diabetes Association and the European Association for the Study of Diabetes call for routine screening of patients with T2D, starting with a check of liver enzymes, such as ALT, but no clear consensus exists for the specifics of screening beyond that. Dr. Mantzoros, Dr. Cusi, and other experts agree that the scheme for assessing liver disease in patients with T2D starts with regular monitoring of elevations in liver enzymes including ALT. Next is noninvasive ultrasound assessment of the extent of liver fibrosis inferred from the organ’s stiffness using transient elastography. Another frequently cited initial screening tool is the Fibrosis-4 (FIB-4) score, which incorporates a patient’s age, platelet count, and levels of ALT and a second liver enzyme, AST.

“There is more consensus about FIB-4 and then elastography, but some people use tests other than FIB-4. Unfortunately there is no perfect diagnostic test today. A top priority is to define the best diagnostic test,” said Dr. Mantzoros, who is leading an effort to try to refine screening using artificial intelligence.

“FIB-4 is simple, easy, and well validated,” commented Dr. Cusi during the WCIRDC last December. “FIB-4 and elastography should get you pretty close” to identifying patients with T2D and significant liver disease.

But in a recent editorial, Dr. Cusi agreed on the need for “more reliable tests for the diagnosis of NASH and advanced fibrosis in patients with T2D. Significant work is being done in the field to validate novel and more sophisticated fibrosis biomarkers. Future studies will help us enter a new era of precision medicine where biomarkers will identify and target therapy to those with more active disease at risk for cirrhosis,” he wrote.

“The ultimate goal is to diagnose fibrosis at an early stage to prevent people from developing cirrhosis,” Dr. Cusi said in a recent written statement. “We’re trying to identify these problems before they’re unfixable. Once someone has cirrhosis, there isn’t a whole lot you can do.”
 

Pioglitazone remains the best-documented treatment

Perhaps some of the inertia in diagnosing NAFLD, NASH, and liver fibrosis in patients with T2D is dissatisfaction with current treatment options, although several proven options exist, notably weight loss and diet, and thiazolidinedione (TZD) pioglitazone. But weight loss and diet pose issues for patient compliance and durability of the intervention, and many clinicians consider pioglitazone flawed by its potential adverse effects.

“When we don’t have an established treatment for something, we tend to not measure it or go after it. That’s been true of liver disease” in patients with T2D, said Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of the Metabolic Institute of America in Tarzana, Calif., during the WCIRDC.

Treatment with pioglitazone has resolved NASH in about a third of patients compared with placebo, prevented fibrosis progression, and cut cardiovascular disease events, noted Dr. Cusi during the WCIRDC.

“Pioglitazone is used in only 8% of patients with T2D, or less, but we need to use it more often because of its proven efficacy in patients with T2D and NASH” said Dr. Mantzoros. “The problem is that pioglitazone has side effects, including weight gain and fluid retention, that makes it less attractive unless one thinks about the diagnosis of NASH.”

Others highlight that the adverse effects of pioglitazone have been either misunderstood, or can be effectively minimized with careful dosing.

“The data with the TZDs are much stronger than the data from anything else. TZDs have gotten a bad name because they also work in the kidney and enhance fluid reabsorption. We use modest dosages of pioglitazone, 15 mg or 30 mg a day, to avoid excess fluid retention,” Ralph A. DeFronzo, MD, chief of the diabetes division and professor of medicine at the University of Texas Health Science Center, San Antonio, said during the WCIRDC. “The best drug for NASH is pioglitazone. No other drug beats it” based on current data, Dr. DeFronzo asserted.

Other strategies include the potential to pair pioglitazone with other interventions that can blunt a weight-gain effect. One intriguing combination would combine pioglitazone with a GLP-1 receptor agonist, a drug class that can produce significant weight loss. Results from a phase 2 study showed promise for semaglutide (Rybelsus) in treating patients with NASH.
 

Getting the name right

Another factor that may be keeping NAFLD and NASH from achieving a higher profile for patients with T2D are those names, which focus on what the diseases are not – nonalcoholic – rather than what they are.

