The efficacy of Elbasvir/Grazoprevir fixed-dose combination for 8 weeks in HCV treatment and health-related quality of life (HRQoL) in treatment-naïve, non-cirrhotic, genotype 4-infected patients (ELEGANT-4): A single-center, single-arm, open-label, phase 3 trial.

Background: Cost, adverse events, and long treatment duration can be significant obstacles in treating hepatitis C virus (HCV)-infected individuals. Shortening the treatment regimen can minimize these barriers, thereby enhancing adherence and increasing medication availability to more patients. Methods: This is a single-centre, single-arm, open-label, phase 3 clinical trial on treatment naïve, non-cirrhotic, HCV genotype 4 patients. The study aimed to evaluate an 8-week course of Elbasvir (ELB)/Grazoprevir (GZR) in this population. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR-12). The secondary endpoints were SVR-4, adverse events, and changes in health- and hepatitis-related quality of life (HRQoL). Results: Of the 30 patients who were enrolled, 29 (97%) achieved SVR-12 and SVR-4 (95% CI: 90-100%). No patients experienced serious or life-threatening adverse events (AEs), but mild/moderate AEs were reported by 16 (53%). The most commonly reported AEs were itching/skin rash (20%), headache (16.7%), abdominal/epigastric pain and decreased appetite (13.3% each), and nausea/vomiting (10%). Marked improvements in HRQoL were reported between the first (baseline) and third (SVR-12) timepoints. HRQoL score improvements involved the physical, mental, and hepatitis-specific indices, and ranged between 6 and 42 points (out of 100, P ≤0.003). Conclusion: The trial provides empirical evidence that HCV genotype 4-infected patients can achieve viral eradication with an 8-week-regimen of ELB/GZR. Further, this course of treatment is associated with a minimal adverse event profile and potentially significant improvements in quality of life. (ClinicalTrials.gov number, NCT03578640).

Peroral endoscopic myotomy (POEM) for the treatment of achalasia: A multicenter Middle Eastern experience.

BACKGROUND: Peroral endoscopic myotomy (POEM) was proposed in 2010 as a minimally invasive procedure for the treatment of achalasia. In this article, we describe the Middle Eastern experience with the procedure in terms of efficacy, length of admission, and short- and long-term complications. METHODS: A retrospective analysis of our prospectively collected data on patients who underwent a POEM procedure was conducted between March 2019 and May 2020. The primary outcome was clinical success rate, defined as a postprocedure Eckardt score ≤3 at ≥3 months. Secondary outcomes included the length of hospital stay, presence of reflux symptoms or need for proton pump inhibitors (PPIs) ≥3 months, and adverse events. RESULTS: During the study period, 67 patients (35 females) underwent the procedure for achalasia. The participants' ages ranged from 11 to 80 years (mean 41 ± 18 years). Eckardt scores before the treatment ranged between 4 and 12 (mean 8.85 ± 1.75). Sixty-four patients (95.5%) achieved Eckardt scores of ≤3 at ≥3 months after the procedure (95% confidence interval [CI]: 91%-100%). The difference between pre- and post-procedural Eckardt scores averaged around -8 points (95% CI: -7.5 to -8.5 P < 0.0001). Adverse events were reported in 24 patients (35.8%) and included pneumoperitoneum (32.8%), reflux symptoms at 3 months (29.9%), and surgical emphysema (3%). Six patients had adverse events that led to prolongation of admission; 3% of whom had aspiration pneumonia, 3% had pneumoperitoneum, 1.5% had both, and 1.5% had an esophageal tear. CONCLUSIONS: POEM is a promising procedure for the treatment of achalasia with a high clinical success rate, short hospital admission, and a reassuring safety profile.

Week 2 Adalimumab Levels Predict Short-term Clinical Remission in Patients With Inflammatory Bowel Disease.

BACKGROUND AND GOALS: The role of early proactive therapeutic drug level monitoring for anti-tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes. MATERIALS AND METHODS: This was a retrospective study of consecutive IBD patients with a week 2 serum adalimumab level available. Receiver operating characteristic curve analysis was conducted to determine an optimal week 2 threshold level for adalimumab. Patients above the threshold were compared for the primary outcome of week 12 clinical remission (CR) and the secondary outcome of short-term endoscopic healing. Multivariate logistic regression analysis was performed to evaluate the relationship between week 2 adalimumab level and CR. RESULTS: Forty-six patients had a week 2 adalimumab level performed. Receiver operating characteristic curve analysis suggested an optimal adalimumab level of 11.9 mcg/mL based on the area under the curve. Patients with week 2 adalimumab levels >11.9 mcg/mL had higher odds of week 12 CR than those with levels below or equal to this threshold (odds ratio=3.34, 95% confidence interval: 1.01-12.11, P =0.04). Other covariates were not found to have a significant association with the primary outcome. The rate of short-term endoscopic healing was numerically higher in patients with adalimumab week 2 levels above 11.9 mcg/mL; however, was not statistically significant (71.4% vs. 28.5%, P =0.11). CONCLUSIONS: Serum adalimumab levels at week 2 appears to be a predictor of short-term CR. Further research should explore whether patients with a week 2 adalimumab level equal to or below 11.9 mcg/mL benefit from early dose optimization.

Infliximab-induced autoimmune hepatitis requiring liver transplantation.

Autoimmune hepatitis is an infrequent but significant side effect of infliximab treatment. Diagnosis of autoimmune hepatitis is based on clinical, laboratory, and histological findings. Initial treatment involves cessation of infliximab and trial of prednisone. We present a rare case of infliximab-induced autoimmune hepatitis leading to liver failure requiring transplantation.