CROI 2010: Moderate Liver Fibrosis Predicts Disease and Death in HIV/HCV Coinfected People, but Successful Treatment Appears Protective

Even moderate liver fibrosis (greater than stage F1) in HIV/HCV coinfected patients is associated with adverse clinical outcomes including liver cancer, liver failure, and death, investigators reported at the 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010) last week in San Francisco. However, effective HIV treatment producing long-term viral suppression and successful hepatitis C treatment leading to sustained virological response appeared to be protective.

Over years or decades, chronic hepatitis C virus (HCV) infection can progress to advanced liver disease, including cirrhosis and liver cancer. Progression tends to be more rapid in HIV/HCV coinfected individuals, especially those with low CD4 cell counts.

Only people who experience liver disease progression need hepatitis C treatment, but this is not easy to monitor. Liver biopsies are recommended for disease staging in HIV/HCV coinfected patients, but the degree to which histological stage predicts clinical outcomes is unclear.

Mark Sulkowski from Johns Hopkins University and colleagues conducted a study to prospectively assess clinical outcomes and mortality according to hepatic fibrosis stage in a cohort of well-characterized HIV/HCV coinfected adults.

The researchers hypothesized that patients with significant liver fibrosis (Metavir stage F2 or higher) would be more likely to progress to end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death.

The study included 637 HIV/HCV coinfected patients seen at the Johns Hopkins HIV clinic between July 1993 and March 2009. A majority (67%) were men, most (80%) were black, and the median age was about 46 years. Three-quarters had a history of injection drug use and about half had a history of heavy alcohol use. Almost all (94%) had hard-to-treat HCV genotype 1.

With regard to HIV disease, 64% were on combination antiretroviral therapy (ART), 56% had undetectable HIV viral load, one-third had a well-preserved CD4 cell count of 500 cells/mm3 or more, but 18% had less than 200 cells/mm3.

Liver biopsies were performed at baseline, evaluated by a single pathologist and scored using the Metavir system. Over a median follow-up duration of about 5 years, clinical outcomes were abstracted from medical records and national death databases. The primary endpoint was the combined outcome of progression to ESLD, HCC, or death since the baseline biopsy.

Results

Based on these results, the researchers concluded, "Coinfected patients with more than portal fibrosis (F1) are at increased risk of clinical outcomes."

"Liver disease staging should be routine," they recommended. "Effective treatment of HIV (long-term suppression) and HCV (SVR) appeared to be protective."

Discussing these findings, Dr Sulkowski noted that individuals with stage F0-F1 fibrosis were not a zero risk for progression, but that this happened less often or more slowly. He suggested that perhaps 25% of people at these stages will progress probably driving the observed risk in the F0-F1 group while the remainder will have sustained absent or mild fibrosis.

Johns Hopkins University, Baltimore, MD.

2/26/10

Reference

M Sulkowski, S Mehta, C Sutcliffe, and others. Baseline Liver Disease Is Independently Associated with Risk of Death among 631 HIV/HCV Co-infected Adult with Histologic Staging. 17th Conference on Retroviruses & Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. Abstract 166.