Meta-analysis: The efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes

Zhou, Jian; Yang, Ke; Lei, Xuefen; Wu, Taihu; Li, Yuehua; Bao, Tianhao; Tang, Haoran; Zhang, Cheng; Wu, Xuesong; Wang, Ge; Li, Jinze; Zhang, Heng; Fan, Ni; Ye, Zhengchen; Wang, Lin

doi:10.1016/j.aohep.2019.11.008

Cited by 42 publications

(34 citation statements)

References 24 publications

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“…The differences in the results could be attributed to unmeasured confounding factors, as HbA1c levels are altered by erythrocyte longevity, particularly in patients with chronic liver illness, chronic kidney disease, and severe metabolic abnormalities [ 80 ]. Furthermore, earlier research has shown that metformin has a preventive impact on diabetic treatments, but insulin and sulphonylureas are pro-oncogenic [ 81 , 82 ]. In this study, the association was not significant.…”

Section: Discussionmentioning

confidence: 99%

Risk factors of hepatocellular carcinoma in type 2 diabetes patients: A two-centre study in a developing country

Azit

Sahran

Meng³

et al. 2021

PLoS ONE

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Type 2 diabetes mellitus (T2DM) is increasingly known as a risk factor of hepatocellular carcinoma (HCC). In this study, we determined the risk factors associated with HCC in T2DM patients. This was a matched case-control study conducted at two hepatobiliary referral centres in a developing country. Patients’ sociodemographic, clinical, and biochemical characteristics between 1 January 2012 and 30 June 2018 were extracted from the electronic medical records and analysed using multivariate logistic regression analysis. A total of 212 case-control pairs were included. Significant risk factors included Chinese and Malay ethnicities that interacted with viral hepatitis (adjusted odds ratio [AOR] = 11.77, 95% confidence interval [CI]: 1.39–99.79) and (AOR = 37.94, 95% CI: 3.92–367.61) respectively, weight loss (AOR = 5.28, 95% CI: 2.29–12.19), abdominal pain/ discomfort (AOR = 6.73, 95% CI: 3.34–13.34), alcohol (AOR = 4.08, 95% CI: 1.81–9.22), fatty liver (AOR = 3.29, 95% CI: 1.40–7.76), low platelet (AOR = 4.03, 95% CI:1.90–8.55), raised alanine transaminase (AOR = 2.11, 95% CI: 1.16–3.86). and alkaline phosphatase (ALP) levels (AOR = 2.17, 95% CI: 1.17–4.00). Statins reduced the risk of HCC by 63% (AOR = 0.37, 95% CI: 0.21–0.65). The identification of these factors aids the risk stratification for HCC among T2DM patients for early detection and decision-making in patient management in the primary care setting.

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Section: Discussionmentioning

confidence: 99%

Risk factors of hepatocellular carcinoma in type 2 diabetes patients: A two-centre study in a developing country

Azit

Sahran

Meng³

et al. 2021

PLoS ONE

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“…In this regard, an international cohort study demonstrated that metformin significantly reduced the risk of HCC in MAFLD patients with HbA1c levels above 7.0% [245]. A meta-analysis has also shown that metformin prolongs the survival of HCC patients with T2DM after the curative treatment of the cancer [246]. Thus, metformin may be a beneficial treatment along with life-style intervention, in MAFLD-related HCC patients with T2DM.…”

Section: Management Of Mafld-related Hccmentioning

confidence: 98%

“…prospective or randomized [245,246]. Importantly, both GLP-1a and SGLT2i have been shown to be beneficial in cardiovascular outcome in patients with T2DM.…”

Section: Recommendationsmentioning

confidence: 99%

The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease

et al. 2020

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Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its Electronic supplementary material The online version of this article (

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“…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. 67 Future studies on treatments for NAFLD and non-alcoholic steatohepatitis will need to show whether their anti-fibrotic/anti-inflammatory properties translate into protection against HCC (Table 2).…”

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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Meta-analysis: The efficacy of metformin and other anti-hyperglycemic agents in prolonging the survival of hepatocellular carcinoma patients with type 2 diabetes

Cited by 42 publications

References 24 publications

Risk factors of hepatocellular carcinoma in type 2 diabetes patients: A two-centre study in a developing country

Risk factors of hepatocellular carcinoma in type 2 diabetes patients: A two-centre study in a developing country

The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease

Systemic treatment of HCC in special populations

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