Liver Disease

Eradicating chronic hepatitis C virus (HCV) infection led to significant decreases in liver stiffness in a systematic review and meta-analysis of nearly 3,000 patients.

Mean liver stiffness fell by 4.1 kPa (kilopascals) (95% confidence interval, 3.3-4.9 kPa) 12 or more months after patients achieved sustained virologic response to treatment, but did not significantly change in patients who did not achieve SVR, reported Siddharth Singh, MD, of the University of San Diego, La Jolla, Calif., and his associates in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.038). The results were especially striking among patients who received direct-acting antiviral agents (DAAs) or who had high baseline levels of inflammation, the investigators added.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Based on these findings, about 47% of patients with advanced fibrosis or cirrhosis at baseline will drop below 9.5 kPa after achieving SVR, they reported. “With this decline in liver stiffness, it is conceivable that risk of liver-related complications would decrease, particularly in patients without cirrhosis,” they added. “Future research is warranted on the impact of magnitude and kinetics of decline in liver stiffness on improvement in liver-related outcomes.”

Eradicating HCV infection was known to decrease liver stiffness, but the magnitude of decline was not well understood. Therefore, the reviewers searched the literature through October 2016 for studies of HCV-infected adults who underwent liver stiffness measurement by vibration-controlled transient elastography before and at least once after completing HCV treatment. All studies also included data on median liver stiffness among patients who did and did not achieve SVR. The search identified 23 observational studies and one post hoc analysis of a randomized controlled trial, for a total of 2,934 patients, of whom 2,214 achieved SVR.

Among patients who achieved SVR, mean liver stiffness dropped by 2.4 kPa at the end of treatment (95% CI, 1.7-3.0 kPa), by 3.1 kPa 1-6 months later (95% CI, 1.6-4.7 kPa), and by 3.2 kPa 6-12 months after completing treatment (90% CI, 2.6-3.9 kPa). A year or more after finishing treatment, patients who achieved SVR had a 28% median decrease in liver stiffness (interquartile range, 22%-35%). However, liver stiffness did not significantly change among patients who did not achieve SVR, the reviewers reported.

Mean liver stiffness declined significantly more among patients who received DAAs (4.5 kPa) than among recipients of interferon-based regimens (2.6 kPa; P = .03). However, studies of DAAs included patients with greater liver stiffness at baseline, which could at least partially explain this discrepancy, the investigators said. Baseline cirrhosis also was associated with a greater decline in liver stiffness (mean, 5.1 kPa, vs. 2.8 kPa in patients without cirrhosis; P = .02), as was high baseline alanine aminotransferase level (P less than .01). Among patients whose baseline liver stiffness measurement exceeded 9.5 kPa, 47% had their liver stiffness drop to less than 9.5 kPa after achieving SVR.

Coinfection with HIV did not significantly alter the magnitude of decline in liver stiffness 6-12 months after treatment in patients who achieved SVR, the reviewers noted. “[Follow-up] assessment after SVR was relatively short; hence, long-term evolution of liver stiffness after antiviral therapy and impact of decline in liver stiffness on patient clinical outcomes could not be ascertained,” they wrote. The studies also did not consistently assess potential confounders such as nonalcoholic fatty liver disease, diabetes, and alcohol consumption.

One reviewer disclosed funding from the National Institutes of Health/National Library of Medicine. None had conflicts of interest.

Eradicating chronic hepatitis C virus (HCV) infection led to significant decreases in liver stiffness in a systematic review and meta-analysis of nearly 3,000 patients.

Mean liver stiffness fell by 4.1 kPa (kilopascals) (95% confidence interval, 3.3-4.9 kPa) 12 or more months after patients achieved sustained virologic response to treatment, but did not significantly change in patients who did not achieve SVR, reported Siddharth Singh, MD, of the University of San Diego, La Jolla, Calif., and his associates in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.038). The results were especially striking among patients who received direct-acting antiviral agents (DAAs) or who had high baseline levels of inflammation, the investigators added.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Based on these findings, about 47% of patients with advanced fibrosis or cirrhosis at baseline will drop below 9.5 kPa after achieving SVR, they reported. “With this decline in liver stiffness, it is conceivable that risk of liver-related complications would decrease, particularly in patients without cirrhosis,” they added. “Future research is warranted on the impact of magnitude and kinetics of decline in liver stiffness on improvement in liver-related outcomes.”

Eradicating HCV infection was known to decrease liver stiffness, but the magnitude of decline was not well understood. Therefore, the reviewers searched the literature through October 2016 for studies of HCV-infected adults who underwent liver stiffness measurement by vibration-controlled transient elastography before and at least once after completing HCV treatment. All studies also included data on median liver stiffness among patients who did and did not achieve SVR. The search identified 23 observational studies and one post hoc analysis of a randomized controlled trial, for a total of 2,934 patients, of whom 2,214 achieved SVR.

Among patients who achieved SVR, mean liver stiffness dropped by 2.4 kPa at the end of treatment (95% CI, 1.7-3.0 kPa), by 3.1 kPa 1-6 months later (95% CI, 1.6-4.7 kPa), and by 3.2 kPa 6-12 months after completing treatment (90% CI, 2.6-3.9 kPa). A year or more after finishing treatment, patients who achieved SVR had a 28% median decrease in liver stiffness (interquartile range, 22%-35%). However, liver stiffness did not significantly change among patients who did not achieve SVR, the reviewers reported.

Mean liver stiffness declined significantly more among patients who received DAAs (4.5 kPa) than among recipients of interferon-based regimens (2.6 kPa; P = .03). However, studies of DAAs included patients with greater liver stiffness at baseline, which could at least partially explain this discrepancy, the investigators said. Baseline cirrhosis also was associated with a greater decline in liver stiffness (mean, 5.1 kPa, vs. 2.8 kPa in patients without cirrhosis; P = .02), as was high baseline alanine aminotransferase level (P less than .01). Among patients whose baseline liver stiffness measurement exceeded 9.5 kPa, 47% had their liver stiffness drop to less than 9.5 kPa after achieving SVR.

Coinfection with HIV did not significantly alter the magnitude of decline in liver stiffness 6-12 months after treatment in patients who achieved SVR, the reviewers noted. “[Follow-up] assessment after SVR was relatively short; hence, long-term evolution of liver stiffness after antiviral therapy and impact of decline in liver stiffness on patient clinical outcomes could not be ascertained,” they wrote. The studies also did not consistently assess potential confounders such as nonalcoholic fatty liver disease, diabetes, and alcohol consumption.

One reviewer disclosed funding from the National Institutes of Health/National Library of Medicine. None had conflicts of interest.

Eradicating chronic hepatitis C virus (HCV) infection led to significant decreases in liver stiffness in a systematic review and meta-analysis of nearly 3,000 patients.

Mean liver stiffness fell by 4.1 kPa (kilopascals) (95% confidence interval, 3.3-4.9 kPa) 12 or more months after patients achieved sustained virologic response to treatment, but did not significantly change in patients who did not achieve SVR, reported Siddharth Singh, MD, of the University of San Diego, La Jolla, Calif., and his associates in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.038). The results were especially striking among patients who received direct-acting antiviral agents (DAAs) or who had high baseline levels of inflammation, the investigators added.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Based on these findings, about 47% of patients with advanced fibrosis or cirrhosis at baseline will drop below 9.5 kPa after achieving SVR, they reported. “With this decline in liver stiffness, it is conceivable that risk of liver-related complications would decrease, particularly in patients without cirrhosis,” they added. “Future research is warranted on the impact of magnitude and kinetics of decline in liver stiffness on improvement in liver-related outcomes.”

Eradicating HCV infection was known to decrease liver stiffness, but the magnitude of decline was not well understood. Therefore, the reviewers searched the literature through October 2016 for studies of HCV-infected adults who underwent liver stiffness measurement by vibration-controlled transient elastography before and at least once after completing HCV treatment. All studies also included data on median liver stiffness among patients who did and did not achieve SVR. The search identified 23 observational studies and one post hoc analysis of a randomized controlled trial, for a total of 2,934 patients, of whom 2,214 achieved SVR.

