Association between metabolic syndrome components and the risk of primary liver cancer and cirrhosis


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Paul Nderitu1,Hans Garmo2,Lars Holmberg2,Hakan Malmstrom3,Niklas Hammar3,Goran Walldius3,Ingmar Jungner3,Mats Lambe4,Mieke Van Hemelrijck2
1Guy's and St Thomas' NHS Trust Foundation,2King's College London,3Karolinska Institute,4Karolinske Institute

Abstract

Background

Hepatocellular carcinoma (HCC) accounts for the majority of malignant primary liver cancers (PLCs). Metabolic syndrome is associated with non-alcoholic fatty liver disease, progression of which may result in cirrhosis, a significant risk factor of HCC. We therefore aimed to investigate the association between metabolic syndrome components (lipids, raised glucose, diabetes and obesity), PLC and cirrhosis.

Method

A total of 509,436 participants from the Swedish AMORIS cohort, recruited January 1985 to December 1996 (study end-date December 2011), aged ≥20 with baseline triglycerides (TG), total cholesterol (TC) and glucose were included. Those with benign or metastatic liver cancer or cirrhosis at baseline were excluded. Lipids were categorised using clinical cut-offs and quartiles. Multivariate Cox proportional hazards, adjusted for age, gender, socio-economic status, liver disease and metabolic factors were used to estimate the association with PLC and cirrhosis.

Results

There were 766 PLC and 2,775 cirrhosis cases (mean follow-up 13 years). Raised TG, low TC, raised glucose, diabetes and low HDL (according to clinical cut-offs and quartiles) were associated with an increased risk of developing cirrhosis and PLC (e.g. TG≥1.71mmol/l vs <1.71mmol/l, HR: 1.38 (95% CI:1.17-1.63)). Raised ApoB and ApoB/ApoA-I were also associated with an increased risk of PLC whilst low LDL quartiles, raised TG/HDL and low ApoA-I were associated with an increased risk of cirrhosis (e.g. ApoA-I<1.05g/L vs ≥1.05g/L, HR: 1.78 (95% CI:1.31-1.63)). Obesity (BMI >30kg/m2) was not independently associated with PLC or cirrhosis, but raised glucose and diabetes remained significant risk factors after additional BMI adjustment. Raised TG, low TC, raised glucose and diabetes showed stronger associations with PLC in patients with a history of cirrhosis. Many patients developed PLC without a history of cirrhosis.

Conclusion

Metabolic serum biomarkers (triglycerides, cholesterol, apolipoproteins B and A-1, and glucose) were independently associated with an increased risk of developing PLC and cirrhosis, but obesity was not.