Factors Influencing the Rate of Fibrosis Progression in Chronic Hepatitis C

Alcohol consumption, age at infection, and male gender have been identified as risk factors for faster fibrosis progression in patients with chronic hepatitis C (CHC). Yet the influence of liver steatosis, light to moderate alcohol consumption, or iron overload on this progression remains controversial. To analyze the effect of individual risk factors and their interaction on fibrosis progression in a group of patients with CHC and a definite date of infection, we studied 133 consecutive untreated patients. Covariates included were age, body mass index (BMI), gender, age at infection, alcohol intake, serum lipids, glycemia, serum ALT, AST, GGT, iron, and ferritin, grade and stage (METAVIR and Scheuer), and hepatic stainable iron (Perl's stain). The rate of fibrosis progression was inferred from the METAVIR score. By logistic regression analysis, hepatic steatosis (odds ratio [OR], 3.035; 95% confidence interval [CI], 1.16-7.93), serum ferritin levels higher than 290 ng/ml (OR, 5.5; 1.6-18.65), and light to moderate ethanol intake (1-50 g/day) (OR, 5.22; 1.5-17.67) were independently associated with faster fibrosis progression. There was no effect of interaction between these variables on the rate of fibrosis progression. Liver steatosis, serum ferritin levels, and light to moderate alcohol intake are associated with faster fibrosis progression in chronic hepatitis C. Combination of these factors did not further accelerate this progression. The impact of modification of these factors on progression should be tested in longitudinal studies.     

Management of Early-stage Esophageal Neoplasia (MESEN) Consensus

Background

Treatment of esophageal adenocarcinoma often involves surgical resection. Newer technologies in interventional endoscopy have led to a substantial paradigm shift in the management of early-stage neoplasia in Barrett’s esophagus comprising high-grade dysplasia (HGD), intramucosal carcinoma, and, in some cases, submucosal carcinoma. However, there has been no consensus regarding the indications for esophageal preservation in these cases. In this work, consensus guidelines were established for the management of early-stage esophageal neoplasia considering clinically relevant aspects (age, comorbidities, and social environment) in each scenario.

Methods

Seventeen experts were invited to participate based on their background and clinical expertise at high-volume centers. A questionnaire was created that included four clinical scenarios covering a wide range of situations within HGD and/or early esophageal neoplasia, particularly where controversies are likely to exist. Each of the clinical scenarios was open to discussion subdivided by patient age (20, 50, and 80 s). For each clinical scenario an expert was chosen to defend that position. Each defense triggered a subsequent discussion during a consensus meeting. Conclusions of that discussion together with an accompanying literature analysis allowed experts to confirm or change their original choices and served as the basis for the recommendations stated in this article.

Results

There was 100 % consensus supporting esophageal preservation in patients with HGD, independent of patient age or Barrett’s length. In patients with T1a adenocarcinoma, consensus for preservation was not reached (65 %) for young and middle-aged individuals but was supported for elderly patients (100 %). For T1b adenocarcinoma, consensus was reached for surgical resection (90 %), leaving organ preservation for patients with very low risk of nodal invasion or poor surgical candidates.

Conclusion

Advances in endoscopic imaging and therapy allow for organ preservation in most settings of early-stage neoplasia of the esophagus, provided that the patient understands the implications of this decision.     

Principles and practice to facilitate complete photodocumentation of the upper gastrointestinal tract: World Endoscopy Organization position statement

