Uzma Sarwar MD
Faculty Peer Reviewed
With advancement in therapy, life expectancy has significantly increased among HIV-infected patients, and patients are now more likely to succumb to chronic disease processes. At present, approximately one third of deaths in HIV patients are related to liver disease, which has become the leading cause of death amongst HIV patients. The risk of death from liver disease in HIV patients is inversely related to their CD4 count. Infection with hepatitis C virus (HCV) accounts for the bulk of this burden, reflecting the fact that it shares a route of transmission with HIV, intravenous drug use, with lower rates of transmission via the sexual route and with vertical transmission. However, it should be noted that the risk of sexual and vertical transmission of HCV are increased in patients infected with HIV. The prevalence of HCV among HIV infected patients can range from 30-80%, varying by geographic region and route of transmission.
In addition to being directly hepatotoxic, HCV also may indirectly cause liver damage by increasing the hepatotoxicity of anti-retroviral therapy. A prospective cohort study of 184 HIV/HCV co-infected patients identified concomitant alcohol use, increasing age, HCV genotype 3 and CD4<200 as risk factors associated with faster progression. Additional reports have identified an increased incidence of hepatocellular carcinoma amongst HIV/HCV co-infected patients.
Before considering treatment for HIV-HCV co-infected patients, infection should be confirmed by quantifying HCV RNA levels in patients with positive serologies against HCV. Additional tests should include liver function tests and CD4 cell counts. For these patients clinicians should have a lower threshold for performing a liver biopsy even if the labwork does not identify a transaminitis, as HIV-HCV co-infected patients can have a progression of disease irrespective of laboratory abnormalities. Histology will help in determining the progression of disease in these patients and help guide management. If there is minimal damage noted on liver biopsy, treatment may be deferred with a liver biopsy repeated in three years. Signs of activity or fibrosis on biopsy should prompt consideration of treatment. However it is still a matter of debate whether to treat HIV or HCV first. Although there are no clear guidelines for therapy, the consensus is that treatment for HCV should be considered first if the patient has a stable CD4 count greater than 300cells/mm. If the patient has more advanced HIV disease, HAART should be instituted first before treatment for HCV to increase likelihood of successful HCV response.
Once the decision has been made to proceed with treatment, subcutaneous pegylated interferon(IFN) and oral ribavarin is typically used. Several clinical trials have shown that pegylated IFN therapy is superior to the standard IFN and can be dosed weekly, rather than thrice weekly. Therapy is typically continued for forty eight weeks, though it may be shortened to 24 weeks in those infected with genotypes 2 or 3. Regardless, the sustained virologic response (SVR), defined as the attainment of an undetectable HCV plasma viral load six months after cessation of therapy, is significantly lower among the HIV co-infected patients compared to HCV mono-infected individuals.
The risk of adverse side effects with this therapy is high and includes flu-like symptoms, weight loss, anemia, thrombocytopnenia, an increase in mitochondrial toxicity in patients receiving nucleoside analogues and, lastly, opportunistic infections.
Dr. Sarwar is a third year internal medicine resident at NYU Medical Center.
Reviewed by Michael Poles MD, Associate Editor, Clinical Correlations, Assistant Professor of Medicine, NYU Division of Gastroenterology
References
1. Kozei, M, Peters, Marion G. Viral Hepatitis in HIV infection. NEJM 2007; 356; 14:1445-54
2. Sulkowski M, Mehta, S, Torbenson, M, Higgins, Y, Brinkley, S, deOca, R, Moore, R, Afdhal, N, Thomas, D.Rapid fibrosis progression among HIV/Hepatitis C virus co-infected adults, AIDS 2007;21(16):2209-16
3. Merchante N, Giron-Gonzalez, J, Torre, C, Julian, G, Jose, A, Ana, R, Josefa, CL, Pilar, L, Fernando, MS, Carmen, MJ, Pineda, J Survival and prognostic factors of HIV infected patients with HCV related end stage liver disease, AIDS 2006;20 (1):49-57
4. Sanchez-Conde M, Berenguer, J, Miralles, P, Alvarez, F, Carlos Lopez, J, Cosin J, Pilar, C, Ramirez, M, Gutierrez, I, Alvarez, E. Liver biopsy findings for HIV infected patients with chronic hepatitis C and persistently normal levels of alanine aminotransferases, Clin Infect Dis 2006 Sep 1; 43(5):640-4
5. Thio, CL, Seaberg, EC, Skolasky, R, Phair, J, Visscher, B, Munoz, A, Thomas, DL. HIV-1, hepatitis B virus and risk of liver related mortality in the Multicenter Cohort study. Lancet 2002 Dec 14; 360 (9349):1921-6
6. Roland, ME, Perspective:Solid organ transplantation in HIV infected patients in potent anti-retroviral therapy era. Topics in HIV medicine; 12(3):73-6
7. Schreibman, I, Gaynor, J, Jayaweera, D, Pyrsopoulos, N, Weppler, D, Tzakis, A, Schiff, E, Regev, A.Outcomes after orthotropic liver transplantation in fifteen HIV infected patients. Transplantation 2007; 84(6):697-704
8. Powderly, William. Antiretroviral therapy in patients with Hepatitis and HIV: weighing risks and benefits, CID 2004; 38(Suppl2):109-113
9. Vennarecci, G, Ettore, G, Antonini, R, Santoro, L, Perracchio, G, Visco, G, Santoro, E. Liver Transplantation in HIV positive patients. Transplantation Proceedings 2007; 39:1936-38
10. Hadler, SC, Judson, FN, O’Malley PM, Altman, N, Penley, K, Buchbinder, S, Schable, C, Coleman, PJ, Ostrow, DN, Francis, DP. Outcome of hepatitis B virus infection in homosexual men and its relation to prior HIV infection. J Infect Dis. 1991 Mar; 163(3):454-9
11. Wilcox, CM. Evaluation of the HIV infected patient with hepatobilliary complaints. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2008.
12. McGovern, BH. Management and treatment of hepatitis C in the HIV infected patient. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2008
13. Kasper, D, Braunwald, E, Hauser, S, Longo, D, Jameson, JL, Fauci, A. Harrison’s Principles of Internal Medicine. Seventeenth ed. McGraw Hill medical publishing division; 2008