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

Abstract

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.

External Validation of the FSAC Model Using On-Therapy Changes in Noninvasive Fibrosis Markers in Patients with Chronic Hepatitis B: A Multicenter Study

“…Furthermore, along with the dynamic changes in APRI or FIB-4 index during AVT, assessment of transient elastography, which proved to have higher predictive efficacy after 12 months as an easier predictive algorithm, might give useful information. Actually, when we tried to stratify the risk of HCC development by the on-treatment LS value (cutoff value: 6.4 kPa) from the subgroup with available paired TE results (n = 1102, 36.4%) [18], we confirmed their significant association (p < 0.001). Hence, further large-scale study with the serial follow-up of transient elastography during long-term AVT should be required.…”

“…Meanwhile, other HCC prediction models using fibrosis parameters assessed during long-term AVT (i.e., modified REACH-B, CAGE-B, and SAGE-B scores) have also been introduced with promising results [16,17]. Most recently, given that baseline fibrosis and/or necro-inflammation can be partially modified or regressed through long-term AVT [18][19][20], Nam et al [21] recently suggested a novel HCC prediction model using fibrosis markers assessed at dual time points, named the Fibrosis marker response, Sex, Age, and Cirrhosis (FSAC) score. The model incorporates on-therapy changes, including a fibrosis index based on four factors (FIB-4) [22,23] and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) [24] at 12 months, as well as sex, age, and cirrhosis.…”