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Hep C sofosbuvir/daclatasvir combo promising for COVID-19
research from an open-label Iranian study shows.
And the good news is that the treatment combination “already has a well-established safety profile in the treatment of hepatitis C,” said investigator Andrew Hill, PhD, from the University of Liverpool, United Kingdom.
But although the results look promising, they are preliminary, he cautioned. The combination could follow the path of ritonavir plus lopinavir (Kaletra, AbbVie Pharmaceuticals) or hydroxychloroquine (Plaquenil, Sanofi Pharmaceuticals), which showed promise early but did not perform as hoped in large randomized controlled trials.
“We need to remember that conducting research amidst a pandemic with overwhelmed hospitals is a clear challenge, and we cannot be sure of success,” he added.
Three Trials, 176 Patients
Data collected during a four-site trial of the combination treatment in Tehran during an early spike in cases in Iran were presented at the Virtual COVID-19 Conference 2020 by Hannah Wentzel, a masters student in public health at Imperial College London and a member of Hill’s team.
All 66 study participants were diagnosed with moderate to severe COVID-19 and were treated with standard care, which consisted of hydroxychloroquine 200 mg twice daily with or without the combination of lopinavir plus ritonavir 250 mg twice daily.
The 33 patients randomized to the treatment group also received the combination of sofosbuvir plus daclatasvir 460 mg once daily. These patients were slightly younger and more likely to be men than were those in the standard-care group, but the differences were not significant.
All participants were treated for 14 days, and then the researchers assessed fever, respiration rate, and blood oxygen saturation.
More patients in the treatment group than in the standard-care group had recovered at 14 days (88% vs 67%), but the difference was not significant.
However, median time to clinical recovery, which took into account death as a competing risk, was significantly faster in the treatment group than in the standard-care group (6 vs 11 days; P = .041).
The researchers then pooled their Tehran data with those from two other trials of the sofosbuvir plus daclatasvir combination conducted in Iran: one in the city of Sari with 48 patients and one in the city of Abadan with 62 patients.
A meta-analysis showed that clinical recovery in 14 days was 14% better in the treatment group than in the control group in the Sari study, 32% better in the Tehran study, and 82% better in the Abadan study. However, in a sensitivity analysis, because “the trial in Abadan was not properly randomized,” only the improvements in the Sari and Tehran studies were significant, Wentzel reported.
The meta-analysis also showed that patients in the treatment groups were 70% more likely than those in the standard-care groups to survive.
However, the treatment regimens in the standard-care groups of the three studies were all different, reflecting evolving national treatment guidelines in Iran at the time. And SARS-CoV-2 viral loads were not measured in any of the trials, so the effects of the different drugs on the virus itself could not be assessed.
Still, overall, “sofosbuvir and daclatasvir is associated with faster discharge from hospital and improved survival,” Wentzel said.
These findings are hopeful, “provocative, and encouraging,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and he echoed Hill’s call to “get these kinds of studies into randomized controlled trials.”
But he cautioned that more data are needed before the sofosbuvir and daclatasvir combination can be added to the National Institutes of Health COVID-19 Treatment Guidelines, which clinicians who might be under-resourced and overwhelmed with spikes in COVID-19 cases rely on.
Results from three double-blind randomized controlled trials – one each in Iran, Egypt, and South Africa – with an estimated cumulative enrollment of about 2,000 patients, are expected in October, Hill reported.
“Having gone through feeling so desperate to help people and try new things, it’s really important to do these trials,” said Kristen Marks, MD, from Weill Cornell Medicine in New York City.
“You get tempted to just kind of throw anything at people. And I think we really have to have science to guide us,” she told Medscape Medical News.
This article first appeared on Medscape.com.
research from an open-label Iranian study shows.
And the good news is that the treatment combination “already has a well-established safety profile in the treatment of hepatitis C,” said investigator Andrew Hill, PhD, from the University of Liverpool, United Kingdom.
But although the results look promising, they are preliminary, he cautioned. The combination could follow the path of ritonavir plus lopinavir (Kaletra, AbbVie Pharmaceuticals) or hydroxychloroquine (Plaquenil, Sanofi Pharmaceuticals), which showed promise early but did not perform as hoped in large randomized controlled trials.
“We need to remember that conducting research amidst a pandemic with overwhelmed hospitals is a clear challenge, and we cannot be sure of success,” he added.
Three Trials, 176 Patients
Data collected during a four-site trial of the combination treatment in Tehran during an early spike in cases in Iran were presented at the Virtual COVID-19 Conference 2020 by Hannah Wentzel, a masters student in public health at Imperial College London and a member of Hill’s team.
All 66 study participants were diagnosed with moderate to severe COVID-19 and were treated with standard care, which consisted of hydroxychloroquine 200 mg twice daily with or without the combination of lopinavir plus ritonavir 250 mg twice daily.
The 33 patients randomized to the treatment group also received the combination of sofosbuvir plus daclatasvir 460 mg once daily. These patients were slightly younger and more likely to be men than were those in the standard-care group, but the differences were not significant.
All participants were treated for 14 days, and then the researchers assessed fever, respiration rate, and blood oxygen saturation.
More patients in the treatment group than in the standard-care group had recovered at 14 days (88% vs 67%), but the difference was not significant.
However, median time to clinical recovery, which took into account death as a competing risk, was significantly faster in the treatment group than in the standard-care group (6 vs 11 days; P = .041).
The researchers then pooled their Tehran data with those from two other trials of the sofosbuvir plus daclatasvir combination conducted in Iran: one in the city of Sari with 48 patients and one in the city of Abadan with 62 patients.
A meta-analysis showed that clinical recovery in 14 days was 14% better in the treatment group than in the control group in the Sari study, 32% better in the Tehran study, and 82% better in the Abadan study. However, in a sensitivity analysis, because “the trial in Abadan was not properly randomized,” only the improvements in the Sari and Tehran studies were significant, Wentzel reported.
The meta-analysis also showed that patients in the treatment groups were 70% more likely than those in the standard-care groups to survive.
However, the treatment regimens in the standard-care groups of the three studies were all different, reflecting evolving national treatment guidelines in Iran at the time. And SARS-CoV-2 viral loads were not measured in any of the trials, so the effects of the different drugs on the virus itself could not be assessed.
Still, overall, “sofosbuvir and daclatasvir is associated with faster discharge from hospital and improved survival,” Wentzel said.
These findings are hopeful, “provocative, and encouraging,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and he echoed Hill’s call to “get these kinds of studies into randomized controlled trials.”
But he cautioned that more data are needed before the sofosbuvir and daclatasvir combination can be added to the National Institutes of Health COVID-19 Treatment Guidelines, which clinicians who might be under-resourced and overwhelmed with spikes in COVID-19 cases rely on.
Results from three double-blind randomized controlled trials – one each in Iran, Egypt, and South Africa – with an estimated cumulative enrollment of about 2,000 patients, are expected in October, Hill reported.
“Having gone through feeling so desperate to help people and try new things, it’s really important to do these trials,” said Kristen Marks, MD, from Weill Cornell Medicine in New York City.
“You get tempted to just kind of throw anything at people. And I think we really have to have science to guide us,” she told Medscape Medical News.
This article first appeared on Medscape.com.
research from an open-label Iranian study shows.
And the good news is that the treatment combination “already has a well-established safety profile in the treatment of hepatitis C,” said investigator Andrew Hill, PhD, from the University of Liverpool, United Kingdom.
But although the results look promising, they are preliminary, he cautioned. The combination could follow the path of ritonavir plus lopinavir (Kaletra, AbbVie Pharmaceuticals) or hydroxychloroquine (Plaquenil, Sanofi Pharmaceuticals), which showed promise early but did not perform as hoped in large randomized controlled trials.
“We need to remember that conducting research amidst a pandemic with overwhelmed hospitals is a clear challenge, and we cannot be sure of success,” he added.
Three Trials, 176 Patients
Data collected during a four-site trial of the combination treatment in Tehran during an early spike in cases in Iran were presented at the Virtual COVID-19 Conference 2020 by Hannah Wentzel, a masters student in public health at Imperial College London and a member of Hill’s team.
