A Combination Therapy With Simvastatin and Ursodeoxycholic Acid Is More Effective for Cholesterol Gallstone Dissolution Than Is Ursodeoxycholic Acid Monotherapy

Tazuma, Susumu; Kajiyama, Goro; Mizuno, Toshiyuki; Gunji, Yoshio; Miura, Hiroyuki; Kajihara, Toshiki; Hattori, Yuya; Miyake, Hiroaki; Nishioka, Tomoji; Hyogo, Hideyuki; Sunami, Yasushi; Yasumiba, Shigeyuki; Ochi, Hidenori; Matsumoto, Takuya; Abe, Akio; Adachi, Ken; Omata, Fumio; Ueno, Fumiaki; Sugata, Fumio; Ohguri, Shigeyoshi; Shibata, Hisao; Kokubu, Shigehiro

doi:10.1097/00004836-199806000-00015

Cited by 30 publications

(23 citation statements)

References 20 publications

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“…Overall, these findings point to a likely benefit of life style and dietary modification as effective measures for the prevention of cholelithiasis [39]. In addition, they support previous observations indicating that medications used to treat dyslipidemia may be of value in the prevention and treatment of cholelithiasis [31,40]. …”

Section: Discussionsupporting

confidence: 83%

Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study

et al. 2011

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BackgroundCholelithiasis has become a major health problem in Taiwan. The predominant type of gallstone found in Asian populations differs from that in the West, indicating possible differences in the etiology and risk factors for cholelithiasis. The aim of this study is to investigate the risk factors for cholelithiasis using data representative of the general population.MethodsWe performed a population-based, case-control study in which we analyzed medical data for 3725 patients newly diagnosed with cholelithiasis and 11175 gender- and age-matched controls with no history of cholelithiasis, using information obtained from the 2005 Registry for Beneficiaries of the National Health Insurance Research Database. Coexisting medical conditions were included in the analysis. Relative risks were estimated by adjusted odds ratio (OR) and 95% confidence interval (CI) using a multivariate logistic regression analysis.ResultsAfter controlling for the other covariates, multivariate logistic regression analysis identified the following as risk factors for cholelithiasis (in descending order of contribution): Among all patients - hepatitis C (OR = 2.78), cirrhosis (OR = 2.47), hepatitis B (OR = 2.00), obesity (OR = 1.89), and hyperlipidemia (OR = 1.54); Among women - hepatitis C (OR = 3.05), cirrhosis (OR = 1.92), obesity (OR = 1.91), menopause (OR = 1.61), hepatitis B (OR = 1.54), and hyperlipidemia (OR = 1.49). Diabetes mellitus appeared to have a marked influence on the development of cholelithiasis but was not identified as a significant independent risk factor for cholelithiasis.ConclusionsThe risk factors for cholelithiasis were obesity, hyperlipidemia, hepatitis B infection, hepatitis C infection, and cirrhosis in both genders, and menopause in females. Despite differences in the predominate type of gallstone in Asian versus Western populations, we identified no unique risk factors among the population of Taiwan.

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Section: Discussionsupporting

confidence: 83%

Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study

et al. 2011

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“…At the same time simvastatin and bile acids also regulate the expression of these transporters [28], [30], [31], [32]. Interactions between simvastatin and selected bile acids competing for membrane transport may be responsible for some of the off target effects of the drug [33].…”

Section: Discussionmentioning

confidence: 99%

Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment

et al. 2011

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Although statins are widely prescribed medications, there remains considerable variability in therapeutic response. Genetics can explain only part of this variability. Metabolomics is a global biochemical approach that provides powerful tools for mapping pathways implicated in disease and in response to treatment. Metabolomics captures net interactions between genome, microbiome and the environment. In this study, we used a targeted GC-MS metabolomics platform to measure a panel of metabolites within cholesterol synthesis, dietary sterol absorption, and bile acid formation to determine metabolite signatures that may predict variation in statin LDL-C lowering efficacy. Measurements were performed in two subsets of the total study population in the Cholesterol and Pharmacogenetics (CAP) study: Full Range of Response (FR), and Good and Poor Responders (GPR) were 100 individuals randomly selected from across the entire range of LDL-C responses in CAP. GPR were 48 individuals, 24 each from the top and bottom 10% of the LDL-C response distribution matched for body mass index, race, and gender. We identified three secondary, bacterial-derived bile acids that contribute to predicting the magnitude of statin-induced LDL-C lowering in good responders. Bile acids and statins share transporters in the liver and intestine; we observed that increased plasma concentration of simvastatin positively correlates with higher levels of several secondary bile acids. Genetic analysis of these subjects identified associations between levels of seven bile acids and a single nucleotide polymorphism (SNP), rs4149056, in the gene encoding the organic anion transporter SLCO1B1. These findings, along with recently published results that the gut microbiome plays an important role in cardiovascular disease, indicate that interactions between genome, gut microbiome and environmental influences should be considered in the study and management of cardiovascular disease. Metabolic profiles could provide valuable information about treatment outcomes and could contribute to a more personalized approach to therapy.

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“…Statins could potentially reduce risk of BTCs through suppression of biliary cholesterol secretion and saturation and anti-inflammatory and endothelial effects 29 30. The reduction in hepatic and gall bladder bile cholesterol concentrations could alter bile acid composition and interfere with gallstone production or even promote gallstone dissolution 31. In addition, both experimental and clinical studies provide evidence that statins have anti-inflammatory effects 29 30.…”

Section: Discussionmentioning

confidence: 99%

Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink

Liu

Alsaggaf

McGlynn

et al. 2018

Gut

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ObjectiveTo evaluate the association between statin use and risk of biliary tract cancers (BTC).DesignThis is a nested case–control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders.ResultsWe included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (ptrend=0.016) and cumulative dose of statins (ptrend=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007).ConclusionCompared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.

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A Combination Therapy With Simvastatin and Ursodeoxycholic Acid Is More Effective for Cholesterol Gallstone Dissolution Than Is Ursodeoxycholic Acid Monotherapy

Cited by 30 publications

References 20 publications

Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study

Risk factors associated with symptomatic cholelithiasis in Taiwan: a population-based study

Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment

Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink

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