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Does Type 2 Diabetes Increase the Risk of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease Patients? A Systematic Review.

ABSTRACT: Diabetes is associated with different types of cancers of which hepatocellular carcinoma (HCC) is one among them. In a study comparing patients with diabetes to those who do not have diabetes, it was evident that the risk of HCC is found to increase two-fold in diabetic than that in non-diabetic patients. It is clear that carcinogenesis is advanced due to diabetes in the liver by a variety of mechanisms. We searched PubMed and Google Scholar for articles from 2010 to 2021 that have an association between diabetes, nonalcoholic fatty liver disease (NAFLD), and HCC. For the development of HCC, diabetes is likely related at both the molecular and epidemiological levels. Both diabetes mellitus and hepatic malignancy have the worst impact on mankind socioeconomically. There is a significant relationship between diabetes and HCC independent of alcohol consumption and viral hepatitis. It is noteworthy that not only the elderly but also people of all age groups should monitor their hemoglobin A1C levels. Diet restriction and lifestyle modification can reduce the risk of complications like HCC; the increased physical activity itself can have a major influence on health and can manage comorbidities like diabetes, NAFLD, and HCC.

SUBMITTER: Venugopal S

PROVIDER: S-EPMC10101195 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Does Type 2 Diabetes Increase the Risk of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease Patients? A Systematic Review.

Venugopal Sathish S Dhanoa Ravneet K RK Selvamani Tharun Yadhav TY Shoukrie Shoukrie I SI Zahra Anam A Malla Jyothirmai J Selvaraj Ramaneshwar R Hamouda Ranim K RK Mohammed Lubna L

Cureus 20230313 3

Diabetes is associated with different types of cancers of which hepatocellular carcinoma (HCC) is one among them. In a study comparing patients with diabetes to those who do not have diabetes, it was evident that the risk of HCC is found to increase two-fold in diabetic than that in non-diabetic patients. It is clear that carcinogenesis is advanced due to diabetes in the liver by a variety of mechanisms. We searched PubMed and Google Scholar for articles from 2010 to 2021 that have an associatio ...[more]

PMID: 37065332

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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:BACKGROUND:Fatty liver is associated with obesity, type 2 diabetes, hyperlipidemia, hypertension, and metabolic syndrome. While there are no approved drugs for the treatment of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis, strategies to ameliorate fatty liver often target these related diseases. We sought to determine if any medications approved by the US Food and Drug Administration to treat diabetes are helpful in reducing weight and improving steatohepatitis in patients with NAFLD. METHODS:We conducted a systematic review of published and unpublished studies evaluating the comparative effectiveness and harms of diabetes medications for the treatment of NAFLD. We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials through 3rd quarter, 2019 using terms for included drugs and indications. RESULTS:We screened 1591 citations and included 18 trials of diabetes drugs to treat NAFLD. Studies of metformin found no difference from placebo in steatosis, fibrosis, NAFLD activity score, or resolution of NASH. While weight and glucose control were improved with metformin, it did not substantially impact liver disease. Studies of pioglitazone in NASH patients found benefits in liver function, liver fat, and NASH resolution, though significant increases in weight may be cause for concern. Evidence for other thiazolinediones was more limited and had somewhat mixed results, but findings were generally consistent with those for pioglitazone: liver fat and function and glucose measures improved, but weight also increased. We found some evidence that liraglutide improves liver fat, liver function, and HbA1c and is effective at resolving NASH and reducing weight. Exenatide performed less well but also resulted in significant reductions in liver fat and weight. CONCLUSIONS:Consistent with existing clinical practice guidelines, which recommend lifestyle intervention and treatment for comorbidities related to fatty liver disease as first-line treatment, trial evidence supports the efficacy of some diabetes drugs (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with some diabetes drugs may warrant caution. Larger trials are needed to better characterize the efficacy and harms of diabetes pharmacotherapy in these patients.

Dataset Information

Does Type 2 Diabetes Increase the Risk of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease Patients? A Systematic Review.

Publications

Does Type 2 Diabetes Increase the Risk of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease Patients? A Systematic Review.

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