Hepatology

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.

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.

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.

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.

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.

[email protected]

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.

[email protected]

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.

[email protected]

SOURCE: Loomba R et al. Aliment Pharmacol Ther. 2020 May 5. doi: 10.1111/apt.15679.

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.

Readily available and inexpensive noninvasive tests, when used in combination with liver markers obtained with the extra-large probe, can improve the ability to predict risk for decompensation and other adverse outcomes in obese and overweight patients with compensated advanced chronic liver disease (cACLD), according to study results reported in the upcoming issue of the journal Clinical Gastroenterology and Hepatology.

The retrospective study of 272 obese and overweight patients in Bern, Switzerland, and Montreal with cACLD is the first to fully assess the noninvasive marker of portal hypertension along with using the extra-large probe for controlled attenuation parameter (CAP) to determine risk, wrote Yuly Mendoza, MD, of the University of Bern and colleagues. Decompensation in cACLD carries a higher risk of death. The study noted that portal hypertension is a key driver of progression to decompensation, “and as such, it should be identified as soon as possible and treated as needed.”

“Prediction of prognosis in cACLD is challenging, and noninvasive tests are important tools for clinicians to avoid as much as possible the use of more invasive tests,” wrote Dr. Mendoza and colleagues. Based on the extra-large probe, 76% (n = 206) of study patients had metabolic syndrome, sometimes with other etiologies of liver disease, and 57% (n = 154) had cACLD because of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH).

Twelve patients had decompensation and five developed severe bacterial infections.

“Readily available noninvasive tests can be used to identify obese or overweight patients with cACLD who are at increased risk for decompensation and severe bacterial infections,” wrote the researchers.

The study noted that obesity is a challenge for noninvasive tests and is a major limitation to liver stiffness measurement on transient elastography using the standard M probe. The XL probe has been specifically designed to overcome this challenge in obese patients, but it hasn’t been evaluated for the prediction of clinical decompensation in obese patients with cACLD.

This study claimed to provide further evidence that liver stiffness measurement in combination with noninvasive tests for liver stiffness measurement, spleen size/platelet count (LSPS), portal hypertension and portal hypertension risk score can help identify patients at risk for clinical decompensation and severe bacterial infections.

The study used average area under the receiving operator curve (AUC) to calculate the ability of the markers to distinguish risk, all with 95% confidence interval: 0.803 for liver stiffness measurement, 0.829 for portal hypertension risk score, and 0.845 for LSPS (P < .001). The markers showed an even better ability to differentiate between patients at risk for developing classical clinical decompensation in follow-up from those not at risk (all 95% CI): 0.848 for liver stiffness measurement, 0.881 for portal hypertension risk score, and 0.890 for LSPS (P < .001).

“The results of the present study validate the use of [extra-large] probe for liver stiffness measurement and CAP to stratify the risk of clinical decompensation and clinically relevant events in overweight/obese patients with cACLD, particularly in case of NAFLD/NASH etiology,” wrote Dr. Mendoza and colleagues.

All study participants were followed for at least 6 months, with a median of 17 months. Patients who developed decompensation or severe bacterial infections had slightly worse liver function (higher international normalized ratio and lower albumin), lower mean platelet count (117 vs. 179 x 10⁹/L; P < .001) and lower mean CAP (297 vs. 318 dBm; P = .030) than did patients who stayed compensated.

CAP above 220 dB/m was marginally associated with a lower risk of decompensation or severe bacterial infections on univariate analysis, as were elevated Model for End-Stage Liver Disease score, elevated Child Pugh score, low platelet count, low serum albumin, elevated serum bilirubin and increased liver stiffness measurement, LSPS, and portal hypertension risk scores.

Dr. Mendoza and colleagues have no relevant financial disclosures. The study received funding from the Swiss government.

SOURCE: Mendoza Y et al. Clin Gastroenterol Hepatol. 2020. doi: 10.1016/j.cgh.2020.04.018.

Readily available and inexpensive noninvasive tests, when used in combination with liver markers obtained with the extra-large probe, can improve the ability to predict risk for decompensation and other adverse outcomes in obese and overweight patients with compensated advanced chronic liver disease (cACLD), according to study results reported in the upcoming issue of the journal Clinical Gastroenterology and Hepatology.

