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Purpose: To report outcomes in hepatocellular carcinoma (HCC) patients with lobar and segmental vascular invasion treated with resin Yttrium-90 transarterial radioembolization (Y90-TARE) with single-compartment MIRD (Medical Internal Radiation Dose) model., Materials and Methods: This was a retrospective IRB approved study of patients with a diagnosis of HCC with vascular invasion undergoing resin Y90-TARE from 2014 to 2022 (n = 61). Patients with Body Surface Area dosimetry (n = 20), main portal vein invasion (n = 6) and patients with an ECOG of > 2 were excluded (n = 1) with a final cohort of 34 patients., Results: Study population consisted of 34 patients, median age 62 years [60-71], tumor size 4.2 (2.8-7.4) cm, and 82% male. The median prescribed dose was 170 (126-200) Gy. The objective response rate at 6 months was 67% and disease control rate was 72%. The median survival was 18 months, median progression-free survival was 9.8 months. The 1- and 3-year survival rates were 76% and 57% in patients prescribed > 180 Gy, compared to 29% and 15% in patients with < 180 Gy (p = 0.01). Five of 15 Childs-Pugh A, ECOG < 1 patients (33%) were downstaged to resection, with complete pathologic necrosis in 40%, and 1 and 3-year survival rates of 100%. Grade-3 adverse events were seen in only 5/34 (15%), with no grade-4 or 5 adverse events., Conclusion: Resin Y90-TARE using single compartment MIRD model for HCC with segmental and lobar vascular invasion can result in downstaging to resection in 33% of patients and higher prescribed doses (> 180 Gy) result in improved survival., Competing Interests: Declarations. Conflict of Interest: Ammar Sarwar (not directly related to the manuscript): Grant Support—Sirtex Medical Inc; Consultant—Sirtex Medical Inc; Consultant—Boston Scientific Inc; Consultant—ABK Biomedical Inc; Grant Support—TriSalus LifeSciences; Grant Support—ABK Biomedical Inc; Medical Advisory Board—Boston Scientific Inc. Andrea Bullock (not directly related to the manuscript): Consultant—Oncolytics; Conference travel—Agenus; Advisory—Sirtex. Other Authors: None. Human Subject Research: IRB approval was obtained. Informed Consent: A waiver of HIPAA authorization was granted by the IRB., (© 2025. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Direct-acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment. The changing landscape of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients lacks a thorough description of the outcomes of HCC based on etiology., Objective: To assess the waitlist (WL) dropout and graft survival in HCC LT candidates based on the etiology of HCC in the post-DAA era., Methods: This retrospective cohort study analyzed United Network Organ Sharing/Organ Procurement Transplant Network data from 2015 to 2022. Graft survival was analyzed using Kaplan-Meier curves, and predictors of WL dropout and graft failure were assessed using multivariate analysis., Results: Among LT recipients, etiologies were HCV (53.6%), alcohol-associated liver disease (ALD) (12.0%), metabolic dysfunction-associated steatotic liver disease (MASLD) (16.6%), hepatitis B virus (HBV) (5.6%), and other (12.1%). MASLD and ALD had the highest dropout rates (1-year: 20.4%, 21.7%; 3-year: 58.2%, 51.1%; P < 0.001). Dropout was linked to diabetes, low albumin, high Model of End-Stage Liver Disease, high alpha-fetoprotein, tumor number, and size. MASLD had the worst 1-, 3-, and 5-year graft survival (89.8%, 81.8%, and 74.1%) and higher failure risk than HCV (hazard ratio: 1.143, 95% CI: 1.021-1.281). Diabetes negated MASLD's impact on graft failure but worsened survival for MASLD-HCC compared with HBV and ALD, matching HCV., Conclusion: MASLD has the highest WL dropout and post-LT graft failure among HCC LT candidates, surpassing HCV in the post-DAA era. The worst graft survival in MASLD-HCC is associated with pre-LT diabetes., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background & Aims: Acute variceal bleeding (AVB) portends significant 6-week mortality in patients with cirrhosis. It remains unclear if the correlation between liver prognostic scores and 6-week mortality are similar across different etiologies of liver cirrhosis, particularly alcohol-related liver disease (ALD) vs non-alcohol-related liver disease (non-ALD). This study aims to compare the 6-week mortality following AVB in these 2 patient populations., Methods: We assessed outcomes after AVB in 2 large multicenter cohorts from the United States and Singapore of patients with cirrhosis presenting with AVB. Using multivariable logistic regression, 6-week mortality between ALD and non-ALD cirrhosis was compared. Sensitivity analyses were performed with propensity-score matching analyses of the overall cohort., Results: A total of 1349 patients with AVB from the United States (n = 469) and Singapore (n = 880) cohorts were included. The aggregated cohort consisted of 379 patients (27.5%) with ALD cirrhosis. The overall 6-week mortality was 14.4%. Non-ALD cirrhosis was associated with a significantly higher 6-week mortality than ALD cirrhosis after accounting for Child-Turcotte-Pugh (CTP) score (adjusted odds ratio [aOR], 2.9; 95% confidence interval [CI], 1.5-5.3), Model of End-stage Liver Disease (MELD) score (aOR, 3.0; 95% CI, 1.6-5.6), and MELD 3.0 score (aOR, 3.3; 95% CI, 1.7-6.4). Addition of cirrhosis etiology (ALD vs non-ALD) to existing prognostic scores improved the prediction of 6-week mortality following AVB (MELD 3.0 c-statistic: 0.784 vs 0.770; P < .001). An etiology-adjusted updated MELD 3.0 model was the best prediction model for 6-week mortality after AVB., Conclusion: Patients with non-ALD cirrhosis presenting with AVB had a higher risk of 6-week mortality, at each severity of liver disease by standard indices, than patients with ALD cirrhosis. Cirrhosis etiology (ALD vs non-ALD) should be incorporated into the risk stratification of patients with AVB., (Copyright © 2024 AGA Institute. All rights reserved.)

