Insights into the pathophysiology of liver disease in HCV/HIV: Does it end with HCV cure?

HCV-HIV coinfected patients exhibit rapid progression of liver damage relative to HCV monoinfected patients. The availability of new directly acting antiviral agents has dramatically improved outcomes for coinfected patients as sustained virologic response rates now exceed 95% and fibrosis-related parameters are improved. Nevertheless, coinfected patients still have a higher mortality risk and more severe hepatocellular carcinoma compared to HCV monoinfected patients, implying the existence of pathways unique to people living with HIV that continue to promote accelerated liver disease. In this article, we review the pathobiology of liver disease in HCV-HIV coinfected patients in the directly acting antiviral era and explore the mechanisms through which HIV itself induces liver damage. Since liver disease is one of the leading causes of non-AIDS-related mortality in HIV-positive patients, enhancing our understanding of HIV-associated fibrotic pathways will remain important for new diagnostic and therapeutic strategies to slow or reverse liver disease progression, even after HCV cure.