Conservation of hepatitis C virus nonstructural protein 3 amino acid sequence in viral isolates during liver transplantation

As a consequence of selective pressure exerted by the immune response during hepatitis C virus (HCV) infection, a high rate of nucleotide mutations in the viral genome is observed which leads to the emergence of viral escape mutants. The aim of this study was to evaluate the evolution of the amino acid (aa) sequence of the HCV nonstructural protein 3 (NS3) in viral isolates after liver transplantation. Six patients with HCV-induced liver disease undergoing liver transplantation (LT) were followed up for sequence analysis. Hepatitis C recurrence was observed in all patients after LT. The rate of synonymous (dS) nucleotide substitutions was much higher than that of nonsynonymous (dN) ones in the NS3 encoding region. The high values of the dS/dN ratios suggest no sustained adaptive evolution selection pressure and, therefore, absence of specific NS3 viral populations. Clinical genotype assignments were supported by phylogenetic analysis. Serial samples from each patient showed lower mean nucleotide genetic distance when compared with samples of the same HCV genotype and subtype. The NS3 samples studied had an N-terminal aa sequence with several differences as compared with reference ones, mainly in genotype 1b-infected patients. After LT, as compared with the sequences before, a few reverted aa substitutions and several established aa substitutions were observed at the N-terminal of NS3. Sites described to be involved in important functions of NS3, notably those of the catalytic triad and zinc binding, remained unaltered in terms of aa sequence. Rare or frequent aa substitutions occurred indiscriminately in different positions. Several cytotoxic T lymphocyte epitopes described for HCV were present in our 1b samples. Nevertheless, the deduced secondary structure of the NS3 protease showed a few alterations in samples from genotype 3a patients, but none were seen in 1b cases. Our data, obtained from patients under important selective pressure during LT, show that the NS3 protease remains well conserved, mainly in HCV 3a patients. It reinforces its potential use as an antigenic candidate for further studies aiming at the development of a protective immune response.

Cardiopulmonary Manifestations of Hepatosplenic Schistosomiasis

Background -Schistosomiasis is a highly prevalent disease with >200 million infected people. Pulmonary hypertension is one of the pulmonary manifestations in this disease, particularly in its hepatosplenic presentation. The aim of this study was to determine the prevalence of pulmonary hypertension in schistosomiasis patients with the hepatosplenic form of the disease. Methods and Results -All patients with hepatosplenic schistosomiasis followed up at the gastroenterology department of our university hospital underwent echocardiographic evaluation to search for pulmonary hypertension. Patients presenting with systolic pulmonary artery pressure >40 mm Hg were further evaluated through right heart catheterization. Our study showed an 18.5% prevalence of patients with elevated systolic pulmonary artery pressure at echocardiography. Invasive hemodynamics confirmed the presence of pulmonary hypertension in 7.7% (95% confidence interval, 3.3 to 16.7) of patients, with a prevalence of precapillary (arterial) pulmonary hypertension of 4.6% (95% confidence interval, 1.5 to 12.7). Conclusions -Our study reinforces the role of echocardiography as a screening tool in the investigation of pulmonary hypertension, together with the need for invasive monitoring for a proper diagnosis. We conclude that hepatosplenic schistosomiasis may account for one of the most prevalent forms of pulmonary hypertension worldwide, justifying the development of further studies to evaluate the effect of specific pulmonary hypertension treatment in this particular form of the disease. (Circulation. 2009; 119: 1518-1523.)

Do the Effects of Pentoxifylline on the Inflammatory Process and Pancreatic Infection Justify Its Use in Acute Pancreatitis?

Severe acute pancreatitis is associated with high morbidity and mortality rates. At the present time, no specific therapy has been shown to be uniformly effective in reducing morbidity and mortality in this disease. The aim of this study was to determine the effects of pentoxifylline on the pancreatic and systemic inflammatory process, pancreatic infection, and mortality rate in severe acute pancreatitis in rats. Methods: One hundred and twenty male Wistar rats were divided into 3 groups: sham, pancreatitis, and pentoxifylline (acute pancreatitis induction plus administration of 25 mg/kg pentoxifylline). Inflammatory response was measured by histological studies, inflammatory cytokine production (IL-6, IL-10, and TNF-alpha), and mortality rate. Pancreatic infection was evaluated by bacterial cultures expressed in colony-forming units per gram. Results: Pentoxifylline-treated animals had a statistically significant reduction of inflammatory cytokine levels, pancreatic histological damage, occurrence of bacterial translocation and pancreatic infection (p < 0.05), associated with a significant reduction in mortality rate. Conclusions: Pentoxifylline administration in this experimental model of acute pancreatitis reduces local and systemic inflammatory responses and decreases the pancreatic infection and the mortality rate. Copyright (C) 2009 S. Karger AG, Basel and IAP

