Departments of Infectious Diseases, Peking University First Hospital, NO.8, Xishiku Street, Xicheng District, Beijing 100034, China.
Department of Gastroenterology, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing 100038, China.
Dis Markers. 2020 Oct 1;2020:8539804. doi: 10.1155/2020/8539804. eCollection 2020.
The success of direct-acting antivirals (DAAs) against hepatitis C virus is a major breakthrough in hepatology. Previous studies have shown that chitinase 3-like protein 1 (CHI3L1) was a marker for staging of liver fibrosis caused by HCV. In this investigation, we used CHI3L1 as a surrogate marker to compare dynamic hepatic fibrosis variations following the elimination of HCV among cases receiving sofosbuvir (SOF)-based regimens and pegylated interferon/ribavirin (PR) treatments.
The study enrolled 105 patients, including 46 SOF-based regimens treated patients, 34 PR-experienced patients, and 25 untreated patients. Serum samples and clinical data were obtained at the baseline, the end of treatment, and at weeks 24 and 48 after treatments.
First, we found that serum level of CHI3L1 correlated moderately but significantly with LSM ( = 0.615, < 0.001) at the baseline, and diagnosed liver cirrhosis at baseline with high accuracy (AUC = 0.939) by ROC analysis. So we explored CHI3L1 as a sensitive biomarker to monitor the regression of liver fibrosis after HCV eradication. We found that the serum CHI3L1 level of CHC cases receiving SOF-based regimen treatments was markedly reduced immediately after treatment compared with that at the baseline (123.79 (118.55) vs. 118.20 (103.68), = 0.001). For cases undergoing PR treatment, the serum CHI3L1 decreased significantly at week 24 posttreatment compared with that at the baseline (69.98 (51.44) vs 89.15 (110.59), = 0.016). For the untreated cirrhotic patients, CHI3L1 levels increased at week 96 follow-up compared with that at the baseline (194.73 (172.46) vs. 89.50 (242.97), = 0.048), reflecting continued worsening of liver fibrosis.
CHI3L1 is suggested to be the sensitive marker to monitor fibrosis variations in weeks during treatments and after achieving SVR. It has the potential to allow the identification of early treatment failure for a timely switch to alternative treatment and to allow monitoring progression of fibrosis as a risk factor for liver cirrhosis.
直接作用抗病毒药物（DAAs）治疗丙型肝炎病毒的成功是肝病学的重大突破。先前的研究表明，几丁质酶 3 样蛋白 1（CHI3L1）是丙型肝炎引起的肝纤维化分期的标志物。在这项研究中，我们使用 CHI3L1 作为替代标志物，比较了接受基于索非布韦（SOF）的方案和聚乙二醇化干扰素/利巴韦林（PR）治疗的丙型肝炎病毒消除后动态肝纤维化变化。
该研究纳入了 105 例患者，包括 46 例接受基于 SOF 的方案治疗的患者、34 例 PR 治疗经验患者和 25 例未治疗患者。在基线、治疗结束时以及治疗后 24 周和 48 周时采集血清样本和临床数据。
首先，我们发现血清 CHI3L1 水平与 LSM 中度但显著相关（ = 0.615， < 0.001），并通过 ROC 分析以高准确度（AUC = 0.939）诊断基线时的肝硬化。因此，我们探索了 CHI3L1 作为监测丙型肝炎病毒清除后肝纤维化消退的敏感生物标志物。我们发现，接受 SOF 为基础方案治疗的 CHC 患者的血清 CHI3L1 水平在治疗后立即显著降低，与基线相比（123.79（118.55）vs. 118.20（103.68）， = 0.001）。对于接受 PR 治疗的患者，与基线相比，治疗后第 24 周时血清 CHI3L1 显著降低（69.98（51.44）vs 89.15（110.59）， = 0.016）。对于未治疗的肝硬化患者，与基线相比，第 96 周随访时 CHI3L1 水平升高（194.73（172.46）vs. 89.50（242.97）， = 0.048），反映出肝纤维化持续恶化。
提示 CHI3L1 是监测治疗期间和 SVR 后几周纤维化变化的敏感标志物。它有可能识别早期治疗失败，以便及时切换到替代治疗，并监测纤维化进展作为肝硬化的一个危险因素。
