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

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.背景 近期流行病学证据显示，胆结石或胆囊切除术与肝癌发病风险存在关联，但现有研究结果并不一致。本研究针对观察性研究开展荟萃分析，以明确二者之间的关联。 方法 我们通过检索截至2014年3月的PubMed、EMBASE、Cochrane对照试验中心注册库及相关会议论文集来筛选研究。采用随机效应模型计算合并后的多变量校正比值比（odds ratio, OR）与95%置信区间（confidence interval, CI）。使用Cochran Q统计量与I²值评估研究间异质性。 结果 本分析共纳入15项研究，其中5项为病例对照研究，10项为队列研究，总计纳入4487662名研究对象，确诊肝癌病例17945例，存在胆结石病史者328420名，接受过胆囊切除术者884507名。合并分析结果显示，有胆结石病史者的肝癌发病风险显著升高（OR=2.54；95%CI：1.71~3.79；共纳入11项研究），有胆囊切除术史者的肝癌发病风险同样显著升高（OR=1.62；95%CI：1.29~2.02；共纳入12项研究），但上述研究间存在显著异质性。按性别、研究设计、研究区域及研究质量进行分层分析后，效应估计值未出现明显变化。多变量荟萃回归分析表明，研究区域与研究质量可解释胆囊切除术亚组分析中观察到的异质性。 结论 本研究结果提示，存在胆结石病史及接受过胆囊切除术的个体，其肝癌发病风险可能升高。