A series of recent publications in both the endocrinology and hepatology literature have called for renaming these disorders either “metabolic (dysfunction)–associated fatty liver disease (MALFD)”, or “dysmetabolism-associated fatty liver disease (DALFD)”.

“The names NAFLD and NASH indicate absence of alcohol as a cause, but the disease is also characterized by the absence of other causes, such as autoimmune disorders or hepatitis. The names were coined when we did not know much about these diseases. We now know that it is dysmetabolism that causes these conditions, and so we need to adopt a new, more accurate name,” explained Dr. Mantzoros, who has published support for a name change.

While many agree, some have raised concerns as to whether a name change now is premature. A group of hepatologists recently published a rebuttal to an immediate name change , saying that, “although we are in agreement that metabolic fatty liver disease may more accurately and positively reflect the relevant risk factors better than the age-old term nonalcoholic fatty liver disease, the term still leaves a great deal of ambiguity. A name change will be appropriate when informed by a new understanding of the molecular basis of the disease entity, insights that fundamentally change risk stratification, or other important aspects of the disease. We may be on the cusp of this, but we are not there yet.”

Dr. Mantzoros agreed, but for somewhat different reasons.

“We need to be careful and deliberate, because there is a significant body of knowledge and a lot of data from clinical trials collected using the old definitions. We need to find an appropriate time frame for a [name] transition. We need to find a nice and robust way to productively bridge the old to the new,” he said. “We also need new diagnostic criteria, and new therapies. A new name and definition will facilitate progress.”

Dr. Mantzoros been a shareholder of and consultant to Coherus and Pangea, he has been a consultant to AstraZeneca, Eisai, Genfit, Intercept, Novo Nordisk, P.E.S., and Regeneron, and has received travel support from the Metabolic Institute of America and the California Walnut Commission. Dr. Cusi has been a consultant to and has received research funding from numerous drug companies. Dr. McLaughlin is a consultant to January AI. Dr. Handelsman has been a consultant to numerous drug companies. Dr. DeFronzo received research grants from AstraZeneca, Janssen, and Merck; he has been an adviser to AstraZeneca, Boehringer Ingelheim, Intarcia, Janssen, and Novo Nordisk; and he has been a speaker on behalf of AstraZeneca and Novo Nordisk.

[email protected]

In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.

sarathsasidharan/Thinkstock

An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.

The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.

The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
 

Goal-setting

There are five main goals outlined in the plan, according to the HHS:

• Prevent new hepatitis infections.
• Improve hepatitis-related health outcomes of people with viral hepatitis.
• Reduce hepatitis-related disparities and health inequities.
• Improve hepatitis surveillance and data use.
• Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.

“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.

[email protected]

In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.

sarathsasidharan/Thinkstock

An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.

The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.

The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
 

Goal-setting

There are five main goals outlined in the plan, according to the HHS:

• Prevent new hepatitis infections.
• Improve hepatitis-related health outcomes of people with viral hepatitis.
• Reduce hepatitis-related disparities and health inequities.
• Improve hepatitis surveillance and data use.
• Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.

“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.

[email protected]

In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.

sarathsasidharan/Thinkstock

An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.

The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.

The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
 

Goal-setting

There are five main goals outlined in the plan, according to the HHS:

• Prevent new hepatitis infections.
• Improve hepatitis-related health outcomes of people with viral hepatitis.
• Reduce hepatitis-related disparities and health inequities.
• Improve hepatitis surveillance and data use.
• Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.

“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.

[email protected]

A growing body of evidence suggests that patients with COVID-19 and preexisting liver disease face increased risks of decompensation and mortality, according to a review of recent literature.

The review aimed to bring together the best approaches for caring for patients with preexisting liver conditions based on recommendations from three major hepatology societies. Findings in included studies could guide clinical decision-making, but a reliable framework for patient management has yet to be established, most likely because of limited research, according to lead author Abdul Mohammed, MD, of Case Western Reserve University, Cleveland, and colleagues.

The relationship between chronic liver diseases and “COVID-19 is not well documented in the literature,” Dr. Mohammed and colleagues wrote in the Journal of Clinical Gastroenterology. “The intricate interplay between immune dysfunction in preexisting liver diseases and the immune dysregulation triggered by the SARS-CoV-2 virus needs further evaluation.”