Among patients who achieved SVR, mean liver stiffness dropped by 2.4 kPa at the end of treatment (95% CI, 1.7-3.0 kPa), by 3.1 kPa 1-6 months later (95% CI, 1.6-4.7 kPa), and by 3.2 kPa 6-12 months after completing treatment (90% CI, 2.6-3.9 kPa). A year or more after finishing treatment, patients who achieved SVR had a 28% median decrease in liver stiffness (interquartile range, 22%-35%). However, liver stiffness did not significantly change among patients who did not achieve SVR, the reviewers reported.

Mean liver stiffness declined significantly more among patients who received DAAs (4.5 kPa) than among recipients of interferon-based regimens (2.6 kPa; P = .03). However, studies of DAAs included patients with greater liver stiffness at baseline, which could at least partially explain this discrepancy, the investigators said. Baseline cirrhosis also was associated with a greater decline in liver stiffness (mean, 5.1 kPa, vs. 2.8 kPa in patients without cirrhosis; P = .02), as was high baseline alanine aminotransferase level (P less than .01). Among patients whose baseline liver stiffness measurement exceeded 9.5 kPa, 47% had their liver stiffness drop to less than 9.5 kPa after achieving SVR.

Coinfection with HIV did not significantly alter the magnitude of decline in liver stiffness 6-12 months after treatment in patients who achieved SVR, the reviewers noted. “[Follow-up] assessment after SVR was relatively short; hence, long-term evolution of liver stiffness after antiviral therapy and impact of decline in liver stiffness on patient clinical outcomes could not be ascertained,” they wrote. The studies also did not consistently assess potential confounders such as nonalcoholic fatty liver disease, diabetes, and alcohol consumption.

One reviewer disclosed funding from the National Institutes of Health/National Library of Medicine. None had conflicts of interest.

As the evidence supporting the idea of transplanting livers infected with hepatitis C into patients who do not have the disease continues to mount, a multi-institutional team of researchers has developed a mathematical model that shows when hepatitis C–positive-to-negative transplant may improve survival for patients who might otherwise die awaiting a disease-free liver.

In a report published in the journal Hepatology (doi: 10.1002/hep.29723), the researchers noted how direct-acting antivirals (DAAs) have changed the calculus of hepatitis C (HCV) status in liver transplant by reducing the number of HCV-positive patients on the wait list and providing treatment for HCV-negative patients who receive HCV-positive livers. “It is important that further research in this area continues, as we expect that the supply of HCV-positive organs may continue to increase in light of the growing opioid epidemic,” said lead author Jagpreet Chhatwal, PhD, of Massachusetts General Hospital Institute for Technology Assessment in Boston.

Dr. Chhatwal and coauthors claimed their study provides some of the first empirical data for transplanting livers from patients with HCV into patients who do not have the disease.

The researchers performed their analysis using a Markov-based mathematical model known as Simulation of Liver Transplant Candidates (SIM-LT). The model had been validated in previous studies that Dr. Chhatwal and some coauthors had published (Hepatology. 2017;65:777-88; Clin Gastroenterol Hepatol 2018;16:115-22). Dr. Chhatwal and coauthors revised the SIM-LT model to simulate a virtual trial of HCV-negative patients on the liver transplant waiting list to compare outcomes in patients willing to accept any liver to those willing to accept only HCV-negative livers.

The patients willing to receive HCV-positive livers were given 12 weeks of DAA therapy preemptively and had a higher risk of graft failure. The model incorporated data from published studies using the United Network for Organ Sharing (UNOS) and used reported outcomes of the Organ Procurement and Transplantation Network to validate the findings.

The study showed that the clinical benefits of an HCV-negative patient receiving an HCV-positive liver depend on the patient’s Model for End-Stage Liver Disease (MELD) score. Using the measured change in life-years, the researchers found that patients with a MELD score below 20 actually witnessed reduction in life-years when accepting any liver, but that the benefits of accepting any liver started to accrue at MELD score 20. The benefit topped out at MELD 28, with 0.172 life years gained, but even sustained at 0.06 life years gained at MELD 40.

The effectiveness of using HCV-positive livers may also depend on region. UNOS Region 1 – essentially New England minus western Vermont – has the highest rate of HCV-positive organs, and a patient there with MELD 28 would gain 0.36 life-years by accepting any liver regardless of HCV status. However, Region 7 – the Dakotas and upper Midwest plus Illinois – has the lowest HCV-positive organ rate, and a MELD 28 patient there would gain only 0.1 life-year accepting any liver.

“Transplanting HCV-positive livers into HCV-negative patients receiving preemptive DAA therapy could be a viable option for improving patient survival on the LT waiting list, especially in UNOS regions with high HCV-positive donor organ rates,” said Dr. Chhatwal and coauthors. They concluded that their analysis could help direct future clinical trials evaluating the effectiveness of DAA therapy in liver transplant by recognizing patients who could benefit most from accepting HCV-positive donor organs.

The study authors reported having no financial disclosures. The study was supported by grants from the American Cancer Society, Health Resources and Services Administration, National Institutes of Health, National Science Foundation, and Massachusetts General Hospital Research Scholars Program. Coauthor Fasiha Kanwal, MD, received support from the Veterans Administration Health Services, Research & Development Center for Innovations in Quality, Effectiveness and Safety and Public Health Service.

SOURCE: Chhatwal J et al. Hepatology. doi:10.1002/hep.29723.

As the evidence supporting the idea of transplanting livers infected with hepatitis C into patients who do not have the disease continues to mount, a multi-institutional team of researchers has developed a mathematical model that shows when hepatitis C–positive-to-negative transplant may improve survival for patients who might otherwise die awaiting a disease-free liver.

In a report published in the journal Hepatology (doi: 10.1002/hep.29723), the researchers noted how direct-acting antivirals (DAAs) have changed the calculus of hepatitis C (HCV) status in liver transplant by reducing the number of HCV-positive patients on the wait list and providing treatment for HCV-negative patients who receive HCV-positive livers. “It is important that further research in this area continues, as we expect that the supply of HCV-positive organs may continue to increase in light of the growing opioid epidemic,” said lead author Jagpreet Chhatwal, PhD, of Massachusetts General Hospital Institute for Technology Assessment in Boston.

Dr. Chhatwal and coauthors claimed their study provides some of the first empirical data for transplanting livers from patients with HCV into patients who do not have the disease.

The researchers performed their analysis using a Markov-based mathematical model known as Simulation of Liver Transplant Candidates (SIM-LT). The model had been validated in previous studies that Dr. Chhatwal and some coauthors had published (Hepatology. 2017;65:777-88; Clin Gastroenterol Hepatol 2018;16:115-22). Dr. Chhatwal and coauthors revised the SIM-LT model to simulate a virtual trial of HCV-negative patients on the liver transplant waiting list to compare outcomes in patients willing to accept any liver to those willing to accept only HCV-negative livers.

The patients willing to receive HCV-positive livers were given 12 weeks of DAA therapy preemptively and had a higher risk of graft failure. The model incorporated data from published studies using the United Network for Organ Sharing (UNOS) and used reported outcomes of the Organ Procurement and Transplantation Network to validate the findings.

The study showed that the clinical benefits of an HCV-negative patient receiving an HCV-positive liver depend on the patient’s Model for End-Stage Liver Disease (MELD) score. Using the measured change in life-years, the researchers found that patients with a MELD score below 20 actually witnessed reduction in life-years when accepting any liver, but that the benefits of accepting any liver started to accrue at MELD score 20. The benefit topped out at MELD 28, with 0.172 life years gained, but even sustained at 0.06 life years gained at MELD 40.