All 66 study participants were diagnosed with moderate to severe COVID-19 and were treated with standard care, which consisted of hydroxychloroquine 200 mg twice daily with or without the combination of lopinavir plus ritonavir 250 mg twice daily.
The 33 patients randomized to the treatment group also received the combination of sofosbuvir plus daclatasvir 460 mg once daily. These patients were slightly younger and more likely to be men than were those in the standard-care group, but the differences were not significant.
All participants were treated for 14 days, and then the researchers assessed fever, respiration rate, and blood oxygen saturation.
More patients in the treatment group than in the standard-care group had recovered at 14 days (88% vs 67%), but the difference was not significant.
However, median time to clinical recovery, which took into account death as a competing risk, was significantly faster in the treatment group than in the standard-care group (6 vs 11 days; P = .041).
The researchers then pooled their Tehran data with those from two other trials of the sofosbuvir plus daclatasvir combination conducted in Iran: one in the city of Sari with 48 patients and one in the city of Abadan with 62 patients.
A meta-analysis showed that clinical recovery in 14 days was 14% better in the treatment group than in the control group in the Sari study, 32% better in the Tehran study, and 82% better in the Abadan study. However, in a sensitivity analysis, because “the trial in Abadan was not properly randomized,” only the improvements in the Sari and Tehran studies were significant, Wentzel reported.
The meta-analysis also showed that patients in the treatment groups were 70% more likely than those in the standard-care groups to survive.
However, the treatment regimens in the standard-care groups of the three studies were all different, reflecting evolving national treatment guidelines in Iran at the time. And SARS-CoV-2 viral loads were not measured in any of the trials, so the effects of the different drugs on the virus itself could not be assessed.
Still, overall, “sofosbuvir and daclatasvir is associated with faster discharge from hospital and improved survival,” Wentzel said.
These findings are hopeful, “provocative, and encouraging,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and he echoed Hill’s call to “get these kinds of studies into randomized controlled trials.”
But he cautioned that more data are needed before the sofosbuvir and daclatasvir combination can be added to the National Institutes of Health COVID-19 Treatment Guidelines, which clinicians who might be under-resourced and overwhelmed with spikes in COVID-19 cases rely on.
Results from three double-blind randomized controlled trials – one each in Iran, Egypt, and South Africa – with an estimated cumulative enrollment of about 2,000 patients, are expected in October, Hill reported.
“Having gone through feeling so desperate to help people and try new things, it’s really important to do these trials,” said Kristen Marks, MD, from Weill Cornell Medicine in New York City.
“You get tempted to just kind of throw anything at people. And I think we really have to have science to guide us,” she told Medscape Medical News.
This article first appeared on Medscape.com.
AGA meta-analysis leads to new COVID-19 GI and liver best practices
The American Gastroenterological Association has released a new guideline for consultative management of patients with COVID-19.
The recommendations, which were written by Shahnaz Sultan, MD, AGAF, chair of the AGA Clinical Guidelines Committee, of the University of Minnesota, Minneapolis, and colleagues, were based on a meta-analysis of data from 47 studies involving 10,890 unique patients.
“We seek to summarize international data on the GI and liver manifestations of COVID-19 infection and treatment,” the panelists wrote in Gastroenterology. “Additionally, this document provides evidence-based clinical guidance on clinical questions that gastroenterologists may be consulted for.”
The guideline includes seven best practice statements.
The first three statements relate to COVID-19–related GI symptoms, which are estimated to occur in less than 10% of patients, and rarely in the absence of other COVID-19–related symptoms, according to Dr. Sultan and her copanelists.
“The overall prevalence of GI symptoms in the context of COVID-19, including nausea, vomiting, abdominal pain, and diarrhea, is lower than estimated previously,” the panelists wrote, referencing a previous meta-analysis by Ka Shing Cheung, MBBS, and colleagues that showed a prevalence of 17.6%.
“It is important to note that the majority of studies were focused on hospitalized patients with COVID-19, and the prevalence of diarrhea in patients with mild symptoms who were not hospitalized is not known.”
Since GI issues may precede other symptoms of COVID-19, the guideline recommends questioning outpatients with new-onset GI symptoms about other symptoms of COVID-19, with viral testing recommended in areas of high prevalence. Conversely, the panelists recommended that patients with suspected or known COVID-19 should undergo thorough history taking for GI symptoms, “including onset, characteristics, duration, and severity.”
The fourth practice statement advises against COVID-19 stool testing in routine clinical practice, either for diagnostic or monitoring purposes.
Although Dr. Cheung and colleagues reported that 48.1% of fecal specimens from patients with COVID-19 contained viral RNA, the panelists concluded that the practical relevance of this finding remains unknown.
“Stool infectivity and transmission have not been confirmed,” the panelists wrote, citing a lack of evidence and conflicting findings.
The final three practice statements address liver concerns.
First, any patient with suspected or confirmed COVID-19 who has elevated liver function tests should be evaluated for alternative etiologies. Second, hospitalized patients with suspected or confirmed COVID-19 should undergo baseline liver function testing, followed by liver monitoring throughout their stay, “particularly in the context of drug treatment for COVID-19.” And third, any patient receiving drugs to treat COVID-19 should be monitored for treatment-related hepatic and GI adverse effects.
Dr. Sultan and colleagues found that approximately 15% of patients with COVID-19 included in their meta-analysis had abnormal liver function tests, more often because of secondary effects rather than virally induced liver injury.
Although liver function test abnormalities were inconsistently reported across studies, and when available, often lacked relevant contextual data, such as information about underlying liver disease, published data suggest that abnormal liver values could predict more severe COVID-19, supporting baseline and serial liver testing, the panelists wrote.
Following these recommendations, the guideline includes a discussion of GI and hepatic adverse effects related to specific COVID-19 treatments.
According to the panelists, chloroquine and hydroxychloroquine may infrequently lead to GI disturbances, and rarely, liver injury, with the latter thought to be a sequela of a hypersensitivity reaction; among antiviral medications, lopinavir/ritonavir and favipiravir may cause GI adverse effects in approximately 5%-15% of patients, with potentially higher rates in children and those receiving higher doses.
“In particular, GI adverse events are poorly understood for both favipiravir and remdesivir,” the panelists wrote.
Hepatic adverse effects, ranging from mild elevations in aminotransferases to acute liver failure, have been documented, albeit rarely, among patients receiving lopinavir/ritonavir, according to the panelists. For remdesivir, liver injury has also been reported, although frequency is unknown, and for favipiravir, hepatic adverse events may be seen in 3% of patients, although, again, the panelists noted a scarcity of relevant findings.
In their concluding remarks, Dr. Sultan and colleagues called for more high-quality data, and encouraged clinicians to contribute to international registries, as these could help guide COVID-19 recommendations for patient subgroups.
The article was funded by the American Gastroenterological Association Institute.
SOURCE: Sultan S et al. Gastroenterology. 2020 May 11. doi: 10.1053/j.gastro.2020.05.001.
The American Gastroenterological Association has released a new guideline for consultative management of patients with COVID-19.
The recommendations, which were written by Shahnaz Sultan, MD, AGAF, chair of the AGA Clinical Guidelines Committee, of the University of Minnesota, Minneapolis, and colleagues, were based on a meta-analysis of data from 47 studies involving 10,890 unique patients.
“We seek to summarize international data on the GI and liver manifestations of COVID-19 infection and treatment,” the panelists wrote in Gastroenterology. “Additionally, this document provides evidence-based clinical guidance on clinical questions that gastroenterologists may be consulted for.”
The guideline includes seven best practice statements.
The first three statements relate to COVID-19–related GI symptoms, which are estimated to occur in less than 10% of patients, and rarely in the absence of other COVID-19–related symptoms, according to Dr. Sultan and her copanelists.
“The overall prevalence of GI symptoms in the context of COVID-19, including nausea, vomiting, abdominal pain, and diarrhea, is lower than estimated previously,” the panelists wrote, referencing a previous meta-analysis by Ka Shing Cheung, MBBS, and colleagues that showed a prevalence of 17.6%.
“It is important to note that the majority of studies were focused on hospitalized patients with COVID-19, and the prevalence of diarrhea in patients with mild symptoms who were not hospitalized is not known.”
