Over a third of HIV-positive gay men develop significant liver fibrosis after an episode of acute hepatitis C virus (HCV) infection, German investigators report in the Journal of Viral Hepatitis. Over three years of follow-up, 39% of individuals developed fibrosis stage F2 or higher. Risk factors included older age, alcoholism and non-response to therapy based on interferon during acute infection.
“We observed a high rate of significant liver fibrosis…and even cirrhosis (11.6%),” comment the investigators. “We interpret this finding as an effect of acute HCV on the liver, and the short HCV infection duration in this HIV-infected population was apparently sufficient to induce significant liver damage.”
Globally, between 5 and 15% of HIV-positive people have co-infection with HCV. There are well-established epidemics of HCV among HIV-positive gay and other men who have sex with men (MSM) in Europe, Australia and the US. HCV-related liver disease is now a major cause of illness and death in people with co-infection.
Glossary
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
Highly effective HCV therapy using direct-acting antiviral agents (DAAs) is now available and can achieve a cure in almost all people. However, it is not currently indicated for the treatment of acute infection. Moreover, since the introduction of DAAs, the proportion of European patients with acute HCV infection opting for therapy with older interferon-based treatments has dropped dramatically, potentially increasing the risk of significant fibrosis over time.
Rapid progression of fibrosis in men with co-infection has been reported previously in small studies in the United States and Europe. The findings published in the Journal of Viral Hepatitis represent the largest population yet studied.
Investigators in Berlin designed a single-centre, observational study to describe rates of fibrosis progression and mortality among HIV-positive MSM with acute HCV infection. Risk factors for fibrosis progression were also analysed.
A total of 213 cases of acute HCV were diagnosed in 178 HIV-positive MSM between 2002 and 2013. Almost a fifth (18%) of cases were re-infections. Over a third of men (38%) reported intravenous drug use during sexual encounters (“chemsex”) and 40% had a recent sexually transmitted infection, especially syphilis.
Maximum ALT level during acute infection was a median of 421 u/l. Median HCV RNA viral load was 6.09 log10 IU/ml. The majority of cases (77%) involved HCV genotype 1a.
A spontaneous cure was observed in 11% of individuals. This was associated with increased age, lower HCV RNA and elevated ALT levels.
Of the men without spontaneous clearance, 86% initiated interferon-based therapy. Treatment lasted a medium of 13 weeks. At the end of therapy, a sustained virological response (SVR) – or cure – was observed in 71% of men and was associated with lower age. Individuals with physician-declared alcoholism were significantly less likely to attain SVR.
At baseline, 90% of men had no evidence of serious liver fibrosis. But after a median of three years of follow-up, 39% had fibrosis stage F2 or higher, with 12% having cirrhosis. Older age (p = 0.02) and non-response to HCV therapy (p = 0.02) were both associated with significant fibrosis progression.
No patient developed decompensated liver disease or liver cancer. There were ten deaths overall, (1.4 per 100 person-years). Four deaths were due to cardiovascular disease. None had liver disease as their cause.
“With a mortality rate of 1.4/100 person-years in our cohort, rates are similar to those described in other HIV-monoinfected cohorts,” observe the investigators.
“Older men, chronic drinkers, and those with uncontrolled HCV RNA replication are at particularly high risk of fibrosis progression,” conclude the authors. “This subgroup could warrant closer monitoring by non-invasive markers of fibrosis and should be considered for early treatment.”