Objective: As metabolic dysfunction-associated steatotic liver disease (MASLD) becomes more prevalent worldwide, it is imperative to create more accurate technologies that make it easy to assess the liver in a point-of-care setting. The aim of this study is to test the performance of a new software tool implemented in Velacur (Sonic Incytes), a liver stiffness and ultrasound attenuation measurement device, on patients with MASLD. This tool employs a deep learning-based method to detect and segment shear waves in the liver tissue for subsequent analysis to improve tissue characterization for patient diagnosis., Methods: This new tool consists of a deep learning based algorithm, which was trained on 15,045 expert-segmented images from 103 patients, using a U-Net architecture. The algorithm was then tested on 4429 images from 36 volunteers and patients with MASLD. Test subjects were scanned at different clinics with different Velacur operators. Evaluation was performed on both individual images (image based) and averaged across all images collected from a patient (patient based). Ground truth was defined by expert segmentation of the shear waves within each image. For evaluation, sensitivity and specificity for correct wave detection in the image were calculated. For those images containing waves, the Dice coefficient was calculated. A prototype of the software tool was also implemented on Velacur and assessed by operators in real world settings., Results: The wave detection algorithm had a sensitivity of 81% and a specificity of 84%, with a Dice coefficient of 0.74 and 0.75 for image based and patient-based averages respectively. The implementation of this software tool as an overlay on the B-Mode ultrasound resulted in improved exam quality collected by operators., Conclusion: The shear wave algorithm performed well on a test set of volunteers and patients with metabolic dysfunction-associated steatotic liver disease. The addition of this software tool, implemented on the Velacur system, improved the quality of the liver assessments performed in a real world, point of care setting., Competing Interests: Conflict of interest M.H., J.L., and C.S. are employees of Sonic Incytes. N.W. is a consultant for Sonic Incytes. S.G.: Research grant support for Viking, Zydus, Sonic Incytes, DSM. R.L. Is the Co-founder of LipoNexus Inc. and was an investigator of clinical trials sponsored by Sonic Incytes. R.L. receives funding support from NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515), NHLBI (P01HL147835), John C Martin Foundation (RP124). A.R.: Advisor /consultant for Abbvie, Gilead, Intercept/ Advanz, Janssen, Novo-Nordisc. He was an investigator of clinical trials sponsored by Sonic Incytes. T.H.: Receives Grant/Research Support from AbbVie, Allergan, Amgen, Biolinq, Bristol-Myers Squibb, Cytodyn, Assembly, Astra Zeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, CARA, DURECT Corporation, Enanta, Escient, Fractyl, Galectin, Gilead, Grifols, HepQuant, Intercept, Janssen, Merck, Mirum, Novartis, Novo Nordisk, Nucorion, Pfizer, Provepharm, Regeneron, Salix Pharmaceuticals, Sonic Incytes, Terns Pharmaceuticals, Valeant. He was an investigator of clinical trials sponsored by Sonic Incytes. E.Y.: Dr. Eric Yoshida is an investigator of clinical research and clinical trials sponsored by: Sonic Incytes Inc, Pfizer Inc, Gilead Inc, Intercept Inc, Madrigal Inc, Novodisc Inc, Genfit Inc. He has also received a research grant from Paladin Laboratories. EP: None. MC has received research support from CareDx, Intercept and Sonic Incytes and consults for International Healthcare and Pfizer. He was an investigator of clinical trials sponsored by Sonic Incytes. N.A. has received consulting fees from Gilead, Glaxo Smith Kline, Jannsen, Sonic Incytes, Precision Biosciences, Intercept Pharmaceuticals. He has stock in Allurion. He is director, Liver Institute for Education and Research. He was an investigator of clinical trials sponsored by Sonic Incytes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine whether international normalized ratio (INR), bilirubin, and creatinine predict bleeding risk following percutaneous liver biopsy., Methods: A total of 870 consecutive patients (age 53 ± 14 years; 53% (459/870) male) undergoing non-targeted, ultrasound-guided, percutaneous liver biopsy at a single tertiary center from 01/2016 to 12/2019 were retrospectively reviewed. Results were analyzed using descriptive statistics and logistic regression models to evaluate the relationship between individual and combined laboratory values, and post-biopsy bleeding risk. Receiver operating characteristic (ROC) curves and area under ROC (AUC) curves were constructed to evaluate predictive ability., Results: Post-biopsy bleeding occurred in 2.0% (17/870) of patients, with 0.8% (7/870) requiring intervention. The highest INR within 3 months preceding biopsy demonstrated the best predictive ability for post-biopsy bleeding and was superior to the most recent INR (AUC = 0.79 vs 0.61, p = 0.003). Total bilirubin is an independent predictor of bleeding (AUC = 0.73) and better than the most recent INR (0.61). Multivariate regression analysis of the highest INR and total bilirubin together yielded no improvement in predictive performance compared to INR alone (0.80 vs 0.79). The MELD score calculated using the highest INR (AUC = 0.79) and most recent INR (AUC = 0.74) were similar in their predictive performance. Creatinine is a poor predictor of bleeding (AUC = 0.61). Threshold analyses demonstrate an INR of > 1.8 to have the highest predictive accuracy for bleeding., Conclusion: The highest INR in 3 months preceding ultrasound-guided percutaneous liver biopsy is associated with, and a better predictor for, post-procedural bleeding than the most recent INR and should be considered in patient risk stratification., Clinical Relevance Statement: Despite correction of coagulopathic indices, the highest international normalized ratio within the 3 months preceding percutaneous liver biopsy is associated with, and a better predictor for, bleeding and should considered in clinical decision-making and determining biopsy approach., Key Points: • Bleeding occurred in 2% of patients following ultrasound-guided liver biopsy, and was non-trivial in 41% of those patients who needed additional intervention and had an associated 23% 30-day mortality rate. • The highest INR within 3 months preceding biopsy (AUC = 0.79) is a better predictor of bleeding than the most recent INR (AUC = 0.61). • The MELD score is associated with post-procedural bleeding, but with variable predictive performance largely driven by its individual laboratory components., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 ( 90 Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with 90 Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with 90 Y resin microspheres between July 2014 and December 2022. Posttreatment PET/CT and dosimetry were performed. Adverse events were assessed using the Common Terminology Criteria for Adverse Events, version 5.0. Per-lesion and overall response rates (ie, complete response [CR], objective response, disease control, and duration of response) were assessed at imaging using the Modified Response Evaluation Criteria in Solid Tumors, and overall survival (OS) was assessed using Kaplan-Meier analysis. Results Among 67 patients (median age, 69 years [IQR, 63-78 years]; 54 male patients) with HCC, median tumor absorbed dose was 232 Gy (IQR, 163-405 Gy). At 3 months, per-lesion and overall (per-patient) CR was achieved in 47 (70%) and 41 (61%) of 67 patients, respectively. At 6 months ( n = 46), per-lesion rates of objective response and disease control were both 94%, and per-patient rates were both 78%. A total of 88% (95% CI: 79 99) and 72% (95% CI: 58, 90) of patients had a per-lesion and overall duration of response of 1 year or greater. At 1 month, a grade 3 clinical adverse event (abdominal pain) occurred in one of 67 (1.5%) patients. Median posttreatment OS was 26 months (95% CI: 20, not reached). Disease progression at 2 years was lower in the group that received 300 Gy or more than in the group that received less than 300 Gy (17% vs 61%; P = .047), with no local progression in the former group through the end of follow-up. Conclusion Among patients with HCC who underwent RS with 90 Y resin microspheres, 88% and 72% achieved a per-lesion and overall duration of response of 1 year or greater, respectively, with one grade 3 adverse event. In patients whose tumors received 300 Gy or more according to posttreatment dosimetry, a disease progression benefit was noted. © RSNA, 2024 Supplemental material is available for this article.

Hepatorenal syndrome-acute kidney injury (HRS-AKI), a serious complication of decompensated cirrhosis, has limited therapeutic options and significant morbidity and mortality. Terlipressin improves renal function in some patients with HRS-1, while liver transplantation (LT) is a curative treatment for advanced chronic liver disease. Renal failure post-LT requiring renal replacement therapy (RRT) is a major risk factor for graft and patient survival. A post hoc analysis with a 12-month follow-up of LT recipients from a placebo-controlled trial of terlipressin (CONFIRM; NCT02770716) was conducted to evaluate the need for RRT and overall survival. Patients with HRS-1 were treated with terlipressin plus albumin or placebo plus albumin for up to 14 days. RRT was defined as any type of procedure that replaced kidney function. Outcomes compared between groups included the incidence of HRS-1 reversal, the need for RRT (pretransplant and posttransplant), and overall survival. Of the 300 patients in CONFIRM (terlipressin n = 199; placebo, n = 101), 70 (23%) underwent LT alone (terlipressin, n = 43; placebo, n = 27) and 5 had simultaneous liver-kidney transplant (terlipressin, n = 3, placebo, n = 2). The rate of HRS reversal was significantly higher in the terlipressin group compared with the placebo group (37%, n = 16 vs. 15%, n = 4; p = 0.033). The pretransplant need for RRT was significantly lower among those who received terlipressin ( p = 0.007). The posttransplant need for RRT, at 12 months, was significantly lower among those patients who received terlipressin and were alive at Day 365, compared to placebo ( p = 0.009). Pretransplant treatment with terlipressin plus albumin in patients with HRS-1 decreased the need for RRT pretransplant and posttransplant., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: As the prevalence of metabolic dysfunction-associated steatotic liver disease increases, it is imperative to have noninvasive alternatives to liver biopsy. Velacur offers a non-invasive, point-of-care ultrasound-based method for the assessment of liver stiffness and attenuation. The aim of this study was to perform a head-to-head comparison of liver stiffness and liver fat determined by Velacur and FibroScan using MRI-based measurements as the reference standard., Methods: This prospective cross-sectional study included 164 adult participants with well-characterized metabolic dysfunction-associated steatotic liver disease. Patients underwent a research exam including Velacur, FibroScan and contemporaneous magnetic resonance elastography, and magnetic resonance imaging proton density fat fraction (MRI-PDFF) scans. The primary outcome was the presence of advanced fibrosis (>F2) as measured by magnetic resonance elastography and the presence of liver fat (>5%) as measured by MRI-PDFF., Results: The mean age and body mass index were 57±12 years and 30.6±4.8 kg/m2, respectively. The mean liver stiffness on magnetic resonance elastography was 3.22±1.39 kPa and the mean liver fat on MRI-PDFF was 14.2±8%. The liver stiffness assessments by Velacur and FibroScan were similar for the detection of advanced fibrosis (AUC 0.95 vs. 0.97) and were not statistically different (p=0.43). Velacur was significantly better than FibroScan (AUC 0.94 vs. 0.79, p=0.01), for the detection of MRI-PDFF >5% (diagnosis of metabolic dysfunction-associated liver disease)., Conclusions: Velacur was superior to FibroScan for liver fat detection with MRI-PDFF as the reference. Velacur and FibroScan were not statistically different for liver stiffness assessment as defined by magnetic resonance elastography., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

