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Journal: Annals of hepatology

138

The recent discovery of bile acid (BA) receptors and a better delineation of the multiple roles of BAs in relevant biological processes have revamped BA research. The vasoactive actions of BAs were recognized more than three decades ago but the underlying mechanisms of the BA-induced vasorelaxation are now being clarified. Recent evidence shows that the BA receptors FXR and TGR5 are expressed in endothelial cells and may have important effects on both systemic and portal circulation. The availability of genetically engineered mice with ablation of BA receptors and the development of BA receptor agonists has allowed to explore the modulation of XR and, in a lesser extent, of TGR5 in the setting of portal hypertension (PHT) with promising results. In this review, we summarize recent data on how BA-dependent pathways influence several processes that impact in PHT and the preclinical data showing that pharmacological modulation of those pathways may hold promise in the treatment of PHT.

Concepts: DNA, Protein, Receptor antagonist, Cardiovascular system, Serotonin, Steroid, Inverse agonist, Vasoconstriction

26

Background and aim. In patients with chronic hepatitis C receiving Peg interferon/ribavirin (PEG-IFN/RBV) who do not achieve ≥ 2log-reduction in HCV-RNA at week 12 (null responders, NR) and in those with ≥ 2log-decrease but detectable at week 24 (partial responders, PR) the probability to achieve the sustained virological response (SVR) is almost null. The aim of this study was to investigate the efficacy of individualized schedule of progressively increased RBV doses in the setting of PEG-IFN/RBV treatment. Material and methods. PR or NR to PEG-IFN/RBV instead of discontinuing treatment were enrolled to receive increasing doses of RBV until a target theoretical concentration ([tRBV]) of ≥ 15 μmol/L (by pharmacokinetic formula based on glomerular filtration rate). HCV-RNA was assessed every 4 weeks and, if detectable, RBV dose was gradually increased until negativization. Twelve weeks later, patients with detectable HCV-RNA discontinued therapy while those with undetectable HCV-RNA continued for further 48 weeks. Results. Twenty genotype-1 patients (8 NR and 12 PR) were enrolled. After 12 weeks 9 (45%) were still HCV-RNA positive and were discontinued, while remaining 11 had undetectable HCV-RNA. One stopped treatment for side effects. Ten completed treatment. Five (all PR) achieved SVR. Side effects incidence was similar to that observed during PEG-IFN/RBV. Conclusions. In conclusion, RBV high doses, according to individualized schedule, increase SVR in PR on a similar extent to that of triple therapy but without increase of side effects. Such treatment should be considered in PR with no access or intolerant to protease inhibitors (PI).

Concepts: Pharmacology, Glomerulus, Renal function, Hepatitis, Dose, Hepatitis C, Hepatitis A, Conclusion

1

The primary bile acids (BAs) are synthetized from colesterol in the liver, conjugated to glycine or taurine to increase their solubility, secreted into bile, concentrated in the gallbladder during fasting, and expelled in the intestine in response to dietary fat, as well as bio-transformed in the colon to the secondary BAs by the gut microbiota, reabsorbed in the ileum and colon back to the liver, and minimally lost in the feces. BAs in the intestine not only regulate the digestion and absorption of cholesterol, triglycerides, and fat-soluble vitamins, but also play a key role as signaling molecules in modulating epithelial cell proliferation, gene expression, and lipid and glucose metabolism by activating farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor-1 (GPBAR-1, also known as TGR5) in the liver, intestine, muscle and brown adipose tissue. Recent studies have revealed the metabolic pathways of FXR and GPBAR-1 involved in the biosynthesis and enterohepatic circulation of BAs and their functions as signaling molecules on lipid and glucose metabolism.

Concepts: Cholesterol, Protein, Metabolism, Nutrition, Liver, Fat, Bile, Bile acid

0

The Transplanted Organ Questionnaire (TOQ), developed in France, is a disease-targeted instrument designed to evaluate what the transplanted organ represents to the recipient in patients who have undergone liver transplantation. The present study sought to validate a version of the TOQ for use in the Brazilian population. Translation and cross-cultural adaptation were carried out in accordance with international standard practices. Convergent validity was measured by correlations between TOQ domains and the Beck Depression Inventory (BDI), while reliability was assessed by measurement of internal consistency (Cronbach’s alpha coefficient), reproducibility (intraclass correlation coefficient), sensitivity to change (effect size), and floor and ceiling effects.

Concepts: Spearman's rank correlation coefficient, Psychometrics, Correlation and dependence, Reliability, Pearson product-moment correlation coefficient, Covariance and correlation, Cronbach's alpha, Beck Depression Inventory

0

To investigate the association of adolescent obesity with nonalcoholic fatty liver disease (NAFLD) and related risk factors in Xi ‘an, China.

Concepts: Cancer, Obesity, Cirrhosis, Metabolic syndrome, Non-alcoholic fatty liver disease, Fatty liver, Steatosis, Steatohepatitis

0

Transplant recipients are chronically ill patients who rely on medical treatment throughout life to achieve positive results. Despite that, medication nonadherence after liver transplantation is extremely common. The self-report, one of several methods for measuring adherence, is easy to apply and low cost. Thus, this study aims to translate and validate the Immunosuppressant Therapy Adherence Instrument (ITAS) in Brazilian Portuguese for liver transplant recipients.

Concepts: Medicine, Cirrhosis, Liver, Organ transplant, Immunosuppression, Brazil, Liver transplantation, Liver dialysis

0

We sought to describe: 1) The influence of orthotopic liver transplantation (OLT) on exercise capacity, pulmonary function and respiratory muscle strength after surgery, 2) The relationship between exercise capacity and symptoms of anxiety and depression.

Concepts: Muscle, Cirrhosis, Liver, Organ transplant, Liver transplantation

0

Risk and Prognosis of Acute Liver Injury Among Hospitalized Patients with Hemodynamic Instability: A Nationwide Analysis Introduction and aim. Critically ill patients in states of circulatory failure are at risk of acute liver injury, from mild elevations in aminotransferases to substantial rises consistent with hypoxic hepatitis or “shock liver”. The present study aims to quantify the national prevalence of acute liver injury in patients with hemodynamic instability, identify risk factors for its development, and determine predictors of mortality.

Concepts: Present, Epidemiology, Medical terms, Hospital, Medical statistics, Illness, Hemodynamics, Physical trauma

0

Prognostic ability of BCLC-B Subclassification in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Background and aims. A subclassification system for intermediate hepatocellular carcinoma (HCC) was recently proposed to optimize treatment allocation. The aim of this study was to assess the prognostic ability of that substaging proposal.

Concepts: Cancer, Proposal, Proposals

0

The objective of this study was to evaluate short- and long-term survival after surgical treatment between young and older hepatocellular carcinoma (HCC) patients beyond the Milan criteria.

Concepts: Hepatocellular carcinoma