Cholesterol gallstone disease

Department of Internal and Public Medicine, University Medical School, Bari, Italy.
The Lancet (Impact Factor: 45.22). 08/2006; 368(9531):230-9. DOI: 10.1016/S0140-6736(06)69044-2
Source: PubMed


With a prevalence of 10-15% in adults in Europe and the USA, gallstones are the most common digestive disease needing admission to hospital in the West. The interplay between interprandial and postprandial physiological responses to endogenous and dietary lipids underscores the importance of coordinated hepatobiliary and gastrointestinal functions to prevent crystallisation and precipitation of excess biliary cholesterol. Indeed, identifying the metabolic and transcriptional pathways that drive the regulation of biliary lipid secretion has been a major achievement in the field. We highlight scientific advances in protein and gene regulation of cholesterol absorption, synthesis, and catabolism, and biliary lipid secretion with respect to the pathogenesis of cholesterol gallstone disease. We discuss the physical-chemical mechanisms of gallstone formation in bile and the active role of the gallbladder and the intestine. We also discuss gaps in our knowledge of the pathogenesis of gallstone formation and the potential for gene targeting in therapy.

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Available from: Piero Portincasa
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    • "Cholesterol gallstone disease is a global problem that is influenced by several interacting genetic and environmental factors[16]. The pathogenesis of gallstone disease is complex involving imbalances in the secretion of biliary cholesterol and bile acids, crystallization/nucleation of cholesterol, impaired gallbladder and intestinal motility, and altered mucin secretion. "
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    ABSTRACT: Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "Many previous studies have shown that the gallstone disease risk factors are multifactorial (Panpimanmas & Manmee, 2009). These risk factors include increasing age, sex, dietary, high calorie intake, low fiber intake, high refined carbohydrates, hyper triglyceridaemia, physical inactivity, pregnancy, parity, overweight and obesity (Portincasa et al., 2006; Cariati, 2013; Storti et al, 2005; Panpimanmas & Manmee, 2009; Henao-Morán et al., 2014; Chandran et al., 2014). "
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    ABSTRACT: Objective: The present study aimed to evaluate the prevalence and possible risk factors of gallstone disease in the general population. Patients & methods: This cross sectional study was carried out on a total of 1522 males and females aged ≥30 years in Zahedan district, South-East of Iran. Data were collected by a validated questionnaire and gallstone diagnosis was assessed by an experienced radiologist using ultrasonography. Logistic regression model was used to identify the association between selected variables and gallstone disease. Results: The overall prevalence of gallstone in participants was 2.4%. The risk of gallstone was 2.60 times higher in people age 45 and older than those aged 30 - 44 years (Odds Ratio = 2.60, 95% CI; 1.22 - 5.55). Females were 2.73 (95% CI; 1.34 - 5.56) times more likely to have disease compared to males as well. The risk in unmarried individuals was also three times higher than married ones (OR = 2.99: 95% CI 1.02 - 9.16). Additionally, daily physical activity reduced the risk of gallstone disease by 66% (95% CI; 0.18 - 0.86). Conclusion: In conclusion, increasing age and female gender were risk factors, whereas daily physical activity and marriage identified as protective factors in aetiology of gallstone disease.
    Full-text · Article · Jul 2015 · Global journal of health science
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    • "Consumption of simple sugars and saturated fat has been mostly associated to a higher risk, while fibre intake consistently reduces the risk (Portincasa, 2006). "
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    ABSTRACT: Dietary hypocholesterolemic spices - curcumin (active compound of turmeric (Curcuma longa) and capsaicin (active compound of red pepper (Capsicum annuum), the active principles of spices - turmeric (Curcuma longa) and red pepper (Capsicum annuum), fenugreek (Trigonella foenum-graecum) seeds, garlic (Allium sativum), and onion (Allium cepa) are documented to have anti-cholelithogenic property in animal model. These spices prevent the induction of cholesterol gallstones by lithogenic high cholesterol diet and also regress the pre-established cholesterol gallstones, by virtue of their hypolipidemic potential. The antilithogenic influence of these spices is primarily attributable to their hypocholesterolemic effect. Increased cholesterol saturation index, cholesterol: phospholipid ratio and cholesterol: bile acid ratio in the bile caused by the lithogenic diet was countered by these spices. The anti-lithogenicity of these hypocholesterolemic spices was considered to be due also to their influence on biliary proteins which have pro-nucleating activity and anti-nucleating activity. Investigations on the involvement of biliary proteins in cholesterol crystal nucleation revealed that in an in vitro bile model, low molecular weight biliary proteins of the lithogenic diet fed animals have a pro-nucleating activity. On the contrary, low molecular weight biliary proteins of the animals fed hypocholesterolemic spices along with lithogenic diet showed a potent anti-nucleating activity.
    Full-text · Article · Jul 2015 · Critical reviews in food science and nutrition
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