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Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma.

ABSTRACT: Obesity-related complications such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are well-established risk factors for the development of hepatocellular carcinoma (HCC). This review provides insights into the molecular mechanisms that underlie the role of steatosis, hyperinsulinemia and hepatic inflammation in HCC development and progression. We focus on recent findings linking intracellular pathways and transcription factors that can trigger the reprogramming of hepatic cells. In addition, we highlight the role of enzymes in dysregulated metabolic activity and consequent dysfunctional signalling. Finally, we discuss the potential uses and challenges of novel therapeutic strategies to prevent and treat NAFLD/T2D-associated HCC.

SUBMITTER: Talamantes S

PROVIDER: S-EPMC10413159 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma.

Talamantes Stephanie S Lisjak Michela M Gilglioni Eduardo H EH Llamoza-Torres Camilo J CJ Ramos-Molina Bruno B Gurzov Esteban N EN

JHEP reports : innovation in hepatology 20230609 9

Obesity-related complications such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are well-established risk factors for the development of hepatocellular carcinoma (HCC). This review provides insights into the molecular mechanisms that underlie the role of steatosis, hyperinsulinemia and hepatic inflammation in HCC development and progression. We focus on recent findings linking intracellular pathways and transcription factors that can trigger the reprogramming of hepatic ...[more]

PMID: 37575883

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Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully.AimWe explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients.MethodsThis is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software.ResultsAmong 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03-1.14; p = 0.004), obesity (BMI ≥ 27.5 kg/m2, OR = 2.64; 95% CI: 1.28-5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40-13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02-1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00-1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98-1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18-17.62; p = 0.028) were independent factors associated with increased liver stiffness.ConclusionsOur study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.

Dataset Information

Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma.

Publications

Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma.

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