Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis

Objectives:To estimate stage-specific transition probabilities in individuals coinfected with HIV and hepatitis C virus (HCV), to examine the effect of covariates on these rates, and to investigate the effect of HIV on HCV-related cirrhosis in the era of highly active antiretroviral therapy (HAART). Design:Systematic review of natural history studies among HCV-infected individuals. Methods:Markov maximum likelihood estimation method was used to estimate stage-specific transition probabilities. A meta-analysis was performed to obtain pooled transition probabilities, and a meta-regression to investigate the impact of covariates on these rates. Risk of cirrhosis between individuals monoinfected with HCV and coinfected with HIV/HCV were compared by HAART status. Results:The estimated mean (95% confidence intervals) annual transition probabilities of 3567 individuals coinfected with HIV/HCV (n = 17 studies) were as follows: fibrosis stage (F) F0 → F1 0.122 (0.098–0.153); F1 → F2 0.115 (0.095–0.140); F2 → F3 0.124 (0.097–0.159); and F3 → F4 0.115 (0.098–0.135) units/year. The prevalence of cirrhosis after 20 and 30 years of HCV infection was 21% (16–28%) and 49% (40–59%), respectively. Longer duration of HCV infection was significantly associated with slower rate of fibrosis progression. The overall rate ratio of cirrhosis between individuals coinfected with HIV/HCV and monoinfected with HCV (n = 27 studies) was 2.1 (1.5–3.0), 2.5 (1.8–3.4) in the non-HAART group, and 1.7 (1.1–2.8) in the HAART group. Conclusion:The rate of fibrosis progression among individuals coinfected with HIV/HCV appears constant. Our results confirm that chronic hepatitis C outcomes are worse among coinfected individuals. Over the period studied, HAART did not appear to fully correct the adverse effect of HIV infection on HCV prognosis.

[1]  Christopher M. Taylor,et al.  Impact of human immunodeficiency virus (HIV) infection on the progression of liver fibrosis in hepatitis C virus infected patients , 2003, Gut.

[2]  S. Pol,et al.  Natural history and predictors of severity of chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection. , 2006, Journal of hepatology.

[3]  U. Spengler,et al.  Liver histopathology in patients with concurrent chronic hepatitis C and HIV infection , 1997, Virchows Archiv.

[4]  D. Neau,et al.  Intrahepatic HCV RNA loads in 37 HIV‐HCV co‐infected patients with controlled HIV infection , 2002, Journal of medical virology.

[5]  S. Govindarajan,et al.  Utility of a discriminant score for diagnosing advanced fibrosis or cirrhosis in patients with chronic hepatitis C virus infection. , 1997, The American journal of gastroenterology.

[6]  R. Chaisson,et al.  Hepatotoxicity associated with nevirapine or efavirenz‐containing antiretroviral therapy: Role of hepatitis C and B infections , 2002, Hepatology.

[7]  C. Katlama,et al.  Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients , 1999, Hepatology.

[8]  A. Lazzarin,et al.  Liver Fibrosis in HIV-Positive Patients With Hepatitis C Virus: Role of Persistently Normal Alanine Aminotransferase Levels , 2006, Journal of acquired immune deficiency syndromes.

[9]  P. Bedossa,et al.  Natural history of liver fibrosis progression in patients with chronic hepatitis C , 1997, The Lancet.

[10]  J. Kaldor,et al.  Estimating progression to cirrhosis in chronic hepatitis C virus infection , 2001, Hepatology.

[11]  D. Costagliola,et al.  Impact of early-untreated HIV infection on chronic hepatitis C in intravenous drug users: a case–control study , 2001, AIDS.

[12]  P. Scheuer,et al.  Classification of chronic viral hepatitis: a need for reassessment. , 1991, Journal of hepatology.

[13]  F. Rosendaal,et al.  The natural history of chronic hepatitis C in haemophiliacs , 1996, British journal of haematology.

[14]  J. Macías,et al.  Prevalence of non-significant liver fibrosis and rate of fibrosis progression in HIV/hepatitis C virus- co-infected patients: still a role for liver biopsy? , 2004, AIDS.

[15]  A. Mocroft,et al.  Is there evidence for an increase in the death rate from liver-related disease in patients with HIV? , 2005, AIDS.

[16]  Y. Allory,et al.  Impact of human immunodeficiency virus infection on the histological features of chronic hepatitis C: a case-control study. The MULTIVIRC group. , 2000, Human pathology.

[17]  F. Carnot,et al.  Predictive factors for development of cirrhosis in parenterally acquired chronic hepatitis C: a comparison between immunocompetent and immunocompromised patients. , 1998, Journal of hepatology.

[18]  D. Ouzan,et al.  Impact of antiretroviral treatment on progression of hepatic fibrosis in HIV/hepatitis C virus co-infected patients , 2004, AIDS.