Since GI issues may precede other symptoms of COVID-19, the guideline recommends questioning outpatients with new-onset GI symptoms about other symptoms of COVID-19, with viral testing recommended in areas of high prevalence. Conversely, the panelists recommended that patients with suspected or known COVID-19 should undergo thorough history taking for GI symptoms, “including onset, characteristics, duration, and severity.”
The fourth practice statement advises against COVID-19 stool testing in routine clinical practice, either for diagnostic or monitoring purposes.
Although Dr. Cheung and colleagues reported that 48.1% of fecal specimens from patients with COVID-19 contained viral RNA, the panelists concluded that the practical relevance of this finding remains unknown.
“Stool infectivity and transmission have not been confirmed,” the panelists wrote, citing a lack of evidence and conflicting findings.
The final three practice statements address liver concerns.
First, any patient with suspected or confirmed COVID-19 who has elevated liver function tests should be evaluated for alternative etiologies. Second, hospitalized patients with suspected or confirmed COVID-19 should undergo baseline liver function testing, followed by liver monitoring throughout their stay, “particularly in the context of drug treatment for COVID-19.” And third, any patient receiving drugs to treat COVID-19 should be monitored for treatment-related hepatic and GI adverse effects.
Dr. Sultan and colleagues found that approximately 15% of patients with COVID-19 included in their meta-analysis had abnormal liver function tests, more often because of secondary effects rather than virally induced liver injury.
Although liver function test abnormalities were inconsistently reported across studies, and when available, often lacked relevant contextual data, such as information about underlying liver disease, published data suggest that abnormal liver values could predict more severe COVID-19, supporting baseline and serial liver testing, the panelists wrote.
Following these recommendations, the guideline includes a discussion of GI and hepatic adverse effects related to specific COVID-19 treatments.
According to the panelists, chloroquine and hydroxychloroquine may infrequently lead to GI disturbances, and rarely, liver injury, with the latter thought to be a sequela of a hypersensitivity reaction; among antiviral medications, lopinavir/ritonavir and favipiravir may cause GI adverse effects in approximately 5%-15% of patients, with potentially higher rates in children and those receiving higher doses.
“In particular, GI adverse events are poorly understood for both favipiravir and remdesivir,” the panelists wrote.
Hepatic adverse effects, ranging from mild elevations in aminotransferases to acute liver failure, have been documented, albeit rarely, among patients receiving lopinavir/ritonavir, according to the panelists. For remdesivir, liver injury has also been reported, although frequency is unknown, and for favipiravir, hepatic adverse events may be seen in 3% of patients, although, again, the panelists noted a scarcity of relevant findings.
In their concluding remarks, Dr. Sultan and colleagues called for more high-quality data, and encouraged clinicians to contribute to international registries, as these could help guide COVID-19 recommendations for patient subgroups.
The article was funded by the American Gastroenterological Association Institute.
SOURCE: Sultan S et al. Gastroenterology. 2020 May 11. doi: 10.1053/j.gastro.2020.05.001.
The American Gastroenterological Association has released a new guideline for consultative management of patients with COVID-19.
The recommendations, which were written by Shahnaz Sultan, MD, AGAF, chair of the AGA Clinical Guidelines Committee, of the University of Minnesota, Minneapolis, and colleagues, were based on a meta-analysis of data from 47 studies involving 10,890 unique patients.
“We seek to summarize international data on the GI and liver manifestations of COVID-19 infection and treatment,” the panelists wrote in Gastroenterology. “Additionally, this document provides evidence-based clinical guidance on clinical questions that gastroenterologists may be consulted for.”
The guideline includes seven best practice statements.
The first three statements relate to COVID-19–related GI symptoms, which are estimated to occur in less than 10% of patients, and rarely in the absence of other COVID-19–related symptoms, according to Dr. Sultan and her copanelists.
“The overall prevalence of GI symptoms in the context of COVID-19, including nausea, vomiting, abdominal pain, and diarrhea, is lower than estimated previously,” the panelists wrote, referencing a previous meta-analysis by Ka Shing Cheung, MBBS, and colleagues that showed a prevalence of 17.6%.
“It is important to note that the majority of studies were focused on hospitalized patients with COVID-19, and the prevalence of diarrhea in patients with mild symptoms who were not hospitalized is not known.”
Since GI issues may precede other symptoms of COVID-19, the guideline recommends questioning outpatients with new-onset GI symptoms about other symptoms of COVID-19, with viral testing recommended in areas of high prevalence. Conversely, the panelists recommended that patients with suspected or known COVID-19 should undergo thorough history taking for GI symptoms, “including onset, characteristics, duration, and severity.”
The fourth practice statement advises against COVID-19 stool testing in routine clinical practice, either for diagnostic or monitoring purposes.
Although Dr. Cheung and colleagues reported that 48.1% of fecal specimens from patients with COVID-19 contained viral RNA, the panelists concluded that the practical relevance of this finding remains unknown.
“Stool infectivity and transmission have not been confirmed,” the panelists wrote, citing a lack of evidence and conflicting findings.
The final three practice statements address liver concerns.
First, any patient with suspected or confirmed COVID-19 who has elevated liver function tests should be evaluated for alternative etiologies. Second, hospitalized patients with suspected or confirmed COVID-19 should undergo baseline liver function testing, followed by liver monitoring throughout their stay, “particularly in the context of drug treatment for COVID-19.” And third, any patient receiving drugs to treat COVID-19 should be monitored for treatment-related hepatic and GI adverse effects.
Dr. Sultan and colleagues found that approximately 15% of patients with COVID-19 included in their meta-analysis had abnormal liver function tests, more often because of secondary effects rather than virally induced liver injury.
Although liver function test abnormalities were inconsistently reported across studies, and when available, often lacked relevant contextual data, such as information about underlying liver disease, published data suggest that abnormal liver values could predict more severe COVID-19, supporting baseline and serial liver testing, the panelists wrote.
Following these recommendations, the guideline includes a discussion of GI and hepatic adverse effects related to specific COVID-19 treatments.
According to the panelists, chloroquine and hydroxychloroquine may infrequently lead to GI disturbances, and rarely, liver injury, with the latter thought to be a sequela of a hypersensitivity reaction; among antiviral medications, lopinavir/ritonavir and favipiravir may cause GI adverse effects in approximately 5%-15% of patients, with potentially higher rates in children and those receiving higher doses.
“In particular, GI adverse events are poorly understood for both favipiravir and remdesivir,” the panelists wrote.
Hepatic adverse effects, ranging from mild elevations in aminotransferases to acute liver failure, have been documented, albeit rarely, among patients receiving lopinavir/ritonavir, according to the panelists. For remdesivir, liver injury has also been reported, although frequency is unknown, and for favipiravir, hepatic adverse events may be seen in 3% of patients, although, again, the panelists noted a scarcity of relevant findings.
In their concluding remarks, Dr. Sultan and colleagues called for more high-quality data, and encouraged clinicians to contribute to international registries, as these could help guide COVID-19 recommendations for patient subgroups.
The article was funded by the American Gastroenterological Association Institute.
SOURCE: Sultan S et al. Gastroenterology. 2020 May 11. doi: 10.1053/j.gastro.2020.05.001.
FROM GASTROENTEROLOGY
Minority-serving hospitals had similar survival after liver cancer surgery
Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.
“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.®
Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).
Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.
“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).
Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).
Dr. Mehtsun reported having no relevant conflicts of interest.
SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.
Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.
“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.®
Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).
Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.
“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).
Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).
Dr. Mehtsun reported having no relevant conflicts of interest.
SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.
Overall survival after liver cancer surgery was similar regardless of whether patients were treated at minority-serving hospitals or at hospitals with proportionally fewer African American or Hispanic patients, investigators have found.
“[T]reatment of racial minorities is largely restricted to a subset of hospitals, often referred to as minority-serving hospitals. We sought to examine whether racial and ethnic minorities with hepatocellular carcinoma receive their surgical care at minority-serving hospitals, and whether treatment at minority-serving hospitals is associated with differences in overall survival,” explained Winta T. Mehtsun, MD, MPH, of Dana-Farber Cancer Institute in Boston and associates in an abstract released as part of the annual Digestive Disease Week.®
Hepatocellular carcinoma continues to have a low 5-year survival rate and exhibits marked racial and ethnic disparities in diagnosis, treatment, and outcomes. In a recent study of Surveillance Epidemiology and End Results (SEER) data, African American patients with hepatocellular carcinoma were significantly younger at diagnosis, were more likely to have metastatic disease, and were less likely to receive surgical treatment compared with whites (Am J Prevent Med 2018;55:S40-48). Among patients with early-stage liver cancer, Hispanic and African American patients are less likely to receive curative therapy and die sooner, on average, than do other patients (Clin Gastroenterol Hepatol. 2019;17:551-9).