The retrospective study of 272 obese and overweight patients in Bern, Switzerland, and Montreal with cACLD is the first to fully assess the noninvasive marker of portal hypertension along with using the extra-large probe for controlled attenuation parameter (CAP) to determine risk, wrote Yuly Mendoza, MD, of the University of Bern and colleagues. Decompensation in cACLD carries a higher risk of death. The study noted that portal hypertension is a key driver of progression to decompensation, “and as such, it should be identified as soon as possible and treated as needed.”

“Prediction of prognosis in cACLD is challenging, and noninvasive tests are important tools for clinicians to avoid as much as possible the use of more invasive tests,” wrote Dr. Mendoza and colleagues. Based on the extra-large probe, 76% (n = 206) of study patients had metabolic syndrome, sometimes with other etiologies of liver disease, and 57% (n = 154) had cACLD because of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH).

Twelve patients had decompensation and five developed severe bacterial infections.

“Readily available noninvasive tests can be used to identify obese or overweight patients with cACLD who are at increased risk for decompensation and severe bacterial infections,” wrote the researchers.

The study noted that obesity is a challenge for noninvasive tests and is a major limitation to liver stiffness measurement on transient elastography using the standard M probe. The XL probe has been specifically designed to overcome this challenge in obese patients, but it hasn’t been evaluated for the prediction of clinical decompensation in obese patients with cACLD.

This study claimed to provide further evidence that liver stiffness measurement in combination with noninvasive tests for liver stiffness measurement, spleen size/platelet count (LSPS), portal hypertension and portal hypertension risk score can help identify patients at risk for clinical decompensation and severe bacterial infections.

The study used average area under the receiving operator curve (AUC) to calculate the ability of the markers to distinguish risk, all with 95% confidence interval: 0.803 for liver stiffness measurement, 0.829 for portal hypertension risk score, and 0.845 for LSPS (P < .001). The markers showed an even better ability to differentiate between patients at risk for developing classical clinical decompensation in follow-up from those not at risk (all 95% CI): 0.848 for liver stiffness measurement, 0.881 for portal hypertension risk score, and 0.890 for LSPS (P < .001).

“The results of the present study validate the use of [extra-large] probe for liver stiffness measurement and CAP to stratify the risk of clinical decompensation and clinically relevant events in overweight/obese patients with cACLD, particularly in case of NAFLD/NASH etiology,” wrote Dr. Mendoza and colleagues.

All study participants were followed for at least 6 months, with a median of 17 months. Patients who developed decompensation or severe bacterial infections had slightly worse liver function (higher international normalized ratio and lower albumin), lower mean platelet count (117 vs. 179 x 10⁹/L; P < .001) and lower mean CAP (297 vs. 318 dBm; P = .030) than did patients who stayed compensated.

CAP above 220 dB/m was marginally associated with a lower risk of decompensation or severe bacterial infections on univariate analysis, as were elevated Model for End-Stage Liver Disease score, elevated Child Pugh score, low platelet count, low serum albumin, elevated serum bilirubin and increased liver stiffness measurement, LSPS, and portal hypertension risk scores.

Dr. Mendoza and colleagues have no relevant financial disclosures. The study received funding from the Swiss government.

SOURCE: Mendoza Y et al. Clin Gastroenterol Hepatol. 2020. doi: 10.1016/j.cgh.2020.04.018.

Readily available and inexpensive noninvasive tests, when used in combination with liver markers obtained with the extra-large probe, can improve the ability to predict risk for decompensation and other adverse outcomes in obese and overweight patients with compensated advanced chronic liver disease (cACLD), according to study results reported in the upcoming issue of the journal Clinical Gastroenterology and Hepatology.

The retrospective study of 272 obese and overweight patients in Bern, Switzerland, and Montreal with cACLD is the first to fully assess the noninvasive marker of portal hypertension along with using the extra-large probe for controlled attenuation parameter (CAP) to determine risk, wrote Yuly Mendoza, MD, of the University of Bern and colleagues. Decompensation in cACLD carries a higher risk of death. The study noted that portal hypertension is a key driver of progression to decompensation, “and as such, it should be identified as soon as possible and treated as needed.”

“Prediction of prognosis in cACLD is challenging, and noninvasive tests are important tools for clinicians to avoid as much as possible the use of more invasive tests,” wrote Dr. Mendoza and colleagues. Based on the extra-large probe, 76% (n = 206) of study patients had metabolic syndrome, sometimes with other etiologies of liver disease, and 57% (n = 154) had cACLD because of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH).

Twelve patients had decompensation and five developed severe bacterial infections.