Such knowledge gaps likely explain the inconsistencies in recommendations between major hepatology societies, including clinical guidance from the American Association for the Study of Liver Disease, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver.

Both the literature review and the societal guidance address nonalcoholic fatty liver disease (NAFLD), hepatitis B virus (HBV) infection, autoimmune hepatitis, hepatocellular carcinoma (HCC), cirrhosis, and liver transplantation.

Dr. Mohammed and colleagues first offered an update of the relationship between COVID-19 and liver pathology. While it is clear that SARS-CoV-2 gains hepatic access through binding to ACE2 receptors in bile duct epithelial cells, it remains unclear whether this results in direct hepatic injury or indirect damage from virus-mediated cytokine release. Regardless, more than 90% of patients hospitalized for COVID-19 may develop increased levels of ALT and AST, and these elevations “appear to mirror disease severity,” the investigators wrote.

They noted that severity of COVID-19 appears to correlate with type of preexisting liver disease. For example, one study in the review associated NAFLD with a significantly increased risk of progressive COVID-19 (odds ratio, 6.4; 95% confidence interval, 1.5-31.2), and it also found that patients with NAFLD had longer duration of viral shedding than those without (17 vs. 12 days). Although the AASLD and APASL give no specific recommendations, the EASL recommends prioritizing COVID-19 patients with NAFLD.

Cirrhosis has been associated with a fourfold increased risk of mortality (relative risk, 4.6; 95% CI, 2.6-8.3) According to data from two international self-reporting registries, COVIDHep.net and COVIDCirrhosis.org, likelihood of death appears to move in tandem with Child-Turcotte-Pugh scores. Decompensated cirrhosis appears to predispose patients to having pulmonary complications, but more studies exploring this correlation need to be performed, according to the review authors. One study found that acute-on-chronic liver failure or acute decompensation occurred in 20% of patients who had COVID-19 and cirrhosis. It’s little surprise, then, that both the AASLD and the EASL recommend prioritizing in person evaluation for patients with decompensated cirrhosis.

Chronic HBV infection has also been associated with a higher COVID-19 mortality rate, although Dr. Mohammed and colleagues suggested that “larger studies are needed.” The review notes that the three societies recommend initiating HBV treatment only if there is clinical suspicion of hepatitis flare.

Findings are also cloudy among patients with autoimmune hepatitis and liver transplant recipients; however, the investigators noted that COVID-19 causes tissue damage primarily through cytokine release, and suggested that “immunosuppression can potentially curb this response.” Even so, recommendations from leading hepatology societies allude to a safe middle ground of immunosuppression, albeit with indistinct borders. All three caution against withdrawing immunosuppression, but the societies each describe tailoring regimens in different ways and for different patients, emphasizing continued corticosteroid treatments, according to the review.

Guidance also varies for management of HCC. “Since the tumor doubling time is 4-8 months and current guidelines recommend screening every 6 months, in patients at lower risk for developing HCC, a 2-month delay in ultrasound surveillance has been suggested by the AASLD,” the review authors noted. “In patients with a high risk of developing HCC, 6-month interval screening should be continued.” The AASLD recommends proceeding with treatment with newly diagnosed HCC, the EASL suggests that checkpoint inhibitors should be withheld and locoregional therapies should be postponed, and the APASL calls for a less frequent schedule of tyrosine kinase inhibitors and immunotherapy.

“COVID-19 patients with the preexisting liver disease face a higher risk of decompensation and mortality,” the review authors concluded. “We presented the most up-to-date literature on preexisting liver disease and its interaction with COVID-19.”

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID. 

A growing body of evidence suggests that patients with COVID-19 and preexisting liver disease face increased risks of decompensation and mortality, according to a review of recent literature.

The review aimed to bring together the best approaches for caring for patients with preexisting liver conditions based on recommendations from three major hepatology societies. Findings in included studies could guide clinical decision-making, but a reliable framework for patient management has yet to be established, most likely because of limited research, according to lead author Abdul Mohammed, MD, of Case Western Reserve University, Cleveland, and colleagues.