Minority-serving hospitals also have improved significantly less over time on measures of critical care, length of stay, and mortality, but whether these issues extend to hepatocellular carcinoma remains unclear. Therefore, Dr. Mehtsun and her associates studied all 2,609 patients in the National Cancer Database who received surgical resection (not transplantation or local therapy) for nonmetastatic hepatocellular carcinoma between 2004 and 2014. They compared survival at minority-serving hospitals – those in the top 10% based on the proportion of patients who were African American or Hispanic – with survival at other hospitals.
“There was no association between minority-serving hospital and overall survival,” the researchers reported (multivariable hazard ratio for death, 0.89; 95% confidence interval, 0.72-1.11). In contrast, survival was significantly shorter among patients with more advanced disease (HR, 2.5; 95% CI, 2.1-2.8), patients who were treated at a community cancer program (HR, 1.7; 95% CI, 1.3-2.4), and patients whose Charlson Comorbidity Index was greater than 2 (HR, 1.2; 95% CI, 1.1-1.4).
Stage at diagnosis, comorbidities, and sex were not significantly related to hospital type, the investigators noted. A total of 298 patients (11%) were treated at minority-serving hospitals. Patients treated at minority-serving hospitals were significantly more likely to be uninsured (11% vs. 4% at other hospitals) and significantly less likely to be treated at an academic center (55% vs. 69%; both P less than .001).
Dr. Mehtsun reported having no relevant conflicts of interest.
SOURCE: Mehtsun WT et al. DDW 2020, Abstract Tu2043.
FROM DDW 2020
FibroScan: M probe underestimates hepatic fat content
When performing transient elastography (FibroScan) to evaluate patients for hepatic steatosis, using an M probe instead of an XL probe may significantly underestimate hepatic fat content, according to investigators.
The findings, which were independent of body weight, suggest that probe-specific controlled attenuation parameter (CAP) thresholds are needed to accurately interpret FibroScan results, reported lead author Cyrielle Caussy, MD, PhD, of the University of California, San Diego, and colleagues.
“We have previously determined the optimal threshold of CAP using either [an] M or XL probe for the detection of ... nonalcoholic fatty liver disease (NAFLD),” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, head-to-head comparison of consecutive measurements of CAP with both the M and XL probes versus MRI-PDFF [proton density fat fraction] ... has not been reported yet.”
Dr. Caussy and colleagues set out to do just that. They enrolled 105 individuals with and without NAFLD who had a mean body mass index (BMI) of 30.6 kg/m2, as this represented a typical population screened for NAFLD. After evaluation for other causes of hepatic steatosis and liver disease, participants underwent MRI-PDFF, which served as a gold standard, followed by FibroScan using both M and XL probes on the same day.
The primary outcome was hepatic steatosis (MRI-PDFF of at least 5%), while the secondary outcome was MRI-PDFF–detected hepatic fat content of at least 10%, the latter of which has been “used in several therapeutic trials as inclusion criteria,” the investigators noted.
A total of 100 participants were included in the final analysis, of whom two-thirds (66%) underwent MRI and FibroScan on the same day, with a mean interval between test types of 11 days. Most participants (68%) had an MRI-PDFF of at least 5%, while almost half (48%) exceeded an MRI-PDFF of 10%.
The mean CAP measurement with the M probe was 310 dB/m, which was significantly lower than the mean value detected by the XL probe, which was 317 dB/m (P = .007). In participants with hepatic steatosis, when the M probe was used for those with a BMI of less than 30, and the XL probe was used for those with a BMI of 30 or more, the M probe still provided a significantly lower measure of hepatic fat content (312 vs. 345 dB/m; P = .0035).
“[T]hese results have direct application in routine clinical practice,” the investigators wrote, “as [they] will help clinicians interpreting CAP measurements depending on the type of probe used.”
Dr. Caussy and colleagues went on to offer a diagnostic algorithm involving optimal probe-specific thresholds for CAP based on hepatic fat content. Individuals screened with an M probe who have a CAP of 294 dB/m or more should be considered positive for NAFLD, while patients screened with an XL probe need to have a CAP of at least 307 dB/m to be NAFLD positive.
For the XL probe, but not the M probe, diagnostic accuracy depended upon an interquartile range of less than 30 dB/m. The investigators noted that this finding should alter the interpretation of a 2019 study by Eddowes and colleagues, which concluded that interquartile range was unrelated to diagnostic accuracy.
“As Eddowes et al. did not perform head-to-head comparison of CAP measurement with both the M and XL probes, this important difference could not have been observed,” the investigators wrote, noting that “an interquartile range of CAP below 30 dB/m should be considered as a quality indicator that significantly improves the diagnostic performance of CAP using the XL probe for the detection of hepatic steatosis in NAFLD.”
The investigators concluded by suggesting that their findings will drive research forward.
“The use of these new thresholds will help to further assess the clinical utility of CAP for the detection of hepatic steatosis and its cost-effectiveness, compared with other modalities, to develop optimal strategies for the screening of NAFLD,” they wrote.
The study was funded by Atlantic Philanthropies, the John A. Hartford Foundation, the American Gastroenterological Association, and others. The investigators disclosed no conflicts of interest.
SOURCE: Caussy C et al. Clin Gastro Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.060.
When performing transient elastography (FibroScan) to evaluate patients for hepatic steatosis, using an M probe instead of an XL probe may significantly underestimate hepatic fat content, according to investigators.
The findings, which were independent of body weight, suggest that probe-specific controlled attenuation parameter (CAP) thresholds are needed to accurately interpret FibroScan results, reported lead author Cyrielle Caussy, MD, PhD, of the University of California, San Diego, and colleagues.
“We have previously determined the optimal threshold of CAP using either [an] M or XL probe for the detection of ... nonalcoholic fatty liver disease (NAFLD),” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, head-to-head comparison of consecutive measurements of CAP with both the M and XL probes versus MRI-PDFF [proton density fat fraction] ... has not been reported yet.”
Dr. Caussy and colleagues set out to do just that. They enrolled 105 individuals with and without NAFLD who had a mean body mass index (BMI) of 30.6 kg/m2, as this represented a typical population screened for NAFLD. After evaluation for other causes of hepatic steatosis and liver disease, participants underwent MRI-PDFF, which served as a gold standard, followed by FibroScan using both M and XL probes on the same day.
The primary outcome was hepatic steatosis (MRI-PDFF of at least 5%), while the secondary outcome was MRI-PDFF–detected hepatic fat content of at least 10%, the latter of which has been “used in several therapeutic trials as inclusion criteria,” the investigators noted.
A total of 100 participants were included in the final analysis, of whom two-thirds (66%) underwent MRI and FibroScan on the same day, with a mean interval between test types of 11 days. Most participants (68%) had an MRI-PDFF of at least 5%, while almost half (48%) exceeded an MRI-PDFF of 10%.
The mean CAP measurement with the M probe was 310 dB/m, which was significantly lower than the mean value detected by the XL probe, which was 317 dB/m (P = .007). In participants with hepatic steatosis, when the M probe was used for those with a BMI of less than 30, and the XL probe was used for those with a BMI of 30 or more, the M probe still provided a significantly lower measure of hepatic fat content (312 vs. 345 dB/m; P = .0035).
“[T]hese results have direct application in routine clinical practice,” the investigators wrote, “as [they] will help clinicians interpreting CAP measurements depending on the type of probe used.”
Dr. Caussy and colleagues went on to offer a diagnostic algorithm involving optimal probe-specific thresholds for CAP based on hepatic fat content. Individuals screened with an M probe who have a CAP of 294 dB/m or more should be considered positive for NAFLD, while patients screened with an XL probe need to have a CAP of at least 307 dB/m to be NAFLD positive.
