Preventive Efficacy Of Statins For Gallstone Formation And Reduction The Risk Of Cholecystectomy :A Systematic Review

Background:Cholecystolithiasis is a digestive system disease worldwide,The prevalence of gallstones varies between 5% and 25%,with a higher prevalence in western countries.Recently,the incidence of gallstones in developing country is also increased,it is approximately 3% and 11% in china.Cholecystolithiasis is the main factors of inpatient admissions for gastrointestinal digestive disease.The traditional classification method based on the content of the cholesterol divided gallstones into three types, including cholesterol stone,pigment stone and mixed stone.Gallstones disease is a multifactorial disease influenced by a variety of factors,including genetic and environmental factors.Some factors is certain,for example increaing with age,female,genetics,ethnicity.some other factors are variegated,such as rapid weight loss,obesity,high carbohydrate diet,lack of physical activity,high dose oestrogen treatment,high serum triglyceride levels,low levels HDL,diabetes mellitus,gastrointestinal infections,liver cirrhosis,Crohn’s disease and so on.IT represents a failure of biliary cholesterol homeostasis.The most basic pathological change is persistent hepatic hypersecretion of biliary cholesterol.The survey showed about 2-4%of people with gallbladder stone develop symptoms.The clinical feature of gallstone is abdominal distension,intolerance to fired foods and steady biliary colic.There are some serious complication related to cholecystolithiasis,including acute chlolecystitis,acute pancreatitis,obstructive jaundice which are life threatening.about 3-40%mortality with pancreatitis.Some studies also shows that the occurrence of long-term gallstone is related to cancer of the biliary tract.Therefore,it is very important for the treatment of gallstones. Recently,Laparoscopic cholecystectomy is a major surgical treatment for gallstones.But,it is invasive and can cause serious surgical complications,and not every symptom patient want to underwent surgical treatment.It is controversial wheather patients with asymptomatic needs operation.UDCA has become main medical treatment for small,radiolucent cholesterol gallstones,but the dose of UDCA is difficult to control.so it is not to maximize clinical curative effect.Therefore a new,effective and noninvasive treatment is crucial for gallstone.Statins are competitive inhibitor of HMG-COA.Most studies have shown that statins can reduce the content of cholesterol in the gallbladder,and extend the time of cholesterol crystal nucleation.Besides statins can reduce the output of biliary cholesterol by reducing liver cholesterol biosynthesis.Some other sudies show that statins can reduce the risk of the gallbladder excision,it have observed that statins can decrease the risk of cholecystectomy in some large epidemiological studies.Some studies reported that statins can relieve symptom of gallstones and even dissolve the small gallstone,however,other studies can not support the opinion,So,there is a large controversial about the effect of statins.There are some studies reported that statins can relieve the abdominal pain and have some effect on the dissolution of gallbladder stones.But others didn’t show any relation between statins and dissolution of gallstones.It is a controversial problem.Up to now,there is still not any evidence-based basis at home and abroad.This research intends to adopt the method of the Cochrane system evaluation to provide evidence for the treatment of statins.Objective:To evaluate the preventive efficacy of statins for gallstone formation and reduction the risk of cholecystectomy by Cochrane Meta-analysis.Methods:We searched the Pub Med, Cochrane Central Register of Controlled Trials,EMBASE, VIP,CBM,CNKI to collect prospective and retrospective literature which discuss the the preventive efficacy of statins for gallstone formation and reduction the risk of cholecystectomy.The primary outcome is the relationship between statins exposure of gallbladder excision and the risk of cholecystectomy,the secondary outcome are the change of biliary cholesterol saturation index and bile cholesterol concentration.we strictly analyed data by Cochrane collaboration Rev Man5.0 Stata11.0 software.Results:14 study, were included.5 for RCTs,3 for before-after study were included with a total of 140 people; And then 4 for case-control study, 2 for cohort study were included with a total of 811 393 people observed,65 605 cases,745 788 controls. The result of RCTs and self-control studies showed that there were significance statistical differences between statin group and control group in lowing biliary cholesterol concentration[SMD=0.41, 95%CI(0.08,0.73),P=0.009]. The cholesterol saturation index [SMD=0.53, 95%CI(0.22,0.84),P=0.0008] in the statin group was significant lower than in the control group. The meta analysis result of case-control and cohort studies showed that the exposure duration of statins between one to two years[OR=0.89,95%CI(0.84,0.94)] or more than two years [OR=0.79,95%CI(0.67,0.94)] has more significant effect in lowing the risk of gallbladder excision than less one year [OR=1.13,95%CI(1.04,1.22)].Conclusions:The research results show that statins have significantly reduced the gallbladder cholesterol and bile cholesterol saturation index.It may be have certain early prevention effect for patient at high risk of gallstone disease.In addition, long-term use of statins may have an reduction the risk of gallbladder excision for patients who are reluctant to laparoscopic or surgical removal of the gallbladder. If in the future to further study whether statin drugs to dissolve gallstones, Some prospective multi-center studies are needed to prove the viewpoint.