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

Hye Won Lee,1– 3,* Hyun Woong Lee,4,* Jae Seung Lee,1– 3 Yun Ho Roh,5 Hyein Lee,3 Seung Up Kim,1– 3 Jun Yong Park,1– 3 Do Young Kim,1– 3 Sang Hoon Ahn,1– 3 Beom Kyung Kim1– 3 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea; 4Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Beom Kyung KimDepartment of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun–Gu, Seoul, 03722, Republic of KoreaTel +82-2-2228-1930Fax +82-2-393-6884Email beomkkim@yuhs.acBackground: 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.Keywords: antiviral treatment, hepatitis B, liver stiffness, hepatocellular carcinoma