EUS-guided percutaneous endoscopic gastrostomy for enteral feeding tube placement

Background: Patients without adequate abdominal-wall transillumination are at a high risk of developing complications after PEG. Objective: We evaluated the feasibility and utility of EUS to guide PEG in patients lacking abdominal-wall transillumination. Design: Single-center case series. Setting: Tertiary-referral center. Patients: Six patients who lacked adequate abdominal-wall transillumination and 2 patients with a large laparotomy scar deemed to be at high risk of developing complications after PEG. Interventions: Patients underwent EUS-guided PEG and deployment of a standard enteral feeding tube. Main Outcome Measurements: Technical success and complication rates. Results: PEG was Successful Under EUS guidance in 5 of 8 patients. Causes of failure included all inadequate EUS window because of a prior Billroth 1 gastrectomy in one and suspected bowel interposition in 2 patients. There were no complications. Limitations: A small number of patients, uncontrolled study, and short follow-up period. Conclusions: This technique may facilitate deployment of PEG in patients who lack adequate abdominal-wall transillumination.

Cost-Effectiveness of Palliation of Unresectable Esophageal Cancer

Introduction Different modalities of palliation for obstructive symptoms in patients with unresectable esophageal cancer (EC) exist. However, these therapeutic alternatives have significant differences in costs and effectiveness. Methods A Markov model was designed to compare the cost-effectiveness (CE) of self-expandable stent (SES), brachytherapy and laser in the palliation of unresectable EC. Patients were assigned to one of the strategies, and the improvement in swallowing function was compared given the treatment efficacy, probability of survival, and risks of complications associated to each strategy. Probabilities and parameters for distribution were based on a 9-month time frame. Results Under the base-case scenario, laser has the lowest CE ratio, followed by brachytherapy at an incremental cost-effectiveness ratio (ICER) of $4,400.00, and SES is a dominated strategy. In the probabilistic analysis, laser is the strategy with the highest probability of cost-effectiveness for willingness to pay (WTP) values lower than $3,201 and brachytherapy for all WTP yielding a positive net health benefit (NHB) (threshold $4,440). The highest probability of cost-effectiveness for brachytherapy is 96%, and consequently, selection of suboptimal strategies can lead to opportunity losses for the US health system, ranging from US$ 4.32 to US$ 38.09 million dollars over the next 5-20 years. Conclusion Conditional to the WTP and current US Medicare costs, palliation of unresectable esophageal cancers with brachytherapy provides the largest amount of NHB and is the strategy with the highest probability of CE. However, some level of uncertainly remains, and wrong decisions will be made until further knowledge is acquired.

Effectiveness of Endoclips for the Treatment of Stigmata of Recent Hemorrhage in the Colon of Patients with Acute Lower Gastrointestinal Tract Bleeding

Coaptive thermo coagulation (CTC) for the treatment of stigmata of recent hemorrhage (SRH) in the colon is risky. We evaluated the safety and effectiveness of endoclips in 13 patients with acute lower gastrointestinal bleeding (GIB). Thirty-day re-bleeding and complication rates were comparable to a historical cohort of 41 patients (group 2) who underwent CTC/IE (injection epinephrine) for the management of acute lower GIB. There was no difference in the 30-day re-bleeding rates in the two groups. In group I, immediate hemostasis was successful in all patients. Three of 13 patients (23.1%) developed re-bleeding. In group II, 41 patients from six prior studies underwent CTC and/or IE for the treatment of HRS where 12 (29.3%) developed re-bleeding. There were no immediate complications. Endoclip deployment is as effective as CTC and/or IE for treatment of SRH in the colon.

Management of Common Bile Duct Stones in Cirrhotic Patients with Coagulopathy: A Comparison of Supra-Papillary Puncture and Standard Cannulation Technique

Bleeding is not uncommon following endoscopic sphincterotomy. Supra-papillary puncture (SPP) might be safer than standard cannulation (SC) techniques in patients with coagulopathy. The aim of the study was to compare the safety and effectiveness of SPP and SC. This was a prospective case control intervention study. Decompensated cirrhotic patients with coagulopathy and choledocolithiasis underwent SC and SPP methods for biliary access. One hundred five patients (56 [53.3%] men, mean [SD] age 56 [15.8]) underwent ERCP. SC and SPP were performed in 63 and 42 patients, respectively. Biliary access was achieved in 56/63 (89%) and 40/42 (95%) of patients undergoing SC and SPP, respectively (P = 0.13; 95% CI [-0.16; 0.03]). Complications occurred in 10/63 (15.8%) patients undergoing SC and 5/42 (11.9%) SPP (P = 0.28; 95% CI [-0.17, 0.16]). Five (7.9%) and two (3.2%) episodes of post-sphincterotomy bleeding was seen in the SC and SPP groups, respectively (P = 0.36; 95% CI [-0.16, 0.05]). In contrast, three (4.8%) episodes of pancreatitis were seen in the SC and none in the SPP group (P = 0.05; 95% CI [0.001; 0.004]). A cost-effectiveness analysis demonstrated that SPP is an acceptable alternative at an ICER of US$ 5,974.92 per additional successful procedure. SPP is a safe and effective technique for the management of common bile duct stones in decompensated cirrhotic patients. Conditional to the willingness-to-pay and to the local ERCP-related costs, SPP is also a cost-effective alternative to the SC methods. SPP is associated with a lower rate of complications but larger studies to validate these findings are necessary.