The effectiveness of using HCV-positive livers may also depend on region. UNOS Region 1 – essentially New England minus western Vermont – has the highest rate of HCV-positive organs, and a patient there with MELD 28 would gain 0.36 life-years by accepting any liver regardless of HCV status. However, Region 7 – the Dakotas and upper Midwest plus Illinois – has the lowest HCV-positive organ rate, and a MELD 28 patient there would gain only 0.1 life-year accepting any liver.

“Transplanting HCV-positive livers into HCV-negative patients receiving preemptive DAA therapy could be a viable option for improving patient survival on the LT waiting list, especially in UNOS regions with high HCV-positive donor organ rates,” said Dr. Chhatwal and coauthors. They concluded that their analysis could help direct future clinical trials evaluating the effectiveness of DAA therapy in liver transplant by recognizing patients who could benefit most from accepting HCV-positive donor organs.

The study authors reported having no financial disclosures. The study was supported by grants from the American Cancer Society, Health Resources and Services Administration, National Institutes of Health, National Science Foundation, and Massachusetts General Hospital Research Scholars Program. Coauthor Fasiha Kanwal, MD, received support from the Veterans Administration Health Services, Research & Development Center for Innovations in Quality, Effectiveness and Safety and Public Health Service.

SOURCE: Chhatwal J et al. Hepatology. doi:10.1002/hep.29723.

As the evidence supporting the idea of transplanting livers infected with hepatitis C into patients who do not have the disease continues to mount, a multi-institutional team of researchers has developed a mathematical model that shows when hepatitis C–positive-to-negative transplant may improve survival for patients who might otherwise die awaiting a disease-free liver.

In a report published in the journal Hepatology (doi: 10.1002/hep.29723), the researchers noted how direct-acting antivirals (DAAs) have changed the calculus of hepatitis C (HCV) status in liver transplant by reducing the number of HCV-positive patients on the wait list and providing treatment for HCV-negative patients who receive HCV-positive livers. “It is important that further research in this area continues, as we expect that the supply of HCV-positive organs may continue to increase in light of the growing opioid epidemic,” said lead author Jagpreet Chhatwal, PhD, of Massachusetts General Hospital Institute for Technology Assessment in Boston.

Dr. Chhatwal and coauthors claimed their study provides some of the first empirical data for transplanting livers from patients with HCV into patients who do not have the disease.

The researchers performed their analysis using a Markov-based mathematical model known as Simulation of Liver Transplant Candidates (SIM-LT). The model had been validated in previous studies that Dr. Chhatwal and some coauthors had published (Hepatology. 2017;65:777-88; Clin Gastroenterol Hepatol 2018;16:115-22). Dr. Chhatwal and coauthors revised the SIM-LT model to simulate a virtual trial of HCV-negative patients on the liver transplant waiting list to compare outcomes in patients willing to accept any liver to those willing to accept only HCV-negative livers.

The patients willing to receive HCV-positive livers were given 12 weeks of DAA therapy preemptively and had a higher risk of graft failure. The model incorporated data from published studies using the United Network for Organ Sharing (UNOS) and used reported outcomes of the Organ Procurement and Transplantation Network to validate the findings.

The study showed that the clinical benefits of an HCV-negative patient receiving an HCV-positive liver depend on the patient’s Model for End-Stage Liver Disease (MELD) score. Using the measured change in life-years, the researchers found that patients with a MELD score below 20 actually witnessed reduction in life-years when accepting any liver, but that the benefits of accepting any liver started to accrue at MELD score 20. The benefit topped out at MELD 28, with 0.172 life years gained, but even sustained at 0.06 life years gained at MELD 40.

The effectiveness of using HCV-positive livers may also depend on region. UNOS Region 1 – essentially New England minus western Vermont – has the highest rate of HCV-positive organs, and a patient there with MELD 28 would gain 0.36 life-years by accepting any liver regardless of HCV status. However, Region 7 – the Dakotas and upper Midwest plus Illinois – has the lowest HCV-positive organ rate, and a MELD 28 patient there would gain only 0.1 life-year accepting any liver.

“Transplanting HCV-positive livers into HCV-negative patients receiving preemptive DAA therapy could be a viable option for improving patient survival on the LT waiting list, especially in UNOS regions with high HCV-positive donor organ rates,” said Dr. Chhatwal and coauthors. They concluded that their analysis could help direct future clinical trials evaluating the effectiveness of DAA therapy in liver transplant by recognizing patients who could benefit most from accepting HCV-positive donor organs.

The study authors reported having no financial disclosures. The study was supported by grants from the American Cancer Society, Health Resources and Services Administration, National Institutes of Health, National Science Foundation, and Massachusetts General Hospital Research Scholars Program. Coauthor Fasiha Kanwal, MD, received support from the Veterans Administration Health Services, Research & Development Center for Innovations in Quality, Effectiveness and Safety and Public Health Service.

SOURCE: Chhatwal J et al. Hepatology. doi:10.1002/hep.29723.

In patients hospitalized with cirrhosis, biliary cirrhosis, recent health care exposure, nonwhite race, and cultures taken more than 48 hours after admission all independently predicted that bacteremia would be caused by multidrug-resistant organisms (MDROs), according to a medical record review at CHI St. Luke’s Medical Center, an 850-bed tertiary care center in Houston.

“These variables along with severity of infection and liver disease may help clinicians identify patients who will benefit most from broader-spectrum empiric antimicrobial therapy,” wrote the investigators, led by Jennifer Addo Smith, PharmD, of St. Luke’s, in the Journal of Clinical Gastroenterology.

But local epidemiology remains important. “Although a gram-positive agent (e.g., vancomycin) and a carbapenem-sparing gram-negative agent (e.g., ceftriaxone, cefepime) are reasonable empiric agents at our center, other centers with different resistance patterns may warrant different empiric therapy. Given the low prevalence of VRE [vancomycin-resistant Enterococcus] in this study ... and E. faecium in other studies (4%-7%), an empiric agent active against VRE does not seem to be routinely required,” they said.

The team looked into the issue because there hasn’t been much investigation in the United States of the role of multidrug resistant organisms in bacteremia among patients hospitalized with cirrhosis.

Thirty patients in the study had bacteremia caused by MDROs while 60 had bacteremia from non-MDROs, giving a 33% prevalence of MDRO bacteremia, which was consistent with previous, mostly European studies.

Enterobacteriaceae (43%), Staphylococcus aureus (18%), Streptococcus spp. (11%), Enterococcus spp. (10%), and nonfermenting gram-negative bacilli (6%) were the main causes of bacteremia overall.

Among the 30 MDRO cases, methicillin-resistant S. aureus was isolated in seven (23%); methicillin-resistant coagulase-negative Staphylococci in four (13%); fluoroquinolone-resistant Enterobacteriaceae in nine (30%); extended spectrum beta-lactamase–producing Enterobacteriaceae in three (10%), and VRE in two (7%). No carbapenemase-producing gram-negative bacteria were identified.

The predictors of MDRO bacteremia emerged on multivariate analysis and included biliary cirrhosis (adjusted odds ratio, 11.75; 95% confidence interval, 2.08-66.32); recent health care exposure (aOR, 9.81; 95% CI, 2.15-44.88); blood cultures obtained 48 hours after hospital admission (aOR, 6.02; 95% CI, 1.70-21.40) and nonwhite race (aOR , 3.35; 95% CI, 1.19-9.38).

Blood cultures past 48 hours and recent health care exposure – generally hospitalization within the past 90 days – were likely surrogates for nosocomial infection.

The link with biliary cirrhosis is unclear. “Compared with other cirrhotic patients, perhaps patients with PBC [primary biliary cholangitis] have had more cumulative antimicrobial exposure because of [their] higher risk for UTIs [urinary tract infections] and therefore are at increased risk for MDROs,” they wrote.

The median age in the study was 59 years. Half of the patients were white; 46% were women. Hepatitis C was the most common cause of cirrhosis, followed by alcohol.

MDRO was defined in the study as bacteria not susceptible to at least one antibiotic in at least three antimicrobial categories; 90 cirrhosis patients without bacteremia served as controls.

