ALANINE AMINOTRANSFERASE NORMALIZATION DURING ENTECAVIR TREATMENT AND THE HEPATOCELLULAR CARCINOMA RISK IN HEPATITIS B VIRUS-ASSOCIATED CIRRHOSIS

초록

Background and Aims: Sustained abnormal serum alanine aminotransferase (ALT) levels can increase the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. This study is aimed to confirm the impact of abnormal ALT levels (>30 IU/L) on HCC risk in patients with hepatitis B virus (HBV) associated-cirrhosis during entecavir (ETV) treatment. Methods: A total of 578 treatment-naïve patients with HBV-associated cirrhosis were treated with ETV for more than 1 year. Serum ALT and HBV DNA levels were measured at 3 time points (baseline, 6, and 12 months after ETV treatment) and subjected to risk factor analysis. Results: Mean age was 51 ± 9 years and 366(63.3%) were male. The median follow up period was 43(12–98) months. At baseline, 303 patients (52.4%) were seropositive for HBeAg. The numbers of patients of Child-Pugh class A, B, and C were 417(72.1%), 140 (24.2%), and 21(3.6%), respectively. The number of patients with undetectable HBV DNA (<120 copies/mL) at 6 months or at 12 months were 333(57.6%) and 455(78.7%), respectively. The number of patients with normal ALT at 6 months and at 12 months were 258(44.6%) and 313(54.2%), respectively. Of the 578 patients with HBV-associated cirrhosis, 81 patients (14%) developed HCC during follow-up. Cumulative incidences of HCC at 1, 3, 5, and 7 years were 0.3%, 8.5%, 19.5%, and 30.6%, respectively. Univariate Cox-regression analysis showed that older age, abnormal ALT at 6 months or 12 months, and lower platelet count were significant risk factors of HCC. However, gender, HBeAg positivity, abnormal ALT and HBV DNA levels at baseline, detectable HBV DNA at 6 months or 12 months were not risk factors. Multivariate analysis showed that older age (HR: 1.062, 95% CI: 1.035–1.089, p < 0.001), abnormal ALT at 12 months (HR: 1.876, 95% CI: 1.198–2.937, p = 0.006) and lower platelet count (HR: 0.993, 95% CI: 0.987–0.999, p = 0.034) were the risk factors of HCC. Figure shows the cumulative incidences of HCC according to the patterns of ALT change at 6 and 12 months after ETV treatment. Cumulative incidences of HCC were significantly lower in group with sustained normal ALT at 6 months and 12 months than other groups. Conclusions: Abnormal serum ALT levels during ETV treatment are significant risk factor of HCC. Therefore, ALT should be rapidly and sustained normalized to minimize the risk of HCC development in patients with HBV-associated cirrhosis.