进行性胆汁淤积和相关的硬化性胆管炎是慢性肝病患者 COVID-19 的常见并发症。

Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID-19 in patients with chronic liver disease.

机构信息

Division of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.

Vienna Hepatic Hemodynamic LabDivision of Gastroenterology and HepatologyDepartment of Medicine IIIMedical University of ViennaViennaAustria.

出版信息

Hepatology. 2022 Dec;76(6):1563-1575. doi: 10.1002/hep.32582. Epub 2022 Jun 18.

DOI:10.1002/hep.32582

PMID:35596929

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9347407/

Abstract

BACKGROUND AND AIMS

Cholestasis is associated with disease severity and worse outcome in COVID-19. Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been described.

APPROACH AND RESULTS

Hospitalized patients with COVID-19 between 03/2020 and 07/2021 were included. Patients were stratified as having (i) no chronic liver disease (CLD), (ii) non-advanced CLD (non-ACLD), or (iii) advanced CLD (ACLD). Patients with CLD and non-COVID-19 pneumonia were matched to patients with CLD and COVID-19 as a control cohort. Liver chemistries before (Pre) and at first, second, and third blood withdrawal after SARS-CoV-2 infection (T1-T3) and at last available time point (last) were recorded. A total of 496 patients were included. In total, 13.1% (n = 65) had CLD (non-ACLD: 70.8%; ACLD: 29.2%); the predominant etiology was NAFLD/NASH (60.0%). COVID-19-related liver injury was more common among patients with CLD (24.6% vs. 10.6%; p = 0.001). After SARS-CoV-2 infection, patients with CLD exhibited progressive cholestasis with persistently increasing levels of alkaline phosphatase (Pre: 91.0 vs. T1: 121.0 vs. last: 175.0 U/L; p < 0.001) and gamma-glutamyl transferase (Pre: 95.0 vs. T1: 135.0 vs. last: 202.0 U/L; p = 0.001). A total of 23.1% of patients with CLD (n = 15/65) developed cholestatic liver failure (cholestasis plus bilirubin ≥6 mg/dl) during COVID-19, and 15.4% of patients (n = 10/65) developed SSC. SSC was significantly more frequent among patients with CLD and COVID-19 than in patients with CLD and non-COVID-19 pneumonia (p = 0.040). COVID-19-associated SSC occurred predominantly in patients with NAFLD/NASH and metabolic risk factors. A total of 26.3% (n = 5/19) of patients with ACLD experienced hepatic decompensation after SARS-CoV-2 infection.

CONCLUSIONS

About 20% of patients with CLD develop progressive cholestasis after SARS-CoV-2 infection. Patients with NAFLD/NASH and metabolic risk factors are at particular risk for developing cholestatic liver failure and/or SSC after COVID-19.

摘要

背景与目的

胆汁淤积与 COVID-19 患者的疾病严重程度和预后不良相关。有研究描述了严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染后发生的继发性硬化性胆管炎（SSC）病例。

方法和结果

本研究纳入了 2020 年 3 月至 2021 年 7 月期间住院的 COVID-19 患者。患者分为无慢性肝病（CLD）（i）、非进展性 CLD（非 ACLD）（ii）或进展性 CLD（ACLD）（iii）。将 CLD 合并 COVID-19 的患者与 CLD 合并非 COVID-19 肺炎的患者相匹配作为对照队列。记录 SARS-CoV-2 感染前（Pre）和感染后第 1、2、3 次采血（T1-T3）以及最后一次可用时间点（last）的肝生化指标。共纳入 496 例患者。共有 13.1%（n=65）患有 CLD（非 ACLD：70.8%；ACLD：29.2%）；主要病因是非酒精性脂肪性肝病/非酒精性脂肪性肝炎（NAFLD/NASH）（60.0%）。与无 CLD 的患者相比，CLD 患者的 COVID-19 相关肝损伤更为常见（24.6% vs. 10.6%；p=0.001）。在 SARS-CoV-2 感染后，CLD 患者出现进行性胆汁淤积，碱性磷酸酶（Pre：91.0 vs. T1：121.0 vs. last：175.0 U/L；p<0.001）和γ-谷氨酰转移酶（Pre：95.0 vs. T1：135.0 vs. last：202.0 U/L；p=0.001）持续升高。在 COVID-19 期间，共有 23.1%（n=15/65）的 CLD 患者（n=15/65）发展为胆汁淤积性肝衰竭（胆汁淤积合并胆红素≥6mg/dl），15.4%（n=10/65）的患者发展为 SSC。与 CLD 合并非 COVID-19 肺炎的患者相比，CLD 合并 COVID-19 的患者 SSC 更为常见（p=0.040）。COVID-19 相关的 SSC 主要发生在患有 NAFLD/NASH 和代谢危险因素的患者中。在 SARS-CoV-2 感染后，共有 26.3%（n=5/19）的 ACLD 患者出现肝功能失代偿。