Bouveret's syndrome complicated by distal gallstone ileus after laser lithotropsy using Holmium: YAG laser

BACKGROUND: Bouveret's syndrome is an unusual presentation of duodenal obstruction caused by the passage of a large gallstone through a cholecystoduodenal fistula. Endoscopic therapy has been used as first-line treatment, especially in patients with high surgical risk. CASE PRESENTATION: We report a 67-year-old woman who underwent an endoscopic attempt to fragment and retrieve a duodenal stone using a Holmium: Yttrium-Aluminum-Garnet Laser (Ho:YAG) which resulted in small bowel obstruction. The patient successfully underwent enterolithotomy without cholecystectomy or closure of the fistula. CONCLUSION: We conclude that, distal gallstone obstruction, due to migration of partially fragmented stones, can occur as a possible complication of laser lithotripsy treatment of Bouveret's syndrome and might require urgent enterolithotomy

Safety profile of boceprevir and telaprevir in chronic hepatitis C: Real world experience from HCV-TARGET

The safety profiles of boceprevir and telaprevir in the treatment of chronic hepatitis C, administered in academic and community centres across the United States, were evaluated

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Acute Hepatitis A Causing Severe Hemolysis and Renal Failure in Undiagnosed Glucose-6-Phosphate Dehydrogenase Deficient Patient: A Case Report and Review of the Literature

Infection with hepatitis A virus is usually a self-limited illness that rarely results in fulminant liver failure. Severe hemolysis is an uncommon complication but has been reported in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Here, we report a case with undiagnosed G6PD deficiency who presented with hyperbilirubinemia, severe hemolysis, and acute renal failure precipitated by acute hepatitis A infection

Accuracy of noninvasive fibrosis scoring systems in african american and white patients with nonalcoholic fatty liver disease

OBJECTIVES: Nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4) score, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) score, and AST-alanine aminotransferase (ALT) ratio are noninvasive fibrosis scoring systems for the staging of liver fibrosis in patients with chronic liver disease. METHODS: In a large cohort of patients with nonalcoholic fatty liver disease, we compared AST-ALT ratio, NFS, FIB-4 score, and APRI score in predicting advanced fibrosis (defined as fibrosis stage ‡ 3) in histologically confirmed African American (AA) and white patients. We identified 907 patients: 677 (74.6%) white and 230 (25.3%) AA patients with nonalcoholic fatty liver disease. RESULTS: Of the 907 patients, 115 (12.8%) patients had advanced fibrosis (stages 3 and 4) in the total cohort: 6 (2.6%) AAs, and 109 (16.2%) whites. In AAs, the area under the receiver operating characteristic (area under the curve) for predicting advanced fibrosis was 0.58 by NFS, 0.86 by APRI score, 0.77 by FIB-4 score, and 0.65 by AST-ALT ratio. In whites, the area under the receiver operating characteristic for predicting advanced fibrosis was 0.82 by NFS, 0.82 by APRI score, 0.88 by FIB-4 score, and 0.76 by AST-ALT ratio. In the AA population, NFS \u3e 0.675, FIB-4 score \u3e 2.67, and APRI score \u3e 1.5 each has a negative predictive value of 98%, whereas the negative predictive values in whites are 91%, 88%, and 85%, respectively. DISCUSSION: Noninvasive fibrosis scoring systems can reliably exclude advanced fibrosis in both AAs and whites and have acceptable discriminatory ability to predict advanced fibrosis in whites. The utility of noninvasive fibrosis scoring systems in predicting advanced fibrosis in AAs needs further validation in a larger multicenter cohort

Safety and efficacy of treatment with once-daily ledipasvir/sofosbuvir (90/400 mg) for 12 weeks in genotype 1 hcv-infected patients with severe renal impairment.

Background: Despite higher concentrations of the primary circulating sofosbuvir (SOF) metabolite, GS‐331007, in patients with severe renal impairment, retrospective case series and claims database analyses have suggested substantial use of ledipasvir (LDV)/SOF in this population with no untoward effects described. The current study evaluated the safety, efficacy, and pharmacokinetics (PK) of LDV/SOF (90/400 mg) once‐daily for 12 weeks in patients with genotype (GT) 1 HCV‐infection and severe renal impairment. Methods: Treatment naïve or experienced patients with or without compensated cirrhosis and creatinine clearance (CLcr) ≤ 30 mL/min (Cockcroft‐Gault equation), not on dialysis, received open‐label treatment with LDV/SOF once daily for 12 weeks. Virologic response, pharmacokinetics (PK), and safety, including echocardiograms, were assessed. Results: Of the 18 patients enrolled and treated, the majority were male (67%), 10 (56%) were African‐American, 8 (44%) had BMI \u3e30 kg/ m2 and mean (range) CLcr at baseline was 24 9 (9 0‐39 6) mL/min. In terms of liver disease characteristics, all 18 had GT1 HCV infection (14 GT1a and 4 GT1b), 14 (78%) were treatment naïve, and 2 (11%) had cirrhosis. All patients completed 12 weeks of LDV/SOF treatment. There were no early discontinuations nor any on‐treatment virologic failures. The SVR4 rate is 100% (18/18). Preliminary PK data in subjects with severe renal impairment demonstrate that the exposure of SOF and GS‐331007 were approximately 2.6‐ and 5.1‐fold higher, respectively, than in subjects in the LDV/SOF Phase 3 studies; LDV exposure was similar in both populations. The most common adverse events (AEs) were fatigue (22%), headache (22%), and hyperkalemia (22%). Six serious AEs were reported among 4 patients (22%), including 2 renal events; no SAEs were considered related to study drugs. Preliminary analysis of echocardiogram data from the first 8 subjects demonstrated stable parameters from screening through the end of treatment. Complete SVR12, PK, and echocardiogram results will be presented. Conclusions: Treatment with LDV/SOF (90/400 mg) for 12 weeks in genotype 1 patients with and without cirrhosis and severe renal impairment resulted in 100% SVR4 rate. The regimen was safe and well‐tolerated with no treatment discontinuations and no treatment‐related SAEs