The funding source was not reported. Dr. Addo Smith had no disclosures.

[email protected]

SOURCE: Smith JA et al. J Clin Gastroenterol. 2017 Nov 23. doi: 10.1097/MCG.0000000000000964.

*This story was updated on 1/10/2018.

In patients hospitalized with cirrhosis, biliary cirrhosis, recent health care exposure, nonwhite race, and cultures taken more than 48 hours after admission all independently predicted that bacteremia would be caused by multidrug-resistant organisms (MDROs), according to a medical record review at CHI St. Luke’s Medical Center, an 850-bed tertiary care center in Houston.

“These variables along with severity of infection and liver disease may help clinicians identify patients who will benefit most from broader-spectrum empiric antimicrobial therapy,” wrote the investigators, led by Jennifer Addo Smith, PharmD, of St. Luke’s, in the Journal of Clinical Gastroenterology.

But local epidemiology remains important. “Although a gram-positive agent (e.g., vancomycin) and a carbapenem-sparing gram-negative agent (e.g., ceftriaxone, cefepime) are reasonable empiric agents at our center, other centers with different resistance patterns may warrant different empiric therapy. Given the low prevalence of VRE [vancomycin-resistant Enterococcus] in this study ... and E. faecium in other studies (4%-7%), an empiric agent active against VRE does not seem to be routinely required,” they said.

The team looked into the issue because there hasn’t been much investigation in the United States of the role of multidrug resistant organisms in bacteremia among patients hospitalized with cirrhosis.

Thirty patients in the study had bacteremia caused by MDROs while 60 had bacteremia from non-MDROs, giving a 33% prevalence of MDRO bacteremia, which was consistent with previous, mostly European studies.

Enterobacteriaceae (43%), Staphylococcus aureus (18%), Streptococcus spp. (11%), Enterococcus spp. (10%), and nonfermenting gram-negative bacilli (6%) were the main causes of bacteremia overall.

Among the 30 MDRO cases, methicillin-resistant S. aureus was isolated in seven (23%); methicillin-resistant coagulase-negative Staphylococci in four (13%); fluoroquinolone-resistant Enterobacteriaceae in nine (30%); extended spectrum beta-lactamase–producing Enterobacteriaceae in three (10%), and VRE in two (7%). No carbapenemase-producing gram-negative bacteria were identified.

The predictors of MDRO bacteremia emerged on multivariate analysis and included biliary cirrhosis (adjusted odds ratio, 11.75; 95% confidence interval, 2.08-66.32); recent health care exposure (aOR, 9.81; 95% CI, 2.15-44.88); blood cultures obtained 48 hours after hospital admission (aOR, 6.02; 95% CI, 1.70-21.40) and nonwhite race (aOR , 3.35; 95% CI, 1.19-9.38).

Blood cultures past 48 hours and recent health care exposure – generally hospitalization within the past 90 days – were likely surrogates for nosocomial infection.

The link with biliary cirrhosis is unclear. “Compared with other cirrhotic patients, perhaps patients with PBC [primary biliary cholangitis] have had more cumulative antimicrobial exposure because of [their] higher risk for UTIs [urinary tract infections] and therefore are at increased risk for MDROs,” they wrote.

The median age in the study was 59 years. Half of the patients were white; 46% were women. Hepatitis C was the most common cause of cirrhosis, followed by alcohol.

MDRO was defined in the study as bacteria not susceptible to at least one antibiotic in at least three antimicrobial categories; 90 cirrhosis patients without bacteremia served as controls.

The funding source was not reported. Dr. Addo Smith had no disclosures.

[email protected]

SOURCE: Smith JA et al. J Clin Gastroenterol. 2017 Nov 23. doi: 10.1097/MCG.0000000000000964.

*This story was updated on 1/10/2018.

In patients hospitalized with cirrhosis, biliary cirrhosis, recent health care exposure, nonwhite race, and cultures taken more than 48 hours after admission all independently predicted that bacteremia would be caused by multidrug-resistant organisms (MDROs), according to a medical record review at CHI St. Luke’s Medical Center, an 850-bed tertiary care center in Houston.

“These variables along with severity of infection and liver disease may help clinicians identify patients who will benefit most from broader-spectrum empiric antimicrobial therapy,” wrote the investigators, led by Jennifer Addo Smith, PharmD, of St. Luke’s, in the Journal of Clinical Gastroenterology.

But local epidemiology remains important. “Although a gram-positive agent (e.g., vancomycin) and a carbapenem-sparing gram-negative agent (e.g., ceftriaxone, cefepime) are reasonable empiric agents at our center, other centers with different resistance patterns may warrant different empiric therapy. Given the low prevalence of VRE [vancomycin-resistant Enterococcus] in this study ... and E. faecium in other studies (4%-7%), an empiric agent active against VRE does not seem to be routinely required,” they said.

The team looked into the issue because there hasn’t been much investigation in the United States of the role of multidrug resistant organisms in bacteremia among patients hospitalized with cirrhosis.

Thirty patients in the study had bacteremia caused by MDROs while 60 had bacteremia from non-MDROs, giving a 33% prevalence of MDRO bacteremia, which was consistent with previous, mostly European studies.

Enterobacteriaceae (43%), Staphylococcus aureus (18%), Streptococcus spp. (11%), Enterococcus spp. (10%), and nonfermenting gram-negative bacilli (6%) were the main causes of bacteremia overall.

Among the 30 MDRO cases, methicillin-resistant S. aureus was isolated in seven (23%); methicillin-resistant coagulase-negative Staphylococci in four (13%); fluoroquinolone-resistant Enterobacteriaceae in nine (30%); extended spectrum beta-lactamase–producing Enterobacteriaceae in three (10%), and VRE in two (7%). No carbapenemase-producing gram-negative bacteria were identified.

The predictors of MDRO bacteremia emerged on multivariate analysis and included biliary cirrhosis (adjusted odds ratio, 11.75; 95% confidence interval, 2.08-66.32); recent health care exposure (aOR, 9.81; 95% CI, 2.15-44.88); blood cultures obtained 48 hours after hospital admission (aOR, 6.02; 95% CI, 1.70-21.40) and nonwhite race (aOR , 3.35; 95% CI, 1.19-9.38).

Blood cultures past 48 hours and recent health care exposure – generally hospitalization within the past 90 days – were likely surrogates for nosocomial infection.

The link with biliary cirrhosis is unclear. “Compared with other cirrhotic patients, perhaps patients with PBC [primary biliary cholangitis] have had more cumulative antimicrobial exposure because of [their] higher risk for UTIs [urinary tract infections] and therefore are at increased risk for MDROs,” they wrote.

The median age in the study was 59 years. Half of the patients were white; 46% were women. Hepatitis C was the most common cause of cirrhosis, followed by alcohol.

MDRO was defined in the study as bacteria not susceptible to at least one antibiotic in at least three antimicrobial categories; 90 cirrhosis patients without bacteremia served as controls.

The funding source was not reported. Dr. Addo Smith had no disclosures.

[email protected]

SOURCE: Smith JA et al. J Clin Gastroenterol. 2017 Nov 23. doi: 10.1097/MCG.0000000000000964.

*This story was updated on 1/10/2018.

A one-two combination consisting of a drug to deplete amyloid fibrils from circulation and a monoclonal antibody to mop up residual amyloid protein appears to be safe and shows promising activity against systemic amyloidosis in an early clinical trial.

Pairing the investigational small molecule agent miridesap and the experimental monoclonal antibody dezamizumab resulted in clearance or reductions in amyloid deposits in the livers, spleens, and kidneys of adults with systemic amyloidosis, reported Prof. Sir Mark B. Pepys of University College, London, and his colleagues.

©Nephron/Wikimedia Commons/CC BY SA 3.0

Source: Richards D et al. Sci. Transl. Med. 2018. doi: 10.1126/scitranslmed.aan3128.

