Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with transient elastography-defined subclinical cirrhosis

Early detection of liver cirrhosis in its subclinical stage is of paramount importance to identify high-risk individuals for developing hepatocellular carcinoma (HCC). This study investigated whether transient elastography (TE) can identify patients with subclinical cirrhosis (SCC) who are at increased risk of developing HCC among chronic hepatitis B (CHB) patients without clinical evidence of cirrhosis. A total of 2,876 CHB patients without clinical cirrhosis who received TE examinations between April 2006 and December 2012 were enrolled in this prospective study. SCC was defined as a nonclinical cirrhosis, but with a liver stiffness (LS) value 13 kilopascals (kPa). Mean age of the study population was 46.1 years, and male gender was predominant (n=1,775; 61.7%). Mean LS value was 7.9 kPa, and SCC was identified in 285 (9.9%) patients. During the median follow-up period of 48.9 months (range, 6.6-96.2), HCC developed in 16 patients (13.3 per 1,000 person-years) in the SCC group and 36 (3.4 per 1,000 person-years) in the non-SCC group. Cumulative incidence rate of HCC in the SCC group was significantly higher than that in the non-SCC group (P<0.001, log-rank test). On multivariate analysis, SCC was independently associated with a risk of developing HCC, regardless of antiviral therapy (without antiviral therapy: hazard ratio [HR]: 4.680; 95% confidence interval [CI]: 1.187-18.441; P=0.027; with antiviral therapy: HR, 3.344; 95% CI: 1.526-7.328; P=0.003). Conclusion: TE can identify CHB patients with SCC who are at increased risk of developing HCC, even when cirrhosis is not clinically apparent. (Hepatology 2015;61:1851-1859)