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Insulin Resistance Quadruples Liver Cancer Risk in People With HIV/HCV
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51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago
Mark Mascolini
Insulin resistance independently quadrupled the risk of hepatocellular carcinoma in a French cohort of people with HIV, hepatitis C virus (HCV) infection, and cirrhosis [1]. Age over 50 and higher alpha-fetoprotein also independently raised the risk of liver cancer.
Hepatocellular carcinoma occurs at a younger age, is harder to treat, and has more severe outcomes in people coinfected with HIV and HCV than in those infected with HCV alone [2]. To identify factors associated with hepatocellular carcinoma risk in people with HIV and HCV, French researchers analyzed 247 of 1175 coinfected people in the ANRS CO13 HEPAVIH cohort. All cohort members in this analysis had histologically proved cirrhosis, or liver stiffness at or above 12.5 kPa on Fibroscan, or hepatic decompensation. No one had detectable hepatocellular carcinoma when follow-up began.
Through a median follow-up of 2.6 years (interquartile range [IQR] 1.7 to 3.5), hepatocellular carcinoma developed in 24 people (10%). The ANRS team had histologic proof of hepatocellular carcinoma in 5 of these 24 people and noninvasive indicators of liver cancer in the remaining 19. Liver cancer incidence was 3.6% after 1 year and 6.2% after 2 years, which the researchers noted is similar to incidence in HIV-negative people with HCV infection and cirrhosis.
Compared with people in whom liver cancer did not get diagnosed, at diagnosis those with liver cancer were older (49.2 versus 46.6, P = 0.06), included a higher proportion over 50 years old (41.7% versus 23.3%, P = 0.048), had a lower platelet count (105,000 versus 148,000 cells/mm3, P = 0.004), had higher alpha-fetoprotein levels (56.7 versus 15 ng/mL, P = 0.0004), and were more likely to have insulin resistance as indicated by a HOMA value above 3.8 (66.7% versus 35.3%, P = 0.016). Variables that did not differ between the cancer and no-cancer groups included nadir CD4 count, hepatitis B surface antigen positivity, duration of HCV infection, previous liver decompensation, and previous anti-HCV therapy.
Univariate analysis found a higher risk of hepatocellular carcinoma in older cohort members (risk ratio [RR] 1.8, P = 0.019) and in those with a HOMA above 3.8 (RR 3.6, P = 0.02), previous liver decompensation (RR 2.8, P = 0.02), higher alpha-fetoprotein (RR 1.9, P = 0.0003), lower platelet count, lower prothrombin level, and higher alkaline phosphatase. Having liver stiffness or type 2 diabetes did not discriminate between people with and without hepatocellular carcinoma.
Multivariate analysis identified independent associations between three factors and development of hepatocellular carcinoma:
-- Age over 50 tripled the risk of liver cancer: adjusted risk ratio [ARR] 3.3, 95% confidence interval [CI] .09 to 2.0, P = 0.04.
-- Insulin resistance indicated by a HOMA value above 3.8 almost quadrupled the risk of hepatocellular carcinoma: ARR 3.8, 95% CI 1.1 to 2.6, P = 0.02.
-- Every 100 ng/mL higher alpha-fetoprotein level raised the risk 10%: ARR 1.1, 95% CI 1.03 to 1.12, P = 0.0003.
The ANRS researchers suggested that the association with alpha-fetoprotein and hepatocellular carcinoma probably reflects subclinical tumors that cannot be diagnosed by ECHO scans. They proposed that any HIV/HCV-coinfected person with increasing alpha-fetoprotein should have an MRI scan.
The investigators also suggested that antiretroviral regimens less likely to promote insulin resistance "should probably be preferred in HIV/HCV-coinfected patients with cirrhosis."
References
1. Bani-Sadr F, Loko M, Winnock M, et al. Insulin resistance predicts hepatocarcinoma occurrence in HIV/HCV co-infected patients. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract H3-814.
2. MacDonald DC, Nelson M, Bower M, Powles T. Hepatocellular carcinoma, human immunodeficiency virus and viral hepatitis in the HAART era. World J Gastroenterol. 2008;14:1657-1663. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695905/?tool=pubmed.
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