Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review

Cunha, Victor M.; Cotrim, Helma Pinchemel; Rocha, Raquel; Carvalho, Kellyane Santana Dias; Lins-Kusterer, Liliane

doi:10.1016/j.aohep.2019.10.005

Cited by 77 publications

(57 citation statements)

References 24 publications

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“…To date, there remains uncertainty about whether metformin reduces risk of major CVD events [124,145]. Interestingly, however, several pre-clinical and observational studies and recent meta-analyses suggest that metformin reduces risk of developing some types of cancer, especially HCC [146,147]. It has also become well accepted that metformin has favourable effects on the intestinal microbiome.…”

Section: Metformin and Other Newer Anti-hyperglycaemic Agentsmentioning

confidence: 99%

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

Targher

Byrne

Tilg

2020

Gut

524

365

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Non-alcoholic fatty liver disease (NAFLD) is a public health problem, affecting up to a third of the world’s adult population. Several cohort studies have consistently documented that NAFLD (especially in its more advanced forms) is associated with a higher risk of all-cause mortality and that the leading causes of death among patients with NAFLD are cardiovascular diseases (CVDs), followed by extrahepatic malignancies and liver-related complications. A growing body of evidence also indicates that NAFLD is strongly associated with an increased risk of major CVD events and other cardiac complications (ie, cardiomyopathy, cardiac valvular calcification and cardiac arrhythmias), independently of traditional cardiovascular risk factors. This narrative review provides an overview of the literature on: (1) the evidence for an association between NAFLD and increased risk of cardiovascular, cardiac and arrhythmic complications, (2) the putative pathophysiological mechanisms linking NAFLD to CVD and other cardiac complications and (3) the current pharmacological treatments for NAFLD that might also benefit or adversely affect risk of CVD.

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Section: Metformin and Other Newer Anti-hyperglycaemic Agentsmentioning

confidence: 99%

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

Targher

Byrne

Tilg

2020

Gut

524

365

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“…Recently, a meta-analysis on 8 studies reported a combined odds ratio of 0.468 for the association between HCC and metformin treatment, signalling a potentially protective effect. 65 In the HCC treatment setting, mixed signals have been reported: In a meta-analysis of 6 retrospective cohort studies, the use of metformin in patients with type 2 diabetes was associated with a significantly prolonged OS after curative treatment of HCC (p <0.00001). 66 In contrast, a negative effect of metformin in addition to sorafenib has been suggested.…”

Section: Patients With Diabetes/metabolic Syndromementioning

confidence: 99%

Systemic treatment of HCC in special populations

Rimassa

Personeni

Czauderna

et al. 2021

Journal of Hepatology

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Recent years have seen significant progress in the systemic treatment of hepatocellular carcinoma (HCC), including the advent of immunotherapy. While several large phase III trials have provided the evidence for a multi-line treatment paradigm, they have focused on a highly selected group of patients by excluding potentially confounding comorbidities. As a result, high quality evidence for the systemic treatment of HCC in patients with various comorbidities is missing. This review summarises current knowledge on the use of approved medicines in patients with HIV, autoimmune disease, cardiovascular disease, diabetes, fibrolamellar HCC, mixed HCC-cholangiocarcinoma, decompensated cirrhosis (Child-Pugh B and C), a significant bleeding history, vascular invasion or portal vein thrombosis, as well as the elderly, those on haemodialysis, and those after solid organ transplantation. The article highlights relevant knowledge gaps and current clinical challenges. To improve the safety and efficacy of HCC treatment in these subgroups, future trials should be designed to specifically include patients with comorbidities.

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“…In addition to NSBB, the simultaneous prescription for the comorbidities such as DM and cardiovascular diseases in AC may influence the incidence of HCC. For example, metformin has been reported to reduce the risk of HCC in patients with DM [35]; notably, it is also associated with tumor aggressiveness and drug resistance in advanced HCC [36,37]. Besides, long-term aspirin use lowers the risk of HCC in the general population [38]; interestingly, lack of significant chemopreventive effect in cirrhotic patients has been proposed [39].…”

Section: Discussionmentioning

confidence: 99%

Propranolol Is Associated with Lower Risk of Incidence of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Tertiary-Center Study and Indirect Comparison with Meta-Analysis

Tsai

Hsu

et al. 2020

Gastroenterology Research and Practice

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Alcoholic cirrhosis (AC) leads to enormous disease burden and occupies a substantial proportion in the etiology of hepatocellular carcinoma (HCC), but scarce attention has been paid to this topic. Besides, propranolol has been reported to decrease the rate of HCC in viral hepatitis. We conducted a retrospective tertiary-center cohort study to identify the HCC incidence in AC patients with or without propranolol. A total of 1,046 AC patients with hospitalization had been screened, and those with regular follow-up for three years or otherwise until the date of malignancy diagnosis without meeting exclusion criteria were enrolled; finally, 23 AC patients with propranolol and 46 AC patients without propranolol were analyzed after twofold propensity-score matching. The cumulative incidence of HCC was lower in the propranolol group (log-rank test, P=0.046). Furthermore, we undertook the meta-analysis of annual incidence of HCC in AC patients, and 1,949 publications were screened, within which eight studies were analyzed; the pooled annual incidence was 2.41%, which was higher than the calculated annual incidence of HCC in our AC cohort with propranolol (1.45%). In conclusion, propranolol is associated with decreased risk of HCC incidence in patients with AC.

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Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review

Cited by 77 publications

References 24 publications

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

Systemic treatment of HCC in special populations

Propranolol Is Associated with Lower Risk of Incidence of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Tertiary-Center Study and Indirect Comparison with Meta-Analysis

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