HCC predictors identified for chronic HBV patients with newly diagnosed cirrhosis

By Shreeya Nanda

In patients with chronic hepatitis B virus (HBV) infection who have been newly diagnosed with cirrhosis, the risk of hepatocellular carcinoma (HCC) development can be ascertained using several clinical and molecular factors, study findings indicate.

Lead author Chien-Jen Chen (Academia Sinica, Taipei, Taiwan) and team explain that previous studies assessing HCC risk in cirrhotic HBV patients have not taken into account the onset date of cirrhosis, which may have introduced bias into the hazard ratios for the identified risk predictors.

The current study followed-up a Taiwanese community-based cohort to identify chronic HBV patients with a new diagnosis of cirrhosis, and then followed-up that subgroup to evaluate HCC incidence and associated risk factors. Participants were assumed to be treatment-naïve as reimbursement for antiviral therapy was not available in Taiwan during the study period (follow-up period from 1991 or 1992 to 2004).

Among 301 participants with newly diagnosed cirrhosis, 76 developed HCC in 2462 person-years after the diagnosis of cirrhosis, equating to an average incidence of 3.1% per year. The 15-year cumulative risk from the onset of cirrhosis was 39.8%, while the lifetime risk was 78.5%.

Using multivariate analysis, Chen et al identified several factors significantly associated with the risk of HCC development. These included serum alanine aminotransferase levels of at least 45 U/L (vs <15 U/L) and alpha-fetoprotein levels of at least 20 ng/mL (vs <10 ng/mL) at cirrhosis diagnosis, which significantly predicted HCC risk with hazard ratios (HRs) of 3.68 (p=0.0010) and 3.52 (p=0.0003), respectively.

Increasing age at the diagnosis of cirrhosis was also a risk factor, such that individuals aged 60 years and above and between 50 and 59 years had significant 14.26- (p=0.0005)and 12.36-fold (p=0.0007) elevated risks, respectively, relative to those in the 30 to 39 years age group.

Moreover, patients seropositive for hepatitis B e antigen (HBeAg) and those seronegative for HBeAg but with serum hepatitis B surface antigen (HBsAg) levels of at least 1000 IU/mL had a significantly higher likelihood of developing HCC compared with HBeAg-negative participants with HBsAg levels below 1000 IU/mL (HR=2.85, p=0.0015 and HR=2.64, p=0.0035, respectively).

Finally, carrying the AA or AG versus the GG genotype of the rs671 variant of the ALDH2 gene, known to affect alcohol metabolism in Asian patients, significantly reduced the HCC risk by 65% (p<0.0001), report the researchers.

A model incorporating these parameters predicted the risk of HCC in this population with a "satisfactory" 76% accuracy, they write in the Journal of Gastroenterology and Hepatology.

The team concludes: "[H]ealthcare providers or [chronic HBV] patients may utilize this risk prediction model to determine the long-term HCC risk and clinical management of cirrhotic patients, and to assess the efficacy of antiviral therapy in preventing HCC among cirrhotic patients."

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