For the XL probe, but not the M probe, diagnostic accuracy depended upon an interquartile range of less than 30 dB/m. The investigators noted that this finding should alter the interpretation of a 2019 study by Eddowes and colleagues, which concluded that interquartile range was unrelated to diagnostic accuracy.
“As Eddowes et al. did not perform head-to-head comparison of CAP measurement with both the M and XL probes, this important difference could not have been observed,” the investigators wrote, noting that “an interquartile range of CAP below 30 dB/m should be considered as a quality indicator that significantly improves the diagnostic performance of CAP using the XL probe for the detection of hepatic steatosis in NAFLD.”
The investigators concluded by suggesting that their findings will drive research forward.
“The use of these new thresholds will help to further assess the clinical utility of CAP for the detection of hepatic steatosis and its cost-effectiveness, compared with other modalities, to develop optimal strategies for the screening of NAFLD,” they wrote.
The study was funded by Atlantic Philanthropies, the John A. Hartford Foundation, the American Gastroenterological Association, and others. The investigators disclosed no conflicts of interest.
SOURCE: Caussy C et al. Clin Gastro Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.060.
When performing transient elastography (FibroScan) to evaluate patients for hepatic steatosis, using an M probe instead of an XL probe may significantly underestimate hepatic fat content, according to investigators.
The findings, which were independent of body weight, suggest that probe-specific controlled attenuation parameter (CAP) thresholds are needed to accurately interpret FibroScan results, reported lead author Cyrielle Caussy, MD, PhD, of the University of California, San Diego, and colleagues.
“We have previously determined the optimal threshold of CAP using either [an] M or XL probe for the detection of ... nonalcoholic fatty liver disease (NAFLD),” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, head-to-head comparison of consecutive measurements of CAP with both the M and XL probes versus MRI-PDFF [proton density fat fraction] ... has not been reported yet.”
Dr. Caussy and colleagues set out to do just that. They enrolled 105 individuals with and without NAFLD who had a mean body mass index (BMI) of 30.6 kg/m2, as this represented a typical population screened for NAFLD. After evaluation for other causes of hepatic steatosis and liver disease, participants underwent MRI-PDFF, which served as a gold standard, followed by FibroScan using both M and XL probes on the same day.
The primary outcome was hepatic steatosis (MRI-PDFF of at least 5%), while the secondary outcome was MRI-PDFF–detected hepatic fat content of at least 10%, the latter of which has been “used in several therapeutic trials as inclusion criteria,” the investigators noted.
A total of 100 participants were included in the final analysis, of whom two-thirds (66%) underwent MRI and FibroScan on the same day, with a mean interval between test types of 11 days. Most participants (68%) had an MRI-PDFF of at least 5%, while almost half (48%) exceeded an MRI-PDFF of 10%.
The mean CAP measurement with the M probe was 310 dB/m, which was significantly lower than the mean value detected by the XL probe, which was 317 dB/m (P = .007). In participants with hepatic steatosis, when the M probe was used for those with a BMI of less than 30, and the XL probe was used for those with a BMI of 30 or more, the M probe still provided a significantly lower measure of hepatic fat content (312 vs. 345 dB/m; P = .0035).
“[T]hese results have direct application in routine clinical practice,” the investigators wrote, “as [they] will help clinicians interpreting CAP measurements depending on the type of probe used.”
Dr. Caussy and colleagues went on to offer a diagnostic algorithm involving optimal probe-specific thresholds for CAP based on hepatic fat content. Individuals screened with an M probe who have a CAP of 294 dB/m or more should be considered positive for NAFLD, while patients screened with an XL probe need to have a CAP of at least 307 dB/m to be NAFLD positive.
For the XL probe, but not the M probe, diagnostic accuracy depended upon an interquartile range of less than 30 dB/m. The investigators noted that this finding should alter the interpretation of a 2019 study by Eddowes and colleagues, which concluded that interquartile range was unrelated to diagnostic accuracy.
“As Eddowes et al. did not perform head-to-head comparison of CAP measurement with both the M and XL probes, this important difference could not have been observed,” the investigators wrote, noting that “an interquartile range of CAP below 30 dB/m should be considered as a quality indicator that significantly improves the diagnostic performance of CAP using the XL probe for the detection of hepatic steatosis in NAFLD.”
The investigators concluded by suggesting that their findings will drive research forward.
“The use of these new thresholds will help to further assess the clinical utility of CAP for the detection of hepatic steatosis and its cost-effectiveness, compared with other modalities, to develop optimal strategies for the screening of NAFLD,” they wrote.
The study was funded by Atlantic Philanthropies, the John A. Hartford Foundation, the American Gastroenterological Association, and others. The investigators disclosed no conflicts of interest.
SOURCE: Caussy C et al. Clin Gastro Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.060.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Sex-based disparities in liver allocation driven by organ size mismatch, MELD score
Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.
Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.
“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”
To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.
Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.
The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.
In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.
“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.
Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.
As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.
“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.
James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”
“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.
While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.
“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”
Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.
“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”
According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.
“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”
Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.
“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”
The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.
SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.
Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.
Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.
“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”
To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.
Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.
The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.
In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.
“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.
Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.
As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.
“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.
James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”
“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.
While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.
“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”
Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.
“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”
According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.
“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”
Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.
“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”
The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.
SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.
Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.
Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.
“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”
To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.
Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.
The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.
In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.
“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.
Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.
As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.
“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.
James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”
“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.
While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.
“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”
Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.
“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”
According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.
“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”
Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.
“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”
The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.
SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.
FROM JAMA SURGERY
FDA approves mAb combo for hepatocellular carcinoma
The approval was supported by results from the IMbrave150 trial (N Engl J Med. 2020;382:1894-1905). This phase 3 trial enrolled 501 patients with hepatocellular carcinoma who were randomized to receive either sorafenib or atezolizumab plus bevacizumab.
The median overall survival was not reached in patients who received atezolizumab plus bevacizumab, but it was 13.2 months in patients who received sorafenib (hazard ratio, 0.58; 95% confidence interval, 0.42-0.79; P = .0006). The median progression-free survival was 6.8 months in patients who received atezolizumab plus bevacizumab and 4.3 months for those who received sorafenib.
The most common adverse events seen in the atezolizumab-bevacizumab arm were hypertension, fatigue, and proteinuria.
The recommended atezolizumab dose is 1,200 mg, followed by 15 mg/kg bevacizumab on the same day every 3 weeks.
The FDA collaborated with regulatory agencies from Canada, Australia, and Singapore on the review of the atezolizumab application, as part of Project Orbis. The FDA approved the application ahead of schedule. It is still under review for the other agencies.
The approval was supported by results from the IMbrave150 trial (N Engl J Med. 2020;382:1894-1905). This phase 3 trial enrolled 501 patients with hepatocellular carcinoma who were randomized to receive either sorafenib or atezolizumab plus bevacizumab.
The median overall survival was not reached in patients who received atezolizumab plus bevacizumab, but it was 13.2 months in patients who received sorafenib (hazard ratio, 0.58; 95% confidence interval, 0.42-0.79; P = .0006). The median progression-free survival was 6.8 months in patients who received atezolizumab plus bevacizumab and 4.3 months for those who received sorafenib.
The most common adverse events seen in the atezolizumab-bevacizumab arm were hypertension, fatigue, and proteinuria.
The recommended atezolizumab dose is 1,200 mg, followed by 15 mg/kg bevacizumab on the same day every 3 weeks.
The FDA collaborated with regulatory agencies from Canada, Australia, and Singapore on the review of the atezolizumab application, as part of Project Orbis. The FDA approved the application ahead of schedule. It is still under review for the other agencies.
The approval was supported by results from the IMbrave150 trial (N Engl J Med. 2020;382:1894-1905). This phase 3 trial enrolled 501 patients with hepatocellular carcinoma who were randomized to receive either sorafenib or atezolizumab plus bevacizumab.
The median overall survival was not reached in patients who received atezolizumab plus bevacizumab, but it was 13.2 months in patients who received sorafenib (hazard ratio, 0.58; 95% confidence interval, 0.42-0.79; P = .0006). The median progression-free survival was 6.8 months in patients who received atezolizumab plus bevacizumab and 4.3 months for those who received sorafenib.
The most common adverse events seen in the atezolizumab-bevacizumab arm were hypertension, fatigue, and proteinuria.