“Readily available noninvasive tests can be used to identify obese or overweight patients with cACLD who are at increased risk for decompensation and severe bacterial infections,” wrote the researchers.

The study noted that obesity is a challenge for noninvasive tests and is a major limitation to liver stiffness measurement on transient elastography using the standard M probe. The XL probe has been specifically designed to overcome this challenge in obese patients, but it hasn’t been evaluated for the prediction of clinical decompensation in obese patients with cACLD.

This study claimed to provide further evidence that liver stiffness measurement in combination with noninvasive tests for liver stiffness measurement, spleen size/platelet count (LSPS), portal hypertension and portal hypertension risk score can help identify patients at risk for clinical decompensation and severe bacterial infections.

The study used average area under the receiving operator curve (AUC) to calculate the ability of the markers to distinguish risk, all with 95% confidence interval: 0.803 for liver stiffness measurement, 0.829 for portal hypertension risk score, and 0.845 for LSPS (P < .001). The markers showed an even better ability to differentiate between patients at risk for developing classical clinical decompensation in follow-up from those not at risk (all 95% CI): 0.848 for liver stiffness measurement, 0.881 for portal hypertension risk score, and 0.890 for LSPS (P < .001).

“The results of the present study validate the use of [extra-large] probe for liver stiffness measurement and CAP to stratify the risk of clinical decompensation and clinically relevant events in overweight/obese patients with cACLD, particularly in case of NAFLD/NASH etiology,” wrote Dr. Mendoza and colleagues.

All study participants were followed for at least 6 months, with a median of 17 months. Patients who developed decompensation or severe bacterial infections had slightly worse liver function (higher international normalized ratio and lower albumin), lower mean platelet count (117 vs. 179 x 10⁹/L; P < .001) and lower mean CAP (297 vs. 318 dBm; P = .030) than did patients who stayed compensated.

CAP above 220 dB/m was marginally associated with a lower risk of decompensation or severe bacterial infections on univariate analysis, as were elevated Model for End-Stage Liver Disease score, elevated Child Pugh score, low platelet count, low serum albumin, elevated serum bilirubin and increased liver stiffness measurement, LSPS, and portal hypertension risk scores.

Dr. Mendoza and colleagues have no relevant financial disclosures. The study received funding from the Swiss government.

SOURCE: Mendoza Y et al. Clin Gastroenterol Hepatol. 2020. doi: 10.1016/j.cgh.2020.04.018.

References

1. Hepatitis C questions and answers for health professionals. Centers for Disease Control and Prevention Web site. www.cdc.gov/hepatitis/hcv/hcvfaq.htm#section1. Updated April 9, 2020. Accessed April 17, 2020.
2. Surveillance for Viral Hepatitis–United States, 2017. Centers for Disease Control and Prevention Web site. www.cdc.gov/hepatitis/statistics/2017surveillance/index.htm. Updated November 14, 2019. Accessed April 17, 2020.
3. Hepatitis C virus infection in adolescents and adults: screening. U.S. Preventive Services Task Force Web site. Published March 2, 2020. Accessed April 17, 2020.

References

1. Hepatitis C questions and answers for health professionals. Centers for Disease Control and Prevention Web site. www.cdc.gov/hepatitis/hcv/hcvfaq.htm#section1. Updated April 9, 2020. Accessed April 17, 2020.
2. Surveillance for Viral Hepatitis–United States, 2017. Centers for Disease Control and Prevention Web site. www.cdc.gov/hepatitis/statistics/2017surveillance/index.htm. Updated November 14, 2019. Accessed April 17, 2020.
3. Hepatitis C virus infection in adolescents and adults: screening. U.S. Preventive Services Task Force Web site. Published March 2, 2020. Accessed April 17, 2020.

References

1. Hepatitis C questions and answers for health professionals. Centers for Disease Control and Prevention Web site. www.cdc.gov/hepatitis/hcv/hcvfaq.htm#section1. Updated April 9, 2020. Accessed April 17, 2020.
2. Surveillance for Viral Hepatitis–United States, 2017. Centers for Disease Control and Prevention Web site. www.cdc.gov/hepatitis/statistics/2017surveillance/index.htm. Updated November 14, 2019. Accessed April 17, 2020.
3. Hepatitis C virus infection in adolescents and adults: screening. U.S. Preventive Services Task Force Web site. Published March 2, 2020. Accessed April 17, 2020.

Physicians should consider liver cancer screening for all patients with nonalcoholic fatty liver disease (NAFLD) and cirrhosis, according to a new clinical practice update from the American Gastroenterological Association.

