Therapeutic pipeline in nonalcoholic steatohepatitis

  title={Therapeutic pipeline in nonalcoholic steatohepatitis},
  author={Raj Vuppalanchi and Mazen Noureddin and Naim Alkhouri and Arun J. Sanyal},
  journal={Nature Reviews Gastroenterology \& Hepatology},
  pages={373 - 392}
Our understanding of nonalcoholic fatty liver disease pathophysiology continues to advance rapidly. Accordingly, the field has moved from describing the clinical phenotype through the presence of nonalcoholic steatohepatitis (NASH) and degree of fibrosis to deep phenotyping with a description of associated comorbidities, genetic polymorphisms and environmental influences that could be associated with disease progression. These insights have fuelled a robust therapeutic pipeline across a variety… 

Challenges and opportunities in nonalcoholic steatohepatitis

A critical need exists for novel therapies that can halt or reverse the progression to hepatic fibrosis, cirrhosis, and hepatocellular carcinoma and identifying circulating biomarkers of fibrosis could serve as a valuable, non-invasive diagnostic tool to guide clinical practice.

Emerging advances in the pharmacologic treatment of nonalcoholic steatohepatitis and related cirrhosis

The current concept of the pathophysiology of NASH is presented, focusing on the pathways currently targeted in clinical trials, and the pharmacological agents that are being evaluated in phase IIb of clinical development and beyond are presented.

Updates on novel pharmacotherapeutics for the treatment of nonalcoholic steatohepatitis.

It is anticipated that with improved understanding of NASH pathogenesis and critical endpoints, efficient pharmacotherapeutics will be available for the treatment ofNASH with an acceptable safety profile.

Insights into Nonalcoholic Fatty-Liver Disease Heterogeneity

This review aims to address the understanding of NAFLD heterogeneity and the dominant drivers of disease in patient subgroups through the analysis of existing data on the differential contribution of known factors to the pathogenesis and clinical expression, thus determining the different clinical subphenotypes observed in practice.

Immune cell-mediated features of non-alcoholic steatohepatitis

A better understanding of the mechanisms by which immune cells contribute to NASH pathogenesis should aid the design of innovative drugs to target NASH, for which current therapeutic options are limited.

Emerging Roles of T Cells in the Pathogenesis of Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma

Current knowledge regarding the T cell-mediated mechanisms of inflammation in NASH is summarized and recent preclinical and human studies implicating various subsets of conventional and innate-like T cells in the onset and progression of NASH and HCC are highlighted.

24-Research Progress of Multi-Target Drugs in the Treatment of Non-Alcoholic Steatohepatitis

The multi-target drugs for the treatment of NASH can exert synergistic effects on multiple targets to maximize drug efficacy and minimize adverse side effects, and has a good effect on the Treatment of complex diseases.

Liver enhancer signature and regulatory network of non-alcoholic steatohepatitis resistance in humans with obesity

This study has defined for the first time the active enhancer/super-enhancer landscape and the underlying TF programs of NASH resistance in humans with obesity.

Understanding the cellular interactome of non-alcoholic fatty liver disease




Drug discovery and treatment paradigms in nonalcoholic steatohepatitis

The biological basis of potential therapies in nonalcoholic steatohepatitis (NASH), the current drugs being tested in clinical trials, as well some practical considerations in managing patients in the clinic are reviewed.

Should combination therapy be the paradigm for future nonalcoholic steatohepatitis clinical trials?

There is a significant unmet need in terms of effective available treatments and this un met need may be overcome by adopting alternate therapeutic strategies such as employing different agents to improve insulin resistance and oxidative stress and exploring agents affecting different targets such as apoptosis.

Pathogenesis of Nonalcoholic Steatohepatitis: An Overview

In this review, lipotoxicity, inflammation, and the contribution of interorgan crosstalk in NASH pathogenesis are discussed.

Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management

Health care providers should not only focus on liver disease but also concentrate on aggressively modifying and treating their cardiovascular risk factors.

A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis.

This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients withNASH resolution than placebo, however, the trial did not show a significant between-group difference in the percentage of Patients with an improvement in fibrosis stage.

Report on the AASLD/EASL Joint Workshop on Clinical Trial Endpoints in NAFLD

Important findings from ongoing and completed trials are summarized, the scientific evidence supporting distinct endpoints for NASH are defined, and guidance for future trial design is provided.

Function and therapeutic advances of chemokine and its receptor in nonalcoholic fatty liver disease

Accumulating data show that chemokine and its receptor act vital roles in the pathogenesis of nonalcoholic fatty liver disease and explore the novel pharmacotherapeutic avenues for patients with NAFLD.

The Natural History of Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: Data From the Simtuzumab Trials

In patients with advanced fibrosis due to NASH, the primary determinant of clinical disease progression is fibrosis and its change over time.

Past, present and future perspectives in nonalcoholic fatty liver disease

  • A. Sanyal
  • Medicine
    Nature Reviews Gastroenterology & Hepatology
  • 2019
A timeline of scientific discovery of both basic disease mechanisms and the evolution of knowledge about the clinical course of the disease is provided and related to current approaches to treat and eventually prevent NAFLD.