The recommended atezolizumab dose is 1,200 mg, followed by 15 mg/kg bevacizumab on the same day every 3 weeks.
The FDA collaborated with regulatory agencies from Canada, Australia, and Singapore on the review of the atezolizumab application, as part of Project Orbis. The FDA approved the application ahead of schedule. It is still under review for the other agencies.
Nucleoside polymers show early promise in HBV
For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.
The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.
Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.
Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.
Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.
Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.
The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”
Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.
Manhal Izzy, MD, is assistant professor of medicine, Vanderbilt University Medical Center, division of gastroenterology, hepatology, and nutrition, and transplant hepatology at the Vanderbilt Clinic, Nashville, Tenn. He has no conflicts.
Manhal Izzy, MD, is assistant professor of medicine, Vanderbilt University Medical Center, division of gastroenterology, hepatology, and nutrition, and transplant hepatology at the Vanderbilt Clinic, Nashville, Tenn. He has no conflicts.
Manhal Izzy, MD, is assistant professor of medicine, Vanderbilt University Medical Center, division of gastroenterology, hepatology, and nutrition, and transplant hepatology at the Vanderbilt Clinic, Nashville, Tenn. He has no conflicts.
For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.
The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.
Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.
Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.
Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.
Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.
The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”
Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.
For patients with chronic hepatitis B virus (HBV) infection, triple-combination therapy with tenofovir disoproxil fumarate, pegylated interferon alfa-2a (TDF-pegIFN), and either of two investigational nucleic acid polymers was tolerable and led to long-term functional cures in an open-label phase 2 trial.
The addition of either REP 2139 or REP 2165 to backbone TDF-pegIFN therapy produced functional cures in 39% of patients without lessening HBV DNA control or exacerbating treatment-induced neutropenia or thrombocytopenia, said Michel Bazinet, MD, of Replicor in Montreal and his associates. “Increases in levels of transaminases were significantly more frequent (P < .001 vs. controls) and greater (P = .002 vs. controls) in the nucleic acid polymer groups but did not produce symptoms, correlated with [an] initial decrease in hepatitis B surface antigen [HBsAg], and normalized during therapy and follow-up,” the investigators wrote in Gastroenterology.
Nucleic acid polymers (NAPs) suppress the assembly and secretion of HBV subviral particles. NAP monotherapy is active against HBV but usually does not provide long-term virologic control. In a small study, adding pegIFN or thymosin alpha-1 to an investigational NAP achieved functional control (HBsAg positive, HBV DNA ≤ 2000 IU/mL, and normal alanine aminotransferase levels) in eight of nine patients.
Building on these findings, two triple-combination NAP regimens were evaluated in 40 noncirrhotic HB envelope antigen–negative adults with chronic HBV infection. After 24 weeks of TDF monotherapy, participants were randomly assigned to either 48 weeks of REP 2139 or REP 2165 plus backbone therapy with TDF and pegIFN, or 24 weeks of backbone therapy followed by 48 weeks of triple-combination treatment. Patients were then followed without treatment for 24-48 weeks.
Backbone TDF-pegIFN therapy produced no HBsAg seroconversions, and HBsAg levels dropped by more than 1 log10 IU/mL in only three patients. In contrast, triple-combination NAP therapy produced undetectable HBsAg and HBsAg seroconversions (up to 233,055 mIU/mL) for 60% of patients. Among 36 patients followed for 24-48 weeks after completing treatment, 78% maintained virologic control and 39% showed functional cures (HBsAg < 0.05 IU/mL, undetectable HBV DNA, and normal ALT). “Additional follow-up is planned to confirm the long-term stability of [these] outcomes,” the researchers said.
Both NAPs were formulated with chelated magnesium to improve their tolerability. Although 95% of patients experienced transaminase flares, these “self-resolved or declined during continuing NAP therapy and normalized in 32 of 34 (94%) of participants completing 48 weeks of follow-up,” the researchers said. In keeping with prior studies, transaminase flares were associated with early declines in HBsAg but not with altered liver function or liver disease symptoms.
The study was conducted at three sites in Maldova. Most participants were men with HBV genotype D infection. “During follow-up, viral rebound occurred in participants [in whom] HBsAg was still detectable at the end of 48 weeks of combination therapy (≥ 57.9 IU/mL), who did not complete therapy, or [for whom] HBsAg clearance occurred very late in therapy,” the researchers wrote. Thus, “persistent exposure to pegIFN while HBsAg is cleared may be important for the establishment of virologic control and functional cure.” They recommended evaluating NAP plus nucleos(t)ide analogue (NUC) therapy to assess response in the absence of pegIFN. Such studies should enroll “NUC-experienced participants with well-controlled HBV DNA.”
Replicor provided funding. Dr. Bazinet and the senior investigator reported that they are employees and shareholders of Replicor and have invented patents that Replicor holds. One coinvestigator reported compensation from Replicor to his institution. The remaining 11 coinvestigators reported having no relevant disclosures.
SOURCE: Bazinet M et al. Gastroenterology. 2020 Mar 5. doi: 0.1053/j.gastro.2020.02.058.
FROM GASTROENTEROLOGY
Health care costs nearly doubled for patients with NAFLD
The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.
Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.
The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.
Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.
Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.
“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”
They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.
The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.
SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.
The possibility of FDA approval of NASH-modifying drugs later this year brings the hope of improving outcomes for patients with NAFLD. Inevitably, the cost effectiveness of those drugs also will be scrutinized as we evaluate their impact in the coming years. To that end, Hagstrom et al. provide useful insight regarding the real-world costs of medical care among patients with histologically staged NAFLD in Sweden.
Their main finding is that medical costs for a patient with NAFLD over 20 years is double that for a random control patient from the general population.
It is worth taking a deeper dive into the factors that drove the cost differential. First, higher inpatient and outpatient specialty care costs accounted for the incremental cost of NAFLD care; drug costs were materially similar in the two groups, albeit examined over a very short time period in the study due to limited national registry data. Second, the cost differential was largest in the first year of diagnosis and attributed to the cost of liver biopsy and related expenses. Last, as one would expect, the cost differential was largest between patients who had stage 3-4 fibrosis, possibly explained by the costs of NASH-related complications.
While we hope that NASH-modifying drugs will reduce the risk of liver-specific complications, the cumulative financial impact of such therapies remains to be seen. On the one hand, short-term costs may increase because of the direct expense of the NASH-modifying drugs plus additional expenses related to management of side effects. In addition, it is likely patients treated with NASH-modifying drugs will need more frequent assessments of liver disease severity to evaluate whether the medication is working, which even if done noninvasively, is likely the add to medical costs. In the long term however, NASH-modifying treatments may reduce the risk of NAFLD complications over time, mitigating the cumulative cost of NAFLD care. The true net effect remains to be seen. In the meantime, we need further studies that quantify costs of NAFLD care - ideally by disease severity and that provide greater insight into the cost of caring for the complications of NASH progression, including liver disease clinical decompensations and transplant.
Maya Balakrishnan, MD, MPH, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Baylor College of Medicine, Houston, and director of hepatology at Ben Taub General Hospital, Houston. She has no conflicts of interest.
The possibility of FDA approval of NASH-modifying drugs later this year brings the hope of improving outcomes for patients with NAFLD. Inevitably, the cost effectiveness of those drugs also will be scrutinized as we evaluate their impact in the coming years. To that end, Hagstrom et al. provide useful insight regarding the real-world costs of medical care among patients with histologically staged NAFLD in Sweden.
Their main finding is that medical costs for a patient with NAFLD over 20 years is double that for a random control patient from the general population.
It is worth taking a deeper dive into the factors that drove the cost differential. First, higher inpatient and outpatient specialty care costs accounted for the incremental cost of NAFLD care; drug costs were materially similar in the two groups, albeit examined over a very short time period in the study due to limited national registry data. Second, the cost differential was largest in the first year of diagnosis and attributed to the cost of liver biopsy and related expenses. Last, as one would expect, the cost differential was largest between patients who had stage 3-4 fibrosis, possibly explained by the costs of NASH-related complications.
