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Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease.

ABSTRACT: Diabetes increases the risk of liver disease progression and cirrhosis development in patients with nonalcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellular carcinoma (HCC) in NASH patients with cirrhosis is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation registry for external validation. Cox proportional hazard analysis was performed to investigate the association between diabetes and HCC risk. Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) were male. Mean age at cirrhosis evaluation was 62. During a median follow-up of 47 months, 30 patients developed HCC. Diabetes was associated with an increased risk of developing HCC in univariate (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.1-11.9; P = 0.04) and multivariable analysis (HR = 4.2; 95% CI = 1.2-14.2; P = 0.02). In addition, age (per decade, HR = 1.8; 95% CI = 1.2-2.6; P < 0.01) and low serum albumin (HR = 2.1; 95% CI = 1.5-2.9; P < 0.01) were significantly associated with an increased risk of developing HCC in multivariable analysis. Other metabolic risk factors, including body mass index, hyperlipidemia, and hypertension, were not associated with HCC risk. Among UNOS NASH registrants (N = 6,630), 58% had diabetes. Diabetes was associated with an increased risk of developing HCC in univariate (HR = 1.4; 95% CI = 1.1-1.8; P < 0.01) and multivariable (HR = 1.3; 95% CI = 1.0-1.7; P = 0.03) analysis. Conclusion: Diabetes is associated with an increased risk of HCC in patients with NASH cirrhosis.

SUBMITTER: Yang JD

PROVIDER: S-EPMC6960360 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease.

Yang Ju Dong JD Ahmed Fowsiyo F Mara Kristin C KC Addissie Benyam D BD Allen Alina M AM Gores Gregory J GJ Roberts Lewis R LR

Hepatology (Baltimore, Md.) 20191021 3

Diabetes increases the risk of liver disease progression and cirrhosis development in patients with nonalcoholic steatohepatitis (NASH). The association between diabetes and the risk of hepatocellular carcinoma (HCC) in NASH patients with cirrhosis is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified usin ...[more]

PMID: 31309602

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Project description:Non-alcoholic liver disease (NAFLD) defines liver abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis with or without cirrhosis development, occurring in the absence of significant alcohol consumption, use of teratogenic medication, or hereditary disorders. The association between NAFLD and metabolic syndrome is well documented and widely recognized. Obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia are the most common metabolic risk factors associated with NAFLD. Among the components of metabolic syndrome, current evidence strongly indicates obesity and diabetes as hepatocellular carcinoma (HCC) risk factors. There is also growing evidence that suggests an increased risk of HCC in NAFLD patients, even surpassing other etiologies in some high-income countries. Epidemiologic data demonstrate a parallel rise in prevalence of obesity, diabetes, NAFLD, and HCC. As obesity and its related diseases have steadily afflicted larger populations, HCC incidence is expected to increase in the future. Pathophysiologic mechanisms that underlie NAFLD development and subsequent progression to nonalcoholic steatohepatitis and cirrhosis (insulin resistance and hyperinsulinemia, oxidative stress, hepatic stellate cell activation, cytokine/adipocytokine signaling pathways, and genetic and environmental factors) appear to play a significant role in the development of NAFLD-related HCC. However, a comprehensive view of molecular mechanisms linking obesity, T2DM, and NAFLD-related HCC, as well as the exact sequence of molecular events, is still not understood in its entirety. Good-quality data are still necessary, and efforts should continue towards better understanding the underlying carcinogenic mechanisms of NAFLD-related HCC. In this paper, we aimed to centralize the most important links supporting these relationships, focusing on obesity, T2DM, and NAFLD-related HCC, as well as point out the major gaps in knowledge regarding the underlying molecular mechanisms behind them.

Project description:BackgroundThe risk of advanced fibrosis in first-degree relatives of patients with nonalcoholic fatty liver disease and cirrhosis (NAFLD-cirrhosis) is unknown and needs to be systematically quantified. We aimed to prospectively assess the risk of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis.MethodsThis is a cross-sectional analysis of a prospective cohort of 26 probands with NAFLD-cirrhosis and 39 first-degree relatives. The control population included 69 community-dwelling twin, sib-sib, or parent-offspring pairs (n = 138), comprising 69 individuals randomly ascertained to be without evidence of NAFLD and 69 of their first-degree relatives. The primary outcome was presence of advanced fibrosis (stage 3 or 4 fibrosis). NAFLD was assessed clinically and quantified by MRI proton density fat fraction (MRI-PDFF). Advanced fibrosis was diagnosed by liver stiffness greater than 3.63 kPa using magnetic resonance elastography (MRE).ResultsThe prevalence of advanced fibrosis in first-degree relatives of probands with NAFLD-cirrhosis was significantly higher than that in the control population (17.9% vs. 1.4%, P = 0.0032). Compared with controls, the odds of advanced fibrosis among the first-degree relatives of probands with NAFLD-cirrhosis were odds ratio 14.9 (95% CI, 1.8-126.0, P = 0.0133). Even after multivariable adjustment by age, sex, Hispanic ethnicity, BMI, and diabetes status, the risk of advanced fibrosis remained both statistically and clinically significant (multivariable-adjusted odds ratio 12.5; 95% CI, 1.1-146.1, P = 0.0438).ConclusionUsing a well-phenotyped familial cohort, we demonstrated that first-degree relatives of probands with NAFLD-cirrhosis have a 12 times higher risk of advanced fibrosis. Advanced fibrosis screening may be considered in first-degree relatives of NAFLD-cirrhosis patients.Trial registrationUcsd irb140084.FundingNational Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Environmental Health Sciences, NIH.

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Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease.

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Diabetes Is Associated With Increased Risk of Hepatocellular Carcinoma in Patients With Cirrhosis From Nonalcoholic Fatty Liver Disease.

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