The purpose of this study is to compare the subjective and objective quality and confidence between conventional angiography with cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) for the preoperative evaluation of potential donors for living donor liver transplant. Seventeen patients undergoing preoperative donor evaluation for living donor liver transplantation that underwent angiography with CBCT and contrast-enhanced MRI for evaluation of hepatic vascular anatomy were included in the study. Four attending radiologists interpreted anonymized, randomized angiography with CBCT images and MRIs, rating the diagnostic quality and confidence of their interpretation (on a 3-point scale) for each element, as well as clinically relevant measurements. Overall, the readers rated the quality of angiography with CBCT to be higher than that of MRI (median [interquartile range] = 3 (2, 3) vs. 2 (1-3), p < 0.001) across all patients. Readers of angiography with CBCT had more confidence in their interpretations as an average of all elements evaluated than the MRI readers (3 (3) vs. 3 (2, 3), p < 0.001). When the same reader interpreted both MRI and CBCT, the right hepatic artery diameter (3.8 mm ± 0.72 mm vs. 4.5 mm ± 1.2 mm, p < 0.005) and proper hepatic artery diameter (4.43 mm ± 0.98 mm vs. 5.4 mm ± 1.05 mm, p < 0.003) were significantly different between MRI and CBCT. There was poor interrater reliability for determining segment IV arterial supply for both modalities (κ < 0.2). Angiography with CBCT provides higher subjective diagnostic quality and greater radiologist confidence than MRI. The difference in measurements between CBCT and MRI when the same reader reads both studies suggests CBCT adds additional information over MRI evaluation alone., (© 2023 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Background and Aims: Nonalcoholic fatty liver disease is the leading cause of chronic liver disease globally and can progress to cirrhosis, liver failure, and liver cancer. Current AASLD, AGA, and ADA guidelines recommend assessment for liver fibrosis in all patients with NAFLD. Serum biomarkers for fibrosis, while widely available, have notable limitations. Imaging-based noninvasive testing for liver fibrosis/cirrhosis is more accurate and is becoming more widespread., Methods: We evaluated the feasibility of a novel shear wave absolute vibroelastography (S-WAVE) modality called Velacur® for assessing liver stiffness measurement (LSM) for fibrosis and attenuation coefficient estimation (ACE) in differentiating patients with chronic liver disease from normal healthy controls., Results: Fifty-four healthy controls and 89 patients with NAFLD or cured HCV with a prior known LSM of >8 kPa were enrolled, and all subjects were evaluated with FibroScan® and Velacur®. Velacur® was able to discriminate patients with increased liver stiffness as determined by a FibroScan® score of >8 kPa from healthy controls with an AUC of 0.938 (0.88-0.96). For assessment of steatosis in NAFLD patients only, Velacur® could identify patients with steatosis from healthy controls with an AUC of 0.831 (0.777-0.880). The Velacur® scan quality assessment was superior in healthy controls, as compared to patients, and the scan quality, as assessed by the quality factor (QF) and interquartile range (IQR)/median, was affected by BMI. Velacur® was safe and well tolerated by patients, and there were no adverse events., Conclusion: Velacur® assessment of liver stiffness measurement and liver attenuation is comparable to results obtained by FibroScan® and is an alternative technology for monitoring liver fibrosis progression in patients with chronic liver disease. This trial is registered with NCT03957070., Competing Interests: MC has received research support from Sonic Incytes, Mallinckrodt, and Gilead and consulting fees from Sonic Incytes, Mallinckrodt, Alexion, and Albireo. ET has received consulting and speaking fees from AbbVie, Advanz, Gilead, Intercept, and Sonic Incytes. CS is an employee of Sonic Incytes Medical Corp. Noha Abdelgelil received none. TH has received consulting fees and is on advisory committees for AbbVie, Bristol-Myers Squibb, Gilead, Mallinckrodt, and Organovo. He receives research support from AbbVie, Allergan, Amgen, Biolinq, Bristol-Myers Squibb, CytoDyn, Assembly, AstraZeneca, Boehringer Ingleheim, CARA, DURECT Corporation, Enanta, Escient, Fractyl, Galectin, Jannsen, Merck Mirum, Novartis, Novo Nordisk, Nucorion, Pfizer, Provepharm, Rengeron, Salix Pharmaceuticals, Sonic Incytes, Terns Pharmaceuticals, and Valeant. Nezam H. Afdhal has received consulting fees from Gilead, Glaxo Smith Kline, Jannsen, Sonic Incytes, Precision Biosciences, and Intercept Pharmaceuticals. He has stock in Allurion. He is the director of the Liver Institute for Education and Research., (Copyright © 2024 Michael P. Curry et al.)