While we hope that NASH-modifying drugs will reduce the risk of liver-specific complications, the cumulative financial impact of such therapies remains to be seen. On the one hand, short-term costs may increase because of the direct expense of the NASH-modifying drugs plus additional expenses related to management of side effects. In addition, it is likely patients treated with NASH-modifying drugs will need more frequent assessments of liver disease severity to evaluate whether the medication is working, which even if done noninvasively, is likely the add to medical costs. In the long term however, NASH-modifying treatments may reduce the risk of NAFLD complications over time, mitigating the cumulative cost of NAFLD care. The true net effect remains to be seen. In the meantime, we need further studies that quantify costs of NAFLD care - ideally by disease severity and that provide greater insight into the cost of caring for the complications of NASH progression, including liver disease clinical decompensations and transplant.
Maya Balakrishnan, MD, MPH, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Baylor College of Medicine, Houston, and director of hepatology at Ben Taub General Hospital, Houston. She has no conflicts of interest.
The possibility of FDA approval of NASH-modifying drugs later this year brings the hope of improving outcomes for patients with NAFLD. Inevitably, the cost effectiveness of those drugs also will be scrutinized as we evaluate their impact in the coming years. To that end, Hagstrom et al. provide useful insight regarding the real-world costs of medical care among patients with histologically staged NAFLD in Sweden.
Their main finding is that medical costs for a patient with NAFLD over 20 years is double that for a random control patient from the general population.
It is worth taking a deeper dive into the factors that drove the cost differential. First, higher inpatient and outpatient specialty care costs accounted for the incremental cost of NAFLD care; drug costs were materially similar in the two groups, albeit examined over a very short time period in the study due to limited national registry data. Second, the cost differential was largest in the first year of diagnosis and attributed to the cost of liver biopsy and related expenses. Last, as one would expect, the cost differential was largest between patients who had stage 3-4 fibrosis, possibly explained by the costs of NASH-related complications.
While we hope that NASH-modifying drugs will reduce the risk of liver-specific complications, the cumulative financial impact of such therapies remains to be seen. On the one hand, short-term costs may increase because of the direct expense of the NASH-modifying drugs plus additional expenses related to management of side effects. In addition, it is likely patients treated with NASH-modifying drugs will need more frequent assessments of liver disease severity to evaluate whether the medication is working, which even if done noninvasively, is likely the add to medical costs. In the long term however, NASH-modifying treatments may reduce the risk of NAFLD complications over time, mitigating the cumulative cost of NAFLD care. The true net effect remains to be seen. In the meantime, we need further studies that quantify costs of NAFLD care - ideally by disease severity and that provide greater insight into the cost of caring for the complications of NASH progression, including liver disease clinical decompensations and transplant.
Maya Balakrishnan, MD, MPH, is an assistant professor, department of medicine, section of gastroenterology & hepatology, Baylor College of Medicine, Houston, and director of hepatology at Ben Taub General Hospital, Houston. She has no conflicts of interest.
The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.
Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.
The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.
Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.
Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.
“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”
They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.
The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.
SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.
The health care costs of patients with nonalcoholic fatty liver disease (NAFLD) were nearly twice that of matched population controls, according to the results of a longitudinal cohort study.
Patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) were hospitalized an average of 0.27 times per year versus 0.16 times for controls (P < .001), for an annual incremental cost of $635, reported Hannes Hagström, MD, PhD, of Karolinska University Hospital in Stockholm. Patients with NAFLD also made significantly more outpatient care visits than controls (P < .001), he said. “Patients with advanced fibrosis [had] the highest costs, suggesting that reducing fibrosis progression is important to reduce future health care costs” among patients with NASH, Dr. Hagström and his associates wrote in Clinical Gastroenterology and Hepatology.
The retrospective longitudinal cohort study included all 646 patients diagnosed with biopsy-confirmed NAFLD at two hospitals in Sweden between 1971 and 2019. Patients with other liver diseases were excluded, as were heavy drinkers: men who drank more than 30 g of alcohol (just under four units) daily and women who drank more than 20 g daily. Each patient with NAFLD was matched with 10 population controls matched by age, sex, and county of residence.
Over a mean of 19.9 years of follow-up (range, 0-40 years), patients with NASH were hospitalized a total of 3,478 times, an average of 5.4 hospitalizations per patient. Controls were hospitalized an average of 3.2 times during the same time period (P < .001 vs. NASH patients). “This corresponded to a higher incremental cost in NAFLD patients of $635 per year (95% confidence interval, $407-$864; P < .001),” the researchers reported.
Between 2001 and 2009, patients with NAFLD averaged 5.4 more outpatient visits than controls (P < .001), with annual averages of 1.46 versus 0.86 visits (P < .001). Consequently, patient with NASH incurred $255 more per year in annual outpatient care costs. Liver disease accounted for 6% of outpatient care costs among NASH patients versus 0.2% of costs among controls.
“Cumulative costs in the [fibrosis stage 3 and 4] subgroup were relatively matched with the control population until around year 4 after biopsy, when costs diverged,” the researchers said. “This could possibly be an effect of the larger F3 population developing cirrhosis and increasing costs due to decompensation events.”
They noted that the rising prevalence of NAFLD will further burden health care budgets. “Costs [among patients with NASH] were higher in conjunction with liver biopsy, which is why using noninvasive diagnostic methods (e.g., transient elastography) is likely to reduce total costs,” they added. Of note, although patients with NAFLD also incurred somewhat more per year in prescription costs, the difference was not statistically significant.
The study was supported by Stockholm City Council, the Bengt Ihre Foundation, the County Council of Östergötland, and Gilead. The researchers reported having no conflicts of interest.
SOURCE: Kim H et al. Clin Gastroenterol Hepatol. 2019 Sep 12. doi: 10.1016/j.cgh.2019.10.023.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Medicare claims review builds case for NAFLD/NASH screening
Nonalcoholic fatty liver disease isn’t being diagnosed early enough; by the time it’s caught, patients often have advanced complications such as decompensated cirrhosis or hepatocellular carcinoma, according a review of Medicare claims data from 2007-2015.
Among 10,826,456 enrollees – about 20% of the Medicare population – 621,253 had International Classification of Diseases codes for NAFLD/nonalcoholic steatohepatitis (NASH), yielding a prevalence of 5.7%. That’s substantially lower than modeling estimates of 30% in the general population, indicating that there is “considerable underdiagnosis of NAFLD in real-world clinical practice,” and that less severe disease, and the opportunity to treat it before it progresses, is being missed, said investigators led by Rohit Loomba, MD, director of the NAFLD Research Center at the University of California, San Diego, NAFLD Research Center (Aliment Pharmacol Ther. 2020 May 5. doi: 10.1111/apt.15679).
When the team excluded patients with other causes of liver disease such as alcohol abuse or viral hepatitis, they were left with a study population of 260,950 subjects; 71.1% had NAFLD/NASH alone, and 28.9% had NAFLD cirrhosis, almost all of them first diagnosed with decompensated cirrhosis. More than half of the 581 hepatocellular carcinoma patients had no previous diagnosis of cirrhosis.
The cumulative risk of progression of NAFLD to cirrhosis over the 8-year study period was 39%, and from compensated cirrhosis to decompensated cirrhosis, it was 45%. Among a subgroup of 258 patients with compensated cirrhosis, 19% progressed to decompensated cirrhosis or hepatocellular carcinoma, or died, over a median of a year and a half.
The findings “highlight the urgent need for an algorithm to identify individuals at higher risk of NAFLD/NASH,” so the disease is caught at a point when lifestyle and medical interventions might halt or delay progression, the team said.
Screening isn’t currently recommended in guidelines because of the limited efficacy of current treatments, but “with promising novel NAFLD/NASH interventions currently under development and review,” the team said it might be time to rethink the issue.
The majority of patients with early NAFLD/NASH have nonspecific symptoms, which makes screening difficult. However, the investigators identified several independent predictors of disease progression and death, including cardiovascular disease – present among 68.7% of subjects – dyslipidemia (84.1%), diabetes (55.5%), and renal impairment (24.3%).
The finding “supports the evaluation of certain variables” in a screening algorithm, “including advanced age and certain components of metabolic syndrome. Furthermore, important variables in previously developed noninvasive NAFLD/NASH staging algorithms including body mass index and biomarkers for liver function and insulin resistance may also warrant evaluation as components of an identification algorithm,” the team said.
