Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Microbial Interactions and Processes Research Group, Helmholtz Center for Infection Research, Braunschweig, Germany.
Hepatology. 2021 Jul;74(1):72-82. doi: 10.1002/hep.31700. Epub 2021 Jun 15.
It is well accepted that liver diseases and their outcomes are associated with intestinal microbiota, but causality is difficult to establish. The intestinal microbiota are altered in patients with hepatitis C. As chronic HCV infection can now be cured in almost all patients, it is an ideal model to study the influence of liver disease on the microbiota.
We aimed to prospectively analyze the changes in the gut microbiome in patients who received direct-acting antivirals (DAA) and achieved sustained virological response (SVR). Amplicon sequencing of the V1-V2 region in the 16S ribosomal RNA gene was performed in stool samples of patients with chronic hepatitis C. Patients in the treatment group received DAA (n = 65), whereas in the control group, no DAA were given (n = 33). Only patients achieving SVR were included. The alpha diversity increased numerically but not significantly from baseline to SVR at week 24 or 48 (SVR24/48; 2.784 ± 0.248 vs. 2.846 ± 0.224; P = 0.057). When stratifying for the presence of liver cirrhosis, a significant increase in diversity was only seen in patients without cirrhosis. Differences in the microbial community structure induced by the achievement of SVR were only observed in patients without liver cirrhosis. In patients with liver cirrhosis and in the control group, no significant differences were observed.
In conclusion, the achievement of SVR24/48 in patients with chronic HCV was associated with changes in the intestinal microbiota. However, these changes were only seen in patients without liver cirrhosis. A major role of liver remodeling on the intestinal microbiota is indicated by the dynamics of the intestinal microbial community structure depending on the stage of fibrosis in patients resolving chronic hepatitis C.
人们普遍认为，肝脏疾病及其结局与肠道微生物群有关，但因果关系难以确定。丙型肝炎患者的肠道微生物群发生改变。由于现在几乎所有患者都可以治愈慢性 HCV 感染，因此它是研究肝脏疾病对微生物群影响的理想模型。
我们旨在前瞻性分析接受直接作用抗病毒药物 (DAA) 治疗并获得持续病毒学应答 (SVR) 的患者肠道微生物组的变化。对慢性丙型肝炎患者粪便样本的 16S 核糖体 RNA 基因 V1-V2 区进行扩增子测序。治疗组患者接受 DAA（n=65），而对照组未给予 DAA（n=33）。仅纳入获得 SVR 的患者。从基线到 SVR24/48 的第 24 或 48 周，alpha 多样性数值上增加但无统计学意义（SVR24/48；2.784±0.248 vs. 2.846±0.224；P=0.057）。在按是否存在肝硬化分层时，仅在无肝硬化的患者中观察到多样性的显著增加。仅在无肝硬化的患者中观察到 SVR 获得引起的微生物群落结构差异。在肝硬化患者和对照组中，未观察到显著差异。
总之，慢性 HCV 患者 SVR24/48 的获得与肠道微生物群的变化有关。然而，这些变化仅见于无肝硬化的患者。依赖于纤维化阶段的慢性丙型肝炎患者肠道微生物群落结构的动态表明，肝重塑对肠道微生物群具有重要作用。