Screening “should be offered for patients with cirrhosis of varying etiologies when the risk of hepatocellular carcinoma is approximately at least 1.5% per year, as has been noted with NAFLD cirrhosis,” wrote Rohit Loomba, MD, of the University of California, San Diego, and associates. Although patients with noncirrhotic NAFLD also can develop hepatocellular carcinoma, “[a]t this point, we believe that [the benefit of screening] is restricted to patients with compensated cirrhosis or those with decompensated cirrhosis listed for liver transplantation,” they wrote in Gastroenterology.

Liver cancer in NAFLD often goes undetected until it is advanced enough that patients are not candidates for curative therapy. Current guidelines provide limited recommendations on which patients with NAFLD to monitor for hepatocellular carcinoma, how best to do so, and how often. To fill this gap, Dr. Loomba and associates reviewed and cited 79 published papers and developed eight suggestions for clinical practice.

Patients with NAFLD and stage 0-2 fibrosis are at “extremely low” risk for hepatocellular carcinoma and should not be routinely screened, the practice update stated. Advanced fibrosis is a clear risk factor but can be challenging to detect in NAFLD – imaging is often insensitive, and screening biopsy tends to be infeasible. Hence, the experts suggest considering liver cancer screening if patients with NAFLD show evidence of advanced fibrosis or cirrhosis on at least two noninvasive tests of distinct modalities (that is, the two tests should not both be point-of-care, specialized blood tests or noninvasive imaging). To improve specificity, the recommended cut-point thresholds for cirrhosis are 16.1 kPa for vibration-controlled transient elastography and 5 kPa for magnetic resonance elastography.

Screening ultrasound accurately detects hepatocellular carcinoma in patients with cirrhosis who have a good acoustic window. However, ultrasound quality is operator dependent, and it can be difficult even for experienced users to detect mass lesions in overweight or obese patients. Thus, it is important always to document parenchymal heterogeneity, beam attenuation, and whether the entire liver was visualized. If ultrasound quality is inadequate, patients should be screened every 6 months with CT or MRI, with or without alpha-fetoprotein, according to the practice update.

The authors advised clinicians to counsel all patients with NAFLD and cirrhosis to avoid alcohol and tobacco. “Irrespective of NAFLD, the bulk of epidemiological data support alcohol drinking as a major risk for hepatocellular carcinoma,” they note. Likewise, pooled studies indicate that current smokers are at about 50%-85% greater risk of liver cancer than never smokers. The experts add that “[al]though specific data do not exist, we believe that e-cigarettes may turn out to be equally harmful and patients be counseled to abstain from those as well.”

They also recommended optimally managing dyslipidemia and diabetes among patients with NAFLD who are at risk for hepatocellular carcinoma. Statins are safe for patients with NAFLD and dyslipidemia and may lower hepatocellular carcinoma risk, although more research is needed, according to the experts. For now, they support “the notion that the benefits of statin therapy among patients with dyslipidemia and NAFLD significantly outweigh the risk and should be utilized routinely.” Type 2 diabetes mellitus clearly heightens the risk of hepatocellular carcinoma, which metformin appears to reduce among patients with NAFLD, cirrhosis, and type 2 diabetes. Glucagonlike peptide–1 receptor agonists and some thiazolidinediones also appear to attenuate liver steatosis, inflammation, degeneration, and fibrosis, but it remains unclear if these effects ultimately lower cancer risk.

It is unclear if obesity directly contributes to hepatocellular carcinoma among patients with NAFLD, but obesity is an “important risk factor” for NAFLD itself, and “weight-loss interventions are strongly recommended to improve NAFLD-related outcomes,” the experts wrote. Pending further studies on whether weight loss reduces liver cancer risk in patients with NAFLD, they called for lifestyle modifications, pharmacotherapy, or bariatric surgery or bariatric endoscopy procedures to optimally manage obesity in patients with NAFLD who are at risk for liver cancer.

The authors disclosed funding from the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the Cancer Prevention & Research Institute of Texas, and the Center for Gastrointestinal Development, Infection and Injury. Dr. Loomba disclosed ties to Intercept Pharmaceuticals, Bird Rock Bio, Celgene, Enanta Pharmaceuticals, and a number of other companies. Two coauthors disclosed ties to Allergan, AbbVie, Conatus Pharmaceuticals, Genfit, Gilead, and Intercept. The remaining coauthor reported having no conflicts of interest.

