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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

Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in the liver and/or serum (< 200 IU/mL) in HBsAgnegative patients with or without serologic markers of previous viral exposure. The clinical significance of OBI is of concern in posttransfusional hepatitis B infection, hepatitis B reactivation, chronic liver disease and hepatocellular carcinoma (HCC). The diagnosis of OBI relays on the use of highly sensitive and specific laboratory techniques. Herein, comments derived from a study analyzing the frequency and characteristics of OBI in HCC Japanese patients are stated. While OBI and other causes of HCC have been highly studied in Asia and Europe, research in Latin America in these topics is limited. Several findings such as population risk groups with high prevalence of overt and OBI infection, HBV genotype F in Argentinean HCC patients, and the clinical impact of the foreign A-D genotypes suggest the need of further investigation. Additionally, alcoholism, obesity, NASH and type 2 diabetes may override the presence of OBI. Therefore, OBI diagnosis is essential. It is known that anti-HBc alone is a predictive signal of potential OBI and given the fluctuations of the HBV infection markers, testing for HBsAg and anti-HBc at baseline and follow-up is recommended. In conclusion, OBI and other causes involved in the epidemiology of HCC in Latin America are unexplored risk factors. Genome-based research is required to decipher the role of gene-environmental interactions associated with chronic liver disease. Novel algorithms to detect OBI supported by basic/applied/clinical research are also needed.

0

Based on high seroprevalence, null surveillance, and lack of diagnostics, Mexico is a high-risk region for hepatitis E Virus (HEV) infection. However, few local news on infection are available. Clinicians and general population are in need of increasing awareness, and preventive measures should be emphasized.

0

HAVCR1 protein is the cellular receptor for hepatitis A virus (HAV). Genetic polymorphism in this gene may alter the outcome of HAV infection. In a previous study, a 6-amino acid insertion (157insMTTTVP) in HAVCR1 gene was associated with more severe disease. We decided to investigate this association further.

0

Decompensated liver cirrhosis has a dismal prognosis, with an overall survival of 2-4 years, which is worse than for many oncological diseases. Albumin is an important tool in the management of patients with cirrhosis, since it decreases for less than half the risk for post-paracentesis cardiocirculatory dysfunction and mortality associated with spontaneous bacterial infection, as well as, it triplicates the response to terlipressin in patients with hepatorenal syndrome. Recently, research on albumin has been a hot topic, with important new insights such as the characterization of the pleiotropic effects of albumin (which surpass its oncotic properties) and the concept of effective albumin concentration. In fact, patients with liver cirrhosis present posttranslational modifications on albumin that compromises its function. Those modified albumin forms were proved to have prognostic value and its knowledge may change the paradigm of albumin treatment. In this review, we critically summarize the latest evidence on the potential benefits of albumin in patients with end-stage liver disease.

0

The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease.

0

Nonalcoholic fatty liver disease (NAFLD) is closely associated with overweight and obesity, becoming one of the most prevalent hepatic diseases nowadays. Circulating hemoglobin (Hb) concentration is significantly higher in people with NAFLD, compared to healthy patients. While liver biopsy remains the gold standard for NAFLD diagnosis, it is not the best technique due to adverse events that may occur. Therefore it is important to find less invasive and more sensitive markers. This study aimed to determine the association of serum Hb levels in patients with steatosis and fibrosis as a noninvasive marker.

0

The prevalence of obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease are increasing. Type 2 diabetes mellitus may aggravate non-alcoholic fatty liver disease, increasing the risk of developing cirrhosis and hepatocellular carcinoma. This study aims to determine the effect of type 2 diabetes mellitus and insulin therapy on non-alcoholic fatty liver disease in the patients with morbid obesity.