Pre-S Mutation Is a Significant Risk Factor for Hepatocellular Carcinoma Development: A Long-Term Retrospective Cohort Study

Several cross-sectional studies have shown an association between pre-S mutation and hepatocellular carcinoma (HCC). We aim to verify whether pre-S mutation represents a risk for HCC development in a longitudinal way. A total of 195 patients with chronic HBV infection [age: 43.7 +/- A 10.8 years, males: 141 (72.3 %), genotype C: 195 (100 %), hepatitis B e antigen (HBeAg) positive: 109 (55.9 %), cirrhosis: 79 (40.5 %), and pre-S mutation positive: 44 (22.6 %)] were followed up for a median of 7.2 years (range 1.0-7.8 years). HCC developed in 24 patients during follow-up. The 1-, 3-, and 5-year cumulative incidences of HCC were 0.5, 4.9, and 10.4 %, respectively. Patients with pre-S mutation had significantly higher 5-year cumulative incidences of HCC than those without (26.5 vs. 5.7 %, p < 0.001) and showed higher hazard ratio for HCC [3.04 (95 % CI 1.24-7.42), p = 0.015, adjusted for age, gender, HBeAg, cirrhosis and baseline HBV DNA level]. Notably, in patients aged a parts per thousand yen50 years, the 5-year cumulative incidences of HCC in patients with pre-S mutation were considerably high (58.3 %), compared to those without (16.1 %, p < 0.001). Patients with pre-S mutations had higher incidence of HCC during follow-up, especially in aged patients. Patients with pre-S mutations, especially older ones, may require careful attention to HCC development.