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Review
. 2023 Jan 1;77(1):323-338.
doi: 10.1002/hep.32542. Epub 2022 Nov 8.

NAFLD-related hepatocellular carcinoma: The growing challenge

Pir Ahmad Shah  1 , Rashmee Patil  2 , Stephen A Harrison  3
Affiliations
Review

NAFLD-related hepatocellular carcinoma: The growing challenge

Pir Ahmad Shah et al. Hepatology. .

Abstract

Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity worldwide. With the obesity pandemic, NAFLD-related HCC is contributing to the burden of disease exponentially. Genetic predisposition and clinical risk factors for NAFLD-related HCC have been identified. Cirrhosis is a well-known and major risk factor for NAFLD-related HCC. However, the occurrence of NAFLD-related HCC in patients without cirrhosis is increasingly recognized and poses a significant challenge regarding cancer surveillance. It is of paramount importance to develop optimal risk stratification scores and models to identify subsets of the population at high risk so they can be enrolled in surveillance programs. In this review, we will discuss the risks and prediction models for NAFLD-related HCC.

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Conflict of interest statement

Dr. Harrison owns stock in Akero Therapeutics, Galectin Therapeutics, Genfit Corp, Hepion Pharmaceuticals, Metactine, NGM Biopharmaceuticals, Chronwell, Cirius Therapeutics, and HistoIndex. Dr. Harrison consults for and advises Altimmune, Alimentiv, Akero Therapeutics, Axcella Pharmaceuticals, Boston Pharmaceuticals, Echosens North America, Enyo Pharma S.A., Galectin Therapeutics, Genfit Corp, Gilead Sciences, Hepion Pharmaceuticals, Medpace, Metacrine, NGM Biopharmaceuticals, Novartis, Northsea Therapeutics, Cirius Therapeutics, HistoIndex, Hightide Therapeutics, Intercept Pharmaceuticals, Madrigal Pharmaceuticals, Novo Nordisk, PathAI, Perspectum Diagnostics, Poxel, Sagimet Biosciences, Sonic Incytes, Terns, and Viking. Dr. Harrison has received grants from Altimmune, Akero, Axcella Pharmaceuticals, Boehringer Ingelheim, Corcept Therapeutics, Enyo Pharma S.A., Ionis, 89Bio, Galectin, Gilead, Genfit, Hepion Therapeutics, Intercept, Madrigal Pharmaceuticals, Novo Nordisk, Novartis, NGM Biopharmaceuticals, Poxel, Sagimet Biosciences, Viking.

Figures

None
Graphical abstract
FIGURE 1
FIGURE 1
Temporal trends of NAFLD‐related hepatocellular carcinoma (HCC) in different countries.–
FIGURE 2
FIGURE 2
Risk and protective factors for NAFLD‐related hepatocellular carcinoma (HCC). GCKR, glucokinase regulator; HSD17B13, 17‐β hydroxysteroid dehydrogenase 13; MBOAT7, membrane bound O‐acyltransferase domain‐containing 7; PNPLA3; patatin‐like phospholipase domain‐containing 3; TM6SF2, transmembrane 6 superfamily member 2.
FIGURE 3
FIGURE 3
Global genetic variation contributing to NAFLD. AGT, angiotensinogen; AGTR1, angiotensin II; APOC3, apolipoprotein C3; ENPP1, ectoenzyme nucleotide pyrophosphate phosphodiesterase 1; IRS, insulin receptor substrate; MTP, microsomal triglyceride transfer protein; PNPLA3, patatin‐like phospholipase domain‐containing protein 3; PPAR, peroxisome proliferator‐activated receptor.–
FIGURE 4
FIGURE 4
Natural history of NAFLD‐related hepatocellular carcinoma (HCC). Data for reported incidences from references.,,, Reported HCC incidence in simple steatosis and NASH in the figure are based on studies that utilized histological diagnosis as inclusion criteria. Given the limited number of studies, these rates might not be a robust reflection of actual incidence.
FIGURE 5
FIGURE 5
Model for risk stratification in NAFLD‐related hepatocellular carcinoma (HCC).
See this image and copyright information in PMC

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