The Risk of Hepatocellular Carcinoma Among Individuals With
Acquired Immunodeficiency Syndrome in the United States
Vikrant V. Sahasrabuddhe, MBBS, DrPH, Meredith S. Shiels, PhD, MHS,
Katherine A. McGlynn, PhD, MPH1; and Eric A. Engels, MD, MPH
BACKGROUND: Hepatocellular carcinoma (HCC) is a concern among individuals with human immunodeficiency virus (HIV) infection
and acquired immunodeficiency syndrome (AIDS). METHODS: The authors analyzed population-based registry linkage data from the
US HIV/AIDS Cancer Match Study (1980-2009) to examine the risk and trends of HCC among individuals with AIDS. Standardized
incidence ratios (SIRs) were used to measure HCC risk relative to the general population, and Poisson regression was used to calcu-
late incidence rate ratios (RR) comparing incidence among individuals with AIDS. People with AIDS were categorized according to
their HIV risk group into high and low hepatitis C virus (HCV) prevalence groups based on their HIV transmission risk category.
RESULTS: Among 615,150 individuals with AIDS, HCC risk was elevated almost 4 times compared with the risk in the general popula-
tion (N ¼ 366; SIR, 3.8; 95% confidence interval, 3.5-4.3). Although HCC incidence increased steadily across calendar periods (Ptrend<
.0001; adjusted for sex and age), the excess risk in individuals with AIDS compared with the general population remained somewhat
constant (SIRs range, 3.5-3.9) between the monotherapy/dual therapy era (1990-1995) and the recent highly active antiretroviral ther-
apy era (2001-2009). In a multivariate model adjusting for sex, race/ethnicity, and attained calendar period, HCC incidence increased
with advancing age (Ptrend< .0001) and was associated with HIV risk groups with a known higher prevalence of HCV (adjusted RR,
2.2; 95% confidence interval, 1.8-2.8). CONCLUSIONS: HCC incidence in individuals with AIDS has increased over time despite
improved HIV treatment regimens, likely reflecting prolonged survival with chronic liver disease. The high incidence in older adults
suggests that this cancer will increase in importance with aging of the HIV-infected population. Cancer 2012;118:6226-33. Published
2012 by the American Cancer Society*.
KEYWORDS: hepatocellular carcinoma, human immunodeficiency virus, acquired immunodeficiency syndrome, epidemiology,
hepatitis C virus.
Hepatocellular carcinoma (HCC) is characterized by aggressive growth, frequent metastases, and recurrences after treat-
ment, and it is a major source of cancer-related morbidity and mortality.1HCC arises as a long-term sequela of chronic
liver disease and cirrhosis, frequently as a result of persistent inflammation associated with chronic hepatitis B virus
(HBV) and/or hepatitis C virus (HCV) infections. HCC is of special concern in individuals who are living with human
immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) because of frequent HBV and HCV
coinfection and accelerated progression of viral hepatitis to chronic liver disease and cirrhosis.2-6Excessive alcohol con-
sumption, obesity, diabetes, and nonalcoholic steatohepatitis (NASH) are other risk factors for chronic liver disease and
HCCthat haveahigher orincreasingburdenamongHIV-infectedpopulations.7-9
The introduction of highly active antiretroviral therapy (HAART) in 1996 led to a dramatic decline among HIV-
infected individuals in the risk of Kaposi sarcoma and non-Hodgkin lymphoma, two AIDS-defining cancers with viral
etiologies. In the era of widespread HAART use, non-AIDS–defining cancers (which include HCC) are now as common
as AIDS-defining cancers among individuals with AIDS in the United States.10HAART would be expected to improve
immune control of HBV and HCV, thereby minimizing liver damage and reducing the risk of HCC. Alternatively, HCC
DOI: 10.1002/cncr.27694, Received: March 5, 2012; Revised: May 2, 2012; Accepted: May 8, 2012, Published online June 26, 2012 in Wiley Online Library
Corresponding author: Vikrant V. Sahasrabuddhe, MBBS, DrPH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive
Boulevard, EPS 5032, Rockville, MD 20852; Fax: (301) 402-0916; firstname.lastname@example.org
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland
The first 2 authors contributed equally to this work.
The authors thank the HIV/AIDS and cancer registry staff in the following states and metropolitan areas for contributing data to the study: 14 registries for data
on individuals with AIDS (the state registries of California, Colorado, Connecticut, Florida, Georgia, Illinois, Maryland, Massachusetts, Michigan, New Jersey, and
Texas; and registries in the metropolitan areas of New York, NY; Seattle, WA; and Washington, DC) and 12 registries for data on individuals with HIV infection in
the absence of AIDS (the state registries of Colorado, Connecticut, Florida, Georgia, Illinois, Maryland, Michigan, New Jersey, and Texas; and registries in the met-
ropolitan areas of Los Angeles, CA; Seattle, WA; and Washington, DC). The authors also thank Tim McNeel (Information Management Systems) for database
*This article is US Government work and, as such, is in the public domain in the United States of America.
December 15, 2012
human immunodeficiency virus and the role of hepatitis C or B vi-
rus infection. JAMA. 2000;283:74-80.
39. Tarwater PM, Mellors J, Gore ME, et al. Methods to assess popula-
tion effectivenessof therapies
virus incident and prevalent cohorts. Am J Epidemiol. 2001;154:
40. Park LS, Tate JP, Justice AC, et al. FIB-4 index is associated with
hepatocellular carcinoma risk in HIV-infected patients. Cancer Epi-
demiol Biomarkers Prev. 2011;20:2512-2517.
41. Mehta SH, Buckle GC. Assessment of liver disease (noninvasive
methods). Curr Opin HIV AIDS. 2011;6:465-471.
in human immunodeficiency
42. Cooper C, Kanters S, Klein M, et al. Liver transplant outcomes in
HIV-infected patients: a systematic review and meta-analysis with
synthetic cohort. AIDS. 2011;25:777-786.
43. Poordad F, Khungar V. Emerging therapeutic options in hepatitis
C virus infection. Am J Manag Care. 2011;17(suppl 4):S123-S130.
44. Fleming CA, Craven DE, Thornton D, Tumilty S, Nunes D. Hep-
atitis C virus and human immunodeficiency virus coinfection in an
urban population: low eligibility for interferon treatment. Clin Infect
45. Mehta SH, Lucas GM, Mirel LB, et al. Limited effectiveness of antiviral treat-
Hepatocellular Carcinoma and AIDS/Sahasrabuddhe et al
December 15, 2012