SOURCE: Loomba R et al. Gastroenterology. 2020 Jan 29. doi: 10.1053/j.gastro.2019.12.053.

Physicians should consider liver cancer screening for all patients with nonalcoholic fatty liver disease (NAFLD) and cirrhosis, according to a new clinical practice update from the American Gastroenterological Association.

Screening “should be offered for patients with cirrhosis of varying etiologies when the risk of hepatocellular carcinoma is approximately at least 1.5% per year, as has been noted with NAFLD cirrhosis,” wrote Rohit Loomba, MD, of the University of California, San Diego, and associates. Although patients with noncirrhotic NAFLD also can develop hepatocellular carcinoma, “[a]t this point, we believe that [the benefit of screening] is restricted to patients with compensated cirrhosis or those with decompensated cirrhosis listed for liver transplantation,” they wrote in Gastroenterology.

Liver cancer in NAFLD often goes undetected until it is advanced enough that patients are not candidates for curative therapy. Current guidelines provide limited recommendations on which patients with NAFLD to monitor for hepatocellular carcinoma, how best to do so, and how often. To fill this gap, Dr. Loomba and associates reviewed and cited 79 published papers and developed eight suggestions for clinical practice.

Patients with NAFLD and stage 0-2 fibrosis are at “extremely low” risk for hepatocellular carcinoma and should not be routinely screened, the practice update stated. Advanced fibrosis is a clear risk factor but can be challenging to detect in NAFLD – imaging is often insensitive, and screening biopsy tends to be infeasible. Hence, the experts suggest considering liver cancer screening if patients with NAFLD show evidence of advanced fibrosis or cirrhosis on at least two noninvasive tests of distinct modalities (that is, the two tests should not both be point-of-care, specialized blood tests or noninvasive imaging). To improve specificity, the recommended cut-point thresholds for cirrhosis are 16.1 kPa for vibration-controlled transient elastography and 5 kPa for magnetic resonance elastography.

Screening ultrasound accurately detects hepatocellular carcinoma in patients with cirrhosis who have a good acoustic window. However, ultrasound quality is operator dependent, and it can be difficult even for experienced users to detect mass lesions in overweight or obese patients. Thus, it is important always to document parenchymal heterogeneity, beam attenuation, and whether the entire liver was visualized. If ultrasound quality is inadequate, patients should be screened every 6 months with CT or MRI, with or without alpha-fetoprotein, according to the practice update.

The authors advised clinicians to counsel all patients with NAFLD and cirrhosis to avoid alcohol and tobacco. “Irrespective of NAFLD, the bulk of epidemiological data support alcohol drinking as a major risk for hepatocellular carcinoma,” they note. Likewise, pooled studies indicate that current smokers are at about 50%-85% greater risk of liver cancer than never smokers. The experts add that “[al]though specific data do not exist, we believe that e-cigarettes may turn out to be equally harmful and patients be counseled to abstain from those as well.”

They also recommended optimally managing dyslipidemia and diabetes among patients with NAFLD who are at risk for hepatocellular carcinoma. Statins are safe for patients with NAFLD and dyslipidemia and may lower hepatocellular carcinoma risk, although more research is needed, according to the experts. For now, they support “the notion that the benefits of statin therapy among patients with dyslipidemia and NAFLD significantly outweigh the risk and should be utilized routinely.” Type 2 diabetes mellitus clearly heightens the risk of hepatocellular carcinoma, which metformin appears to reduce among patients with NAFLD, cirrhosis, and type 2 diabetes. Glucagonlike peptide–1 receptor agonists and some thiazolidinediones also appear to attenuate liver steatosis, inflammation, degeneration, and fibrosis, but it remains unclear if these effects ultimately lower cancer risk.

It is unclear if obesity directly contributes to hepatocellular carcinoma among patients with NAFLD, but obesity is an “important risk factor” for NAFLD itself, and “weight-loss interventions are strongly recommended to improve NAFLD-related outcomes,” the experts wrote. Pending further studies on whether weight loss reduces liver cancer risk in patients with NAFLD, they called for lifestyle modifications, pharmacotherapy, or bariatric surgery or bariatric endoscopy procedures to optimally manage obesity in patients with NAFLD who are at risk for liver cancer.