Purpose: To study the experiences of patients with hepatocellular carcinoma (HCC) contributing to treatment discrepancy in the United States., Materials and Methods: Using Surveillance, Epidemiology, and End Results data from National Cancer Institute (NCI), Medicare (2002-2015) beneficiaries with HCC who completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey were included. Six CAHPS items (3 global scores: global care rating [GCR], primary doctor rating [PDR], and specialist rating [SR]; 3 composite scores: getting needed care [GNC], getting care quickly [GCQ], and doctor communication [DC]) assessed patient experience. Covariates assessed between treated and nontreated groups included patient, disease, hospital, and CAHPS items., Results: Among 548 patients with HCC, 211 (39%) received treatment and 337 (61%) did not receive treatment. Forty-two percent (GCR), 29% (PDR), 30% (SR), 36% (GNC), 78% (GCQ), and 35% (DC) of patients reported less-than-excellent experiences on the respective CAHPS items. Chronic liver disease (CLD) was present in 52% and liver decompensation (LD) in 60%. A minority of the hospitals were NCI-designated cancer centers (47%), transplant centers (27%), and referral centers (9%). On univariable analysis, patients with at least a high school degree (odds ratio [OR], 1.9), admittance to a ≥400-bed hospital (OR, 2.7), CLD (OR, 3.0), or LD (OR, 1.7) were more likely to receive treatment, whereas older patients (≥75 years) (OR, 0.5) were less likely to receive treatment. On multivariable, patients with CLD (OR, 6.8) and an excellent experience in GNC with a specialist (OR, 10.6) were more likely to receive treatment., Conclusions: HCC treatment discrepancy may be associated with patient-related factors, such as lack of specialist care (GNC), and disease-related factors, such as absence of underlying CLD., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Acute variceal hemorrhage is a major decompensating event in patients with cirrhosis and is associated with high 6-week mortality risk. Many prognostic models based on clinical and laboratory parameters have been developed to risk stratify patients on index bleeding presentation, including those based on the Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP). However, consensus on model performance remains unclear., Methods: Using a large US multicenter cohort of hospitalized patients with cirrhosis who presented with acute variceal hemorrhage, this study evaluates, recalibrates, and compares liver severity index-based models, including the more recent MELD 3.0 model, to investigate their predictive performance on 6-week mortality. Models were also recalibrated and externally validated using additional external centers., Results: All recalibrated MELD-based and CTP-based models had excellent discrimination to identify patients at higher risk for 6-week mortality on initial presentation. The recalibrated CTP score model maintained the best calibration and performance within the validation cohort. Patients with low CTP scores (Class A, score 5-6) were strongly associated with < 5% mortality, while high CTP score (Class C, score > 9) were associated with > 20% mortality., Conclusion: Use of liver severity index-based models accurately predict 6-week mortality risk for patients admitted to the hospital with acute variceal hemorrhage and supports the utilization of these models in future clinical trials as well as their use in clinical practice., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Whole-exome sequencing (WES) is an effective tool for diagnosis in patients who remain undiagnosed despite a comprehensive clinical work-up. While WES is being used increasingly in pediatrics and oncology, it remains underutilized in non-oncological adult medicine, including in patients with liver disease, in part based on the faulty premise that adults are unlikely to harbor rare genetic variants with large effect size. Here, we aim to assess the burden of rare genetic variants underlying liver disease in adults at two major tertiary referral academic medical centers., Methods: WES analysis paired with comprehensive clinical evaluation was performed in fifty-two adult patients with liver disease of unknown etiology evaluated at two US tertiary academic health care centers., Findings: Exome analysis uncovered a definitive or presumed diagnosis in 33% of patients (17/52) providing insight into their disease pathogenesis, with most of these patients (12/17) not having a known family history of liver disease. Our data shows that over two-thirds of undiagnosed liver disease patients attaining a genetic diagnosis were being evaluated for cholestasis or hepatic steatosis of unknown etiology., Interpretation: This study reveals an underappreciated incidence and spectrum of genetic diseases presenting in adulthood and underscores the clinical value of incorporating exome sequencing in the evaluation and management of adults with liver disease of unknown etiology., Funding: S.V. is supported by the NIH/NIDDK (K08 DK113109 and R01 DK131033-01A1) and the Doris Duke Charitable Foundation Grant #2019081. This work was supported in part by NIH-funded Yale Liver Center, P30 DK34989., Competing Interests: Declaration of interests A.M.D., R.A.H., A.M.H., L.K., P.L., P.N., M.E.P., and L.D.W., are employees of Alnylam Pharmaceuticals. A.M.D. and L.D.W., also hold stock options in Alnylam Pharmaceuticals. M.G.S., is a principal investigator for clinical studies from Novartis, Gilead, Pliant, Cymabay, Genfit, Target PharmaSolutions. Z.G.J., consults for Olix Pharmaceuticals and receives grants from Gilead Sciences and Pfizer Pharmaceuticals. M.P.C., consults for Mallinckrodt LLC, Alexion Pharmaceuticals, and Albireo Pharma and has also received grants from Sonic Incytes. M.H.C., has received grant support from Bayer. S.V., served as consultant for Albireo Pharma. The other authors do not report any potential conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by severe hepatic dysfunction leading to multiorgan failure in patients with end-stage liver disease. ACLF is a challenging clinical syndrome with a rapid clinical course and high short-term mortality. There is no single uniform definition of ACLF or consensus in predicting ACLF-related outcomes, which makes comparing studies difficult and standardizing management protocols challenging. This review aims to provide insights into the common prognostic models that define and grade ACLF., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To report the safety and effectiveness of transjugular intrahepatic portosystemic shunt and mechanical thrombectomy (TIPS-thrombectomy) for symptomatic acute noncirrhotic portal vein thrombosis (NC-PVT)., Materials and Methods: Patients with acute NC-PVT who underwent TIPS-thrombectomy between 2014 and 2021 at a single academic medical center were retrospectively reviewed. Thirty-two patients were included (men, 56%; median age, 51 years [range, 39-62 years]). The causes for PVT included idiopathic (n = 12), prothrombotic disorders (n = 11), postsurgical sequelae (n = 6), pancreatitis (n = 2), and Budd-Chiari syndrome (n = 1). The indications for TIPS-thrombectomy included refractory abdominal pain (n = 14), intestinal venous ischemia (n = 9), ascites (n = 4), high-risk varices (n = 3), and variceal bleeding (n = 2). Variables studied included patient, disease, and procedure characteristics. Patients were monitored over the course of 1-year follow-up., Results: Successful recanalization of occluded portal venous vessels occurred in all 32 patients (100%). Compared with pretreatment patency, recanalization with TIPS-thrombectomy resulted in an increase in patent veins (main portal vein [28% vs 97%, P < .001], superior mesenteric vein [13% vs 94%, P < .001], and splenic vein [66% vs 91%, P < .001]). Three procedure-related adverse events occurred (Society of Interventional Radiology grade 2 moderate). Hepatic encephalopathy developed in 1 (3%) of 32 patients after TIPS placement. At 1-year follow-up, return of symptoms occurred in 3 (9%) of 32 patients: (a) ascites (n = 1), (b) variceal bleeding (n = 1), and (c) intestinal venous ischemia (n = 1). The intention-to-treat 1-year portal vein and TIPS primary and secondary patency rates were 78% (25/32) and 100% (32/32), respectively. Seven patients required additional procedures, and the 1-year mortality rate was 3% (1/32)., Conclusions: TIPS-thrombectomy is a safe and effective method for treating patients with symptomatic acute NC-PVT., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Worsened by the COVID-19 pandemic, alcohol use is one of the leading causes of preventable death in the US, in large part due to alcohol-associated liver disease. Throughout history, liver transplantation for this population has been controversial, and many policies and regulations have existed to limit access to lifesaving transplant for patients who use alcohol. In recent years, the rates of liver transplantation for patients with alcohol-associated liver disease have increased dramatically; however, disparities persist. For instance, many criteria used in evaluation for transplant listing, such as social support and prior knowledge of the harms of alcohol use, are not evidence based and may selectively disadvantage patients with alcohol use disorder. In addition, few transplant providers have adequate training in the treatment of alcohol use disorder, and few transplant centers offer specialized addiction treatment. Finally, current approaches to liver transplantation would benefit from adopting principles of harm reduction, which have demonstrated efficacy in the realm of addiction medicine for years. As we look toward the future, we must emphasize the use of evidence-based measures in selecting patients for listing, ensure access to high-quality addiction care for all patients pretransplant and posttransplant, and adopt harm reduction beliefs to better address relapse when it inevitably occurs. We believe that only by addressing each of these issues will we be able to ensure a more equitable distribution of resources in liver transplantation for all patients., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Introduction and Objectives: The association between type 2 diabetes, non-alcoholic fatty liver disease, and liver fibrosis is well established, but it is unknown whether complications of type 2 diabetes influence fibrosis levels. We defined the complications of type 2 diabetes by the presence of diabetic nephropathy, retinopathy, or neuropathy and aimed to evaluate their association with the degree of liver fibrosis measured by the fibrosis-4 (FIB-4) index., Materials and Methods: This is a cross-sectional study evaluating the association of type 2 diabetes complications with liver fibrosis. A total of 2389 participants were evaluated from a primary care practice. FIB-4 was evaluated as a continuous and categorical measure using linear and ordinal logistic regression., Results: Patients with complications were older, had higher hemoglobin A1c, and a higher median FIB-4 score (1.34 vs. 1.12, P<0.001). On adjusted analysis, type 2 diabetes complications were associated with higher fibrosis by continuous FIB-4 score (Beta-coefficient: 0.23, 95% confidence interval [CI]: 0.004-1.65) and demonstrated increased odds of fibrosis by categorical FIB-4 score (odds ratio [OR]: 4.48, 95% CI: 1.7-11.8, P=0.003), independent of hemoglobin A1c level., Conclusions: The presence of type 2 diabetes complications is associated with the degree of liver fibrosis, independent of hemoglobin A1c level., (Copyright © 2023 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Hepatorenal syndrome type 1 (HRS-1) is a serious complication of advanced cirrhosis and a potentially reversible form of acute kidney injury that is associated with rapidly deteriorating kidney function. Liver transplantation remains the only curative treatment for decompensated cirrhosis. However, terlipressin, a vasopressin analog, successfully reverses HRS-1, and may improve patient survival while awaiting liver transplantation. Patients with higher baseline serum creatinine have a reduced response to treatment with terlipressin. These post hoc analyses examined pooled data from 352 patients with HRS-1 treated with terlipressin in 3 North American-centric, Phase III, placebo-controlled clinical studies (i.e. OT-0401, REVERSE, and CONFIRM)-across 3 serum creatinine subgroups (i.e. <3, ≥3-<5, and ≥5 mg/dL)-to further delineate their correlation with HRS reversal, renal replacement therapy-free survival, and overall survival. Serum creatinine was significantly associated with HRS reversal in univariate and multivariate logistic regression analyses (P<0.001). The incidence of HRS reversal inversely correlated with serum creatinine subgroup (<3 mg/dL, 49.2%; ≥3-<5 mg/dL, 28.0%; ≥5 mg/dL, 9.1%). At Day 30 follow-up, renal replacement therapy-free survival was significantly higher for patients with HRS-1 in the lower serum creatinine subgroups than in the higher subgroup (<5 vs. >5 mg/dL; p=0.01). Terlipressin-treated patients with HRS-1, with a lower baseline serum creatinine level, had a higher overall survival (p<0.001) and higher transplant-free survival at Day 90 (p=0.04). Patients with HRS-1 and lower serum creatinine levels who were treated with terlipressin had higher HRS reversal and survival outcomes, highlighting the significant need to identify and treat patients with HRS-1 early when they often have lower serum creatinine levels, and likely a greater response to terlipressin., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc on behalf of the American Association for the Study of Liver Diseases.)

Background and Aims: Liver organ shortage remains a major health burden in the US, with more patients being waitlisted than the number of liver transplants (LTs) performed. This study investigated US national and regional trends in living donor LT (LDLT) and identified factors associated with recipient survival., Methods: We retrospectively analyzed LDLT recipients and donors from the United Network Organ Sharing/Organ Procurement Transplant Network database from 1998 until 2019 for clinical characteristics, demographic differences, and survival rate. National and regional trends in LDLT, recipient outcomes, and predictors of survival were analyzed., Results: Of the 223,571 candidates listed for an LT, 57.5% received an organ, of which only 4.2% were LDLTs. Annual adult LDLTs first peaked at 412 in 2001 but experienced a significant decline to 168 by 2009. LDLTs then gradually increased to 445 in 2019. Region 2 had the highest LDLT numbers ( n =919), while region 1 had the highest proportion (11.1%). Overall, post-LT mortality was 21.4% among LDLT recipients. Post-LDLT survival rates after 1-, 5-, and 10-years were 92%, 87%, and 70%, respectively. Interval analysis (2004-2019) showed that patients undergoing LDLT in recent years had lower mortality than in earlier years (hazard ratio=0.81, 95% confidence interval=0.75-0.88)., Conclusions: Following a substantial decline after a peak in 2001, the number of adult LDLTs steadily increased from 2011 to 2019. However, LDLTs still constitute the minority of the transplant pool in the US. Life-saving policies to increase the use of LDLTs, particularly in regions of high organ demand, should be implemented., Competing Interests: AB declares activities with Scientific Advisory Boards, Intercept, Primary Investigator for trials for Gilead and CARA. BS has been an editorial board member of Journal of Clinical and Translational Hepatology since 2016. All other authors have no conflict of interests related to this publication., (© 2022 Authors.)

