Recommendations for Women With Chronic Hepatitis C
Recommendations for Women With Chronic Hepatitis C
Since the implementation of blood product screening, injection drug use (IDU) has become the most common mode of HCV acquisition. Sex does not affect the risk of acquiring HCV. Although women in the United States historically have demonstrated a lower prevalence of HCV infection, their sex likely reflected their lower rate of IDU because sex differences in HCV prevalence are not seen in other cultures. 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. Female injection drug users also exhibit higher rates of HCV infection than their male counterparts, a difference that is related to behavior rather than biology: Female injection drug users frequently share injection equipment and engage in unsafe sex practices, including having intercourse with people with whom they also inject drugs.
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. 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. 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; however, even when controlling for the IL-28B genotype, women remain more likely than men to spontaneously clear HCV infection.
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. 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. Male sex was identified as an independent risk factor for developing hepatocellular carcinoma in several studies. 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. Animal models suggest that estrogen suppresses hepatic fibrosis, and a recent in vitro study proposed that estrogen inhibits the production of HCV virions. Multiparous women exhibit lower stages of fibrosis than nulliparous women, and fibrosis progression accelerates after menopause. In observational studies, women who received hormone therapy (HT) appeared to have a slower progression to fibrosis; 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.
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. Sex does not affect the risk of acquiring HCV. Although women in the United States historically have demonstrated a lower prevalence of HCV infection, their sex likely reflected their lower rate of IDU because sex differences in HCV prevalence are not seen in other cultures. 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. Female injection drug users also exhibit higher rates of HCV infection than their male counterparts, a difference that is related to behavior rather than biology: Female injection drug users frequently share injection equipment and engage in unsafe sex practices, including having intercourse with people with whom they also inject drugs.
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. 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. 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; however, even when controlling for the IL-28B genotype, women remain more likely than men to spontaneously clear HCV infection.
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. 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. Male sex was identified as an independent risk factor for developing hepatocellular carcinoma in several studies. 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. Animal models suggest that estrogen suppresses hepatic fibrosis, and a recent in vitro study proposed that estrogen inhibits the production of HCV virions. Multiparous women exhibit lower stages of fibrosis than nulliparous women, and fibrosis progression accelerates after menopause. In observational studies, women who received hormone therapy (HT) appeared to have a slower progression to fibrosis; 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.
