Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan

Type 2 diabetes mellitus characteristics affect hepatocellular carcinoma development in chronic hepatitis B patients with cirrhosis

“…On the contrary, metformin treatment was reported to be associated with a reduced risk of HCC[ 12 ]. A large-scale study also showed that the use of metformin among DM patients can significantly reduce the HCC risk in chronic hepatitis C patients[ 23 ]. The underlying mechanism has not been fully understood, but it may be related with the anti-proliferative and immune-modulating effect of metformin[ 24 ].…”

Metabolic dysfunction outperforms ultrasonographic steatosis to stratify hepatocellular carcinoma risk in patients with advanced hepatitis C cured with direct‐acting antivirals

“…All in all, evidence suggests that in patients with advanced HCV cured with DAAs, HCC risk stratification based on MD and even more in the presence of diabetes, rather than US, should be used together with additional non‐invasive biomarkers 14 to guide reinforced HCC surveillance by, for example, magnetic resonance imaging, including with abbreviated protocols, in high‐risk patients 42,43 . In addition, pharmacological approaches targeting metabolic co‐morbidities, such as metformin in patients with diabetes or fasting hyperglycaemia but without decompensated cirrhosis, may decrease HCC incidence 15,44 …”

Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms

“…In DM patients, metformin use is associated with a significantly reduced risk of HCC This study evaluated the OS (primary outcome); After curative treatment of HCC, compared to other antidiabetic drugs, metformin use The use of metformin in HCC patients with DM Zhou et al [55] the RFS and the PFS were also evaluated (secondary outcomes) Medline and EMBASE databases were searched until January 2019 to this end. Eight published studies, globally enrolling 13,985 patients, were included in this metanalytic review was associated with significantly longer OS at 1, 3, and 5 years (all P < 0.00001) and RFS at 1 and 3 years (all P < 0.00001) treated with curative options was associated with significantly improved OS and RFS Tan et al [56] Medline and Embase databases were searched to identify studies published in English before February 2018 Seven studies were retrieved (5 cohort studies and 2 case-control studies), totaling 21,842 HBV chronically infected individuals Compared to DM-free individuals, the DM population was prone to an increased incidence of HCC (pooled HR 1.77, 95%CI: 1.28-2.47; fixed effect) and higher overall mortality (pooled RR 1.93, 95%CI: 1.64-2.27; fixed effect) Among individuals with chronic infection owing to HBV, DM is associated with increased HCC risk Wang et al [57] PUBMED and MEDLINE databases were searched for studies published before February 2011 Overall, 17 case-control studies and 32 cohortselected studies were included in the present meta-analysis Data have shown a statistically significant increased prevalence of HCC among diabetic individuals (RR = 2.31, 95%CI: 1.87-2.84) The risk of HCC was decreased by metformin treatment and increased by DM duration and treatment with sulfonylureas or insulin Individuals with DM (compared to those DM-free) had a statistically significant increased risk of HCC mortality (RR = 2.43, 95%CI: 1.66-3.55) DM is associated with a moderately increased risk of HCC prevalence and mortality Wang et al [60] Studies published before 2010 were retrieved through a literature search of Medline from 1966 and EMBASE from January 1974. Overall, 25 cohort studies meeting inclusion and exclusion criteria were selected Compared to non-diabetic controls, DM was associated with an increased incidence of HCC (SRRs = 2.01, 95%CI: 1.61-2.51), independent of confounding factors (i.e., geographic location, alcohol consumption, history of cirrhosis, or infections with either HBV or HCV) Moreover, DM was positively associated with HCC mortality (SRR = 1.56; 95%CI: 1.…”

“…Studies in Table 1 support the notion that DM is a risk factor for the development of and mortality associated with HCC [57] . Interestingly, the association of DM and HCC is independent of sex, geographic location, alcohol consumption, history of cirrhosis, or chronic viral hepatitis [60] ; however, the risk of developing HCC is affected by DM duration and type of antidiabetic treatment [57] , and DM synergizes with HCV infection in increasing the risk of HCC [52] . This increased risk of developing HCC is also observed among those with DM following treatment with DAAs for HCV infection [53] .…”