The relationship between chronic liver diseases and “COVID-19 is not well documented in the literature,” Dr. Mohammed and colleagues wrote in the Journal of Clinical Gastroenterology. “The intricate interplay between immune dysfunction in preexisting liver diseases and the immune dysregulation triggered by the SARS-CoV-2 virus needs further evaluation.”

Such knowledge gaps likely explain the inconsistencies in recommendations between major hepatology societies, including clinical guidance from the American Association for the Study of Liver Disease, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver.

Both the literature review and the societal guidance address nonalcoholic fatty liver disease (NAFLD), hepatitis B virus (HBV) infection, autoimmune hepatitis, hepatocellular carcinoma (HCC), cirrhosis, and liver transplantation.

Dr. Mohammed and colleagues first offered an update of the relationship between COVID-19 and liver pathology. While it is clear that SARS-CoV-2 gains hepatic access through binding to ACE2 receptors in bile duct epithelial cells, it remains unclear whether this results in direct hepatic injury or indirect damage from virus-mediated cytokine release. Regardless, more than 90% of patients hospitalized for COVID-19 may develop increased levels of ALT and AST, and these elevations “appear to mirror disease severity,” the investigators wrote.

They noted that severity of COVID-19 appears to correlate with type of preexisting liver disease. For example, one study in the review associated NAFLD with a significantly increased risk of progressive COVID-19 (odds ratio, 6.4; 95% confidence interval, 1.5-31.2), and it also found that patients with NAFLD had longer duration of viral shedding than those without (17 vs. 12 days). Although the AASLD and APASL give no specific recommendations, the EASL recommends prioritizing COVID-19 patients with NAFLD.

Cirrhosis has been associated with a fourfold increased risk of mortality (relative risk, 4.6; 95% CI, 2.6-8.3) According to data from two international self-reporting registries, COVIDHep.net and COVIDCirrhosis.org, likelihood of death appears to move in tandem with Child-Turcotte-Pugh scores. Decompensated cirrhosis appears to predispose patients to having pulmonary complications, but more studies exploring this correlation need to be performed, according to the review authors. One study found that acute-on-chronic liver failure or acute decompensation occurred in 20% of patients who had COVID-19 and cirrhosis. It’s little surprise, then, that both the AASLD and the EASL recommend prioritizing in person evaluation for patients with decompensated cirrhosis.

Chronic HBV infection has also been associated with a higher COVID-19 mortality rate, although Dr. Mohammed and colleagues suggested that “larger studies are needed.” The review notes that the three societies recommend initiating HBV treatment only if there is clinical suspicion of hepatitis flare.

Findings are also cloudy among patients with autoimmune hepatitis and liver transplant recipients; however, the investigators noted that COVID-19 causes tissue damage primarily through cytokine release, and suggested that “immunosuppression can potentially curb this response.” Even so, recommendations from leading hepatology societies allude to a safe middle ground of immunosuppression, albeit with indistinct borders. All three caution against withdrawing immunosuppression, but the societies each describe tailoring regimens in different ways and for different patients, emphasizing continued corticosteroid treatments, according to the review.

Guidance also varies for management of HCC. “Since the tumor doubling time is 4-8 months and current guidelines recommend screening every 6 months, in patients at lower risk for developing HCC, a 2-month delay in ultrasound surveillance has been suggested by the AASLD,” the review authors noted. “In patients with a high risk of developing HCC, 6-month interval screening should be continued.” The AASLD recommends proceeding with treatment with newly diagnosed HCC, the EASL suggests that checkpoint inhibitors should be withheld and locoregional therapies should be postponed, and the APASL calls for a less frequent schedule of tyrosine kinase inhibitors and immunotherapy.

“COVID-19 patients with the preexisting liver disease face a higher risk of decompensation and mortality,” the review authors concluded. “We presented the most up-to-date literature on preexisting liver disease and its interaction with COVID-19.”

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID. 

A growing body of evidence suggests that patients with COVID-19 and preexisting liver disease face increased risks of decompensation and mortality, according to a review of recent literature.

