Liver Fibrosis Tests Predict Mortality in HIV/HCV Coinfected Women


More advanced liver fibrosis, as diagnosed by 2 non-invasive biomarker tests, is associated with a higher risk of death for HIV positive women coinfected with hepatitis C virus (HCV), according to a report in the March 13, 2012, issue of AIDS.

Experts estimate that about one-third of people with HIV also have hepatitis C. On average, HIV/HCV coinfected people experience more rapid liver disease progression and do not respond as well to interferon-based hepatitis C therapy.

Over years or decades chronic hepatitis C can lead to serious liver damage including advanced fibrosis, cirrhosis (scarring), and hepatocellular carcinoma (a form of primary liver cancer). Hepatitis C treatment is recommended for people with progressive liver disease.

Liver biopsy is the "gold standard" for determining extent of fibrosis, but it is invasive and expensive, and therefore not well-suited for repeated assessments of fibrosis progression over time. Researchers have therefore studied a variety of non-invasive methods, including transient elastometry (FibroScan) and blood biomarkers.

Kiran Bambha from the University of California at San Francisco and colleagues evaluated the ability of 2 indirect biomarker indices of fibrosis to predict mortality among HCV/HIV coinfected participants in the Women's Interagency HIV Study (WIHS).

WIHS enrolled a total of 3 766 adult women living with or at high risk for HIV infection in 2 cohorts (1994-1995 and 2001-2002) at 6 clinical sites in the U.S. Overall, 32% of HIV positive participants were coinfected with HCV at study entry.

This analysis included 450 HCV/HIV coinfected WIHS women on combination antiretroviral therapy (ART). Only women older than 35 years (average 43 years) who had adequate available laboratory data were included. Nearly two-thirds were black and the median CD4 cell count was about 300 cells/mm3. Women with very high aspartate transaminase (AST) or alanine transaminase (ALT) levels at were excluded in an effort to rule out those with acute viral hepatitis, as were those with very low platelet counts.

Over a median follow-up period of 6.6 years the researchers looked at changes 2 non-invasive fibrosis scores:

  • APRI: AST-to-platelet ratio index;
  • FIB-4: an index calculated from AST, ALT, platelet count, and age.


  • 191 out of the 450 women died during follow-up.
  • Women with high APRI or FIB-4 scores indicating severe fibrosis had significantly increased risk of all-cause mortality compared to those with lower scores:
    • APRI: hazard ratio (HR) 2.78, or nearly 3 times higher risk;
    • FIB-4: HR 2.58, or about 2.5-fold higher risk.
  • Crude death rates increased with increasing extent of liver fibrosis according to FIB-4:
    • 34.8 per 1000 person-years for mild fibrosis;
    • 51.3 per 1000 person-years for moderate fibrosis;
    • 167.9 per 1000 person-years for severe fibrosis.
  • For all women, both APRI and FIB-4 index scores increased during the 5 years prior to death.
  • Fibrosis scores rose more rapidly (that is, had an increased slope) for women who died due to liver-related causes.

Based on these findings, the study authors concluded, "Both APRI and FIB-4 are independently associated with all-cause mortality in HCV/HIV coinfected women and may have clinical prognostic utility among women with HIV and HCV."

"Both fibrosis markers utilize standard laboratory values that are simple and regularly performed in clinical care of patients with HIV or HCV," they added in their discussion.

"Assessment of the degree of hepatic fibrosis carries important prognostic information and has therapeutic implications with respect to timing of HCV treatment and monitoring for evidence of complications of portal hypertension," they continued. "If women have no liver fibrosis, they may elect to await newer all oral HCV therapies, but if they have severe fibrosis (fibrosis stage 3-4) they should undergo current treatment for HCV."

"Our study is the first longitudinal study of noninvasive markers of fibrosis solely in women coinfected with HCV and HIV," the researchers concluded. "The fibrosis markers were predictive of all-cause mortality, but were abnormal some years before death and were higher in women dying a liver-related death. This suggests that these noninvasive markers can be of practical value in all women coinfected with HIV and HCV to determine whether liver disease is progressing and, if so, to reinforce the need for therapy for HCV."



K Bambha, C Pierce, C Cox, M Peters, et al. Assessing mortality in women with hepatitis C virus and human immunodeficiency virus using indirect markers of fibrosis. AIDS 26(5):599-607. March 13, 2012.