Understanding the mechanisms of fibrogenesis in HIV/HCV-coinfected patients: Implications for clinical practice

HIV/HCV coinfection is associated with accelerated progressive liver disease. Understanding the pathogenesis of liver fibrosis remains crucial to improving the global management of this patient population. This review will mainly focus on the mechanisms involved in the faster progression of liver fibrosis seen in HIV/HCV coinfection, which is caused by a multiplicity of complex factors including virus features, the immune system, interactions between viruses and the immune response, the direct effects of HIV on hepatocytes, fibrinogenetic/inflammatory mediators, microbial translocation, and metabolic abnormalities. The direct role of viruses as well as chronic inflammation, deterioration of immune status, and the harmful effect of antiretroviral agents may all concur to produce dyslipidemia and insulin resistance. Metabolic abnormalities play an important role in the genesis of hepatic steatosis, which is closely linked to liver fibrosis progression. There is also a link between immunologic and metabolic abnormalities: increased expression of leptin and reduced expression of adiponectin seems to be associated with advanced hepatic injury. New antifibrotic strategies are outlined. Ultimately, sustained virological response to hepatitis C therapy is associated with liver fibrosis regression in patients with HIV/HCV coinfection.