Language
English
Publication Date
8-1-2023
Journal
Nature Reviews Gastroenterology & Hepatology
DOI
10.1038/s41575-023-00754-7
PMID
36932227
PMCID
PMC12165718
PubMedCentral® Posted Date
6-13-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Nonalcoholic fatty liver disease (NAFLD), including its more severe manifestation, nonalcoholic steatohepatitis (NASH), has a global prevalence of 20-25% and is a major public health problem. Its incidence is increasing in parallel to the rise in obesity, diabetes and metabolic syndrome. Progression from NASH to NASH-related hepatocellular carcinoma (HCC) (~2% of cases per year) is influenced by many factors, including the tissue and immune microenvironment, germline mutations in PNPLA3, and the microbiome. NASH-HCC has unique molecular and immune traits compared with other aetiologies of HCC and is equally prevalent in men and women. Comorbidities associated with NASH, such as obesity and diabetes mellitus, can prevent the implementation of potentially curative therapies in certain patients; nonetheless, outcomes are similar in patients who receive treatment. NASH-HCC at the early to intermediate stages is managed with surgery and locoregional therapies, whereas advanced HCC is treated with systemic therapies, including anti-angiogenic therapies and immune-checkpoint inhibitors. In this Review, we present the latest knowledge of the pathogenic mechanisms and clinical management of NASH-HCC. We discuss data highlighting the controversy over varying responses to immune-checkpoint inhibitors according to underlying aetiology and suggest that the future of NASH-HCC management lies in improved surveillance, targeted combination therapies to overcome immune evasion, and identifying biomarkers to recognize treatment responders.
Keywords
Male, Humans, Female, Carcinoma, Hepatocellular, Non-alcoholic Fatty Liver Disease, Liver Neoplasms, Immune Checkpoint Inhibitors, Disease Progression, Obesity, Diabetes Mellitus, Tumor Microenvironment
Published Open-Access
no
Recommended Citation
Llovet, Josep M; Willoughby, Catherine E; Singal, Amit G; et al., "Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma: Pathogenesis and Treatment" (2023). Faculty and Staff Publications. 3272.
https://digitalcommons.library.tmc.edu/baylor_docs/3272
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Digestive System Diseases Commons, Gastroenterology Commons, Hepatology Commons, Medical Sciences Commons, Oncology Commons, Pediatrics Commons