Lee Hye Won, Lee Hyun Woong, Lee Jae Seung, Roh Yun Ho, Lee Hyein, Kim Seung Up, Park Jun Yong, Kim Do Young, Ahn Sang Hoon, Kim Beom Kyung
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
J Hepatocell Carcinoma. 2021 May 25;8:467-476. doi: 10.2147/JHC.S300382. eCollection 2021.
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.
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.
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).
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.
慢性乙型肝炎长期抗病毒治疗(AVT)过程中纤维化标志物会发生动态变化。我们评估了治疗期间肝脏硬度(LS)相比于超声检查结果的预后价值,并确定了其最佳临界值。
在880例接受恩替卡韦或替诺福韦治疗≥2年的患者中评估肝细胞癌(HCC)的累积发生概率。使用瞬时弹性成像测量LS。
AVT≥2年后,超声检查显示肝硬化患者的比例从54.7%降至44.9%,平均LS从13.6 kPa降至8.2 kPa(均p<0.001)。然而,与AVT前超声检查显示的肝硬化情况(p<0.001)不同,AVT≥2年后的肝硬化情况并不能区分HCC风险(p=0.792)。使用Contal和O'Quigley方法,AVT前和治疗期间LS的最佳临界值分别选择为12.0 kPa和6.4 kPa,以成功区分HCC风险(均p<0.001)。然而,通过同时使用AVT前和治疗期间LS进行分层,最终根据治疗期间6.4 kPa的LS确定预后,而不考虑AVT前12.0 kPa的LS。对于接受长期AVT的慢性乙型肝炎患者,采用白种人建议的治疗期间12 kPa的LS,LS较高的患者比LS较低的患者更易发生HCC(p=0.017);然而,治疗期间LS为6.4 - 11.9 kPa和≥12.0 kPa的患者之间无显著差异(p=0.920)。
对于接受长期AVT的患者进行HCC风险分层时,治疗期间LS的临界值应降至6.4 kPa,这比12 kPa或超声检查显示的肝硬化更具预测性。需要进一步研究进行验证。