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Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma

Clifford, Gary Ma; Rickenbach, Martinb; Polesel, Jerryc; Dal Maso, Luiginoc; Steffen, Ingridd; Ledergerber, Brunoe; Rauch, Andrif; Probst-Hensch, Nicole Mg; Bouchardy, Christineh; Levi, Fabioi,j; Franceschi, Silviaa; and the Swiss HIV Cohort Study

doi: 10.1097/QAD.0b013e32831103ad
Clinical Science

Objective: To investigate HIV-related immunodeficiency as a risk factor for hepatocellular carcinoma (HCC) among persons infected with HIV, while controlling for the effect of frequent coinfection with hepatitis C and B viruses.

Design: A case–control study nested in the Swiss HIV Cohort Study.

Methods: Twenty-six HCC patients were identified in the Swiss HIV Cohort Study or through linkage with Swiss Cancer Registries, and were individually matched to 251 controls according to Swiss HIV Cohort Study centre, sex, HIV-transmission category, age and year at enrolment. Odds ratios and corresponding confidence intervals were estimated by conditional logistic regression.

Results: All HCC patients were positive for hepatitis B surface antigen or antibodies against hepatitis C virus. HCC patients included 14 injection drug users (three positive for hepatitis B surface antigen and 13 for antibodies against hepatitis C virus) and 12 men having sex with men/heterosexual/other (11 positive for hepatitis B surface antigen, three for antibodies against hepatitis C virus), revealing a strong relationship between HIV transmission route and hepatitis viral type. Latest CD4+ cell count [Odds ratio (OR) per 100 cells/μl decrease = 1.33, 95% confidence interval (CI) 1.06–1.68] and CD4+ cell count percentage (OR per 10% decrease = 1.65, 95% CI 1.01–2.71) were significantly associated with HCC. The effects of CD4+ cell count were concentrated among men having sex with men/heterosexual/other rather than injecting drug users. Highly active antiretroviral therapy use was not significantly associated with HCC risk (OR for ever versus never = 0.59, 95% confidence interval 0.18–1.91).

Conclusion: Lower CD4+ cell counts increased the risk for HCC among persons infected with HIV, an effect that was particularly evident for hepatitis B virus-related HCC arising in non-injecting drug users.

aInternational Agency for Research on Cancer, Lyon, France

bCoordination and Data Center, Swiss HIV Cohort Study, Lausanne, Switzerland

cEpidemiology and Biostatistics Unit, Aviano Cancer Center, Aviano, Italy

dInstitute for Medical Microbiology, University of Basel, Basel

eDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich

fDepartment of Infectious Diseases, University Hospital Inselspital, and University of Bern, Bern

gCancer Registry of the Canton of Zurich, Zurich

hCancer Registry of the Canton of Geneva, Geneva

iCancer Registry of the Canton of Vaud, Lausanne

jCancer Registry of the Canton of Neuchâtel, Neuchâtel, Switzerland.

*The members of the Swiss HIV Cohort Study are M. Battegay, E. Bernasconi, J. Böni, HC Bucher, Ph. Bürgisser, A. Calmy, S. Cattacin, M. Cavassini, R. Dubs, M. Egger, L. Elzi, M. Fischer, M. Flepp, A. Fontana, P. Francioli (President of the SHCS, Centre Hospitalier Universitaire Vaudois, CH-1011- Lausanne), H. Furrer (Chairman of the Clinical and Laboratory Committee), C. Fux, M. Gorgievski, H. Günthard (Chairman of the Scientific Board), H. Hirsch, B. Hirschel, I. Hösli, Ch. Kahlert, L. Kaiser, U. Karrer, C. Kind, Th. Klimkait, B. Ledergerber, G. Martinetti, B. Martinez, N. Müller, D. Nadal, M. Opravil, F. Paccaud, G. Pantaleo, A. Rauch, S. Regenass, M. Rickenbach (Head of Data Center), C. Rudin (Chairman of the Mother & Child Substudy), P. Schmid, D. Schultze, J. Schüpbach, R. Speck, P. Taffé, A. Telenti, A. Trkola, P. Vernazza, R. Weber, S. Yerly.

Received 07 April, 2008

Revised 10 July, 2008

Accepted 17 July, 2008

Correspondence to Clifford, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon cedex 08, France. Tel: +33 4 72 73 84 25; fax: +33 4 72 73 83 45; e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.