The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430.

Background The COVID-19 pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well-described. Methods We performed a multi-center cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. Results Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (IQR 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [aOR 3.0, 95%CI 1.7-5.5, p<0.001], congestive heart failure [aOR 3.2, 95%CI 1.4-7.0, p=0.004], chronic lung disease [aOR 2.5, 95%CI 1.2-5.2, p=0.018], obesity [aOR 1.9, 95% CI 1.0-3.4, p=0.039]) and presenting findings (lymphopenia [aOR 1.9, 95%CI 1.1-3.5, p=0.033], abnormal chest imaging [aOR 2.9, 95%CI 1.1-7.5, p=0.027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. Conclusions Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.

Purpose:To compare the accuracy of several magnetic resonance (MR) imaging-based methods for hepatic proton-density fat fraction (FF) estimation at 3.0 T, with spectroscopy as the reference technique. Materials and Methods:This prospective study was institutional review board approved and HIPAA compliant. Informed consent was obtained. One hundred sixty-three subjects (39 with known hepatic steatosis, 110 with steatosis risk factors, 14 without risk factors) underwent proton MR spectroscopy and non-T1-weighted gradient-echo MR imaging of the liver. At spectroscopy, the reference FF was determined from frequency-selective measurements of fat and water proton densities. At imaging, FF was calculated by using two-, three-, or six-echo methods, with single-frequency and multifrequency fat signal modeling. The three-and sixecho methods corrected for T2 * ; the two-echo methods did not. For each imaging method, the fat estimation accuracy was assessed by using linear regression between the imaging FF and spectroscopic FF. Binary classifi cation accuracy of imaging was assessed at four reference spectroscopic thresholds (0.04, 0.06, 0.08, and 0.10 FF). Results:Regression intercept of two-, three-, and six-echo methods were 2 0.0211, 0.0087, and 2 0.0062 ( P , .001 for all three) without multifrequency modeling and 2 0.0237 ( P , .001), 0.0022, and 2 0.0007 with multifrequency modeling, respectively. Regression slope of two-, three-, and six-echo methods were 0.8522, 0.8528, and 0.7544 ( P , .001 for all three) without multifrequency modeling and 0.9994, 0.9775, and 0.9821 with multifrequency modeling, respectively. Signifi cant deviation of intercept and slope from 0 and 1, respectively, indicated systematic error. Classification accuracy was 82.2%-90.1%, 93.9%-96.3%, and 83.4%-89.6% for two-, three-, and six-echo methods without multifrequency modeling and 88.3%-92.0%, 95.1%-96.3%, and 94.5%-96.3% with multifrequency modeling, respectively, depending on the FF threshold. T2 * -corrected (three-and six-echo) multifrequency imaging methods had the overall highest FF estimation and classifi cation accuracy. Among methods without multifrequency modeling, the T2 * -corrected threeecho method had the highest accuracy.

Administration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844.

BACKGROUND & AIMS The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure. METHODS We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12. RESULTS The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%–98%), 97% receiving the drugs for 12 weeks (95% CI, 96%–98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%–97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%–99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%–99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%–99% vs 98%; 95% CI, 95%–99%). Factors that predicted SVR12 were higher albumin (≤3.5 g/dL), lower total bilirubin (≥1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use. CONCLUSIONS Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.