Simplified criteria for the diagnosis of autoimmune hepatitis

Diagnosis of autoimmune hepatitis (AIH) may be challenging. However, early diagnosis is important because immunosuppression is life-saving. Diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) were complex and purely meant for scientific purposes. This study of the IAIHG aims to define simplified diagnostic criteria for routine clinical practice. Candidate criteria included sex, age, autoantibodies, immunoglobutins, absence of viral hepatitis, and histology. The training set included 250 AIH patients and 193 controls from 11 centers worldwide. Scores were built from variables showing predictive ability in univariate analysis. Diagnostic value of each score was assessed by the area under the receiver operating characteristic (ROC) curve. The best score was validated using data of an additional 109 AIH patients and 284 controls. This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis. The area under the curve for prediction of AIH was 0.946 in the training set and 0.91 in the validation set. Based on the ROC curves, two cutoff points were chosen. The score was found to have 88% sensitivity and 97% specificity (cutoff >= 6) and 81% sensitivity and 99% specificity (cutoff 2:7) in the validation set. Conclusion: A reliable diagnosis of AIH can be made using a very simple diagnostic score. We propose the diagnosis of probable AIH at a cutoff point greater than 6 points and definite AIH 7 points or higher.

Long-term outcomes of acute gastric variceal bleeding in 48 patients following treatment with cyanoacrylate

Objectives (1) Study the effectiveness of intravariceal injection of n-butyl-2-cyanoacrylate to treat acute gastric variceal (GV) bleeding and (2) study the impact of the type of GV and hepatic function on endoscopic hemostasis and mortality outcomes. Methods Fourty-eight patients with acute GV bleeding underwent intravariceal injection of n-butyl-2-cyanoacrylate and were followed until death or study conclusion (12-52 months). Results Primary hemostasis (no re-bleeding within 48 h) was accomplished in 42 patients (87.5%). Appearance of the bleeding site at the time of initial endoscopy, grade of cirrhosis and location of GV were not significant predictors of immediate hemostasis. Early re-bleeding (48 h to 6 weeks) occurred in 20.5% of patients and late re-bleeding (beyond 6 weeks) in 20.5% of patients. While the Child-Pugh score was predictive of re-bleeding and mortality, the type of GV and stigmata at initial endoscopy were not significant predictors of re-bleeding and mortality. Over a mean follow-up of 18 months, mortality rates were 43.9% and bleeding was the commonest cause of death. Conclusion Endoscopic injection of n-butyl-2-cyanoacrylate is effective and safe for treating bleeding GV. Patients with poor hepatic function are at higher risk of re-bleeding and death after acute gastric variceal bleed.

A pilot study to evaluate the safety, tolerance, and efficacy of a novel stationary antral balloon (SAB) for obesity

Background: A 150 cm(3) pear-shaped gastric balloon with a 30 cm-long duodenal stem and a 7 g metallic weight at its distal end was designed and developed to facilitate weight loss by (a) delaying gastric emptying thus enhancing interprandial satiety, and (b) stimulating antral and duodenal receptors of satiation. Methods: Twenty-six patients (body mass index of 29 to 40 kg/m(2)) who failed to lose weight despite dietary intervention underwent endoscopic implantation of the balloon device. Patients were monitored for tolerance to the balloon, complications, weight loss, and compliance with a restricted caloric intake. Results: Six men and 20 women with a median body weight of 93.0kg (range, 73.5 to 119.9), median body mass index 34.3 kg/m(2) (range, 28.8 to 39.5) underwent balloon implantation for a median period of 4.0 months (range, 0.75 to 6.0). Twenty-two patients successfully complied with a 1250 to 1500 kcal daily diet restriction during the study period. Median weight reduction was 6.5 kg (range, 3.7 to 19.9). Patients with initial body weight of > 90 kg tended to loose more weight (8.1 kg) than patients weighing < 90 kg (4.5 kg) (P = 0.14). Nine patients with dwell times of 6 months lost 11.5 +/- 4.6 kg. The balloon malfunctioned in 4 patients (in I patient, the balloon leaked spontaneously but remained in the stomach and in 3 patients, the balloon migrated distally). Conclusions: Our novel balloon device may be effective in inducing weight loss by promoting compliance with a restricted caloric intake and is well tolerated due to its small size. Complications resulted from balloon rupture, which can be easily prevented by enhancements in design and use of alternative materials.