Introduction: Transplantation of organs exposed to hepatitis C virus (HCV) into uninfected patients has yielded excellent outcomes and more widespread adoption may lead to fewer discarded organs and more transplants. Patient perceptions may shed light on acceptability and likely the uptake of HCV+/HCV- transplantation, gaps in understanding, and perceived benefits/risks., Methods: We surveyed 435 uninfected kidney and liver transplant candidates at four centers about their attitude towards HCV-infected organs., Results: The percentage of patients willing to accept HCV-infected organs increased from 58% at baseline, to 86% following education about HCV, direct-acting antiviral agents (DAAs), and HCV+/HCV- transplantation benefits/risks. More willingness to accept an organ from an intravenous drug user (P < 0.001), age >50 y old (P = 0.02), longer waiting time (P = 0.02), more trust in the transplant system (P = 0.03), and previous awareness of DAAs (P = 0.04) were associated with higher willingness to accept an HCV-infected organ. The most important reasons for accepting an HCV-infected organ were a decrease in waiting time (65%), lower mortality and morbidity risk while on the waiting list (63%), effectiveness of DAAs (54%), and a quicker return to higher functional status (51%)., Conclusions: Presenting patients with information about HCV+/HCV- transplantation in small doses that are calibrated to account for varying levels of health and numerical literacy is recommended., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Previous studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute-on-chronic liver failure (ACLF)., Aim: To assess mortality and respiratory failure (RF) in patients with HRS1 and ACLF treated with terlipressin., Methods: In the CONFIRM study, we randomised 299 patients with HRS1 2:1 to terlipressin or placebo, both with albumin. At enrolment, all patients were assessed for organ failure (OF) using a validated ACLF grading system. Post hoc analyses assessed the effects of terlipressin vs. placebo on the incidence of RF and 90-day mortality., Results: The incidence of RF with terlipressin (n = 200) was 9.4% in patients with grades 1-2 ACLF, and 30% with grade 3 ACLF (p = 0.0002); no such difference was observed in placebo-treated patients (n = 99) (6.2% grades 1-2 vs. 0% grade 3 ACLF, p > 0.05). RF incidence between terlipressin and placebo in patients with grade 3 ACLF was significant (p = 0.01). Baseline predictors of RF with terlipressin were INR (p = 0.011), mean arterial pressure (p = 0.037), and SpO 2 (p = 0.014). Prior albumin as a continuous variable was not a predictor of RF. 90-day survival between terlipressin and placebo arms was similar for grades 1-2 ACLF (55.5% and 56.6%, respectively), but lower for grade 3 ACLF (27.55% vs. 50.0%) (p = 0.122), mainly related to RF., Conclusion: Terlipressin should be used with caution in patients with HRS1 and grade 3 ACLF. Patients with hypoxaemia are at increased risk of RF and mortality., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Real-world data are limited on tenofovir alafenamide (TAF). We aimed to study TAF real-world outcomes with other first-line regimens for chronic hepatitis B (CHB). We enrolled patients with CHB from 10 centers retrospectively and followed them for 36 months prospectively. We analyzed switching patterns of antiviral therapy and treatment outcomes of TAF, tenofovir disoproxil fumarate (TDF), and entecavir therapy. For efficacy and safety, we analyzed a subset of patients with complete data at 24 months after switching to TAF or remaining on TDF or entecavir. Among 1037 enrollees, 889 patients were analyzed. The mean age was 52%, and 72% were hepatitis B e antigen-negative. After enrollment, shifts in therapies were mostly in reduced use of TDF from 63% to 30% due to switching to TAF. Clinical parameters were compared at enrollment or initiation to measures at 24 months for patients remaining on TAF (187), TDF (229), or entecavir (181). At 24 months, a significantly higher portion of patients on TAF achieved hepatitis B virus (HBV) DNA ≤ 20 IU/ml (93% vs. 86%; p = 0.012) and normalized alanine aminotransferase (ALT) (66% vs. 56%; p = 0.031) with stable estimated glomerular filtration rates (eGFRs). However, a higher percentage of the patient with eGFR < 60 ml/mi/1.7 m 2 was observed in the TDF-treated group (9% vs. 4%; p = 0.010). In patients who remained on entecavir or TDF for 24 months, ALT and HBV-DNA results did not differ significantly from baseline. Treatment of CHB in the United States has significantly shifted from TDF to TAF. Our data suggest that switching from TDF or entecavir to TAF may result in increased frequency of ALT normalization and potential clearance of viremia at the 24-month time point., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

BACKGROUND. Heart failure (HF) is an uncommon complication after TIPS placement; its development represents a poor prognostic factor. OBJECTIVE. The purpose of our study was to evaluate the frequency, risk factors, and association with survival of HF developing within 90 days after TIPS placement in patients with cirrhosis. METHODS. This retrospective single-center study included patients with cirrhosis who underwent nonemergent covered-stent TIPS placement from June 2003 to December 2018 and who underwent echocardiography within 2 months before TIPS placement and had at least 90 days of post-TIPS follow-up. Development of HF within 90 days after TIPS was recorded. Frequency of TIPS reduction for post-TIPS HF was determined. Univariable logistic regression analysis and ROC curve analysis were performed to assess potential risk factors for post-TIPS HF. Association of post-TIPS HF and 1-year survival was assessed by the log rank test. RESULTS. The study sample included 107 patients (71 men and 36 women; median age, 58 years). Post-TIPS HF developed in 11 of 107 (10%) patients; median time to development of HF was 16 days (range, 2-62 days). Of these 11 patients, three (27%) required TIPS reduction to achieve resolution of HF symptoms after unsuccessful diuretic therapy. Pre-TIPS right atrium size (odds ratio [OR], 3.26 [95% CI, 1.22-10.16]; p = .03], left ventricle (LV) end-systolic dimension (OR, 5.43 [95% CI, 1.44-24.50], p = .02), LV end-diastolic dimension (OR, 4.12 [95% CI, 1.51-13.47]; p = .009), and estimated peak pulmonary artery systolic pressure (PASP) (OR, 1.27 [95% CI, 1.12-1.50]; p = .001) were associated with post-TIPS HF. AUC of right atrium size, LV end-systolic dimension, LV end-diastolic dimension, and estimated peak PASP for development of post-TIPS HF were 0.71, 0.74, 0.72, and 0.83, respectively. At a cutoff of 31 mm Hg, PASP achieved sensitivity of 70% and specificity of 86% for post-TIPS HF. Patients with post-TIPS HF and those without post-TIPS HF had 1-year survival of 46% versus 73% ( p = .06). CONCLUSION. Multiple pre-TIPS echocardiographic variables predict the development of post-TIPS HF in patients with cirrhosis. CLINICAL IMPACT. Preprocedural echocardiography may guide risk stratification in patients with cirrhosis being considered for TIPS placement.