The review aimed to bring together the best approaches for caring for patients with preexisting liver conditions based on recommendations from three major hepatology societies. Findings in included studies could guide clinical decision-making, but a reliable framework for patient management has yet to be established, most likely because of limited research, according to lead author Abdul Mohammed, MD, of Case Western Reserve University, Cleveland, and colleagues.

The relationship between chronic liver diseases and “COVID-19 is not well documented in the literature,” Dr. Mohammed and colleagues wrote in the Journal of Clinical Gastroenterology. “The intricate interplay between immune dysfunction in preexisting liver diseases and the immune dysregulation triggered by the SARS-CoV-2 virus needs further evaluation.”

Such knowledge gaps likely explain the inconsistencies in recommendations between major hepatology societies, including clinical guidance from the American Association for the Study of Liver Disease, the European Association for the Study of the Liver, and the Asian Pacific Association for the Study of the Liver.

Both the literature review and the societal guidance address nonalcoholic fatty liver disease (NAFLD), hepatitis B virus (HBV) infection, autoimmune hepatitis, hepatocellular carcinoma (HCC), cirrhosis, and liver transplantation.

Dr. Mohammed and colleagues first offered an update of the relationship between COVID-19 and liver pathology. While it is clear that SARS-CoV-2 gains hepatic access through binding to ACE2 receptors in bile duct epithelial cells, it remains unclear whether this results in direct hepatic injury or indirect damage from virus-mediated cytokine release. Regardless, more than 90% of patients hospitalized for COVID-19 may develop increased levels of ALT and AST, and these elevations “appear to mirror disease severity,” the investigators wrote.

They noted that severity of COVID-19 appears to correlate with type of preexisting liver disease. For example, one study in the review associated NAFLD with a significantly increased risk of progressive COVID-19 (odds ratio, 6.4; 95% confidence interval, 1.5-31.2), and it also found that patients with NAFLD had longer duration of viral shedding than those without (17 vs. 12 days). Although the AASLD and APASL give no specific recommendations, the EASL recommends prioritizing COVID-19 patients with NAFLD.

Cirrhosis has been associated with a fourfold increased risk of mortality (relative risk, 4.6; 95% CI, 2.6-8.3) According to data from two international self-reporting registries, COVIDHep.net and COVIDCirrhosis.org, likelihood of death appears to move in tandem with Child-Turcotte-Pugh scores. Decompensated cirrhosis appears to predispose patients to having pulmonary complications, but more studies exploring this correlation need to be performed, according to the review authors. One study found that acute-on-chronic liver failure or acute decompensation occurred in 20% of patients who had COVID-19 and cirrhosis. It’s little surprise, then, that both the AASLD and the EASL recommend prioritizing in person evaluation for patients with decompensated cirrhosis.

Chronic HBV infection has also been associated with a higher COVID-19 mortality rate, although Dr. Mohammed and colleagues suggested that “larger studies are needed.” The review notes that the three societies recommend initiating HBV treatment only if there is clinical suspicion of hepatitis flare.

Findings are also cloudy among patients with autoimmune hepatitis and liver transplant recipients; however, the investigators noted that COVID-19 causes tissue damage primarily through cytokine release, and suggested that “immunosuppression can potentially curb this response.” Even so, recommendations from leading hepatology societies allude to a safe middle ground of immunosuppression, albeit with indistinct borders. All three caution against withdrawing immunosuppression, but the societies each describe tailoring regimens in different ways and for different patients, emphasizing continued corticosteroid treatments, according to the review.

Guidance also varies for management of HCC. “Since the tumor doubling time is 4-8 months and current guidelines recommend screening every 6 months, in patients at lower risk for developing HCC, a 2-month delay in ultrasound surveillance has been suggested by the AASLD,” the review authors noted. “In patients with a high risk of developing HCC, 6-month interval screening should be continued.” The AASLD recommends proceeding with treatment with newly diagnosed HCC, the EASL suggests that checkpoint inhibitors should be withheld and locoregional therapies should be postponed, and the APASL calls for a less frequent schedule of tyrosine kinase inhibitors and immunotherapy.

“COVID-19 patients with the preexisting liver disease face a higher risk of decompensation and mortality,” the review authors concluded. “We presented the most up-to-date literature on preexisting liver disease and its interaction with COVID-19.”

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.