People with HIV and hepatitis C co-infection who had fatty liver disease were twice as likely to die during a five-year follow-up period as their counterparts without fatty liver disease, French researchers report in Hepatology.
The researchers say that using non-invasive measures of fatty liver disease can help doctors identify patients at higher risk of death and they urge investigation of other cohorts of people with HIV and hepatitis C to validate the fatty liver index.
Accumulation of fat in liver cells – hepatic steatosis – is caused by metabolic disorders, by insulin resistance and systemic inflammation. Hepatitis C causes insulin resistance and both hepatitis C and HIV cause inflammation.
Hepatitis steatosis can evolve into non-alcoholic steatohepatitis (NASH) – liver inflammation as a result of fat accumulation. In some people, NASH will lead to the development of more serious liver damage – fibrosis, cirrhosis or liver cancer (hepatocellular carcinoma).
The severity of fat accumulation can be estimated by using laboratory measurements and body mass measures in an algorithm called the Fatty Liver Index. The Fatty Liver Index is calculated using body mass index, waist circumference, triglycerides and gamma glutamyl transferase (GGT). A score below 30 rules out hepatic steatosis and a score above 60 confirms hepatic steatosis.
The Fatty Liver Index has been shown to predict liver-related and all-cause mortality in the general population, but it has not been evaluated in people with HIV and hepatitis C co-infection. French researchers investigated the relationship between hepatic steatosis and mortality in the HEPAVIH cohort, a national prospective cohort of people with HIV and hepatitis C.
The study looked at 983 people recruited to the cohort between 2005 and 2008 who had provided detailed behavioural data on alcohol and coffee consumption, smoking, mental health, housing and employment status and who were followed for at least five years or until death.
The study population was 70% male and had a median age of 49 years. Eighty-eight per cent had CD4 counts above 200 cells/mm3 and 89% were taking antiretroviral therapy at the beginning of the follow-up period. Advanced fibrosis (FIB-4 score > 3.25) was rare; only 15% had fibrosis and only 12% had been treated for hepatitis C and cured at the time they joined the study.
An elevated fatty liver index may be a marker of metabolic disorders and cardiovascular risk
Twenty-seven per cent of the cohort had hepatic steatosis at baseline, 12% had a fatty liver index measurement above 60 at all study visits and 31% had a fatty liver index measurement both above and below 60 during follow-up.
People with a fatty liver index score of 60 or above had significantly higher median body mass index, triglycerides and waist circumference and were also more likely to be male, to be over 50, to have advanced fibrosis (23%), to have a history of hepatocellular carcinoma or liver transplantation or to have clinical signs of cirrhosis such as ascites or bleeding from oesophageal varices at enrolment. They were less likely to smoke, more likely to abstain from alcohol and more likely to drink two cups of coffee or less each day.
There was no difference between people with an elevated fatty liver score and those without in terms of employment, housing status, hepatitis C virus (HCV) genotype, HCV treatment status, HIV transmission category, HIV disease stage, antiretroviral treatment, CD4 cell count, mental health status or binge drinking.
Sixty-three people died during the follow-up period, 40% due to hepatitis C, 3% due to non-AIDS cancers, 11% of AIDS-related illnesses and 5% due to cardiovascular disease.
People with a fatty liver index above 60 at baseline were twice as likely to die during the follow-up period (Hazard ratio 1.91, 95% CI 1.17-3.32, p = 0.009) after controlling for other risk factors.
People with a history of hepatocellular carcinoma or liver transplantation at baseline were seven times more likely to die during the follow-up period, independent of Fatty Liver Index status.
Advanced fibrosis or signs of cirrhosis at baseline also increased the risk of death, as did symptomatic HIV disease (CDC stage C).
The investigators say that theirs is the first study to show that an elevated fatty liver index is associated with an increased risk of death, independent of other risk factors, in people with HIV and hepatitis C co-infection.
An elevated fatty liver index may be a marker of metabolic disorders and cardiovascular risk, the investigators say. Future research should attempt to collect more data on insulin resistance in order to clarify the mechanisms involved in the association between an elevated fatty liver index and mortality.
Barré T et al. Elevated fatty liver index as a risk factor for all-cause mortality in HIV-HCV co-infected patients (ANRS CO13 HEPAVIH cohort study). Hepatology, advance online publication, 29 August 2019, https://doi.org/10.1002/hep.30914