A one-two combination consisting of a drug to deplete amyloid fibrils from circulation and a monoclonal antibody to mop up residual amyloid protein appears to be safe and shows promising activity against systemic amyloidosis in an early clinical trial.

Pairing the investigational small molecule agent miridesap and the experimental monoclonal antibody dezamizumab resulted in clearance or reductions in amyloid deposits in the livers, spleens, and kidneys of adults with systemic amyloidosis, reported Prof. Sir Mark B. Pepys of University College, London, and his colleagues.

©Nephron/Wikimedia Commons/CC BY SA 3.0

Source: Richards D et al. Sci. Transl. Med. 2018. doi: 10.1126/scitranslmed.aan3128.

A one-two combination consisting of a drug to deplete amyloid fibrils from circulation and a monoclonal antibody to mop up residual amyloid protein appears to be safe and shows promising activity against systemic amyloidosis in an early clinical trial.

Pairing the investigational small molecule agent miridesap and the experimental monoclonal antibody dezamizumab resulted in clearance or reductions in amyloid deposits in the livers, spleens, and kidneys of adults with systemic amyloidosis, reported Prof. Sir Mark B. Pepys of University College, London, and his colleagues.

©Nephron/Wikimedia Commons/CC BY SA 3.0

Source: Richards D et al. Sci. Transl. Med. 2018. doi: 10.1126/scitranslmed.aan3128.

Primary biliary cholangitis patients who had concomitant nonalcoholic fatty liver disease (NAFLD) experienced no worse disease progression than patients who had PBC alone, according to Gerald Yosel Minuk, MD, and his associates.

At baseline, the 168 patients in the PBC-only group had higher serum alkaline phosphatase and gamma-glutamyl transferase values than the 68 patients in the NAFLD/PBC group, as well as having higher FIB-4 scores. The percentage of patients with aspartate aminotransferase/platelet ratio indexes (APRI) greater than 1.5 was slightly higher in the PBC-only group, but the difference was not significant.

After follow-up periods averaging 6.7 years in the PBC-only group and 6.4 years in the NAFLD/PBC group, yearly increases in FIB-4 and prevalence of APRI greater than 1.5 were greater in the PBC-only group, though the difference did not reach significance. PBC-only patients were more likely to have developed radiologic evidence of cirrhosis during the follow-up period (42% vs. 19%, P less than .001).

“Were the results of the present study to be confirmed by others, the question arises as to why NAFLD does not adversely and may favorably impact on PBC. Here, it is tempting to speculate that because PBC livers are associated with a paucity of immunosuppressive regulator T cells (Tregs) whereas in NAFLD, Tregs are recruited to the liver in increased numbers, a restoration of the immune balance in PBC livers might explain these findings,” the investigators noted.

Find the full study in Liver International (doi: 10.1111/liv.13644).

[email protected]

Primary biliary cholangitis patients who had concomitant nonalcoholic fatty liver disease (NAFLD) experienced no worse disease progression than patients who had PBC alone, according to Gerald Yosel Minuk, MD, and his associates.

At baseline, the 168 patients in the PBC-only group had higher serum alkaline phosphatase and gamma-glutamyl transferase values than the 68 patients in the NAFLD/PBC group, as well as having higher FIB-4 scores. The percentage of patients with aspartate aminotransferase/platelet ratio indexes (APRI) greater than 1.5 was slightly higher in the PBC-only group, but the difference was not significant.

After follow-up periods averaging 6.7 years in the PBC-only group and 6.4 years in the NAFLD/PBC group, yearly increases in FIB-4 and prevalence of APRI greater than 1.5 were greater in the PBC-only group, though the difference did not reach significance. PBC-only patients were more likely to have developed radiologic evidence of cirrhosis during the follow-up period (42% vs. 19%, P less than .001).

“Were the results of the present study to be confirmed by others, the question arises as to why NAFLD does not adversely and may favorably impact on PBC. Here, it is tempting to speculate that because PBC livers are associated with a paucity of immunosuppressive regulator T cells (Tregs) whereas in NAFLD, Tregs are recruited to the liver in increased numbers, a restoration of the immune balance in PBC livers might explain these findings,” the investigators noted.

Find the full study in Liver International (doi: 10.1111/liv.13644).

[email protected]

Primary biliary cholangitis patients who had concomitant nonalcoholic fatty liver disease (NAFLD) experienced no worse disease progression than patients who had PBC alone, according to Gerald Yosel Minuk, MD, and his associates.

At baseline, the 168 patients in the PBC-only group had higher serum alkaline phosphatase and gamma-glutamyl transferase values than the 68 patients in the NAFLD/PBC group, as well as having higher FIB-4 scores. The percentage of patients with aspartate aminotransferase/platelet ratio indexes (APRI) greater than 1.5 was slightly higher in the PBC-only group, but the difference was not significant.

After follow-up periods averaging 6.7 years in the PBC-only group and 6.4 years in the NAFLD/PBC group, yearly increases in FIB-4 and prevalence of APRI greater than 1.5 were greater in the PBC-only group, though the difference did not reach significance. PBC-only patients were more likely to have developed radiologic evidence of cirrhosis during the follow-up period (42% vs. 19%, P less than .001).

“Were the results of the present study to be confirmed by others, the question arises as to why NAFLD does not adversely and may favorably impact on PBC. Here, it is tempting to speculate that because PBC livers are associated with a paucity of immunosuppressive regulator T cells (Tregs) whereas in NAFLD, Tregs are recruited to the liver in increased numbers, a restoration of the immune balance in PBC livers might explain these findings,” the investigators noted.

Find the full study in Liver International (doi: 10.1111/liv.13644).

[email protected]

Training community health providers to treat chronic hepatitis C virus infection is a cost-effective way to expand treatment access and reduce the national burden of this prevalent condition, according to research published in the December issue of Gastroenterology (doi: 10.1053/j.gastro.2017.10.016).

The model, dubbed Project ECHO, “is the best way, to our knowledge, to cost-effectively find and treat HCV patients at scale,” wrote Thilo Rattay, MPH, of the University of Michigan School of Public Health, Ann Arbor, and his associates. “Our analysis demonstrates that fundamentally changing the care delivery model for HCV enables unparalleled reach, in contrast to simply using ever more cost-effective drugs in an inefficient system. Project ECHO can quickly reduce the burden of disease from HCV and accelerate the impact of the new generation of highly effective medications.”

 

Project ECHO (echo.unm.edu) links multidisciplinary teams of specialists (hubs) to physicians and nurse practitioners in community practice (spokes). Each hub, which is usually based at an academic medical center, holds video conferences to mentor and teach providers about best practices for managing conditions ranging from autism to Zika virus infection. Initial reports suggest that Project ECHO can improve health care quality and access as well as job satisfaction among primary care providers, the researchers noted.

Project ECHO has 127 hubs globally, including 77 in the United States, and receives support from foundations, state legislatures, and government agencies. Because patients with chronic HCV vastly outnumber gastroenterologists in the United States, Mr. Rattay and his coinvestigators used Markov models to evaluate Project ECHO’s cost-effectiveness in the HCV setting. To do so, they created a decision tree and Markov models with Microsoft Excel, PrecisionTree, and @RISK by using data from the U.S. Census Bureau, MarketScan, and an extensive literature review

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

The models yielded an incremental cost-effectiveness ratio of $10,351 per quality-adjusted life year when compared with the status quo, said the researchers. Commonly cited willingness-to-pay thresholds are $50,000 and $100,000, indicating that Project ECHO is a cost-effective way to expand HCV treatment, they added. However, insurers would pay substantially more during the first 5 years of rollout – about $708 million versus $368 million with the status quo. During the first year, ECHO would cost payers about $350.5 million more than would the status quo, but 4,446 more patients would be treated, drastically reducing prevalence in the insurance pool. Consequently, subsequent costs would drop by nearly $11 million over the first 5 years of ECHO. Nonetheless, the “high budgetary costs suggest that incremental rollout of [Project] ECHO may be best,” the investigators wrote.

