Risk of Primary Liver Cancer Associated with Gallstones and Cholecystectomy: A Meta-Analysis

Abstract

BackgroundRecent epidemiological evidence points to an association between gallstones or cholecystectomy and the incidence risk of liver cancer, but the results are inconsistent. We present a meta-analysis of observational studies to explore this association.MethodsWe identified studies by a literature search of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and relevant conference proceedings up to March 2014. A random-effects model was used to generate pooled multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Between-study heterogeneity was assessed using Cochran’s Q statistic and the I2. ResultsFifteen studies (five case-control and 10 cohort studies) were included in this analysis. There were 4,487,662 subjects in total, 17,945 diagnoses of liver cancer, 328,420 exposed to gallstones, and 884,507 exposed to cholecystectomy. Pooled results indicated a significant increased risk of liver cancer in patients with a history of gallstones (OR = 2.54; 95% CI, 1.71–3.79; n = 11 studies), as well as cholecystectomy (OR = 1.62; 95% CI, 1.29–2.02; n = 12 studies), but there was considerable heterogeneity among these studies. The effects estimates did not vary markedly when stratified by gender, study design, study region, and study quality. The multivariate meta-regression analysis suggested that study region and study quality appeared to explain the heterogeneity observed in the cholecystectomy analysis.ConclusionsOur results suggest that individuals with a history of gallstones and cholecystectomy may have an increased risk of liver cancer.

Cholecystectomy is associated with higher risk of early recurrence and poorer survival after curative resection for early stage hepatocellular carcinoma

“…Studies demonstrate that removal of the gallbladder will leads to Sphincter of Oddi (SO) dysfunction, which in turn will cause dilation of the CBD, elevated bile duct pressure, and subsequent cholestasis and chronic inflammation67891011. Inflammation-mediated tumor angiogenesis has been confirmed by various studies and release of inflammation related cytokines, chemokines, growth factors plays decisive roles in cancer invasion, recurrence and metastasis5161718. In addition, the accumulation of bile and secondary bile acids, in particular, deoxycholic acid, can act as carcinogens and promote the recurrence and occurrence of cancers3839.…”

“…Recently, much more epidemiological investigations and meta-analyses have addressed the relation between cholecystectomy and hepatocellular carcinoma (HCC)2345. Though a causal association between them remains to be established, the majority of these studies indicate that cholecystectomy is associated with an increased risk of developing HCC.…”

Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes

“…Viral hepatitis B and C are the main causes of HCC in countries with a high incidence, but alcohol, obesity and type 2 diabetes mellitus may be responsible in more developed countries . Risk factors that have not yet been confirmed include Helicobacter pylori infection, gallstones and fibrate use …”

Association Between Screen-Detected Gallstone Disease and Cancer in a Cohort Study

“…1,2 More recently, clinically diagnosed gallstone disease, including symptomatic gallstones or cholecystectomy, has been explored in cohort studies and associated with higher overall occurrence of cancer, 3,4 with gastrointestinal cancers such as hepatic, 5 biliary, [6][7][8] pancreatic, 4,9 esophageal, 10,11 gastric, 8,12 small intestines, 4,13,14 colon, 4,8,[13][14][15][16][17][18][19] and with nongastrointestinal cancers, such as breast 4,20 and prostate. 21 However, these studies may be biased by the increased risk of cancer detection after clinically diagnosed gallstone disease.…”