Women With Chronic Hepatitis C Virus Infection

Recommendations for Clinical Practice

Mary Jane Burton, MD; James B. Brock, MD; Stephen A. Geraci, MD


South Med J. 2013;106(7):422-426. 

In This Article

Prevalence and Natural History of HCV in Women

Since the implementation of blood product screening, injection drug use (IDU) has become the most common mode of HCV acquisition.[1] Sex does not affect the risk of acquiring HCV. Although women in the United States historically have demonstrated a lower prevalence of HCV infection,[3] their sex likely reflected their lower rate of IDU[4] because sex differences in HCV prevalence are not seen in other cultures.[5] In addition, a meta-analysis of 30 studies reported that female prison inmates are 40% more likely than are male prison inmates to be infected with HCV.[6] Female injection drug users also exhibit higher rates of HCV infection than their male counterparts,[7,8] a difference that is related to behavior rather than biology: Female injection drug users frequently share injection equipment and engage in unsafe sex practices,[7,9] including having intercourse with people with whom they also inject drugs.[10,11]

Although sex does not appear to affect the risk of HCV infection, it does influence its outcome. A systematic review of 31 longitudinal studies found that 40% of women versus 19% of men will resolve acute HCV infection.[12] Genome-wide association studies have reported that genetic variation surrounding the interleukin-28B (IL-28B) locus is associated with enhanced response to interferon-based therapies and spontaneous resolution of HCV infection.[13] A cohort study of Danish injection drug users noted that women with favorable IL-28B genotypes were six times as likely as women with unfavorable genotypes to spontaneously clear HCV infection;[14] however, even when controlling for the IL-28B genotype, women remain more likely than men to spontaneously clear HCV infection.[15]

Women also manifest slower progression to two major chronic HCV infection complications, cirrhosis and hepatocellular carcinoma. In a cohort of 376 Irish women chronically infected with HCV from contaminated anti-D immunoglobulin, only 1.9% had progressed to histological cirrhosis after a mean of 17 years following exposure.[16] The low rate of fibrosis progression was confirmed in a 25-year follow-up study of 167 women, of whom 1.2% developed histological cirrhosis.[17] Male sex was identified as an independent risk factor for developing hepatocellular carcinoma in several studies.[18,19] This sex-specific predilection for complications of liver disease is not completely understood. Some experts posit that higher estrogen states exert a protective effect on the liver.[20] Animal models suggest that estrogen suppresses hepatic fibrosis,[21–23] and a recent in vitro study proposed that estrogen inhibits the production of HCV virions.[24] Multiparous women exhibit lower stages of fibrosis than nulliparous women, and fibrosis progression accelerates after menopause.[25,26] In observational studies, women who received hormone therapy (HT) appeared to have a slower progression to fibrosis;[20] however, the benefits of HT in women with HCV have not been established. HT appears to be safe in women with liver disease when indicated for other reasons.[20]