They were unable to determine whether increased treatment under ECHO relates to expanded screening, treatment adherence, or access, but sensitivity analyses suggested that “results are largely independent of the cause,” the researchers wrote. “Importantly, most of the financial benefits of treating HCV are not immediate, while a majority of the costs are upfront,” they stressed. Stakeholders therefore need to adopt a long-term view and consider population-based health care models and reimbursement strategies that “capture the full benefit of this type of ecosystem.”

The investigators had no external funding sources and no conflicts of interest.

Training community health providers to treat chronic hepatitis C virus infection is a cost-effective way to expand treatment access and reduce the national burden of this prevalent condition, according to research published in the December issue of Gastroenterology (doi: 10.1053/j.gastro.2017.10.016).

The model, dubbed Project ECHO, “is the best way, to our knowledge, to cost-effectively find and treat HCV patients at scale,” wrote Thilo Rattay, MPH, of the University of Michigan School of Public Health, Ann Arbor, and his associates. “Our analysis demonstrates that fundamentally changing the care delivery model for HCV enables unparalleled reach, in contrast to simply using ever more cost-effective drugs in an inefficient system. Project ECHO can quickly reduce the burden of disease from HCV and accelerate the impact of the new generation of highly effective medications.”

 

Project ECHO (echo.unm.edu) links multidisciplinary teams of specialists (hubs) to physicians and nurse practitioners in community practice (spokes). Each hub, which is usually based at an academic medical center, holds video conferences to mentor and teach providers about best practices for managing conditions ranging from autism to Zika virus infection. Initial reports suggest that Project ECHO can improve health care quality and access as well as job satisfaction among primary care providers, the researchers noted.

Project ECHO has 127 hubs globally, including 77 in the United States, and receives support from foundations, state legislatures, and government agencies. Because patients with chronic HCV vastly outnumber gastroenterologists in the United States, Mr. Rattay and his coinvestigators used Markov models to evaluate Project ECHO’s cost-effectiveness in the HCV setting. To do so, they created a decision tree and Markov models with Microsoft Excel, PrecisionTree, and @RISK by using data from the U.S. Census Bureau, MarketScan, and an extensive literature review

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

The models yielded an incremental cost-effectiveness ratio of $10,351 per quality-adjusted life year when compared with the status quo, said the researchers. Commonly cited willingness-to-pay thresholds are $50,000 and $100,000, indicating that Project ECHO is a cost-effective way to expand HCV treatment, they added. However, insurers would pay substantially more during the first 5 years of rollout – about $708 million versus $368 million with the status quo. During the first year, ECHO would cost payers about $350.5 million more than would the status quo, but 4,446 more patients would be treated, drastically reducing prevalence in the insurance pool. Consequently, subsequent costs would drop by nearly $11 million over the first 5 years of ECHO. Nonetheless, the “high budgetary costs suggest that incremental rollout of [Project] ECHO may be best,” the investigators wrote.

They were unable to determine whether increased treatment under ECHO relates to expanded screening, treatment adherence, or access, but sensitivity analyses suggested that “results are largely independent of the cause,” the researchers wrote. “Importantly, most of the financial benefits of treating HCV are not immediate, while a majority of the costs are upfront,” they stressed. Stakeholders therefore need to adopt a long-term view and consider population-based health care models and reimbursement strategies that “capture the full benefit of this type of ecosystem.”

The investigators had no external funding sources and no conflicts of interest.

Training community health providers to treat chronic hepatitis C virus infection is a cost-effective way to expand treatment access and reduce the national burden of this prevalent condition, according to research published in the December issue of Gastroenterology (doi: 10.1053/j.gastro.2017.10.016).

The model, dubbed Project ECHO, “is the best way, to our knowledge, to cost-effectively find and treat HCV patients at scale,” wrote Thilo Rattay, MPH, of the University of Michigan School of Public Health, Ann Arbor, and his associates. “Our analysis demonstrates that fundamentally changing the care delivery model for HCV enables unparalleled reach, in contrast to simply using ever more cost-effective drugs in an inefficient system. Project ECHO can quickly reduce the burden of disease from HCV and accelerate the impact of the new generation of highly effective medications.”

 

Project ECHO (echo.unm.edu) links multidisciplinary teams of specialists (hubs) to physicians and nurse practitioners in community practice (spokes). Each hub, which is usually based at an academic medical center, holds video conferences to mentor and teach providers about best practices for managing conditions ranging from autism to Zika virus infection. Initial reports suggest that Project ECHO can improve health care quality and access as well as job satisfaction among primary care providers, the researchers noted.

Project ECHO has 127 hubs globally, including 77 in the United States, and receives support from foundations, state legislatures, and government agencies. Because patients with chronic HCV vastly outnumber gastroenterologists in the United States, Mr. Rattay and his coinvestigators used Markov models to evaluate Project ECHO’s cost-effectiveness in the HCV setting. To do so, they created a decision tree and Markov models with Microsoft Excel, PrecisionTree, and @RISK by using data from the U.S. Census Bureau, MarketScan, and an extensive literature review

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

The models yielded an incremental cost-effectiveness ratio of $10,351 per quality-adjusted life year when compared with the status quo, said the researchers. Commonly cited willingness-to-pay thresholds are $50,000 and $100,000, indicating that Project ECHO is a cost-effective way to expand HCV treatment, they added. However, insurers would pay substantially more during the first 5 years of rollout – about $708 million versus $368 million with the status quo. During the first year, ECHO would cost payers about $350.5 million more than would the status quo, but 4,446 more patients would be treated, drastically reducing prevalence in the insurance pool. Consequently, subsequent costs would drop by nearly $11 million over the first 5 years of ECHO. Nonetheless, the “high budgetary costs suggest that incremental rollout of [Project] ECHO may be best,” the investigators wrote.

They were unable to determine whether increased treatment under ECHO relates to expanded screening, treatment adherence, or access, but sensitivity analyses suggested that “results are largely independent of the cause,” the researchers wrote. “Importantly, most of the financial benefits of treating HCV are not immediate, while a majority of the costs are upfront,” they stressed. Stakeholders therefore need to adopt a long-term view and consider population-based health care models and reimbursement strategies that “capture the full benefit of this type of ecosystem.”

The investigators had no external funding sources and no conflicts of interest.

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

WASHINGTON – Nonalcoholic fatty liver disease (NAFLD) is a complex disease that involves multiple systems, and several standout abstracts at the annual meeting of the American Association for the Study of Liver Diseases emphasized the importance of multisystem management and the potential of combination therapies, Kymberly D. Watt, MD, said during the final debrief.

“The actual underlying mechanisms and the underlying processes that are going on are way more complicated than just inflammation and scarring,” said Dr. Watt, associate professor of medicine and medical director of liver transplantation at the Mayo Clinic, Rochester, Minn. “We have numerous areas to target, including insulin resistance, lipid metabolism, oxidative stress, inflammation, immune modulation, cell death, etc.”

She noted several studies that evaluated the prevalence of NAFLD, including a study that found that “about one-third of patients walking through the door of the clinic had nonalcoholic steatohepatitis [NASH],” suggesting physicians should consider screening at-risk patients (abstract 58). A Korean study found about 18% of asymptomatic lean individuals (body mass index less than 23 kg/m²) had NAFLD and identified sarcopenia as a significant risk factor for NAFLD in these lean patients (abstract 59). “Sarcopenia is something that we really need to pay a lot more attention to,” Dr. Watt said.

Other studies better outlined the increasing association between NAFLD and hepatocellular carcinoma, Dr. Watt noted (abstracts 2119 and 2102). Another study confirmed that men with NAFLD/NASH have almost twice the incidence of hepatocellular carcinoma (HCC) as women — 0.43%-0.5% vs. 0.22%-0.28%, with both groups significantly higher than the general population (abstract 2116). “And looking further, we can actually quote an HCC incidence in NASH of 0.009%,” she added.

