The Role of Pre-Existing Diabetes Mellitus on Hepatocellular Carcinoma Occurrence and Prognosis: A Meta-Analysis of Prospective Cohort Studies

Abstract

BackgroundThe impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis.MethodsWe searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models.ResultsThe database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15–2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39–2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13–1.48) risk of death from all-causes and 91% increased (95%CI: 1.41–2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12–3.33) compared with non-diabetic patients.ConclusionThe findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts.

Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

“…These findings were supported by recent meta-analyses, particularly for patients with HCC after potentially curative approaches [11,15,16]. The impact of diabetes mellitus on the outcome of patients with advanced HCC treated with sorafenib was recently evaluated in a large cohort study [41].…”

Epidemiology and Surveillance of Hepatocellular Carcinoma

“…Multiple cohort or case-control studies have shown an association between the presence of diabetes and risk of HCC development [36][37][38]. A meta-analysis revealed that pre-existing diabetes was significantly associated with increased risk of HCC incidence (meta-RR 1.87, 95% CI 1.15-2.27) and HCC-specific mortality (meta-RR 1.88, 95% CI 1.39-2.55) compared with their nondiabetic counterparts, indicating that diabetes may be associated with elevated risk of both HCC incidence and mortality [39]. Phosphatase and tensin homolog (PTEN) is a multifunctional phosphatase and it is also a ubiquitously expressed tumor suppressor gene that downregulates PI3Ks [40].…”

The Indian National Association for Study of the Liver (INASL) Consensus on Prevention, Diagnosis and Management of Hepatocellular Carcinoma in India: The Puri Recommendations

“…Diabetes mellitus is also known to be associated with elevated risks of both HCC incidence and mortality. [11][12][13] Indian studies have also corroborated these findings and cirrhosis of liver, HBV infection, HCV infection, alcohol consumption, and aflatoxin exposure have been found to be the most important risk factors for HCC development. 7,[14][15][16][17][18][19][20][21][22][23][24][25][26] In addition to these, NAFLD is now increasingly being recognized from India as a cause of HCC.…”