It’s possible the study overestimated the risks of disease progression and mortality with NAFLD/NASH because patients with more severe disease were probably more likely to have been identified in Medicare data, the investigators said.
The mean age of the NAFLD/NASH subjects was 67.4 years, and 60% were women.
The work was funded by Gilead, which has several drugs under development for NAFLD/NASH. Two authors are Gilead employees, and the rest, including Dr. Loomba, reported funding and other ties to the company.
To help your patients better understand NASH, visit the AGA GI Patient Center at https://www.gastro.org/
SOURCE: Loomba R et al. Aliment Pharmacol Ther. 2020 May 5. doi: 10.1111/apt.15679.
Nonalcoholic fatty liver disease isn’t being diagnosed early enough; by the time it’s caught, patients often have advanced complications such as decompensated cirrhosis or hepatocellular carcinoma, according a review of Medicare claims data from 2007-2015.
Among 10,826,456 enrollees – about 20% of the Medicare population – 621,253 had International Classification of Diseases codes for NAFLD/nonalcoholic steatohepatitis (NASH), yielding a prevalence of 5.7%. That’s substantially lower than modeling estimates of 30% in the general population, indicating that there is “considerable underdiagnosis of NAFLD in real-world clinical practice,” and that less severe disease, and the opportunity to treat it before it progresses, is being missed, said investigators led by Rohit Loomba, MD, director of the NAFLD Research Center at the University of California, San Diego, NAFLD Research Center (Aliment Pharmacol Ther. 2020 May 5. doi: 10.1111/apt.15679).
When the team excluded patients with other causes of liver disease such as alcohol abuse or viral hepatitis, they were left with a study population of 260,950 subjects; 71.1% had NAFLD/NASH alone, and 28.9% had NAFLD cirrhosis, almost all of them first diagnosed with decompensated cirrhosis. More than half of the 581 hepatocellular carcinoma patients had no previous diagnosis of cirrhosis.
The cumulative risk of progression of NAFLD to cirrhosis over the 8-year study period was 39%, and from compensated cirrhosis to decompensated cirrhosis, it was 45%. Among a subgroup of 258 patients with compensated cirrhosis, 19% progressed to decompensated cirrhosis or hepatocellular carcinoma, or died, over a median of a year and a half.
The findings “highlight the urgent need for an algorithm to identify individuals at higher risk of NAFLD/NASH,” so the disease is caught at a point when lifestyle and medical interventions might halt or delay progression, the team said.
Screening isn’t currently recommended in guidelines because of the limited efficacy of current treatments, but “with promising novel NAFLD/NASH interventions currently under development and review,” the team said it might be time to rethink the issue.
The majority of patients with early NAFLD/NASH have nonspecific symptoms, which makes screening difficult. However, the investigators identified several independent predictors of disease progression and death, including cardiovascular disease – present among 68.7% of subjects – dyslipidemia (84.1%), diabetes (55.5%), and renal impairment (24.3%).
The finding “supports the evaluation of certain variables” in a screening algorithm, “including advanced age and certain components of metabolic syndrome. Furthermore, important variables in previously developed noninvasive NAFLD/NASH staging algorithms including body mass index and biomarkers for liver function and insulin resistance may also warrant evaluation as components of an identification algorithm,” the team said.
It’s possible the study overestimated the risks of disease progression and mortality with NAFLD/NASH because patients with more severe disease were probably more likely to have been identified in Medicare data, the investigators said.
The mean age of the NAFLD/NASH subjects was 67.4 years, and 60% were women.
The work was funded by Gilead, which has several drugs under development for NAFLD/NASH. Two authors are Gilead employees, and the rest, including Dr. Loomba, reported funding and other ties to the company.
To help your patients better understand NASH, visit the AGA GI Patient Center at https://www.gastro.org/
SOURCE: Loomba R et al. Aliment Pharmacol Ther. 2020 May 5. doi: 10.1111/apt.15679.
Nonalcoholic fatty liver disease isn’t being diagnosed early enough; by the time it’s caught, patients often have advanced complications such as decompensated cirrhosis or hepatocellular carcinoma, according a review of Medicare claims data from 2007-2015.
Among 10,826,456 enrollees – about 20% of the Medicare population – 621,253 had International Classification of Diseases codes for NAFLD/nonalcoholic steatohepatitis (NASH), yielding a prevalence of 5.7%. That’s substantially lower than modeling estimates of 30% in the general population, indicating that there is “considerable underdiagnosis of NAFLD in real-world clinical practice,” and that less severe disease, and the opportunity to treat it before it progresses, is being missed, said investigators led by Rohit Loomba, MD, director of the NAFLD Research Center at the University of California, San Diego, NAFLD Research Center (Aliment Pharmacol Ther. 2020 May 5. doi: 10.1111/apt.15679).
When the team excluded patients with other causes of liver disease such as alcohol abuse or viral hepatitis, they were left with a study population of 260,950 subjects; 71.1% had NAFLD/NASH alone, and 28.9% had NAFLD cirrhosis, almost all of them first diagnosed with decompensated cirrhosis. More than half of the 581 hepatocellular carcinoma patients had no previous diagnosis of cirrhosis.
The cumulative risk of progression of NAFLD to cirrhosis over the 8-year study period was 39%, and from compensated cirrhosis to decompensated cirrhosis, it was 45%. Among a subgroup of 258 patients with compensated cirrhosis, 19% progressed to decompensated cirrhosis or hepatocellular carcinoma, or died, over a median of a year and a half.
The findings “highlight the urgent need for an algorithm to identify individuals at higher risk of NAFLD/NASH,” so the disease is caught at a point when lifestyle and medical interventions might halt or delay progression, the team said.
Screening isn’t currently recommended in guidelines because of the limited efficacy of current treatments, but “with promising novel NAFLD/NASH interventions currently under development and review,” the team said it might be time to rethink the issue.
The majority of patients with early NAFLD/NASH have nonspecific symptoms, which makes screening difficult. However, the investigators identified several independent predictors of disease progression and death, including cardiovascular disease – present among 68.7% of subjects – dyslipidemia (84.1%), diabetes (55.5%), and renal impairment (24.3%).
The finding “supports the evaluation of certain variables” in a screening algorithm, “including advanced age and certain components of metabolic syndrome. Furthermore, important variables in previously developed noninvasive NAFLD/NASH staging algorithms including body mass index and biomarkers for liver function and insulin resistance may also warrant evaluation as components of an identification algorithm,” the team said.
It’s possible the study overestimated the risks of disease progression and mortality with NAFLD/NASH because patients with more severe disease were probably more likely to have been identified in Medicare data, the investigators said.
The mean age of the NAFLD/NASH subjects was 67.4 years, and 60% were women.
The work was funded by Gilead, which has several drugs under development for NAFLD/NASH. Two authors are Gilead employees, and the rest, including Dr. Loomba, reported funding and other ties to the company.
To help your patients better understand NASH, visit the AGA GI Patient Center at https://www.gastro.org/
SOURCE: Loomba R et al. Aliment Pharmacol Ther. 2020 May 5. doi: 10.1111/apt.15679.
FROM ALIMENTARY PHARMACOLOGY & THERAPEUTICS
High rate of fatty liver disease found among 9/11 first responders
First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.
In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.
The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.
“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”
Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.
“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”
The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.
Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.
“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.
Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.
The investigators reported no outside funding or conflicts of interest.
SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.
First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.
In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.
The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.
“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”
Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.
“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”
The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.
Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.
“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.
Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.
The investigators reported no outside funding or conflicts of interest.
SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.
First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.
In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.
The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.
“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”
Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.
“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”
The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.
Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.
“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.
Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.
The investigators reported no outside funding or conflicts of interest.
SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.
FROM DDW 2020
Key clinical point: First responders to the site of the 2001 World Trade Center attack may have a higher risk of fatty liver disease.
Major finding: Eighty-three percent of first responders presenting with gastrointestinal symptoms had toxin-associated fatty liver disease (TAFLD), a subtype of nonalcoholic fatty liver disease (NAFLD).
Study details: A retrospective study involving 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program between January 2014 and August 2019.
Disclosures: The investigators reported no outside funding or conflicts of interest.
Source: Reja M et al. DDW 2020, Abstracts available online May 2.