Small Bowel Endoscopy Using the Double-Balloon Technique: Four-Year Results in a Tertiary Referral Hospital in Brazil

Background: Double-balloon enteroscopy (DBE) allows evaluation and therapy for various small bowel diseases. In this series the outcome of a 4-year experience in a tertiary hospital school in Brazil is reported. Methods: A total of 457 consecutive DBE were performed in 418 patients from August 2004 to August 2008. 93 patients with several indications, whose aim was not the evaluation of suspected diseases of the small bowel mucosa, were excluded, therefore leaving 364 DBE in 325 patients for analysis. Data were retrospectively collected with regard to clinical, endoscopic findings, therapy and complications. Results: Among the 364 DBE performed in 325 patients, 143/325 were males (44%) and 182/325 females (56%) with a mean age of 48.6 +/- 15.7 years (range 17-89). Mean investigation time was 64 +/- 22 min (range 35-135). The depth of insertion beyond the ligament of Treitz was 230 +/- 85 cm (range 30-500) by the antegrade approach and 140 +/- 75 cm (range 0-320) by the retrograde approach. Total enteroscopy was achieved in 41.66% of the attempts (30 of 72 patients). Overall diagnostic yield was 54.95% (200 of 364 procedures) ranging from 0 to 100% in this series, depending on the indication. Angiodysplasia was the main diagnosis in 24.5% (49 of 200 procedures) and endoscopic treatment, including biopsies, hemostasis, tattooing and polypectomy were performed in 65.38% (238 of 364 procedures). No major complications were reported. Conclusions: DBE is a feasible, safe and well-tolerated procedure allowing endoscopic therapy. Selection of indications increases its diagnostic yield. Copyright (C) 2009 S. Karger AG, Basel

ERCP Using Double-Balloon Enteroscopy in Patients with Roux-en-Y Anatomy

Double-balloon enteroscopy (DBE) is a useful method for endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y anatomy. Depending on the distorted anatomy, endoscopic therapies with conventional scopes were very difficult or impossible before the advent of DBE and patients had to be submitted to a percutaneous or surgical approach. The case of 6 patients with different types of Roux-en-Y-altered anatomy in which DBE-ERCP was performed with 83.3% successful rate (5/6) is reported confirming recent data in the literature on the feasibility of this method. Copyright (C) 2009 S. Karger AG, Basel

Secondary Lymphangiectasia of the Small Bowel: Utility of Double Balloon Enteroscopy for Diagnosis and Management

Sporadic lymphangiectasias are commonly found throughout the small bowel and are considered to be normal. Not uncommonly, lymphangiectasias are pathologic and can lead to mid-gastrointestinal bleeding, abdominal pain and protein-losing enteropathy. Pathologic lymphangiectasias of the small bowel include primary lymphangiectasia, secondary lymphangiectasia and lymphaticovenous malformations. In this report we present three different cases of small bowel lymphangiectasia detected by double balloon enteroscopy. The patients were diagnosed with South American blastomycosis, tuberculosis and primary small bowel lymphangioma. Copyright (C) 2009 S. Karger AG, Basel

Treatment of achalasia: lessons learned with Chagas` disease

Chagas` disease (CD) is highly prevalent in South America. Brazilian surgeons and gastroenterologists gained valuable experience in the treatment of CD esophagopathy (chagasic achalasia) due to the high number of cases treated. The authors reviewed the lessons learned with the treatment of achalasia by different centers experienced in the treatment of Chagas` disease. Preoperative evaluation, endoscopic treatment (forceful dilatation and botulinum toxin injection), Heller`s myotomy, esophagectomy, conservative techniques other than myotomy, and reoperations are discussed in the light of personal experiences and review of International and Brazilian literature. Aspects not frequently adopted by North American and European surgeons are emphasized. The review shows that nonadvanced achalasia is frequently treated by Heller`s myotomy. Endoscopic treatment is reserved to limited cases. Treatment for end-stage achalasia is not unanimous. Esophagectomy was a popular treatment in advanced disease; however, the morbidity/mortality associated to the procedure made some authors seek different alternatives, such as Heller`s myotomy and cardioplasties. Minimally invasive approach to esophageal resection may change this concept, although few centers perform the procedure routinely.