Individuals on immunosuppressive (IS) therapy have increased mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and delayed viral clearance may lead to new viral variants. IS therapy reduces antibody responses following coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination; however, a comprehensive assessment of vaccine immunogenicity is lacking. Here we show that IS therapy reduced neutralizing, binding, and nonneutralizing antibody functions in addition to CD4 and CD8 T-cell interferon-γ responses following COVID-19 mRNA vaccination compared to immunocompetent individuals. Moreover, IS therapy reduced cross-reactivity against SARS-CoV-2 variants. These data suggest that the standard COVID-19 mRNA vaccine regimens will likely not provide optimal protection in immunocompromised individuals., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Cirrhosis, a rising cause of death in the United States, has an extended preclinical phase characterized by progressive liver fibrosis. Despite the developments in noninvasive fibrosis measurement, there is no recommended screening, in part due to an incomplete understanding of the disease epidemiology on a national scale. Herein, we aim to define the prevalence of liver fibrosis and compare strategies to identify the at-risk population. We analyzed 4,510 US adults with complete liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in the 2017-2018 National Health and Nutrition Examination Survey to estimate the disease burden of increased liver stiffness. An estimated 11.6 million (95% confidence interval [C.I.], 8.1-15.0 million) US adults had LSM ≥9.5 kPa, indicating advanced fibrosis and representing 1 in every 18 adults. Among them, 7.1 million (95% CI, 5.0-9.1 million) had LSM ≥12.5 kPa, which is concerning for cirrhosis. LSM ≥9.5 kPa is associated with male sex (S), history of other liver diseases (O), diabetes (D), advanced age (A), and an elevated BMI (B). A simple SODA-2B score had a sensitivity of 96.4% in identifying individuals at risk for advanced cirrhosis (LSM ≥9.5 kPa) and a negative predictive value of 99.3% in stratifying more than half of the adult population. When the liver function test (LFT) is available, the inclusion of abnormal LFT and elevated fibrosis-4 index can further increase screening efficiency. Conclusion: Elevated liver stiffness is prevalent among US adults. A SODA-2B score can risk stratify adults for VCTE-based fibrosis screening., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Introduction: Recommendations on non-invasive imaging to assess pre-operative cardiac risk among liver transplant candidates vary amongst societal guidelines and individual institutional practices. In 2018, a standardized pre-transplant coronary evaluation protocol was established at Beth Israel Deaconess Medical Center, Boston MA, to ensure appropriate and consistent pre-operative testing was performed., Methods: All patients who underwent liver transplant evaluation between January 1st, 2016 and December 31st, 2019, were retrospectively analyzed and divided into three cohorts; before the introduction of the protocol (prior to 2018), initial protocol favoring invasive coronary angiography (ICA) (2018), and amended protocol favoring coronary computed tomography angiography (CCTA) (post-2018). We described clinical characteristics, candidacy for transplant, and cardiovascular complications during follow-up. As an unadjusted exploratory analysis, the Cochran-Armitage Exact Trend Test was used to examine univariate differences across time., Results: A total of 462 patients underwent liver transplant evaluation during the study period. Among these, 218 (47.2%) patients underwent stress test, 50 (10.8%) underwent CCTA, and 68 (14.8%) underwent ICA. Across the three time periods, there was an increase in the proportion of CCTAs performed (3%, 6.3%, and 26.3% respectively; p <0.001) and proportion of patients diagnosed with obstructive CAD using CCTA (0%, 30%, and 51.4% respectively; p = 0.04). There was no significant difference in post-transplant cardiac complications among patients evaluated before 2018, during 2018, and after 2018 (5.9% vs. 5.6 vs. 6.0%; p=1.0)., Conclusion: Our findings suggest it is reasonable to shift practice to a less invasive approach utilizing CCTA or nuclear stress testing when assessing liver transplant candidates at increased cardiovascular risk., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Model for End-Stage Liver Disease (MELD) alone and with sodium (MELD-Na) have decreasing predictive capacity as trends in liver disease evolve. We sought to combine transient elastography (TE) with MELD-Na to improve its predictive ability., Methods: This is a retrospective cohort study comparing the use of TE, MELD-Na, and composite MELD-Na-TE to predict liver transplantation and all-cause mortality, with hepatic decompensation as a secondary outcome. Cox proportional hazards regression was used to measure predictive ability and control for confounders., Results: Of the 214 patients, the mean age was 53 years with 35% being female and 76% being Caucasian. Hepatitis C (59%) and nonalcoholic fatty liver disease (22%) were the most frequent liver disease etiologies. On univariable analysis, MELD-Na [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06-1.2, P < 0.001], TE (HR 1.04, 95% CI 1.03-1.06, P < 0.001) and composite MELD-Na-TE (HR 1.13, 95% CI 1.08-1.19, P < 0.001) were associated with death or transplant. On multivariable analysis, MELD-Na was no longer significant (HR 1.08, 95% CI 0.95-1.22, P = 0.27) after adjusting for TE (HR 1.05, 95% CI 1.03-1.07, P < 0.001) while composite MELD-Na-TE remained significant (HR 1.16, 95% CI 1.09-1.24, P < 0.001). Composite MELD-Na-TE predicts mortality or liver transplant with the highest C-statistic of 0.81. Age (HR 1.05, 95% CI 1-1.09, P = 0.04), TE (HR 1.04, 95% CI 1.03-1.06, P < 0.001) and composite MELD-Na-TE (HR 1.11, 95% CI 1.06-1.15, P < 0.001) were significantly associated with hepatic decompensation., Conclusion: Composite MELD-Na-TE better predicts liver transplantation, death, and hepatic decompensation compared to MELD/MELD-Na or TE alone., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing neoadjuvant yttrium-90 ( 90 Y) transarterial radioembolization (TARE) with resin microspheres prescribed using the Medical Internal Radiation Dose (MIRD) model., Materials and Methods: This retrospective institutional review board-approved study included 37 patients with iCCA treated with 90 Y-TARE from October 2015 to September 2020. The primary outcome was overall survival (OS) from 90 Y-TARE. The secondary outcomes were progression-free survival (PFS), Response Evaluation Criteria In Solid Tumors 1.1 imaging response, and downstaging to resection. Patients with tumor proximity to the middle hepatic vein (<1 cm) and/or insufficient future liver remnant were treated with neoadjuvant intent (n = 21). Patients were censored at the time of surgery or at the last follow-up for the Kaplan-Meier survival analysis., Results: For 31 patients (69 years; interquartile range, 64-74 years; 20 men [65%]) included in the study, the first-line therapy was 90 Y-TARE for 23 (74%) patients. Imaging assessment at 6 months showed a disease control rate of 86%. The median PFS was 5.4 months (95% confidence interval [CI], 3-not reached). The PFS was higher after first-line 90 Y-TARE (7.4 months [95% CI, 5.3-not reached]) than that after subsequent 90 Y-TARE (2.7 months [95% CI, 2-not reached]) (P = .007). The median OS was 22 months (95% CI, 7.3-not reached). The 1- and 2-year OS rates were 60% (95% CI, 41%-86%) and 40% (95% CI, 19.5%-81%). In patients treated with neoadjuvant intent, 11 of 21 patients (52%) underwent resections. The resection margins were R0 and R1 in 8 (73%) and 3 (27%) of 11 patients, respectively. On histological review in 10 patients, necrosis of ≥90% tumor was achieved in 7 of 10 patients (70%)., Conclusions: First-line 90 Y-TARE prescribed using the MIRD model as neoadjuvant therapy for iCCA results in good survival outcome and R0 resection for unresectable patients., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

BACKGROUND : Direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) have varying potentials for drug-drug interactions (DDIs). OBJECTIVES: To (1) identify prevalence of potential DDI with glecaprevir-pibrentasvir (GLE-PIB) and sofosbuvir-velpatasvir (SOF-VEL) and (2) describe health care provider actions in response to pharmacist recommendations based on potential interactions with GLE-PIB or SOF-VEL, using 2 complementary data sources. METHODS: Possible interacting drugs were identified among adult patients in a United States electronic medical record database covering 21 health care organizations and 26 million patients in 2018. DDIs were categorized as potential weak interaction (Level 1), potential interaction (Level 2), or contraindicated (Level 3). Real-world recommendations and resultant actions regarding DDIs with GLE-PIB and SOF-VEL were obtained from a specialty pharmacy database. Categorical variable comparisons were done via chi-square analysis with subsequent z-tests of column proportions. RESULTS: DDI prevalence was higher for patients prescribed GLE-PIB (317/769 [41%]) compared with those prescribed SOF-VEL (170/633 [27%]), and the prevalence of a Level 3 (contraindicated) interaction was higher with GLE-PIB than SOF-VEL (61/769 [8%] vs 2/633 [< 1%]). Across all DDI levels, analgesics (139/317 [44%]), proton-pump inhibitors (129/317 [41%]), and lipid-lowering agents (59/317 [19%]) were the top drug classes for the GLE-PIB group with potential for DDI. For SOF-VEL prescribed patients, the top drug classes were proton-pump inhibitors (83/170 [49%]), histamine-2 blockers (42/170[25%]), and lipid-lowering agents (42/170 [25%]). In real-world care management, the overall prevalence of pharmacist recommendations regarding DDIs was significantly lower for SOF-VEL (28/419 [7%]) relative to GLE-PIB (151/1,216 [12%]). Recommended guidance from pharmacists was not followed for 39% (69/179) of patients, 36% (54/151) for GLE-PIB, and 54% (15/28) for SOF-VEL. CONCLUSIONS: The potential for DDIs with pangenotypic HCV DAAs is frequent and may be more frequent with GLE-PIB than SOF-VEL. Physician responses to pharmacist alerts regarding potential interaction can be highly variable, even in cases of contraindication. DISCLOSURES: Funding for this study was provided by Gilead Sciences, Inc. Trio Health Analytics received funding from Gilead Sciences, Inc., to conduct research for this study. Tsai consults for and has received grants and honoraria from Gilead, AbbVie, Merck, and Bristol Myers Squibb; he has also received lecture fees from Gilead and AbbVie. Curry consults for Trio Health Analytics and Gilead and has also consulted for and received grants from Mallinckrodt. Flamm consults for and has received lecture fees from Gilead and AbbVie; he has also received grants from Gilead and AbbVie. Milligan and Wick are employed by Trio Health Analytics and have received research support from Gilead, Merck, and AbbVie. Younossi has received grants from Gilead, Intercept, Bristol Myers Squibb, GlaxoSmithKline, and Novo Nordisk. Afdhal is a paid consultant/advisory board member for Gilead, Echosens, Ligand, Shionogi, and Trio Health; owns stock in Spring-Bank and Allurion and has stock options in SpringBank; receives royalty income from UpToDate; and is on the board of directors for the nonprofit Liver Institute for Education and Research. Data from this study were presented at the American Association for the Study of Liver Disease (AASLD) Liver Meeting 2019; November 8-12, 2019; Boston, MA, and the European Association for Study of the Liver (EASL) International Liver Congress 2020; August 27-29, 2020; virtual.