[19]  J. Macías,et al.  Low-level liver enzyme elevations during HAART are not associated with liver fibrosis progression among HIV/HCV-coinfected patients. , 2006, The Journal of antimicrobial chemotherapy.

[20]  F. Carnot,et al.  Retrospective analysis of the impact of HIV infection and alcohol use on chronic hepatitis C in a large cohort of drug users. , 1998, Journal of hepatology.

[21]  Richard D Moore,et al.  The effect of antiretroviral therapy on liver disease among adults with HIV and hepatitis C coinfection , 2005, Hepatology.

[22]  H. Margolis,et al.  Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease , 1998 .

[23]  P. Marcellin,et al.  The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: A long‐term retrospective cohort study , 2001, Hepatology.

[24]  D. Dieterich,et al.  Intrahepatic CD4+ Cell Depletion in Hepatitis C Virus/HIV–Coinfected Patients , 2004, Journal of acquired immune deficiency syndromes.

[25]  R. Roldán,et al.  Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  G. Satten,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. , 1998, The New England journal of medicine.

[27]  A. Wohl,et al.  Survival in patients with HIV infection and viral hepatitis B or C: a cohort study , 2004, AIDS.

[28]  H. Boshuizen,et al.  Multiple imputation of missing blood pressure covariates in survival analysis. , 1999, Statistics in medicine.

[29]  M. Leal,et al.  Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. , 1997, Journal of hepatology.

[30]  D. Thomas,et al.  Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  C. Katlama,et al.  Serum biochemical markers accurately predict liver fibrosis in HIV and hepatitis C virus co-infected patients , 2003, AIDS.

[32]  A. Rodger,et al.  Assessment of Long‐Term Outcomes of Community‐Acquired Hepatitis C Infection in a Cohort With Sera Stored From 1971 to 1975 , 2000, Hepatology.

[33]  D. Jolley,et al.  Assessment of long‐term outcomes of hepatitis C virus infection in a cohort of patients with acute hepatitis in 1971–1975: Results of a pilot study , 1999, Journal of gastroenterology and hepatology.

[34]  D. Thomas.  Hepatitis C and human immunodeficiency virus infection , 2002, Hepatology.

[35]  V. Soriano,et al.  Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis C , 2001, American Journal of Gastroenterology.

[36]  M. Carrieri,et al.  Factors associated with liver biopsy performance in HCV-HIV coinfected injecting drug users with HCV viremia: Results from a five-year longitudinal assessment , 2004, Journal of Urban Health.

[37]  J. Rodríguez-Orengo,et al.  Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy. , 2006, Journal of hepatology.

[38]  G. Sirera,et al.  Time on antiretroviral therapy is a protective factor for liver fibrosis in HIV and hepatitis C virus (HCV) co‐infected patients , 2003, Journal of viral hepatitis.

[39]  T. Heeren,et al.  Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[40]  D. Snydman,et al.  Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[41]  D. Vlahov,et al.  The natural history of hepatitis C virus infection: host, viral, and environmental factors. , 2000, JAMA.

[42]  J. Rodríguez-Orengo,et al.  Progression to Cirrhosis in Latinos With Chronic Hepatitis C: Differences in Puerto Ricans With and Without Human Immunodeficiency Virus Coinfection and Along Gender , 2006, Journal of clinical gastroenterology.

[43]  C. Tsoukas,et al.  Hepatitis C virus is related to progressive liver disease in human immunodeficiency virus-positive hemophiliacs and should be treated as an opportunistic infection. , 1999, The Journal of infectious diseases.

[44]  F. Schmidt.  Meta-Analysis , 2008 .

[45]  D. Grobbee,et al.  Comparison of methods of handling missing data in individual patient data meta-analyses: an empirical example on antibiotics in children with acute otitis media. , 2007, American journal of epidemiology.

[46]  G. Lüchters,et al.  Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection , 2003, The Lancet.

[47]  Peter J. Richardson,et al.  Cirrhosis and hepatocellular carcinoma in HIV-infected veterans with and without the hepatitis C virus: a cohort study, 1992-2001. , 2004, Archives of internal medicine.

[48]  Paul Landais,et al.  Meta-regression detected associations between heterogeneous treatment effects and study-level, but not patient-level, factors. , 2004, Journal of clinical epidemiology.

[49]  C. Katlama,et al.  Factors affecting liver fibrosis in human immunodeficiency virus–and hepatitis C virus–coinfected patients: Impact of protease inhibitor therapy , 2001, Hepatology.

[50]  J. Macías,et al.  Increased hepatocyte fas expression and apoptosis in HIV and hepatitis C virus coinfection. , 2005, The Journal of infectious diseases.

[51]  K. Ishak,et al.  Histological grading and staging of chronic hepatitis. , 1995 .

[52]  J. Macías,et al.  Insulin resistance is not associated with liver fibrosis progression in HIV/hepatitis C virus‐coinfected patients , 2006, Journal of viral hepatitis.

