Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.).

Consultation for liver disease in pregnant women is a common and oftentimes vexing clinical consultation for the gastroenterologist. The challenge lies in the need to consider the safety of both the expectant mother and the unborn fetus in the clinical management decisions. This practice guideline provides an evidence-based approach to common diagnostic and treatment challenges of liver disease in pregnant women. Am J Gastroenterol 2016; 111:176-194; doi: 10.1038/ajg.2015 Initial evaluation of pregnant patientA pregnant patient presenting with abnormal liver tests should undergo standard workup as with any non-pregnant individual (strong recommendation, very low level of evidence). Imaging in pregnancyUltrasound is safe and the preferred imaging modality used in assessment of abnormal liver tests suggestive of biliary tract disease (strong recommendation, low level of evidence).Magnetic resonance imaging without gadolinium can be used in the second and third trimester (conditional recommendation, low level of evidence).Computed tomography scans carry a risk of teratogenesis and childhood hematologic malignancies but may be used judiciously with minimized radiation protocols (2-5 rads; conditional recommendation, very low level of evidence). Endoscopy in pregnancyEndoscopy is safe in pregnancy but should be deferred until the second trimester if possible (strong recommendation, low level of evidence).Meperidine and propofol can be used for endoscopic sedation (strong recommendation, moderate level of evidence). Management of biliary disease in pregnancyERCP can be performed when indicated for pregnant women presenting with biliary disease that strongly necessitates intervention such as biliary pancreatitis, symptomatic choledocholithiasis, and/or cholangitis. Minimizing fetal exposure to fl uoroscopy is imperative (strong recommendation, low level of evidence).Symptomatic cholecystitis should be managed with early surgical intervention with laparoscopic cholecystectomy (strong recommendation, low level of evidence). Liver masses in pregnancyAsymptomatic hemangioma and focal nodular hyperplasia do not need routine imaging or surveillance during pregnancy (strong recommendation, very low level evidence).Hepatic adenomas should be monitored with ultrasound during pregnancy for growth. Patients with large adenomas (>5 cm) should be referred for resection prior to pregnancy (strong recommendation, low level of evidence). Hepatitis B in pregnancyActive-passive immunoprophylaxis with hepatitis B immunoglobulin and the HBV vaccination series should be administered to all infants born to HBV-infected mothers to prevent perinatal transmission (strong recommendation, low level of evidence).Women chronically infected with HBV and high viral load (>10 6 log copies/ml (200,000 IU/ml) and higher) should be offered antiviral medication with tenofovir or telbivudine in the third trimester to reduce perinatal transmission of HBV (strong recommendation, low level of evidence).C-section should not be performed electively in HBV-pos...

COVID-19 coronavirus disease 2019 SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 CLD chronic liver disease EUA emergency use authorization FDA Food and Drug Administration VE vaccine efficacy BNT162b2 Pfizer-BioNTech mRNA vaccine mRNA-1273 Moderna mRNA vaccine VAERS Vaccine Adverse Event Reporting System CDC Centers for Disease Control and Prevention SOT solid organ transplant ACR acute cellular rejection

Background & Aims The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. Methods We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET—a prospective, observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, 836 patients with HCV genotype 1 infection began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment—a 2 week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. Results The overall rate of SVR rate was 84% (675/802 patients, 95% CI: 81–87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. Conclusions In a large, prospective observational cohort study, a 12 week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811

Well‐tolerated, ribavirin‐free, pangenotypic hepatitis C virus (HCV) treatments for transplant recipients remain a high priority. Once‐daily glecaprevir/pibrentasvir demonstrates high rates of sustained virologic response at 12 weeks posttreatment (SVR12) across all major HCV genotypes (GTs). This trial evaluated the safety and efficacy of glecaprevir/pibrentasvir for patients with chronic HCV GT1‐6 infection who had received a liver or kidney transplant. MAGELLAN‐2 was a phase 3, open‐label trial conducted in patients who were ≥3 months posttransplant. Patients without cirrhosis who were HCV treatment‐naive (GT1‐6) or treatment‐experienced (GT1, 2, 4‐6; with interferon‐based therapy with or without sofosbuvir, or sofosbuvir plus ribavirin) received glecaprevir/pibrentasvir (300/120 mg) once daily for 12 weeks. The primary endpoint compared the percentage of patients receiving glecaprevir/pibrentasvir with SVR12 to a historic SVR12 rate based on the standard of care. Safety of glecaprevir/pibrentasvir was assessed. In total, 80 liver transplant and 20 kidney transplant patients participated in the trial. Most patients had no or minimal fibrosis (80% had fibrosis scores F0‐F1) and were infected with HCV GT1 (57%) or GT3 (24%). The overall SVR12 was 98% (n/N = 98/100; 95% confidence interval, 95.3%–100%), which exceeded the prespecified historic standard‐of‐care SVR12 threshold of 94%. One patient experienced virologic failure. One patient discontinued because of an adverse event considered to be unrelated to treatment; this patient achieved SVR12. Adverse events were mostly mild in severity, and laboratory abnormalities were infrequent. Conclusion: Once‐daily glecaprevir/pibrentasvir for 12 weeks is a well‐tolerated and efficacious, ribavirin‐free treatment for patients with chronic HCV GT1‐6 infection who have received a liver or kidney transplant. (http://ClinicalTrials.gov NCT02692703.) (Hepatology 2018; 00:000‐000).