Again emphasizing the multisystem impact of NAFLD, Dr. Watt cited a study that calculated the cardiovascular risks incumbent with liver disease. Researchers reported that men and women at the time of NAFLD diagnosis had significantly higher rates of either angina/ischemic heart disease or heart failure (abstract 55). Women, specifically, had a higher risk for cardiovascular events earlier than men and overall are at equal risk to men, unlike in the general population where women are at lower risk. “We need to start looking at screening and prevention of other diseases in our patients with NASH,” Dr. Watt said. “In addition, we need to be more aware of the elevated risk in these patients and not just approach them in the same way as the general population.”

Physicians may be tempted to discontinue statin therapy in patients with chronic liver disease, but Dr. Watt cited a poster that showed that this results in worse outcomes (abstract 2106). The researchers found that continued statin use was associated with a lower risk of death with compensated and decompensated liver function. “These data help to educate certain patients of their risk of decompensation over time,” Dr. Watt said.

An international study determined that the severity of advanced compensated liver disease is a key determinant in outcomes, finding that those with bridging fibrosis are at greater risk of vascular events, but those with cirrhosis and Child-Turcotte-Pugh A5 and A6 disease have much higher risks of hepatic decompensation and HCC out to 14 years (abstract 60). “The reason to look at these is to be able to tell your patients that they probably have a 30% increased risk of decompensation by 4 years,” Dr. Watt said.

Dr. Watt pointed out three studies that shed more light on important biomarkers of NAFLD. One study reported that three biomarkers – alpha-2-macroglobulin, hyaluronic acid, and tissue inhibitor of metalloproteinase-1 – have a high sensitivity for differentiating low-stage and stage F3-F4 disease (abstract 95). Another study found that a measure using Pro-C3 and other clinical markers were predictive of F3 or F4 fibrosis in NAFLD (abstract 93). And, other researchers found that a HepQuant-STAT measure of greater than 0.50 microM in patients who ingested deuterated cholic acid (d4-CA) solution may be a minimally invasive alternative to biopsy for diagnosing NASH (abstract 96).

Management studies focusing on varying targets were also presented. A trial of fibroblast growth factor–21 for treatment of NAFLD found that patients in the 10- and 20-mg dose arms showed improvement in MRI hepatic fat fraction, ALT, AST, and liver stiffness at 16 weeks vs. placebo. A few patients had some mild elevation to their liver enzymes on treatment (abstract 182). “So I think we need to remain cautious and watch these patients closely, but overall it seems to be reasonably safe data,” she said. Another drug trial of the acetyl-CoA carboxylase inhibitor GS-0976 also showed promise for overall improvement in MRI steatosis measures (abstract LB-9).

Three preclinical studies of dual-agent therapies in animals have demonstrated improvement in inflammatory and fibrosis scores, Dr. Watt noted (abstracts 2,000, 2,002 and 2,052). “There’s no one drug that’s going to be likely the magic cure,” Dr. Watt said. “There will likely be a lot more focus and data coming out on dual-action agents.” Another animal study addressed the burning question if decaffeinated coffee has the same protective effect against NASH as caffeinated coffee (abstract 2093). Said Dr. Watt: “If you are interested in the potential benefits of coffee but really can’t handle the caffeine, this study suggests, you may still be OK.”

Finally, Dr. Watt noted an early study of three-dimensional printing has shown potential for replicating NASH tissue for bench studies (abstract 1963). “3-D printing is certainly a wave of the future,” she said, pointing out that researchers have created a 3-D model that has some metabolic equivalency to NASH, with the inflammatory cytokine release, hepatic stellate cell activation, “and all of the features that we see in NASH. This may be of potential use down the road to avoid relying on animal models in preclinical studies.”

The Liver Meeting next convenes Nov. 9-13, 2018, in San Francisco.

Dr. Watt disclosed ties to Bristol-Myers Squibb, Exelixis, and Seattle Genetics.

SCOTTSDALE, ARIZ. – A single-center analysis of complications following living liver donation found a low rate of severe complications, and a high quality of life among donors. The results are similar to what has been seen in a previous multicenter study in the United States, and the authors hope that the results can help inform potential donors and their physicians.

There is a significant shortage of deceased liver donors, leading to the death of about 3,500 liver transplant hopefuls in 2016, compared with about 2,900 who received a transplant. Living donor transplant was developed and first attempted in 1996 as an attempt to counter this shortage, and for a brief period it was popular, peaking at 500 donor surgeries in 2001. But that year the death of a donor occurred in New York and received widespread publicity.

Dr. Srinath Chinnakotla

SCOTTSDALE, ARIZ. – A single-center analysis of complications following living liver donation found a low rate of severe complications, and a high quality of life among donors. The results are similar to what has been seen in a previous multicenter study in the United States, and the authors hope that the results can help inform potential donors and their physicians.

There is a significant shortage of deceased liver donors, leading to the death of about 3,500 liver transplant hopefuls in 2016, compared with about 2,900 who received a transplant. Living donor transplant was developed and first attempted in 1996 as an attempt to counter this shortage, and for a brief period it was popular, peaking at 500 donor surgeries in 2001. But that year the death of a donor occurred in New York and received widespread publicity.

Dr. Srinath Chinnakotla

SCOTTSDALE, ARIZ. – A single-center analysis of complications following living liver donation found a low rate of severe complications, and a high quality of life among donors. The results are similar to what has been seen in a previous multicenter study in the United States, and the authors hope that the results can help inform potential donors and their physicians.

There is a significant shortage of deceased liver donors, leading to the death of about 3,500 liver transplant hopefuls in 2016, compared with about 2,900 who received a transplant. Living donor transplant was developed and first attempted in 1996 as an attempt to counter this shortage, and for a brief period it was popular, peaking at 500 donor surgeries in 2001. But that year the death of a donor occurred in New York and received widespread publicity.

Dr. Srinath Chinnakotla

SAN DIEGO – Statin therapy wasn’t effective against a rising rate of hepatic steatosis in HIV patients, and may increase nonalcoholic fatty liver disease (NAFLD) risk, according to a small study.

The findings are contrary to the limited data currently available, which suggest statins can have a beneficial effect on hepatic steatosis, according to the study’s investigators.

NAFLD is one of the leading causes of mortality and morbidity in people living with HIV, said Vanessa El Kamari, MD, of Case Western Reserve University, Cleveland, and rates are continuing to increase. With a lack of therapeutic interventions for NAFLD in patients with HIV, finding effective treatments is a major concern for providers.

Dr. El Kamari and her colleagues conducted a secondary analysis of the SATURN-HIV trial, a randomized, placebo-controlled trial of 147 patients with HIV who were on stable antiretroviral therapy (ART) with LDL cholesterol levels at or below 130 mg/dL. Patients were either treated with 10 mg rosuvastatin or placebo.

Patients in the treatment and placebo arms were an average age of 45 years, most patients were male (81% and 76%, respectively), and a majority was African American (69% and 67%, respectively). The two groups reported average CD4+ counts of 644 and 636, respectively.

Investigators used validated scores to determine hepatic steatosis in patients, although researchers acknowledged that liver biopsy is the gold standard for hepatic steatosis measurement.

“We understand liver fat score has its limitation,” said Dr. El Kamari in a question and answer session following the presentation at an annual scientific meeting on infectious diseases. “Further studies are needed in this area in order to detect, in noninvasive ways, hepatic steatosis.”

Liver fat scores (LFS) were measured on entry, at week 48, and week 96.

After 96 weeks, investigators saw significant increases in LFS in both the placebo and rosuvastatin groups (P = .01 and P less than .01, respectively). Progression from nonsteatosis at baseline to steatosis over 96 weeks was greater in patients given rosuvastatin than in those given placebo (odds ratio, 4.3; P = .03).

Studying predictors for LFS changes, a trend toward insignificance among the randomization group led investigators to the conclusion that statin may have negatively affected the liver fat score of patients over the 96-week time period.

The study researchers identified 92 patients who did not have hepatic steatosis at baseline to study how statins influenced the development of hepatic steatosis.