Introduction and Objectives: Noninvasive liver assessment in type 2 diabetes (T2DM) in a primary care population identifies higher risk non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association of T2DM with liver fibrosis and steatosis by transient elastography (TE)., Materials and Methods: This is a retrospective study of a TE referral program where primary care physicians were able to order TE. Patients with alcohol abuse were excluded. TE and Controlled Attenuation Parameter (CAP) scores were obtained. Multivariable linear and logistic regression models were used to adjust for confounders., Results: 28% had T2DM. The mean TE score in T2DM patients was 8.3 (±6) kilopascal (kPa) and 6.4 (±3.7) kPa in those without T2DM (p = 0.0001). Those with T2DM had a higher CAP (322 ± 51 dB/m vs. 296 ± 57 dB/m, p < 0.0001). In multivariable analysis, T2DM was associated with TE score (β: 1.9, 95% confidence interval [CI]: 0.74-3.1, p = 0.001) and CAP (β: 2.8, 95% CI: 9.3-36.2, p = 0.001). Patients with T2DM had higher-risk TE scores and more steatosis by CAP., Conclusion: T2DM is associated with liver fibrosis and steatosis by TE within a primary care population. A TE referral pathway may be utilized for T2DM patients who are at higher risk of NAFLD and its complications., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Fresh frozen plasma (FFP) transfusion is often used in the management of acute variceal haemorrhage (AVH) despite best practice advice suggesting otherwise., Objective: We investigated if FFP transfusion affects clinical outcomes in AVH., Design, Setting and Patients: We performed a retrospective cohort study of 244 consecutive, eligible patients admitted to five tertiary health care centres between 2013 and 2018 with AVH., Main Outcome Measurements: Multivariable regression analyses were used to study the association of FFP transfusion with mortality at 42 days (primary outcome) and failure to control bleeding at 5 days and length of stay (secondary outcomes)., Results: Patients who received FFP transfusion (n = 100) had higher mean Model for End Stage Liver Disease (MELD) score and more severe variceal bleeding than those who did not received FFP transfusion (n = 144). Multivariable analysis showed that FFP transfusion was associated with increased odds of mortality at 42 days (odds ratio [OR] 9.41, 95% confidence interval [CI] 3.71-23.90). FFP transfusion was also associated with failure to control bleeding at 5 days (OR 3.87, 95% CI 1.28-11.70) and length of stay >7 days (adjusted OR 1.88, 95% CI 1.03-3.42). The independent association of FFP transfusion with mortality at 42 days persisted when the cohort was restricted to high-risk patients and in patients without active bleeding., Limitations and Conclusions: Fresh frozen plasma transfusion in AVH is independently associated with poor clinical outcomes. As this an observational study, there may be residual bias due to confounding; however, we demonstrate no benefit and potential harm with FFP transfusions in AVH., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite achieving sustained virologic response (SVR) to hepatitis C virus (HCV) therapy, there remains a post liver transplantation population with advanced fibrosis/cirrhosis. Emricasan is an orally active, pan-caspase inhibitor that suppresses apoptosis and inflammation, potentially decreasing hepatic inflammation and fibrosis. We aimed to determine the safety and efficacy of emricasan (IDN-6556-07) in a double-blind, randomized, placebo-controlled, multicenter study in reducing or preventing the progression of hepatic fibrosis in HCV liver transplant recipients with residual fibrosis or cirrhosis after achieving SVR. A total of 64 participants were randomly assigned to receive 25 mg twice daily of emricasan or placebo in a 2:1 ratio for 24 months. 41 participants were randomly assigned to emricasan and 23 to placebo; 32 participants in the emricasan group (78.0%) and 19 who took a placebo (82.6%) completed the study. There was no difference in the primary endpoint (Ishak fibrosis stages F2-F5, improvement in fibrosis or stability; Ishak fibrosis stage F6, improvement) between the emricasan (77.1%) and placebo groups (74.1%); P = NS. There was no difference between the emricasan (54.5%) and placebo (60.7%) arms in the rate of fibrosis improvement alone. However, those in the prespecified F3 to F5 subgroup had higher rates of stability or improvement in fibrosis in the emricasan group (95.2%) compared with placebo (54.6%) (P = 0.01). The tolerability and safety profiles were similar in both groups. In conclusion, overall stability in the Ishak fibrosis stage was similar between emricasan and placebo groups at 24 months. However, there was improvement and/or stability in fibrosis stage in the prespecified F3 to F5 subgroup with emricasan versus placebo, suggesting that patients with moderate fibrosis may benefit with emricasan., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Background: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe., Methods: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons., Results: A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group., Conclusions: In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.)., (Copyright © 2021 Massachusetts Medical Society.)

Introduction: Glecaprevir/pibrentasvir (G/P) was approved on 26 September 2019 by the US Food and Drug Administration for 8-week duration in treatment-naïve (TN) hepatitis C virus (HCV)-infected patients with compensated cirrhosis (CC). Evidence from the EXPEDITION-8 study demonstrated that 8 weeks of G/P achieved a 98% intent-to-treat (ITT) sustained virologic response rate 12 weeks post treatment (SVR12) in 343 TN/CC patients. The aim of this study is to demonstrate the first US real-world effectiveness of G/P 8-week treatment in genotype 1-6 TN/CC HCV patients., Methods: Data from 73 TN/CC patients who initiated 8 weeks of G/P treatment between August 2017 and November 2018 were collected electronically from providers and specialty pharmacies of the Trio Health network and analyzed. Cirrhosis was determined by FIB-4 > 5.2 or was physician reported. The primary outcome was Per Protocol (PP) SVR12., Results: The majority (60%) of patients were male, with (mean values): age 59 years, body mass index (BMI) of 30, aspartate aminotransferase (AST) 105, and alanine aminotransferase (ALT) 101 IU/ml. HCV genotypes (GT) were: GT1 81% (59/73), GT2 10% (7/73), GT3 5% (4/73), GT4 3% (2/73), and GT6 1% (1/73). Eight percent (6/73) of patients had concurrent proton pump inhibitor (PPI) use, and 15% (11/72) had a baseline viral load > 6 MM IU/ml. Zero patients discontinued, two patients were reported as lost to follow-up, and there was one virologic failure. PP sustained virologic response at 12 weeks (SVR12) rate was 99% (70/71), and the intent-to-treat (ITT) SVR12 rate was 96% (70/73)., Conclusions: Early real-world experience indicates high effectiveness of the 8-week G/P regimen in a diverse treatment-naïve, compensated cirrhotic US population.

In the modern era, renal and liver transplant candidates present with a greater medical complexity driven in part by a higher prevalence of cardiovascular conditions, including coronary artery disease, valvular heart disease, and cardiomyopathies. In fact, cardiovascular disease is the most common cause of death after kidney transplantation worldwide. Similarly, an increase in the number of patients being listed with end-stage liver disease from nonalcoholic steatohepatitis and a rising model for end-stage liver disease scores at the time of liver transplant in the United States parallel an increasing cardiovascular disease risk profile for liver transplant candidates. A large degree of variation exists among clinical practice guidelines and transplant center practice patterns regarding patient selection for routine cardiac testing and the choice of testing modalities. Here, we review the clinical practice guidelines established at our center by a multidisciplinary group, including transplant nephrology, hepatology, and surgery, as well as general and interventional cardiology, with the goal of improving patient selection and reducing adverse cardiac events posttransplant.

