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HCC risk increases in men with HBV, multiple metabolic risk factors

Men aged 40 to 65 years with chronic hepatitis B and a high burden of metabolic risk factors had increased risk for hepatocellular carcinoma, especially is they were smokers, according to a recently published study.

“If our findings are confirmed, then the results of this study suggest that a substantial fraction of HBV-related HCC cases, especially those with low viral loads, might be prevented by management of metabolic risk factors and cessation of smoking,” Ming-Whei Yu, PhD, from the National Taiwan University, and colleagues wrote.

The study comprised 1,690 men who were HBsAg-positive and a control cohort of 1,289 men negative for both HBsAg and hepatitis C. In the HBsAg-positive cohort, median age was 48.4 years (range, 43.8-56.8 years), median BMI was 23.7 kg/m² (range, 22.1-25.4 kg/m²) and 31.6% were obese. The researchers reported that the control cohort had similar characteristics.

Compared with controls, patients with HBV had lower prevalence of impaired fasting glucose, hypertriglyceridemia, hypercholesterolemia and high blood pressure, even after adjusting for age and alanine aminotransferase levels (P < .05), and a higher proportion of history of chronic liver disease and prevalence of elevated liver enzymes (P < .0001).

In the HBV cohort, 158 developed HCC during follow-up. Overall, 305 patients died; 126 died of liver-related disease, of which HCC caused 94 deaths. The cumulative incidence of HCC (P = .0468) and liver-related death (P = .0068) increased as metabolic risk-factor sum increased.

Results of a 10-year cumulative analysis showed that HCC incidence increased from 4.83% among patients with an optimal risk-factor profile to 13.6% among those with three or more metabolic risk factors, of whom 92.5% were obese and 45.3% had diabetes. After adjusting for age, smoking status, alcohol consumption and family history of HCC, patients with three or more metabolic risk factors still had a significantly higher risk for HCC (HR = 2.32; 95% CI, 1.18-4.54).

In the control cohort, by comparison, there were five cases of HCC during follow-up and 135 deaths, of which three followed HCC development and one followed cirrhosis development. The risk for liver-related events also increased in control participants who had three or more metabolic risk factors (HR = 8.57; 95% CI, 1.18-62.15).

The researchers observed a significant increase in risk for HCC among smokers with three or more metabolic risk factors (HR = 5.06; 95% CI, 2.23-11.47), compared with both smokers with fewer metabolic risk factors and nonsmokers with any number of metabolic risk factors. However, the risk for HCC among those with three or more metabolic risk factors tended to decrease after 5 years of smoking cessation.

“This study demonstrated that metabolic risk factor burden was a significant independent predictor of HBV-related HCC, even after accounting for major viral factors and other recognized risk factors,” the researchers concluded. “Thus, despite the majority of HBV-related HCC cases accounted for by high viral load, our data suggest that there exists some cases of HBV-related HCC arising in the background of metabolic syndrome, which represents a distinct clinicopathological entity that has not yet achieved adequate attention in clinical practice and disease prevention.” – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.