Of the 13 patients who developed steatosis during the trial period, 10 were part of the rosuvastatin group, while only 3 were from the placebo group.

Increases in LFS were associated with increases in insulin resistance, detected presence of HIV-1 RNA, and higher interferon-inducible proteins, according to Dr. El Kamari.

While increased homeostatic assessment of insulin resistance was associated with increased hepatic homeostasis, Dr. El Kamari was not able to determine if statins that are not associated with insulin resistance will have different outcomes.

The investigators cautioned that the findings may not be generalizable to the entire HIV population due to the overwhelming majority of African American patients with increased inflammation, as well as the study patients’ LDL cholesterol levels of less than or equal to 130 mg/dL.

The National Institutes of Health funded the study. Dr. El Kamari had no disclosures.

[email protected]

On Twitter @eaztweets

SAN DIEGO – Statin therapy wasn’t effective against a rising rate of hepatic steatosis in HIV patients, and may increase nonalcoholic fatty liver disease (NAFLD) risk, according to a small study.

The findings are contrary to the limited data currently available, which suggest statins can have a beneficial effect on hepatic steatosis, according to the study’s investigators.

NAFLD is one of the leading causes of mortality and morbidity in people living with HIV, said Vanessa El Kamari, MD, of Case Western Reserve University, Cleveland, and rates are continuing to increase. With a lack of therapeutic interventions for NAFLD in patients with HIV, finding effective treatments is a major concern for providers.

Dr. El Kamari and her colleagues conducted a secondary analysis of the SATURN-HIV trial, a randomized, placebo-controlled trial of 147 patients with HIV who were on stable antiretroviral therapy (ART) with LDL cholesterol levels at or below 130 mg/dL. Patients were either treated with 10 mg rosuvastatin or placebo.

Patients in the treatment and placebo arms were an average age of 45 years, most patients were male (81% and 76%, respectively), and a majority was African American (69% and 67%, respectively). The two groups reported average CD4+ counts of 644 and 636, respectively.

Investigators used validated scores to determine hepatic steatosis in patients, although researchers acknowledged that liver biopsy is the gold standard for hepatic steatosis measurement.

“We understand liver fat score has its limitation,” said Dr. El Kamari in a question and answer session following the presentation at an annual scientific meeting on infectious diseases. “Further studies are needed in this area in order to detect, in noninvasive ways, hepatic steatosis.”

Liver fat scores (LFS) were measured on entry, at week 48, and week 96.

After 96 weeks, investigators saw significant increases in LFS in both the placebo and rosuvastatin groups (P = .01 and P less than .01, respectively). Progression from nonsteatosis at baseline to steatosis over 96 weeks was greater in patients given rosuvastatin than in those given placebo (odds ratio, 4.3; P = .03).

Studying predictors for LFS changes, a trend toward insignificance among the randomization group led investigators to the conclusion that statin may have negatively affected the liver fat score of patients over the 96-week time period.

The study researchers identified 92 patients who did not have hepatic steatosis at baseline to study how statins influenced the development of hepatic steatosis.

Of the 13 patients who developed steatosis during the trial period, 10 were part of the rosuvastatin group, while only 3 were from the placebo group.

Increases in LFS were associated with increases in insulin resistance, detected presence of HIV-1 RNA, and higher interferon-inducible proteins, according to Dr. El Kamari.

While increased homeostatic assessment of insulin resistance was associated with increased hepatic homeostasis, Dr. El Kamari was not able to determine if statins that are not associated with insulin resistance will have different outcomes.

The investigators cautioned that the findings may not be generalizable to the entire HIV population due to the overwhelming majority of African American patients with increased inflammation, as well as the study patients’ LDL cholesterol levels of less than or equal to 130 mg/dL.

The National Institutes of Health funded the study. Dr. El Kamari had no disclosures.

[email protected]

On Twitter @eaztweets

SAN DIEGO – Statin therapy wasn’t effective against a rising rate of hepatic steatosis in HIV patients, and may increase nonalcoholic fatty liver disease (NAFLD) risk, according to a small study.

The findings are contrary to the limited data currently available, which suggest statins can have a beneficial effect on hepatic steatosis, according to the study’s investigators.

NAFLD is one of the leading causes of mortality and morbidity in people living with HIV, said Vanessa El Kamari, MD, of Case Western Reserve University, Cleveland, and rates are continuing to increase. With a lack of therapeutic interventions for NAFLD in patients with HIV, finding effective treatments is a major concern for providers.

Dr. El Kamari and her colleagues conducted a secondary analysis of the SATURN-HIV trial, a randomized, placebo-controlled trial of 147 patients with HIV who were on stable antiretroviral therapy (ART) with LDL cholesterol levels at or below 130 mg/dL. Patients were either treated with 10 mg rosuvastatin or placebo.

Patients in the treatment and placebo arms were an average age of 45 years, most patients were male (81% and 76%, respectively), and a majority was African American (69% and 67%, respectively). The two groups reported average CD4+ counts of 644 and 636, respectively.

Investigators used validated scores to determine hepatic steatosis in patients, although researchers acknowledged that liver biopsy is the gold standard for hepatic steatosis measurement.

“We understand liver fat score has its limitation,” said Dr. El Kamari in a question and answer session following the presentation at an annual scientific meeting on infectious diseases. “Further studies are needed in this area in order to detect, in noninvasive ways, hepatic steatosis.”

Liver fat scores (LFS) were measured on entry, at week 48, and week 96.

After 96 weeks, investigators saw significant increases in LFS in both the placebo and rosuvastatin groups (P = .01 and P less than .01, respectively). Progression from nonsteatosis at baseline to steatosis over 96 weeks was greater in patients given rosuvastatin than in those given placebo (odds ratio, 4.3; P = .03).

Studying predictors for LFS changes, a trend toward insignificance among the randomization group led investigators to the conclusion that statin may have negatively affected the liver fat score of patients over the 96-week time period.

The study researchers identified 92 patients who did not have hepatic steatosis at baseline to study how statins influenced the development of hepatic steatosis.

Of the 13 patients who developed steatosis during the trial period, 10 were part of the rosuvastatin group, while only 3 were from the placebo group.

Increases in LFS were associated with increases in insulin resistance, detected presence of HIV-1 RNA, and higher interferon-inducible proteins, according to Dr. El Kamari.

While increased homeostatic assessment of insulin resistance was associated with increased hepatic homeostasis, Dr. El Kamari was not able to determine if statins that are not associated with insulin resistance will have different outcomes.

The investigators cautioned that the findings may not be generalizable to the entire HIV population due to the overwhelming majority of African American patients with increased inflammation, as well as the study patients’ LDL cholesterol levels of less than or equal to 130 mg/dL.

The National Institutes of Health funded the study. Dr. El Kamari had no disclosures.

[email protected]

On Twitter @eaztweets

When the Food and Drug Administration approved Heplisav-B Nov. 9, it marked the first new vaccine for hepatitis B virus (HBV) to be sanctioned in over 25 years.

Heplisav-B is the only two-dose regimen that protects against all known subtypes of HBV in adults 18 years and older, according to a statement released by Dynavax Technologies, the creator of the drug.

[email protected]

On Twitter @eaztweets

When the Food and Drug Administration approved Heplisav-B Nov. 9, it marked the first new vaccine for hepatitis B virus (HBV) to be sanctioned in over 25 years.

Heplisav-B is the only two-dose regimen that protects against all known subtypes of HBV in adults 18 years and older, according to a statement released by Dynavax Technologies, the creator of the drug.

[email protected]

On Twitter @eaztweets

When the Food and Drug Administration approved Heplisav-B Nov. 9, it marked the first new vaccine for hepatitis B virus (HBV) to be sanctioned in over 25 years.

Heplisav-B is the only two-dose regimen that protects against all known subtypes of HBV in adults 18 years and older, according to a statement released by Dynavax Technologies, the creator of the drug.

[email protected]

On Twitter @eaztweets