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Current Hepatology Reports
Published in: Current Hepatology Reports 4/2018

01-12-2018 | Fatty Liver Disease (Z Younossi, Section Editor)

Pathogenesis of NASH: the Impact of Multiple Pathways

Authors: Mazen Noureddin, Arun J. Sanyal

Published in: Current Hepatology Reports | Issue 4/2018

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Abstract

Purpose of review

Advancing our understanding of the mechanisms that underlie NASH pathogenesis.

Recent findings

Recent findings on NASH pathogenesis have expanded our understanding of its complexity including (1) there are multiple parallel hits that lead to NASH; (2) the microbiota play an important role in pathogenesis, with bacterial species recently shown to accurately differentiate between NAFL and NASH patients; (3) the main drivers of liver cell injury are lipotoxicity caused by free fatty acids (FFAs) and their derivatives combined with mitochondrial dysfunction; (4) decreased endoplasmic reticulum (ER) efficiency with increased demand for protein synthesis/folding/repair results in ER stress, protracted unfolded protein response, and apoptosis; (5) upregulated proteins involved in multiple pathways including JNK, CHOP, PERK, BH3-only proteins, and caspases result in mitochondrial dysfunction and apoptosis; and (6) subtypes of NASH in which these pathophysiological pathways vary may require patient subtype identification to choose effective therapy.

Summary

Recent pathogenesis studies may lead to important therapeutic advances, already seen in patients treated with ACC, ASK1 and SCD1 inhibitors, and FXR agonists. Further, advancing our understanding of mechanisms underlying NASH pathogenesis and the complex interplay between them will be crucial for developing effective therapies.
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Metadata
Title
Pathogenesis of NASH: the Impact of Multiple Pathways
Authors
Mazen Noureddin
Arun J. Sanyal
Publication date
01-12-2018
Publisher
Springer US
Published in
Current Hepatology Reports / Issue 4/2018
Electronic ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-018-0425-7

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LI-RADS v2018: a Primer and Update for Clinicians

Fatty Liver Disease (Z Younossi, Section Editor)

The Impact of Metabolic Syndrome on the Outcome of NASH: Cirrhosis, Hepatocellular Carcinoma, and Mortality

Hepatic Cancer (A Singal and A Mufti, Section Editors)

Stereotactic Ablative Radiotherapy (SABR/SBRT) for Hepatocellular Carcinoma

Hepatitis B (J Lim, Section Editor)

Prevention and Management of HBV Infection in Patients with Chronic Kidney Disease Requiring Renal Transplantation

Hepatic Cancer (A Singal and A Mufti, Section Editors)

The Impact of Direct-acting Antiviral Therapy for Hepatitis C on Hepatocellular Carcinoma Risk
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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