The HCV and HIV coinfected patient: What have we learned about pathophysiology?

Abstract

Hepatitis C virus (HCV) infection is an important problem in individuals who are also infected with HIV. HCV infection is very common in HIV-infected individuals, occurring in approximately one quarter to one third of this group, presumably as a consequence of shared routes of transmission related to virologic and pathogenic aspects of the viral infections. Although both are single-stranded RNA viruses and share similar epidemiologic properties, there are many important differences. Although the quantity of HIV RNA in plasma is an important prognostic determinant of HIV infection, this has not been shown with HCV. A direct relationship is apparent between HIV-related destruction of CD4 cells and the clinical consequences of the disease resulting from immunodeficiency. The pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much more complex. The hepatic stellate cell, the major producer of the extracellular matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is increasingly important in HIV-infected patients due to improved HIV-associated morbidity and mortality and due to the frequency with which HCV occurs in patients with HIV-HCV coinfection. Timing of treatment initiation, management of side effects, and possible effects of anti-HCV therapy on HIV are among the issues that need consideration. Also, because several issues concerning HCV are unique to coinfected patients, further research is needed to determine optimal management of HCV in this setting.

Human Immunodeficiency Virus and Hepatitis C Virus Coinfection: Epidemiology, Natural History, Therapeutic Options and Clinical Management

“…In the advanced stage of HIV disease, the increased production of fibrogenetic Th2-like cytokines and persistent activation of hepatic stellate cells may quicken the extracellular matrix protein deposition and the occurrence of liver fibrosis [46,55,56].…”

Clinical management of HIV/hepatitis C virus coinfection

“…Hepatitis C infection is caused by a single‐stranded RNA virus from the Flaviviridae family (Talal, Canchis, & Jacobson, 2002). HCV has been classified into at least six genotypes and more than 50 subtypes (Major & Feinstone, 1997).…”

“…To summarize, aminotransferase and HCV RNA levels have a poor correlation with the extent of histological disease (Talal et al, 2002), and despite sampling errors, liver biopsy is still the gold standard for grading and staging of the disease and determining the need and timing of therapy. Treatment should be aggressively pursued in those individuals with fibrosis of the liver.…”

“…The main targets of HCV are the hepatocytes and possibly B lymphocytes. The rapid replication and high mutation rate of HCV and its ability to inhibit innate interferon‐stimulated genes may be responsible for the evasion of the immune system and persistence of the infection resulting in chronic liver cell injury (Phillips & Brewer, 2003; Talal et al, 2002). HCV‐infected hepatocytes may produce as many as 10 trillion virions per day during the chronic phase of infection, which is greater than that seen with HIV (Zignego et al, 1995).…”

Integrating Hepatitis C Services into Existing HIV Services: The Experiences of a Sample of U.S. Drug Treatment Units

“…19,20 Coinfection of HCV and HIV is common, with HCV infection occurring in at least 25% of HIV seropositive patients and in the great majority of IDUs with HIV. 17,21,22 Patients coinfected with HIV and HCV have considerably greater morbidity that those with HCV alone; they are twice as likely to develop cirrhosis, and six times more likely to develop end stage liver disease. 23 In addition, the time to progression to cirrhosis for those with coinfection is often considerably shorter than for patients infected only with HCV.…”