HIV/HCV Coinfected People with Moderate or Worse Fibrosis at Risk for Liver-Related Death


HIV-positive people coinfected with hepatitis C virus (HCV) are more likely to die of liver-related causes if they have moderate or worse fibrosis or cirrhosis, and they should therefore be prioritized for the new antiviral treatment, according to a study described in the June 19 edition of AIDS.

Over years or decades chronic HCV infection can lead to serious liver disease including cirrhosis, hepatocellular carcinoma, decompensated liver failure, and the need for a liver transplant. Several studies have found that HIV/HCV coinfected people experience more rapid liver disease progression than those with HCV alone, and liver disease has become a leading cause of death among people with HIV.

Daniel Grint and Amanda Mocroft from University College London and colleagues with the EuroSIDA study looked at outcomes among nearly 4000 cohort members with HIV and hepatitis C, aiming to provide guidance on who should be prioritized for treatment with new direct-acting antiviral (DAA) therapy.

While HIV/HCV coinfected people did not respond as well to interferon-based therapy as those with HCV alone, response is similar using DAAs in interferon-free regimens, with cure rates typically exceeding 90%. Everyone with hepatitis C could potentially benefit from treatment with these highly effective and well-tolerated new drugs, but their high cost has led many insurers and public payers to restrict treatment to the sickest patients.

The EuroSIDA analysis included 3941 HIV-positive patients with positive HCV antibody tests who had follow-up data available after January 2000. A majority (68%) were men, almost all were white, the median age was 37 years, and 70% had a history of injection drug use.

The researchers analyzed mortality rates, causes of death, and factors associated with liver-related death. The median duration of follow-up was 3.5 years. Liver disease severity was classified as absent-to-mild fibrosis (Metavir stage F0/F1), moderate fibrosis (F2), advanced fibrosis (F3), or cirrhosis (F4).


  • Liver-related deaths accounted for 145 of the 670 total deaths in the study population, or 21.6% -- the second most common cause after AIDS-related deaths (24.2%).
  • The overall mortality rate was 42 deaths per 1000 person-years, and the liver-related death rate was 9 per 1000 person-years.
  • Liver-related death peaked in the 35-45 year age group, while overall mortality peaked among those age 55 and older.
  • Liver-related death occurred almost exclusively among people with at least moderate fibrosis at baseline.
  • In an adjusted model, independent risk factors for liver-related death included:

o   Stage F4 cirrhosis: hazard ratio (HR) 6.3 vs stage F0/F1, or 6-fold higher;

o   Stage F2/F3 fibrosis: HR 2.5 vs stage F0/F1;

o   Hepatitis B triple infection: HR 2.2;

o   35-45 year age group: HR 1.6;

o   HIV-positive for more than 10 years: HR 1.95 vs <2 years;

o   Lower current CD4 T-cell count: HR 0.8 per doubling;

o   Lower nadir (lowest-ever) CD4 count.

  • At all fibrosis stages, the risk of liver-related death rose as CD4 counts fell.
  • The 5-year probability of liver-related death was low in people with stage F0/F1 fibrosis (2.2%), but substantial in those with stage F2/F3 fibrosis (10.3%) or stage F4 cirrhosis (14.0%).

"Treatment with DAAs should be prioritized for those with at least F2 fibrosis," the study authors recommended. "Early initiation of combination ART [antiretroviral therapy] with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of liver-related death and the need for HCV treatment."

These findings indicate that coinfected people with moderate liver damage can benefit from hepatitis C treatment before they progress to advanced disease. While the researchers recommend prompt ART as a way to delay the need for hepatitis C treatment, a growing number of experts think everyone should be eligible for interferon-free therapy regardless of the extent of liver damage.



D Grint, L Peters, JK Rockstroh, et al Liver-related death among HIV/hepatitis C virus-co-infected individuals: implications for the era of directly acting antivirals. AIDS 29(10):1205-1215. June 19, 2015.