Journal of hepatology
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Journal of hepatology · Aug 2010
Comparative StudyThe 148M allele of the PNPLA3 gene is associated with indices of liver damage early in life.
Childhood obesity is a growing problem worldwide. Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity in children. Recently, the PNPLA3 gene I148M (rs738409) variant was demonstrated to be strongly associated with hepatic steatosis in obese adults. In this study we add further insight into the role of PNPLA3 by exploring whether this association begins early in life in obese children or becomes manifest only in adulthood. ⋯ Our data show that the PNPLA3 gene I148M variant is associated with increased levels of ALT/AST in obese children and adolescents, suggesting that it confers genetic susceptibility to liver damage from a young age.
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Journal of hepatology · Jul 2010
ReviewMetabolic syndrome and liver transplantation: a review and guide to management.
Metabolic syndrome is common among liver transplant recipients before and after transplantation. The components of metabolic syndrome are often exacerbated in the post-transplant period by transplant specific factors, such as immunosuppression, and are strong predictors of patient morbidity and mortality. ⋯ Early recognition, prevention and treatment of post-transplant hypertension, obesity, dyslipidemia and diabetes may impact long-term post-transplant survival. Further study into the prevention and management of these issues in the transplant patient are needed.
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Increased cardiac output was first described in patients with cirrhosis more than fifty years ago. Later, various observations have indicated the presence of a latent cardiac dysfunction, which includes a combination of reduced cardiac contractility with systolic and diastolic dysfunction and electrophysiological abnormalities. This syndrome is termed cirrhotic cardiomyopathy. ⋯ The QT interval is prolonged in about half of the cirrhotic patients and it may be normalised by beta-blockers. No specific therapy for cirrhotic cardiomyopathy can be recommended, but treatment should be supportive and directed against the cardiac dysfunction. Future research should better describe the prevalence, impact on morbidity and survival, and look for potential treatments.
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Journal of hepatology · Jun 2010
Comparative Study Clinical TrialAssessment of adrenal function in cirrhotic patients: salivary cortisol should be preferred.
Adrenal insufficiency is a common disorder among cirrhotic patients. Adrenal function is usually assessed with serum total cortisol assays. Free cortisol (active fraction) represents only 10% of serum total cortisol, the remaining 90% being linked to cortisol-binding globulin (CBG) and albumin. In cirrhotic patients, the synthesis of these proteins is reduced, which could lead to an overestimation of the prevalence of adrenal insufficiency. Salivary cortisol assessment adequately reflects free cortisol plasma concentration. However, this method has never been validated in cirrhotic patients. The objectives of this report were to assess the following parameters by a prospective observational study: (1) correlation between salivary, serum total and free cortisol, (2) adrenal insufficiency prevalence using salivary and serum assays, (3) parameters associated with a discrepancy between both tests, and (4) adrenal insufficiency risk factors among cirrhotic patients. ⋯ Using serum total cortisol assays overstate adrenal insufficiency prevalence among cirrhotic patients, mainly because of inaccurate concentrations related to hypoalbuminemia. Salivary cortisol assays should be preferably used in these patients.
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Journal of hepatology · May 2010
The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma.
Bcl-xL, an anti-apoptotic member of the Bcl-2 family, is over-expressed in human hepatocellular carcinoma, conferring a survival advantage to tumour cells. The mechanisms underlying its dysregulation have not been clarified. In the present study, we explored the involvement of microRNAs that act as endogenous sequence-specific suppressors of gene expression. ⋯ let-7 microRNAs negatively regulate Bcl-xL expression in human hepatocellular carcinomas and induce apoptosis in cooperation with an anti-cancer drug targeting Mcl-1.