The Prognostic Role of On-Treatment Liver Stiffness for Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B.

Background Dynamic changes in fibrosis markers occur under long-term antiviral treatment (AVT) for chronic hepatitis B. We evaluated prognostic values of on-treatment liver stiffness (LS) compared to ultrasonography findings and determined its optimal cutoff. Methods The cumulative probability of hepatocellular carcinoma (HCC) was assessed among 880 patients receiving entecavir or tenofovir for ≥2 years. LS was measured using transient elastography. Results After ≥2 years' AVT, the proportion of patients with cirrhosis on ultrasonography decreased from 54.7% to 44.9% and the mean LS decreased from 13.6 to 8.2 kPa (both p<0.001). However, unlike cirrhosis on ultrasonography before AVT (p<0.001), that after ≥2 years' AVT did not discriminate HCC risk (p=0.792). Using the Contal and O'Quigley's method, pre-AVT and on-treatment LS of 12.0 and 6.4 kPa, respectively, were chosen as optimal cutoffs to successfully discriminate HCC risk (both p<0.001). However, through stratification using both pre-AVT and on-treatment LS, the prognosis was finally determined according to on-treatment LS of 6.4 kPa, regardless of pre-AVT LS of 12.0 kPa. Using on-treatment LS of 12 kPa suggested by Caucasians with CHB receiving long-term AVT, patients with higher LS were more likely to develop HCC than those with lower LS (p=0.017); however, there was no significant difference between those with on-treatment LS of 6.4-11.9 and ≥ 12.0 kPa (p=0.920). Conclusion For HCC risk stratification in patients receiving long-term AVT, on-treatment LS cutoff should be lowered to 6.4 kPa, which is more predictive than 12 kPa or cirrhosis on ultrasonography. Further studies are required for validation.