口服补充益生菌24周对经活检证实的非酒精性脂肪性肝炎患者的心血管风险标志物没有降低作用：一项双盲安慰剂对照随机研究。

Oral 24-week probiotics supplementation did not decrease cardiovascular risk markers in patients with biopsy proven NASH: A double-blind placebo-controlled randomized study.

作者信息

Barcelos Samantha Thifani Alrutz, Silva-Sperb Amanda Souza, Moraes Helena Abadie, Longo Larisse, de Moura Bruna Concheski, Michalczuk Matheus Truccolo, Uribe-Cruz Carolina, Cerski Carlos Thadeu Schmidt, da Silveira Themis Reverbel, Dall'Alba Valesca, Álvares-da-Silva Mário Reis

机构信息

Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Rio Grande do Sul, Brazil.

Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Rio Grande do Sul, Brazil; Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre 90035-903, Rio Grande do Sul, Brazil.

出版信息

Ann Hepatol. 2023 Jan-Feb;28(1):100769. doi: 10.1016/j.aohep.2022.100769. Epub 2022 Oct 8.

DOI:10.1016/j.aohep.2022.100769

PMID:36216309

Abstract

INTRODUCTION AND OBJECTIVES

Cardiovascular disease (CVD) is the major cause of death in non-alcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Probiotics are often indicated for the disease, but their results are controversial in part due to the poor quality of studies. Thus, we investigated the impact of 24-week probiotics supplementation on cardiovascular risk (CVR) in biopsy-proven non-alcoholic steatohepatitis (NASH) patients.

PATIENTS AND METHODS

Double-blind, placebo-controlled, single-center study (NCT03467282), adult NASH, randomized for 24 weeks daily sachets of probiotic mix (10CFU of Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus paracasei and Bifidobacterium lactis) or placebo. Clinical scores (atherogenic indexes, atherosclerotic cardiovascular disease-ASCVD and systematic coronary risk evaluation-SCORE), biochemistry, miR-122, miR-33a, plasminogen activator inhibitor-1 (PAI-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), were determined before and after the intervention.

RESULTS

Forty-six patients were enrolled (23 received probiotics and 23 placebo), with a mean age of 51.7 years, most of them females and whites. Clinical and demographic features were similar between the groups at the baseline. The Median NAFLD activity score was 4.13 in both groups. Fibrosis was mild in most patients (15.2% and 65.2% F0 and F1, respectively). Treatment did not promote any clinically significant changes in body mass index or laboratory, including lipid and glucose profile. High CVR patients through atherogenic indexes decreased from baseline in both groups, as well as PAI-1 and miR-122 levels, although there was no difference between probiotics and placebo.

CONCLUSIONS

A 24-week probiotic mix administration was not superior to placebo in reducing CVR markers in patients with NASH.

摘要

引言与目的

心血管疾病（CVD）是非酒精性脂肪性肝病（NAFLD）的主要死因，NAFLD是一种尚无任何获批药物治疗的临床病症。益生菌常被用于该疾病的治疗，但其效果存在争议，部分原因是研究质量欠佳。因此，我们研究了补充24周益生菌对经活检证实的非酒精性脂肪性肝炎（NASH）患者心血管风险（CVR）的影响。

患者与方法

双盲、安慰剂对照、单中心研究（NCT03467282），纳入成年NASH患者，随机分为两组，分别每日服用益生菌混合物（嗜酸乳杆菌、鼠李糖乳杆菌、副干酪乳杆菌和双歧杆菌各10CFU）或安慰剂，为期24周。在干预前后测定临床评分（致动脉粥样硬化指数、动脉粥样硬化性心血管疾病-ASCVD和系统性冠状动脉风险评估-SCORE）、生化指标、miR-122、miR-33a、纤溶酶原激活物抑制剂-1（PAI-1）、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）。

结果

共纳入46例患者（23例接受益生菌治疗，23例接受安慰剂治疗），平均年龄51.7岁，大多数为女性和白人。两组在基线时的临床和人口统计学特征相似。两组的NAFLD活动评分中位数均为4.13。大多数患者纤维化程度较轻（F0和F1分别为15.2%和65.2%）。治疗未导致体重指数或实验室指标（包括血脂和血糖谱）出现任何具有临床意义的变化。两组中通过致动脉粥样硬化指数评估的高CVR患者均较基线下降，PAI-1和miR-122水平也下降，尽管益生菌组与安慰剂组之间无差异。