Simeprevir and sofosbuvir with or without ribavirin to treat recurrent genotype 1 hepatitis C virus infection after orthotopic liver transplantation.

Although combination simeprevir (SIM) plus sofosbuvir (SOF) is an approved regimen for genotype 1 chronic hepatitis C virus (HCV), data regarding its safety and efficacy in liver transplant recipients remain limited. A multicenter retrospective study was performed to determine the efficacy and tolerability of a 12-week regimen of SIM/SOF with or without ribavirin (RBV) in 56 consecutive liver transplant recipients in 2014; 79% of patients had genotype 1a, 14% had cirrhosis, and 73% were treatment experienced. Sustained virological response at 12 weeks (SVR12) was 88% by intention to treat analysis (95% confidence interval, 84%-90%). Four patients relapsed, but no on-treatment virological failures occurred. The Q80K polymorphism did not impact SVR12, but there was a trend toward decreased sustained virological response with advanced fibrosis (P = 0.18). HCV RNA was detectable at treatment week 4 in 21% of patients, and those who had detectable levels were less likely to achieve SVR12 (58% versus 95%; P = 0.003). Five patients had baseline Child-Pugh class B cirrhosis, and 2 of them died (1 following early discontinuation of therapy). An additional discontinuation resulted from a severe photosensitivity reaction in a patient on concomitant cyclosporine. Seven patients receiving RBV developed progressive anemia requiring intervention. Immunosuppression dose modifications were minimal. SIM/SOF for 12 weeks was effective and well tolerated by compensated liver transplant recipients especially when administered without concomitant RBV or cyclosporine. SIM/SOF appears to have a niche as the only 12-week RBV-free treatment regimen currently recommended by guidelines for compensated transplant recipients. However, 12 weeks may not be the optimal duration of therapy for those with detectable virus at week 4 or possibly for those with cirrhosis. These data require confirmation by prospective randomized clinical trials. Liver Transplantation 22 635-643 2016 AASLD.

Long-Term Follow-Up of Autonomic and Enteric Measures in Patients Undergoing Vertical Banded Gastroplasty for Morbid Obesity.

BACKGROUND: A multi-component model of autonomic and enteric factors may correlate with ultimate weight loss or gain after restrictive obesity surgery. This study aimed to determine relevant parameters to predict successful long-term weight loss. METHODS: Thirty-nine patients (four males and 35 females) with a mean age of 37.2 years were followed for over 15 years after vertical banded gastroplasty. Baseline adrenergic: postural adjustment ratio (PAR) and vasoconstriction (VC); cholinergic: electrocardiogram R-to-R interval (RRI) and enteric measure: electrogastrogram (EGG) were utilized by a discriminant function analysis to classify patients as a long-term loser or gainer. Using latest weight compared to baseline, patients were divided as 10 gainers and 29 losers. RESULTS: A discriminate model successfully predicted ultimate weight gain in 8/10 (80%) of patients who subsequently gained weight and weight loss in 24/29 (83%) of patients who lost weight for a total correct classification of 32/39 (82%). The same model with data at 3 months postoperatively predicted weight gain in 9/10 (90%) of patients and weight loss in 24/29 (83%) of patients, for a total correct classification of 34/39 (87%). CONCLUSIONS: A multi-component model at baseline and 3 months postoperative can predict long-term weight outcome from restrictive obesity surgery.

Stress prophylaxis in intensive care unit patients and the role of enteral nutrition.

Use of acid-suppressive therapy (AST) to prevent stress gastropathy in the intensive care unit has grown rapidly over the past 20 years. The primary indications for such use of AST include need for mechanical ventilation, overt gastrointestinal bleeding, severe burn, and head trauma. Despite this limited list of indications, proton pump inhibitors (PPIs) often are overprescribed for purposes of stress prophylaxis. Decreased mucosal blood flow with subsequent tissue ischemia is thought to be the mechanism responsible for stress-induced gastropathy. Subsequent activation of inflammatory and vasoconstrictive mediators determines the severity of the gastropathy. Numerous basic science studies suggest that enteral nutrition (EN) can improve mucosal blood flow and reverse the generation of these inflammatory mediators. Clinical studies evaluating the effectiveness of EN vs acid-suppressive medications, however, have shown variable results (and there are no randomized controlled trials to date). In hypersecretory states (such as head trauma and burns), AST should be given, even in patients who are tolerating EN. In the absence of a hypersecretory state, pharmacologic AST may be avoided or discontinued in patients who are tolerating EN. Stress prophylaxis medications also should be discontinued in patients who do not have a clear indication for their use. Overt bleeding in a patient receiving EN for stress prophylaxis should prompt the initiation of a PPI. Randomized controlled studies investigating the efficacy of EN for stress ulcer prophylaxis are needed. Protocols should be developed to alert healthcare teams to consider discontinuation of AST, especially when tolerance of EN is achieved.