Plain language summary
Liver cancer is one of the most common cancers worldwide and chronic liver disease a major cause of death in the US. Viral hepatitis and excessive alcohol intake are important risk factors, but do not explain many cases. Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and several metabolic abnormalities, suggesting a link between metabolic factors and cancer of the liver. This review and meta-analysis pooled data from 19 epidemiological studies, involving 1,561,457 participants, to evaluate the risk of metabolic syndrome for liver related events (LREs). 16 of the 19 studies showed an increased risk of LREs for people with metabolic syndrome, whilst 3 found a negative association. The meta-analysis found that people with metabolic syndrome had increased risks of 76% for liver cancer and of 421% for death from liver related causes. The risk of any LRE was increased by 49%. The risks were higher for people with hepatitis B infection and lower for people living in Asia. The authors state that the mechanisms are not fully understood and hypothesise that people with metabolic syndrome likely share risk factors for cancer, such as low physical activity, oxidative stress and dietary factors such as high caloric food, high fat and low fibre intake. The authors conclude that metabolic syndrome is an important risk factor for liver disease.
Abstract
BACKGROUND Previous studies have suggested that metabolic syndrome (MetS) and its component conditions are linked to the development of many benign or malignant diseases. Some studies have described relationships among metabolic syndrome or diabetes and liver cancer, but not many articles described the relationships between MetS and cirrhosis, acute hepatic failure, end-stage liver disease, and even death. However, liver cancers, cirrhosis, acute hepatic failure, end-stage liver disease, and liver-related mortality-collectively described as liver-related events (LREs)-may have different relationships with MetS. We undertook this meta-analysis to examine the association between MetS and LREs, and to determine whether geographic region or hepatitis B virus (HBV) positivity might influence the association. METHODS Relevant studies were identified from PubMed, EMBASE, and the Cochrane database. Two reviewers independently searched records from January 1980 to December 2017. The search terms included 'metabolic syndrome', 'diabetes mellitus', 'insulin resistance syndrome', and 'metabolic abnormalities', combined with 'cirrhosis', 'hepatic fibrosis ', 'hepatocellular carcinoma', 'complication', 'LRE', 'HCC', 'liver-related events', and 'liver cancer'. No language restriction was applied to the search. We chose the studies reporting an association between MetS and LREs. We used Begg's and Egger's tests and visually examined a funnel plot to assess publication bias. All analyses were conducted in Stata 14.0 software. RESULTS There were 19 studies (18 cohort and 1 case-control) included in the analysis, with a total of 1,561,457 participants. The subjects' ages ranged from 18 to 84 years. The combined analysis showed an overall 86% increase risk of LREs in cases with MetS (RR: 1.86,95% CI: 1.56-2.23). The funnel plot was asymmetrical, and the Egger's test p values showed a publication bias in this meta analysis. However, through the trim and fill method, we obtained a new RR value for LREs with MetS of 1.49 (95% CI: 1.40-1.58, p = 0.000). There was no obvious difference with the two answers, so we concluded that the results were robust. For hepatitis B positive patients, the RR for MetS and LREs was 2.15 (95% CI:1.02-4.53, p = 0.038), but for the hepatitis B negative patients, the RR was 1.85 (95% CI:1.53-2.24, p = 0.000). And for non-Asians, the RR for MetS and LREs was 2.21 (95% CI: 1.66-2.69, p = 0.000), while for Asians, the RR was 1.73 (95% CI: 1.35-2.22, p = 0.000). CONCLUSIONS This meta-analysis showed that MetS is associated with a moderately increased risk of LREs prevalence. Patients with MetS together with hepatitis B are more likely to develop hepatic events. For non-Asians, MetS is more likely to increase the incidence of LREs.
Methodological quality
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