Liang X, Xie Q, Tan D, Ning Q, Niu J, Bai X, Chen S, Cheng J, Yu Y, Wang H, Xu M, Shi G, Wan M, Chen X, Tang H, Sheng J, Dou X, Shi J, Ren H, Wang M, Zhang H, Gao Z, Chen C, Ma H, Chen Y, Fan R, Sun J, Jia J, Hou J
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Infectious Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China.
J Viral Hepat. 2018 Mar;25(3):296-305. doi: 10.1111/jvh.12814. Epub 2017 Nov 29.
Liver biopsy is not routinely performed in treated chronic hepatitis B. Liver stiffness measurement has been validated for noninvasive liver fibrosis assessment in pretreatment chronic hepatitis B but has not been assessed for fibrosis monitoring during antiviral therapy. Liver stiffness was systemically monitored by Fibroscan every 6 months in a cohort of patients with hepatitis B receiving antiviral therapy and compared with liver biopsies at baseline and week 104. A total of 534 hepatitis B e antigen-positive treatment-naive patients receiving telbivudine-based therapy with qualified liver stiffness measurement at baseline and week 104 were analyzed, 164 of which had adequate paired liver biopsies. Liver stiffness decreased rapidly (-2.2 kPa/24 weeks) in parallel with alanine aminotransferase (ALT) from 8.6 (2.6-49.5) kPa at baseline to 6.1 (2.2-37.4) kPa at week 24. Interestingly, liver stiffness decreased slowly (-0.3 kPa/24 weeks) but continually from week 24 to week 104 (6.1 vs 5.3 kPa, P < .001) while ALT levels remained stable within the normal range. More importantly, liver stiffness declined significantly irrespective of baseline ALT levels and liver necroinflammation grades. From baseline to week 104, the proportion of patients with no or mild fibrosis (Ishak, 0-2) increased from 74.4% (122/164) to 93.9% (154/164). Multivariate analysis revealed that percentage decline of 52-week liver stiffness from baseline was independently associated with 104-week liver fibrosis regression (odds ratio, 3.742; P = .016). Early decline of 52-week liver stiffness from baseline may reflect the remission of both liver inflammation and fibrosis and was predictive of 104-week fibrosis regression in treated patients with chronic hepatitis B.
在接受治疗的慢性乙型肝炎患者中，通常不进行肝活检。肝脏硬度测量已被验证可用于慢性乙型肝炎治疗前的非侵入性肝纤维化评估，但尚未用于抗病毒治疗期间的纤维化监测。在一组接受抗病毒治疗的乙型肝炎患者中，每6个月通过Fibroscan系统监测肝脏硬度，并与基线和第104周时的肝活检结果进行比较。对534例初治的乙肝e抗原阳性患者进行分析，这些患者接受基于替比夫定的治疗，且在基线和第104周时进行了合格的肝脏硬度测量，其中164例有足够的配对肝活检样本。肝脏硬度从基线时的8.6（2.6 - 49.5）kPa迅速下降（-2.2 kPa/24周），与丙氨酸氨基转移酶（ALT）水平平行，至第24周时降至6.1（2.2 - 37.4）kPa。有趣的是，从第24周到第104周，肝脏硬度下降缓慢（-0.3 kPa/24周）但持续下降（6.1 kPa对5.3 kPa，P <.001），而ALT水平在正常范围内保持稳定。更重要的是，无论基线ALT水平和肝脏坏死炎症分级如何，肝脏硬度均显著下降。从基线到第104周，无纤维化或轻度纤维化（Ishak分级，0 - 2级）患者的比例从74.4%（122/164）增加到93.9%（154/164）。多变量分析显示，52周时肝脏硬度相对于基线的下降百分比与104周时肝纤维化的消退独立相关（优势比，3.742；P = 0.016）。52周时肝脏硬度相对于基线的早期下降可能反映了肝脏炎症和纤维化的缓解，并可预测慢性乙型肝炎治疗患者104周时的纤维化消退情况。