The authors disclosed funding from the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the Cancer Prevention & Research Institute of Texas, and the Center for Gastrointestinal Development, Infection and Injury. Dr. Loomba disclosed ties to Intercept Pharmaceuticals, Bird Rock Bio, Celgene, Enanta Pharmaceuticals, and a number of other companies. Two coauthors disclosed ties to Allergan, AbbVie, Conatus Pharmaceuticals, Genfit, Gilead, and Intercept. The remaining coauthor reported having no conflicts of interest.

SOURCE: Loomba R et al. Gastroenterology. 2020 Jan 29. doi: 10.1053/j.gastro.2019.12.053.

Physicians should consider liver cancer screening for all patients with nonalcoholic fatty liver disease (NAFLD) and cirrhosis, according to a new clinical practice update from the American Gastroenterological Association.

Screening “should be offered for patients with cirrhosis of varying etiologies when the risk of hepatocellular carcinoma is approximately at least 1.5% per year, as has been noted with NAFLD cirrhosis,” wrote Rohit Loomba, MD, of the University of California, San Diego, and associates. Although patients with noncirrhotic NAFLD also can develop hepatocellular carcinoma, “[a]t this point, we believe that [the benefit of screening] is restricted to patients with compensated cirrhosis or those with decompensated cirrhosis listed for liver transplantation,” they wrote in Gastroenterology.

Liver cancer in NAFLD often goes undetected until it is advanced enough that patients are not candidates for curative therapy. Current guidelines provide limited recommendations on which patients with NAFLD to monitor for hepatocellular carcinoma, how best to do so, and how often. To fill this gap, Dr. Loomba and associates reviewed and cited 79 published papers and developed eight suggestions for clinical practice.

Patients with NAFLD and stage 0-2 fibrosis are at “extremely low” risk for hepatocellular carcinoma and should not be routinely screened, the practice update stated. Advanced fibrosis is a clear risk factor but can be challenging to detect in NAFLD – imaging is often insensitive, and screening biopsy tends to be infeasible. Hence, the experts suggest considering liver cancer screening if patients with NAFLD show evidence of advanced fibrosis or cirrhosis on at least two noninvasive tests of distinct modalities (that is, the two tests should not both be point-of-care, specialized blood tests or noninvasive imaging). To improve specificity, the recommended cut-point thresholds for cirrhosis are 16.1 kPa for vibration-controlled transient elastography and 5 kPa for magnetic resonance elastography.

Screening ultrasound accurately detects hepatocellular carcinoma in patients with cirrhosis who have a good acoustic window. However, ultrasound quality is operator dependent, and it can be difficult even for experienced users to detect mass lesions in overweight or obese patients. Thus, it is important always to document parenchymal heterogeneity, beam attenuation, and whether the entire liver was visualized. If ultrasound quality is inadequate, patients should be screened every 6 months with CT or MRI, with or without alpha-fetoprotein, according to the practice update.

The authors advised clinicians to counsel all patients with NAFLD and cirrhosis to avoid alcohol and tobacco. “Irrespective of NAFLD, the bulk of epidemiological data support alcohol drinking as a major risk for hepatocellular carcinoma,” they note. Likewise, pooled studies indicate that current smokers are at about 50%-85% greater risk of liver cancer than never smokers. The experts add that “[al]though specific data do not exist, we believe that e-cigarettes may turn out to be equally harmful and patients be counseled to abstain from those as well.”

They also recommended optimally managing dyslipidemia and diabetes among patients with NAFLD who are at risk for hepatocellular carcinoma. Statins are safe for patients with NAFLD and dyslipidemia and may lower hepatocellular carcinoma risk, although more research is needed, according to the experts. For now, they support “the notion that the benefits of statin therapy among patients with dyslipidemia and NAFLD significantly outweigh the risk and should be utilized routinely.” Type 2 diabetes mellitus clearly heightens the risk of hepatocellular carcinoma, which metformin appears to reduce among patients with NAFLD, cirrhosis, and type 2 diabetes. Glucagonlike peptide–1 receptor agonists and some thiazolidinediones also appear to attenuate liver steatosis, inflammation, degeneration, and fibrosis, but it remains unclear if these effects ultimately lower cancer risk.

It is unclear if obesity directly contributes to hepatocellular carcinoma among patients with NAFLD, but obesity is an “important risk factor” for NAFLD itself, and “weight-loss interventions are strongly recommended to improve NAFLD-related outcomes,” the experts wrote. Pending further studies on whether weight loss reduces liver cancer risk in patients with NAFLD, they called for lifestyle modifications, pharmacotherapy, or bariatric surgery or bariatric endoscopy procedures to optimally manage obesity in patients with NAFLD who are at risk for liver cancer.

