Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China.
Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Hepatol Int. 2024 Jun;18(3):904-916. doi: 10.1007/s12072-024-10643-z. Epub 2024 Apr 2.
Evidence has proven that liver fibrosis or even cirrhosis can be reversed by anti-HBV treatment. However, the difference of fibrosis regression rates in short-term and long-term antiviral therapy remain unclear. Therefore, we aimed to identify the dynamic changes in fibrosis regression rate in patients with three-time liver biopsies during 5 years antiviral therapy.
CHB patients with three times of liver biopsies (baseline, after 1.5-year and 5-year antiviral therapy) from a prospective cohort were enrolled. All patients were biopsy-proved Ishak stage ≥ 3 at baseline (n = 92). Fibrosis regression was defined as Ishak stage decreased ≥ 1 or predominantly regressive categorized by P-I-R score.
Totals of 65.2% (60/92) and 80.4% (74/92) patients attained fibrosis regression after 1.5-year and 5-year therapy, respectively. Median HBV DNA level declined from 6.5 log IU/ml (baseline) to 0 log IU/ml (1.5 years and 5 years, P < 0.001). The mean level of Ishak fibrosis stage in all patients decreased from stage 4.1 (baseline) to 3.7 (1.5 years) then 3.2 (5 years). Fibrosis regression rates were 0.27 stage/year between baseline to year 1.5 and 0.14 stage/year between year 1.5 and year 5. Furthermore, for patients who attained fibrosis regression after 5-year antiviral therapy, the two-phase regression rates were 0.39 stage/year (0 year-1.5 years) and 0.20 stage/year (1.5 years-5 years). This two-phase feature of regression rate was further confirmed by fully-quantification assessment of liver fibrosis based on SHG/TPEF.
During the 5 years of long-term antiviral treatment, liver fibrosis rapidly regresses in the first 1.5 years before slowing down in the following 3.5 years.
有证据表明，通过抗乙型肝炎病毒（HBV）治疗可以使肝纤维化甚至肝硬化逆转。然而，短期和长期抗病毒治疗的纤维化消退率差异尚不清楚。因此，我们旨在确定在 5 年抗病毒治疗期间进行三次肝活检的患者中纤维化消退率的动态变化。
本研究纳入了前瞻性队列中三次肝活检（基线、1.5 年和 5 年抗病毒治疗后）的 CHB 患者。所有患者基线时均经活检证实为 Ishak 分期≥3（n=92）。纤维化消退定义为 Ishak 分期降低≥1 或根据 P-I-R 评分主要为退行性。
分别有 65.2%（60/92）和 80.4%（74/92）的患者在 1.5 年和 5 年治疗后达到纤维化消退。HBV DNA 水平中位数从基线的 6.5 log IU/ml 下降至 0 log IU/ml（1.5 年和 5 年，P<0.001）。所有患者的 Ishak 纤维化分期平均值从基线的 4.1 期下降至 1.5 年的 3.7 期，然后再下降至 5 年的 3.2 期。纤维化消退率在基线至 1.5 年期间为 0.27 期/年，在 1.5 年至 5 年期间为 0.14 期/年。此外，对于在 5 年抗病毒治疗后达到纤维化消退的患者，两阶段消退率分别为 0.39 期/年（0 年-1.5 年）和 0.20 期/年（1.5 年-5 年）。基于 SHG/TPEF 的肝纤维化全定量评估进一步证实了这种消退率的两阶段特征。
在 5 年的长期抗病毒治疗中，肝纤维化在最初的 1.5 年内迅速消退，然后在接下来的 3.5 年内缓慢消退。
