SEATTLE – Hepatocellular carcinoma (HCC) is on the rise in HIV-positive individuals, its incidence having quadrupled since 1996, and HIV-positive individuals have about a 300% increase risk of HCC, compared with the general population. However, more than 40% of patients with HIV who develop HCC have a Fibrosis-4 score (FIB-4) suggesting a lack of cirrhosis, according to a new retrospective analysis. By contrast, only about 13% of typical HCC patients have no cirrhosis.
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The study also revealed some of the risk factors associated with HCC in this population, including longer duration of HIV viremia and lower CD4 cell counts, as well as markers of metabolic syndrome. “There was some signal that perhaps other markers of metabolic syndrome, obesity and diabetes, were more prevalent in those [who developed HCC] without advanced fibrosis or cirrhosis, suggesting that there may be other underlying etiologies of liver disease that we should be wary of when evaluating somebody for their risk of HCC,” Jessie Torgersen, MD, said in an interview.
Dr. Torgersen is an instructor of medicine at the University of Pennsylvania, Philadelphia. She presented the study at the Conference on Retroviruses & Opportunistic Infections.
The results of the study are tantalizing, but not yet practice changing. “I don’t think we have enough information from this study to recommend a dramatic overhaul of the current HCC screening guidelines, but with the anticipated elimination of hepatitis C, I think the emergence of [metabolic factors and their] contributions to our HIV-positive population’s risk of HCC needs to be better understood. Hopefully this will serve as a first step in further understanding those risks,” Dr. Torgersen said.
She also hopes to get a better handle on the biological mechanisms that might drive HCC in the absence of cirrhosis. “While the mechanisms are unclear as to why HCC would develop in HIV-positive patients without cirrhosis, there are a lot of biologically plausible mechanisms that seem to make [sense],” said Dr. Torgersen. The team hopes to get a better understanding of those mechanisms in order to information evaluation and screening for HCC.
The researchers analyzed data from the Veterans Affairs Cancer Registry as well as EMRs for HIV-positive veterans across the United States. The study included 2,497 participants with a FIB-4 score greater than 3.25, and 29,836 with an FIB-4 score less than or equal to 3.25. At baseline, subjects with FIB-4 greater than 3.25 were more likely to have an alcohol-related diagnosis (47% vs. 29%), be positive for hepatitis C virus RNA (59% vs. 30%), be positive for the hepatitis B surface antigen (10% versus 5%), have HIV RNA greater than or equal to 500 copies/mL (63% vs. 56%), and to have a CD4+ cell count less than 200 cells/m3 (39% vs. 26%).
A total of 278 subjects were diagnosed with HCC; 43% had an FIB-4 less than or equal to 3.25. Among those 43%, more patients had a body mass index of 30 or higher (16% vs. 12%), had diabetes (31% vs. 25%), and tested positive for the hepatitis B surface antigen (26% vs. 17%).
Among subjects with FIB-4 less than or equal to 3.25, factors associated with greater HCC risk included higher HIV RNA level (hazard ratio, 1.24 per 1.0 log10 copies/mL), CD4+ cell count less than 200 cells/m3 (HR, 1.78), hepatitis C virus infection (HR, 6.32), and positive hepatitis B surface antigen (HR, 4.93).
Among subjects with FIB-4 greater than 3.25, increased HCC risk was associated with HCV infection (HR, 6.18) and positive hepatitis B surface antigen (HR, 2.12).
The study was funded by the National Institutes of Health. Dr. Torgersen reported no financial disclosures.
SOURCE: Torgersen J et al. CROI 2019, Abstract 90.