[53]  J. Rodríguez-Baño,et al.  Clinical progression of hepatitis C virus–related chronic liver disease in human immunodeficiency virus–infected patients undergoing highly active antiretroviral therapy , 2007, Hepatology.

[54]  M. Bonacini.  Retrospective analysis of the impact of HIV infection and alcohol use on chronic hepatitis C in a large cohort of drug users. , 1999, Journal of hepatology.

[55]  Bruno Galperim,et al.  Impact of human immunodeficiency virus infection in patients infected with the hepatitis C virus , 2007, Liver international : official journal of the International Association for the Study of the Liver.

[56]  J. J. de la Cruz,et al.  Incidence and predictors of severe liver fibrosis in human immunodeficiency virus-infected patients with chronic hepatitis C: a European collaborative study. , 2004, Clinical Infectious Diseases.

[57]  J. Hoofnagle,et al.  Classification of chronic hepatitis: Diagnosis, grading and staging , 1994, Hepatology.

[58]  M. Vidal,et al.  T-Cell Surface CCR5 Density Is Not Correlated With Hepatitis Severity in Hepatitis C Virus/HIV-Coinfected Individuals: Implications for the Therapeutic Use of CCR5 Antagonists , 2005, Journal of acquired immune deficiency syndromes.

[59]  M. Krajden,et al.  Hepatitis C virus infection in patients infected with the human immunodeficiency virus. , 1993, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[60]  B. Edlin,et al.  HIV/Hepatitis C Virus-Coinfected Patients With Normal Alanine Aminotransferase Levels , 2006, Journal of acquired immune deficiency syndromes.

[61]  J. Goedert,et al.  Natural history of hepatitis C virus infection in multitransfused hemophiliacs: effect of coinfection with human immunodeficiency virus. The Multicenter Hemophilia Cohort Study. , 1993, Journal of acquired immune deficiency syndromes.

[62]  Theo Stijnen,et al.  Advanced methods in meta‐analysis: multivariate approach and meta‐regression , 2002, Statistics in medicine.

[63]  G. Kanel,et al.  Do type and duration of antiretroviral therapy attenuate liver fibrosis in HIV-hepatitis C virus-coinfected patients? , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[64]  M. Krahn,et al.  Improving the accuracy of long‐term prognostic estimates in hepatitis C virus infection , 2004, Journal of viral hepatitis.

[65]  C. Quereda,et al.  The role of liver biopsy in the management of chronic hepatitis C in patients infected with the human immunodeficiency virus. , 2004, Human pathology.

[66]  C. Sabin,et al.  The progression of HCV‐associated liver disease in a cohort of haemophilic patients , 1994, British journal of haematology.

[67]  A. Mocroft,et al.  Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. , 2005, The Journal of infectious diseases.

[68]  F. Carneiro,et al.  Impact of peginterferon alpha-2b and ribavirin treatment on liver tissue in patients with HCV or HCV-HIV co-infection. , 2007, The Journal of infection.

[69]  Neil Kaplowitz,et al.  Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis , 1981, Hepatology.

[70]  L. Bolondi,et al.  What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy. , 1997, Journal of hepatology.

[71]  J. Torre-Cisneros,et al.  Incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among HIV-infected patients with chronic hepatitis C. , 2006, The Journal of antimicrobial chemotherapy.

[72]  P. Kissinger,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. , 1998, The New England journal of medicine.

[73]  S. Kakar,et al.  Hepatic steatosis in HIV/hepatitis C coinfection: Prevalence and significance compared with hepatitis C monoinfection , 2005, Hepatology.

[74]  J. Macías,et al.  Prediction of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients by simple non-invasive indexes , 2005, Gut.

[75]  Valeer J Desmet,et al.  Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis [Hepatology 1981;1:431-435]. , 2003, Journal of hepatology.

[76]  S. Thompson,et al.  How should meta‐regression analyses be undertaken and interpreted? , 2002, Statistics in medicine.

[77]  S. Belle,et al.  Impact of human immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection. , 2001, The Journal of infectious diseases.

[78]  J. Macías,et al.  Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine , 2004, AIDS.

[79]  E. Bini,et al.  Impact of human immunodeficiency virus infection on the prevalence and severity of steatosis in patients with chronic hepatitis C virus infection. , 2006, Journal of hepatology.

[80]  J. Cosín,et al.  Liver biopsy findings for HIV-infected patients with chronic hepatitis C and persistently normal levels of alanine aminotransferase. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[81]  Donato,et al.  Hepatitis C is more severe in drug users with human immunodeficiency virus infection , 2000, Journal of viral hepatitis.

[82]  H J Alter,et al.  An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. , 1990, Science.

[83]  M. Leal,et al.  Influence of human immunodeficiency virus type 1 infection on the natural course of chronic parenterally acquired Hepatitis C , 1995, European Journal of Clinical Microbiology and Infectious Diseases.