Although esophagogastroduodenoscopy (EGD) is the most commonly used procedure in the gastrointestinal (GI) tract, the method of esophageal, gastric and duodenal mucosa photodocumentation varies considerably worldwide. One probable explanation is that for generations, EGD has primarily been taught by GI faculty and instructors based on their perceptions and experience, which has resulted in EGD being a non-standardized procedure. Currently, the procedure is facing a challenging scenario as endoscopy societies are implementing procedure-associated quality indicators aiming for best practice among practitioners and evidence-based care for patients. Contrary to colonoscopy where cecum landmarks photodocumentation is considered proof of completeness, there are currently no reliable performance measures to gauge the completeness of an upper endoscopy nor guidance for complete photodocumentation. This World Endoscopy Organization (WEO) position statement aims to provide practical guidance to practitioners to carry out complete EGD photodocumentation. Hence, an international group of experts from the WEO Upper GI Cancer Committee formulated the following document using the body of evidence established through literature reviews, expert opinions, and other scientific sources. The group acknowledged that although the procedure should be feasible in any facility, what is needed to achieve a global shift on the concept of completeness is a common written statement of agreement on its potential impact and added value. This best practice statement offers endoscopists principles and practical guidance in order to carry out complete photodocumentation from the hypopharynx to the second duodenal portion.     

Naltrexone improves outcome of a controlled drinking program

Naltrexone is widely used in therapeutic programs with abstinence as a goal. However, it has been used in only a few studies aimed at reducing alcohol consumption. The purpose of this study was to evaluate the efficacy of naltrexone as an adjunct in controlled drinking programs. This was an open randomized study of 12 weeks duration that compared two therapeutic strategies: use of naltrexone in a controlled drinking program (NTX+CD) and the controlled drinking program alone (CD), without NTX. Each group comprised 30 male patients with mild alcohol dependence. During treatment, there were no differences between groups in drinking behavior, though the NTX+CD group showed significantly less craving. In the 12-month follow-up period, the NTX+CD group showed significantly fewer drinking days and heavy drinking days and less craving than the CD group. The results of this study suggest a role for naltrexone in controlled drinking programs.     

Financial incentives for employees as part of a policy to upgrade care in a public hospital in Volta Redonda,Rio de Janeiro State,Brazil

The authors present and analyze six years of regular and steady application of an institutional evaluation policy based on financial incentives in a public hospital in Volta Redonda, Rio de Janeiro State, Brazil, as a part of the hospital's administrative modernization policy. This type of policy is considered implicitly capable of developing a sequence of strategic wagers: (1) release of financial resources for payment of bonuses; (2) creation of an operationally feasible and sensitive evaluation instrument; (3) creation of adequate management mechanisms to improve evaluation policy; (4) employee adherence to the hospital upgrading policy based on the bonus system; and (5) maintenance of the effects of evaluation policy over time. The article discusses the "degree of success" of each of these wagers in an attempt to portray possible gains throughout the process, while also identifying inherent difficulties in such a policy.     

Amino acid transporter SNAT5 localizes to glial cells in the rat brain

The SNAT5 transporter is a neutral amino acid carrier whose function remains unclear. Structural and mechanistically, SNAT5 is closely related to the SNAT3 transporter that mediates the efflux of glutamine from glial cells and that participates in the glutamate-glutamine cycle in the brain. In this study, we have analyzed the distribution of SNAT5 in the rat central nervous system using specific antibodies. Through immunoblotting we observed that SNAT5 is ubiquitously but unevenly distributed in the CNS. It accumulates most intensely in the neocortex, the hippocampus, the striatum, and the spinal cord, whereas moderate levels were found in the thalamus, hypothalamus, and brainstem. Light microscopy revealed that the distribution of SNAT5 paralleled that of the vesicular glutamate transporter vGLUT1 in the forebrain regions, whereas in the diencephalon and brainstem, SNAT5 staining was better correlated with that of vGLUT1 and vGLUT2. However, the cellular localization differed from that of the glutamatergic markers, since SNAT5 was expressed exclusively in astrocyte cell bodies and their processes, ensheathing glutamatergic GABAergic and glycinergic terminals. The presence of SNAT5 in astrocyte processes was confirmed by electron microscopy. They were seen not only to surround different neuronal structures, but they were also found in astrocyte endfeet. Taking into consideration the higher levels of SNAT5 in the neighborhood of glutamatergic terminals and the ability of this transporter family to promote the efflux of amino acids from intracellular stores (including glutamine and perhaps glycine), this transporter is likely to be involved in glutamatergic pathways in the brain.