Cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) in patients with HIV/HCV co-infection. However, even among patients with cirrhosis, HCC risk is not uniform. Indeed, most HIV/HCV co-infected patients with cirrhosis do not progress to HCC. We sought to determine risk factors for progression from cirrhosis to HCC in HIV/HCV co-infected patients.
We used the Veterans Affairs HIV and HCV Clinical Case Registries and identified HIV/HCV co-infected patients that were diagnosed with cirrhosis (defined by ICD-9-CM codes [571.5, 571.6, and 571.2] or an aspartate aminotransferase to platelet ratio index >2) from 1999-2010. We excluded female veterans (due to small numbers; <2%), as well as patients lacking HCV RNA, follow-up CD4 count or HIV viral load information, and patients diagnosed with cirrhosis within 90 days of HIV diagnosis. The outcome was incident HCC as indicated by ICD-9-CM (155.0 without 155.1). Patients were censored at death, date of last health care encounter or 12/31/2010. We examined associations with age at HIV diagnosis, race/ethnicity, HCV genotype, and HIV-related (combination anti-retroviral therapy era of diagnosis, CD4 cell count, percent time with undetectable HIV viral load, and use of highly active anti-retroviral therapy [HAART]), clinical (ALT and Deyo without AIDS) and behavioral factors (alcohol use, smoking, hard-drug use). Cox proportional hazards analysis was used to estimate Hazard ratios (HR) and 95% confidence intervals (CI) for associations with HCC.
We included 2689 patients; the majority were aged >40y, African American, most recent CD4 count>200, and HCV genotype 1 or 4. Over a median follow-up of 5.0 (SD, 3.4) years, 88 patients (3.3%) developed HCC. In univariate analysis, HCC incidence varied by age at HIV diagnosis, race/ethnicity, ever HAART, alcohol use, and hard-drug use (all p<.10). Older age at HIV diagnosis (>50 vs. <40y; HR=2.19; 95%CI 1.02-4.70), Hispanic ethnicity (vs. non-Hispanic white; HR=2.46; 95%CI 1.05-5.76), and HCV genotype 1/4 (vs. HCV genotype 2/3; HR=1.95; 95%CI 1.06-3.57) were associated with higher risk of HCC in the multivariable model. Percent undetectable HIV viral load and CD4 count <200 (nadir or most recent) were not associated with HCC.
HCC is common in HIV/HCV co-infected patients with cirrhosis (3.3%) and risk varies by age, ethnicity and HCV genotype. If confirmed in other populations, these findings may lead to enhanced HCC prevention and surveillance efforts.