Intestinal permeability in human nonalcoholic fatty liver disease: A systematic review and meta-analysis.

Toon J I De Munck,Ger H Koek,Jef Verbeek,Harm J A Verwijs,Ad A M Masclee,Daisy Jonkers,Pan Xu

doi:10.1111/liv.14696

Toon J I De Munck, Ger H Koek + Show 5 more

Open Access

https://doi.org/10.1111/liv.14696

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Abstract

BackgroundThe gut‐liver axis is considered to play a critical role in the development and progression of nonalcoholic fatty liver disease (NAFLD). The integrity of the epithelial barrier is crucial to protect the liver against the invasion of microbial products from the gut, although its exact role in NAFLD onset and progression is not clear.MethodsWe performed a systematic review and meta‐analysis of studies that addressed the intestinal permeability (IP) in association with NAFLD presence or severity as defined by the presence of nonalcoholic steatohepatitis (NASH) and the degree of steatosis, hepatic inflammation or fibrosis. A total of 14 studies were eligible for inclusion.ResultsStudies investigating IP in adult (n = 6) and paediatric (n = 8) NAFLD showed similar results. Thirteen of the included studies focussed on small IP, two studies on whole gut permeability and none on colonic permeability. In the pooled analysis, NAFLD patients showed an increased small intestinal permeability compared to healthy controls based on dual sugar tests (standardized mean difference 0.79, 95% CI 0.49‐1.08) and serum zonulin levels (standardized mean difference 1.04 ng/mL, 95% CI 0.40‐1.68). No clear difference in IP was observed between simple steatosis and NASH patients. Furthermore, whole gut and small intestinal permeability increased with the degree of hepatic steatosis in 4/4 studies, while no association with hepatic inflammation or fibrosis was observed.ConclusionBased on the limited number of studies available, IP appears to be increased in NAFLD patients compared to healthy controls and is associated with the degree of hepatic steatosis.

Highlights

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world in both adults and children
nonalcoholic fatty liver disease (NAFLD) patients showed an increased small intestinal permeability by means of lactulose to mannitol ratio (L/M) or lactulose rhamnose ratio (L/R) (standardized mean difference 0.79 95% CI 0.49-1.08 compared to healthy control (HC) (Figure 2A)
We demonstrated that NAFLD patients have an increased intestinal permeability (IP) compared to HC

Summary

| INTRODUCTION

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world in both adults and children. Other substances used to measure IP in vivo are various polymers of polyethylene glycol (PEG) and 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA).[7] More recently, zonulin, a 47-kDa protein, has been introduced as a potentially useful systemic marker for small intestinal and gastroduodenal permeability, but not for colon permeability.[8] Serum zonulin has emerged as a relevant biomarker because it is an important factor to regulating IP by modulating intercellular tight junctions.[9,10] the specificity of serum zonulin as biomarker for small intestinal permeability remains uncertain.[11] In both adults and paediatric NAFLD patients, several studies investigated IP and its role in the pathogenesis and progression from NAFL to NASH.[12,13,14,15,16,17] the exact association between IP and NAFLD severity (degree of steatosis, hepatic inflammation, fibrosis or presence of NASH) is not clear. In the included studies, we will summarize the clinical parameters (eg anthropometric data and blood biochemical variables), which have been observed to correlate with the degree of IP in NAFLD patients

| METHODS

24 HCa 12 HC 16 HC

| DISCUSSION

Findings

40 NAFLD 70 NAFLD