直接抗病毒药物诱导持续病毒学应答后，晚期纤维化慢性丙型肝炎患者存在持续性肝脏炎症。

Persistent liver inflammation in chronic hepatitis C patients with advanced fibrosis after direct-acting antivirals induced sustained virological response.

作者信息

Hsieh Yun-Cheng, Lee Kuei-Chuan, Su Chien-Wei, Lan Ken-Hsin, Huo Teh-Ia, Wang Yuan-Jen, Huang Hui-Chun, Lin Han-Chieh, Chu Chi-Jen, Huang Yi-Hsiang, Hou Ming-Chih

机构信息

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC.

出版信息

J Chin Med Assoc. 2021 May 1;84(5):472-477. doi: 10.1097/JCMA.0000000000000517.

DOI:10.1097/JCMA.0000000000000517

PMID:33742989

Abstract

BACKGROUND

Direct-acting antivirals (DAA) improve sustained virological response (SVR) rates with normalization of liver enzymes in patients with hepatitis C. However, liver inflammation may persist despite virus eradication. We aimed to investigate the rate and risk factors for persistent elevated aminotransferase levels in patients with advanced fibrosis after DAA-induced SVR.

METHODS

From January 2017 to April 2018, chronic hepatitis C patients with advanced fibrosis and SVR after DAA treatment at the Taipei Veterans General Hospital were prospectively enrolled. Persistent liver inflammation after SVR was defined as an increase in levels of alanine aminotransferase (ALT) (>40 U/L) at SVR12.

RESULTS

A total of 461 patients were included (57.9% females, mean age 64 years, 69.6% genotype 1b, 46.4% cirrhosis). At SVR12, there was a decline in ALT levels (90.5 ± 80.8 U/L to 25.3 ± 26.5 U/L) from baseline levels. Persistent liver inflammation at SVR12 was detected in 45 patients (9.8%). The presence of cirrhosis, markers of impaired liver functions, history of interferon-based therapy, steatosis, and elevated ALT levels at baseline was associated with persistent liver inflammation after SVR12. Results of multivariate analysis indicated that levels of baseline serum total bilirubin (odds ratio [OR]: 2.605, 95% CI: 1.158-5.858), international normalized ratio (OR: 14.389, 95% CI: 1.754-118.049), ALT (OR: 1.006, 95% CI: 1.003-1.009), and the presence of steatosis (OR: 3.635, 95% CI: 1.716-7.698) were independent predictors of persistent liver inflammation at SVR12.

CONCLUSION

Persistent liver inflammation is not uncommon in chronic hepatitis C patients with advanced fibrosis after DAA-induced SVR. It is associated with impaired baseline liver function and steatosis. Long-term follow-up is required to assess the implication of liver inflammation on disease progression.

摘要

背景

直接抗病毒药物（DAA）可提高丙型肝炎患者的持续病毒学应答（SVR）率，并使肝酶恢复正常。然而，尽管病毒已被清除，但肝脏炎症可能仍会持续存在。我们旨在调查DAA诱导SVR后晚期纤维化患者氨基转移酶水平持续升高的发生率及危险因素。

方法

2017年1月至2018年4月，前瞻性纳入台北荣民总医院接受DAA治疗后出现晚期纤维化且达到SVR的慢性丙型肝炎患者。SVR后持续性肝脏炎症定义为SVR12时丙氨酸氨基转移酶（ALT）水平升高（>40 U/L）。

结果

共纳入461例患者（女性占57.9%，平均年龄64岁，69.6%为基因1b型，46.4%为肝硬化）。在SVR12时，ALT水平从基线水平下降（90.5±80.8 U/L降至25.3±26.5 U/L）。45例患者（9.8%）在SVR12时检测到持续性肝脏炎症。肝硬化的存在、肝功能受损标志物、基于干扰素治疗的病史、脂肪变性以及基线时ALT水平升高与SVR12后持续性肝脏炎症相关。多因素分析结果表明，基线血清总胆红素水平（比值比[OR]：2.605，95%可信区间[CI]：1.158 - 5.858）、国际标准化比值（OR：14.389，95% CI：1.754 - 118.049）、ALT（OR：1.006，95% CI：1.003 - 1.009）以及脂肪变性的存在（OR：3.635，95% CI：1.716 - 7.698）是SVR12时持续性肝脏炎症的独立预测因素。