The authors disclosed funding from the National Institute of Environmental Health Sciences, the National Center for Advancing Translational Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, the Cancer Prevention & Research Institute of Texas, and the Center for Gastrointestinal Development, Infection and Injury. Dr. Loomba disclosed ties to Intercept Pharmaceuticals, Bird Rock Bio, Celgene, Enanta Pharmaceuticals, and a number of other companies. Two coauthors disclosed ties to Allergan, AbbVie, Conatus Pharmaceuticals, Genfit, Gilead, and Intercept. The remaining coauthor reported having no conflicts of interest.

SOURCE: Loomba R et al. Gastroenterology. 2020 Jan 29. doi: 10.1053/j.gastro.2019.12.053.

In the latest issue of the Morbidity and Mortality Weekly Report, the Centers for Disease Control and Prevention recommended hepatitis C virus screening for all adults and all pregnant women – during each of their pregnancies – in areas where prevalence of the infection is 0.1% or greater.

That’s essentially the entire United States; there’s no state with a statewide adult prevalence below 0.1%, and “few settings are known to exist” otherwise, the CDC noted (MMWR Recomm Rep. 2020 Apr 10;69(2):1-17).

The agency encouraged providers to consult state or local health departments or the CDC directly to determine local HCV prevalence. “As a general guide ... approximately 59% of anti-HCV positive persons are HCV RNA positive,” indicating active infection, the agency noted.

The advice was an expansion from the CDC’s last universal screening recommendation in 2012, which was limited to people born from 1945 to 1965; the incidence of acute infections has climbed since then and is highest now among younger people, so the guideline needed to be revisited, explained authors led by Sarah Schillie, MD, of the CDC’s Division of Viral Hepatitis, Atlanta.

The U.S. Preventive Services Task Force also recently recommended universal adult screening after previously limiting it to baby boomers.

As for pregnancy, the CDC’s past advice was to screen pregnant women with known risk factors, but that needed to be revisited as well. For one thing, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America have since recommended testing all pregnant women.

But also, the CDC said, it’s an opportune time for screening because “many women only have access to health care during pregnancy and the immediate postpartum period,” when treatment, if needed, can be started. Plus, HCV status is important for management decisions, such as using amniocentesis in positive women instead of chorionic villus sampling.

The rest of CDC’s 2012 recommendations stand, including screening all people with risk factors and repeating screening while they persist. Also, “any person who requests hepatitis C testing should receive it, regardless of disclosure of risk,” because people might be reluctant to report things like IV drug use, the authors said.

Screening in the guidelines means an HCV antibody test, followed by a nucleic acid test to check for active infection. The CDC encouraged automatic reflex testing, meaning immediately checking antibody positive samples for HCV RNA. RNA in the blood indicates active, replicating virus.

The new recommendations penciled out in modeling, with an incremental cost-effectiveness ratio (ICER) for universal adult screening of approximately $36,000 per quality-adjusted life year (QALY) gained, and an ICER of approximately $15,000 per QALY gained for pregnancy screening, where HCV prevalence is 0.1%; the 0.1% cost/benefit cutpoint was one of the reasons it was chosen as the prevalence threshold. An ICER under $50,000 is the conservative benchmark for cost-effectiveness, the authors noted.

There was no external funding, and the authors had no disclosures.

[email protected]

SOURCE: Schillie S et al. MMWR Recomm Rep. 2020 Apr 10;69[2]:1-17).

In the latest issue of the Morbidity and Mortality Weekly Report, the Centers for Disease Control and Prevention recommended hepatitis C virus screening for all adults and all pregnant women – during each of their pregnancies – in areas where prevalence of the infection is 0.1% or greater.

That’s essentially the entire United States; there’s no state with a statewide adult prevalence below 0.1%, and “few settings are known to exist” otherwise, the CDC noted (MMWR Recomm Rep. 2020 Apr 10;69(2):1-17).

The agency encouraged providers to consult state or local health departments or the CDC directly to determine local HCV prevalence. “As a general guide ... approximately 59% of anti-HCV positive persons are HCV RNA positive,” indicating active infection, the agency noted.

The advice was an expansion from the CDC’s last universal screening recommendation in 2012, which was limited to people born from 1945 to 1965; the incidence of acute infections has climbed since then and is highest now among younger people, so the guideline needed to be revisited, explained authors led by Sarah Schillie, MD, of the CDC’s Division of Viral Hepatitis, Atlanta.

