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Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide. Due to its association with obesity and diabetes and the fall in hepatitis C virus morbidity, cirrhosis in NAFLD is becoming the most frequent indication to liver transplantation, but the pathogenetic mechanisms are still not completely understood. The so-called gut-liver axis has gained enormous interest when data showed that its alteration can lead to NAFLD development and might favor the occurrence of non-alcoholic steatohepatitis (NASH). Moreover, several therapeutic approaches targeting the gut-pancreas-liver axis, e.g., incretins, showed promising results in NASH treatment. In this review, we describe the role of incretin hormones in NAFLD/NASH pathogenesis and treatment and how metagenomic/metabolomic alterations in the gut microbiota can lead to NASH in the presence of gut barrier modifications favoring the passage of bacteria or bacterial products in the portal circulation, i.e., bacterial translocation.

SUBMITTER: Svegliati-Baroni G

PROVIDER: S-EPMC7461212 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH.

Svegliati-Baroni Gianluca G Patrício Bárbara B Lioci Gessica G Macedo Maria Paula MP Gastaldelli Amalia A

International journal of molecular sciences 20200813 16

Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide. Due to its association with obesity and diabetes and the fall in hepatitis C virus morbidity, cirrhosis in NAFLD is becoming the most frequent indication to liver transplantation, but the pathogenetic mechanisms are still not completely understood. The so-called gut-liver axis has gained enormous interest when data showed that its alteration can lead to NAFLD development and might favor ...[more]

PMID: 32823659

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Project description:BackgroundNoninvasive diagnostic methods are urgently required in disease stratification and monitoring in nonalcoholic fatty liver disease (NAFLD). Multiparametric magnetic resonance imaging (MRI) is a promising technique to assess hepatic steatosis, inflammation, and fibrosis, potentially enabling noninvasive identification of individuals with active and advanced stages of NAFLD.PurposeTo examine the diagnostic performance of multiparametric MRI for the assessment of disease severity along the NAFLD disease spectrum with comparison to histological scores.Study typeProspective, cohort.PopulationThirty-seven patients with NAFLD.Field strength/sequenceMultiparametric MRI at 3.0 T consisted of magnetic resonance (MR) spectroscopy (MRS) with multi-echo stimulated-echo acquisition mode, magnitude-based and three-point Dixon using a two-dimensional multi-echo gradient echo, MR elastography (MRE) using a generalized multishot gradient-recalled echo sequence and intravoxel incoherent motion (IVIM) using a multislice diffusion weighted single-shot echo-planar sequence.AssessmentHistological steatosis grades were compared to proton density fat fraction measured by MRS (PDFFMRS ), magnitude-based MRI (PDFFMRI-M ), and three-point Dixon (PDFFDixon ), as well as FibroScan® controlled attenuation parameter (CAP). Fibrosis and disease activity were compared to IVIM and MRE. FibroScan® liver stiffness measurements were compared to fibrosis levels. Diagnostic performance of all imaging parameters was determined for distinction between simple steatosis and nonalcoholic steatohepatitis (NASH).Statistical testsSpearman's rank test, Kruskal-Wallis test, Dunn's post-hoc test with Holm-Bonferroni P-value adjustment, receiver operating characteristic curve analysis. A P-value <0.05 was considered statistically significant.ResultsHistological steatosis grade correlated significantly with PDFFMRS (rs = 0.66, P < 0.001), PDFFMRI-M (rs = 0.68, P < 0.001), and PDFFDixon (rs = 0.67, P < 0.001), whereas no correlation was found with CAP. MRE and IVIM diffusion and perfusion significantly correlated with disease activity (rs = 0.55, P < 0.001, rs = -0.40, P = 0.016, rs = -0.37, P = 0.027, respectively) and fibrosis (rs = 0.55, P < 0.001, rs = -0.46, P = 0.0051; rs = -0.53, P < 0.001, respectively). MRE and IVIM diffusion had the highest area-under-the-curve for distinction between simple steatosis and NASH (0.79 and 0.73, respectively).Data conclusionMultiparametric MRI is a promising method for noninvasive, accurate, and sensitive distinction between simple hepatic steatosis and NASH, as well as for the assessment of steatosis and fibrosis severity.Level of evidence2 TECHNICAL EFFICACY: 2.

Dataset Information

Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH.

Publications

Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH.

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