The U.S. Preventive Services Task Force also recently recommended universal adult screening after previously limiting it to baby boomers.

As for pregnancy, the CDC’s past advice was to screen pregnant women with known risk factors, but that needed to be revisited as well. For one thing, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America have since recommended testing all pregnant women.

But also, the CDC said, it’s an opportune time for screening because “many women only have access to health care during pregnancy and the immediate postpartum period,” when treatment, if needed, can be started. Plus, HCV status is important for management decisions, such as using amniocentesis in positive women instead of chorionic villus sampling.

The rest of CDC’s 2012 recommendations stand, including screening all people with risk factors and repeating screening while they persist. Also, “any person who requests hepatitis C testing should receive it, regardless of disclosure of risk,” because people might be reluctant to report things like IV drug use, the authors said.

Screening in the guidelines means an HCV antibody test, followed by a nucleic acid test to check for active infection. The CDC encouraged automatic reflex testing, meaning immediately checking antibody positive samples for HCV RNA. RNA in the blood indicates active, replicating virus.

The new recommendations penciled out in modeling, with an incremental cost-effectiveness ratio (ICER) for universal adult screening of approximately $36,000 per quality-adjusted life year (QALY) gained, and an ICER of approximately $15,000 per QALY gained for pregnancy screening, where HCV prevalence is 0.1%; the 0.1% cost/benefit cutpoint was one of the reasons it was chosen as the prevalence threshold. An ICER under $50,000 is the conservative benchmark for cost-effectiveness, the authors noted.

There was no external funding, and the authors had no disclosures.

[email protected]

SOURCE: Schillie S et al. MMWR Recomm Rep. 2020 Apr 10;69[2]:1-17).

In the latest issue of the Morbidity and Mortality Weekly Report, the Centers for Disease Control and Prevention recommended hepatitis C virus screening for all adults and all pregnant women – during each of their pregnancies – in areas where prevalence of the infection is 0.1% or greater.

That’s essentially the entire United States; there’s no state with a statewide adult prevalence below 0.1%, and “few settings are known to exist” otherwise, the CDC noted (MMWR Recomm Rep. 2020 Apr 10;69(2):1-17).

The agency encouraged providers to consult state or local health departments or the CDC directly to determine local HCV prevalence. “As a general guide ... approximately 59% of anti-HCV positive persons are HCV RNA positive,” indicating active infection, the agency noted.

The advice was an expansion from the CDC’s last universal screening recommendation in 2012, which was limited to people born from 1945 to 1965; the incidence of acute infections has climbed since then and is highest now among younger people, so the guideline needed to be revisited, explained authors led by Sarah Schillie, MD, of the CDC’s Division of Viral Hepatitis, Atlanta.

The U.S. Preventive Services Task Force also recently recommended universal adult screening after previously limiting it to baby boomers.

As for pregnancy, the CDC’s past advice was to screen pregnant women with known risk factors, but that needed to be revisited as well. For one thing, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America have since recommended testing all pregnant women.

But also, the CDC said, it’s an opportune time for screening because “many women only have access to health care during pregnancy and the immediate postpartum period,” when treatment, if needed, can be started. Plus, HCV status is important for management decisions, such as using amniocentesis in positive women instead of chorionic villus sampling.

The rest of CDC’s 2012 recommendations stand, including screening all people with risk factors and repeating screening while they persist. Also, “any person who requests hepatitis C testing should receive it, regardless of disclosure of risk,” because people might be reluctant to report things like IV drug use, the authors said.

Screening in the guidelines means an HCV antibody test, followed by a nucleic acid test to check for active infection. The CDC encouraged automatic reflex testing, meaning immediately checking antibody positive samples for HCV RNA. RNA in the blood indicates active, replicating virus.

The new recommendations penciled out in modeling, with an incremental cost-effectiveness ratio (ICER) for universal adult screening of approximately $36,000 per quality-adjusted life year (QALY) gained, and an ICER of approximately $15,000 per QALY gained for pregnancy screening, where HCV prevalence is 0.1%; the 0.1% cost/benefit cutpoint was one of the reasons it was chosen as the prevalence threshold. An ICER under $50,000 is the conservative benchmark for cost-effectiveness, the authors noted.

There was no external funding, and the authors had no disclosures.

[email protected]

SOURCE: Schillie S et al. MMWR Recomm Rep. 2020 Apr 10;69[2]:1-17).

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.