Budd-Chiari syndrome (BCS) is a rare vascular disorder characterized by an obstruction of the hepatic venous outflow. Nodular regenerative hyperplasia (NRH) may develop as a result of an underlying autoimmune disease such as hepatic sarcoidosis. Only a few case reports have described cases with either NRH or hepatic sarcoidosis associated with BCS. We present a 42-year-old man presenting with BCS and signs of portal hypertension who was found to have an underlying pathological diagnosis of both hepatic sarcoidosis and NRH and who was successfully treated with a transjugular intrahepatic portosystemic shunt., (© 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction : The most recent guidelines vary in their approach to the management of variceal bleeding especially with the use of endoscopic sclerotherapy (ES) and endoscopic tissue adhesive (ETA). This review highlights their clinical use for variceal bleeding from different guidelines perspectives. Areas covered : A comprehensive literature review of three major guidelines including the American Association for the Study of Liver Diseases (AASLD) 2017, United Kingdom (UK) guidelines 2015 and Baveno VI Consensus workshop guidelines in 2015 on the use of ES and ETA in variceal bleeding. Expert opinion : While endoscopic band ligation (EBL) completely replaced endoscopic sclerotherapy (ES) for esophageal varices. There is a valuable use of endoscopic sclerotherapy (ES) and endoscopic tissue adhesive (ETA) especially for patients with gastroesophageal varices (GOV2) and isolated gastric varices (IGV2). The current standard of care heading toward portosystemic shunting with Trans-jugular-Intrahepatic Portosystemic Shunt (TIPS) and balloon retrograde transvenous obliteration (BRTO). However, recent advancement in endoscopic ultrasound (EUS) allowing direct injection of sclerosant and tissue adhesive into the varix bringing promising results in achieving hemostasis and lowering the risk of complications. Also, ES and ETA have great clinical value in achieving hemostasis for isolated (ectopic) varices and stomal varices.

Background & Aims: Chronic hepatitis C (CHC) has a negative impact on patient-reported outcomes (PROs). Although most CHC patients who achieve sustained virologic response (SVR) show an improvement in PRO scores, some continue to experience impairment in PROs. The aim was to investigate if serum biomarkers (selected neurotransmitters and cytokines) are associated with changes in PROs in CHC patients who achieve SVR., Methods: Data were utilized from a prospective clinical trial of ledipasvir/sofosbuvir fixed-dose combination. Chronic genotype 1 HCV subjects without cirrhosis (N = 40, age: 45.3 ± 11.5, 48% male, 90% white) were treated for 12 weeks open label with 97% achieving SVR24. PRO questionnaires included Short Form-36 (SF-36), Fatigue Severity Scale (FSS), Beck Depression Inventory-II (BDI-II), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Sera were used for measurement of selected neurotransmitters and cytokines. Data were collected at baseline and follow-up week 24., Results: Changes in physical health correlated with changes in several biomarkers. BDNF negatively correlated with SF-36 physical health summary score (rho = -0.34, P < 0.05), SF-36 physical functioning (rho = -0.34, P < 0.05), SF-36 bodily pain (rho = -0.39, P < 0.05) and FACIT-F physical well-being (rho = -0.54, P < 0.001). Changes in emotional well-being (FACIT-F) were positively associated with changes in serotonin (rho = 0.34, P < 0.05), but negatively associated with changes in GABA and BDNF (rho = -0.4, P = 0.01, and rho = -0.35, P < 0.05 respectively)., Conclusions: These data indicate relationships between PROs and serum biomarkers pre- and post-SVR in CHC. These concomitant changes may have important clinical relevance., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Cardiovascular disease (CVD) is the leading cause of death among non-alcoholic steatohepatitis (NASH) patients and a major source of post-transplant mortality. We sought to examine the effect of comorbidities on listing for orthotopic liver transplant (OLT) in NASH patients., Methods: In this retrospective cohort study, we included all patients (n = 955) referred to Beth Israel Deaconess Medical Center for OLT between January 2002 and September 2011 and followed their outcomes through March 2018., Results: Compared with non-NASH patients (n = 881), NASH patients (n = 74) were older, more likely female, more overweight, with higher rates of diabetes, hypertension and CVD. NASH patients were less likely to be listed for OLT (55% vs 68.9%, P = 0.01) and were more often declined for 'medical comorbidities' (36.1% vs 15.7%, P < 0.001). However, on multivariate analysis, the only significant predictors of listing were model for end-stage liver disease (MELD) score (OR 1.04, P = 0.01), HCC (OR 2.16, P = 0.01), and diagnosis of non-NASH cirrhosis (OR 2.56, P = 0.003) while controlling for comorbidities. NASH patients declined for OLT died primarily from their liver disease and were not more likely to die from CVD than non-NASH patients. There was no difference in outcomes of NASH vs non-NASH patients on the waitlist and post-transplant., Conclusions: This study demonstrates potential bias against NASH patients referred for OLT arising from heightened concern for comorbidities. Despite being declined for comorbidities, NASH patients are likely to die of their liver disease., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Recent studies have reported high rates of reintervention after primary stenting for hepatic artery stenosis (HAS) due to the loss of primary patency. The aims of this study were to evaluate the outcomes of primary stenting after HAS in a large cohort with longterm follow-up. After institutional review board approval, all patients undergoing liver transplantation between 2003 and 2017 at a single institution were evaluated for occurrence of hepatic artery complications. HAS occurred in 37/454 (8%) of patients. HAS was defined as >50% stenosis on computed tomography or digital subtraction angiography. Hepatic arterial patency and graft survival were evaluated at annual intervals. Primary patency was defined as the time from revascularization to imaging evidence of new HAS or reaching a censored event (retransplantation, death, loss to follow-up, or end of study period). Primary stenting was attempted in 30 patients (17 female, 57%; median age, 51 years; range, 24-68 years). Surgical repair of HAS prior to stenting was attempted in 5/30 (17%) patients. Endovascular treatment was performed within 1 week of the primary anastomosis in 5/30 (17%) of patients. Technical success was accomplished in 97% (29/30) of patients. Primary patency was 90% at 1 year and remained unchanged throughout the remaining follow-up period (median, 41 months; interquartile range [IQR], 25-86 months). Reintervention was required in 3 patients to maintain stent patency. The median time period between primary stenting and retreatment was 5.9 months (IQR, 4.4-11.1 months). There were no major complications, and no patient developed hepatic arterial thrombosis or required listing for retransplantation or retransplantation during the follow-up period. In conclusion, primary stenting for HAS has excellent longterm primary patency and low reintervention rates., (© 2018 by the American Association for the Study of Liver Diseases.)

Background: Direct-acting antiviral regimens containing NS5A inhibitors are highly effective treatments for chronic hepatitis C virus (HCV) infection, but are not always successful. In the POLARIS-1 phase 3 study, sofosbuvir-velpatasvir-voxilaprevir for 12 weeks was highly effective in the treatment of chronic HCV infection in patients previously treated with a direct-acting antiviral regimen containing an NS5A inhibitor. We aimed to assess the efficacy and safety of sofosbuvir-velpatasvir-voxilaprevir in patients from the deferred treatment group of POLARIS-1, who were initially assigned to masked placebo treatment., Methods: This open-label, deferred treatment substudy was done at 73 clinical sites (hospitals and clinics) in the USA, France, Canada, the UK, Germany, Australia, and New Zealand. Patients who received placebo in the primary study and who did not have a new clinically significant illness at the post-treatment week 4 assessment were eligible to enter this substudy. Participants received a combination tablet of sofosbuvir (400 mg), velpatasvir (100 mg), and voxilaprevir (100 mg) once daily for 12 weeks. The primary efficacy outcome was achievement of sustained virological response (defined as HCV RNA concentration below the lower limit of quantification) 12 weeks after the end of treatment (SVR12). The primary safety outcome was the proportion of patients who discontinued treatment due to adverse events. This study is registered with ClinicalTrials.gov, number NCT02607735, and the EU Clinical Trials Register, number 2015-003455-21., Findings: 152 patients received placebo in the primary study and were potentially eligible for participation in the open-label substudy, of whom 147 were enrolled from March 30, 2016, to Oct 12, 2016. All 147 patients completed treatment, and 143 (97%; 95% CI 93-99) achieved SVR12. Four (3%) patients had virological relapse; all had HCV genotype 1a infection and one also had compensated cirrhosis. The most common adverse events were fatigue (31 [21%]), headache (29 [20%]), diarrhoea (28 [19%]), and nausea (21 [14%]). No deaths, treatment discontinuations, or treatment-related serious adverse events occurred., Interpretation: Supporting the results from the blinded portion of the phase 3 primary study, the single-tablet regimen of sofosbuvir-velpatasvir-voxilaprevir for 12 weeks was safe, well tolerated, and highly effective in patients with chronic HCV infection who had previous treatment failure with NS5A inhibitor-containing regimens. A salvage regimen for this population represents an important advance for patients with limited retreatment options., Funding: Gilead Sciences., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background & Aims: Treatment with direct-acting antiviral (DAA) agents can reduce Model for End-Stage Liver Disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus. However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy., Methods: We performed a retrospective analysis of data from 4 trials on the effects of sofosbuvir-based therapy in patients with hepatitis C virus-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C). In these trials, patients were given 12 or 24 weeks of treatment with ledipasvir, sofosbuvir, and ribavirin or velpatasvir, sofosbuvir, and/or ribavirin, or 48 weeks of treatment with sofosbuvir and ribavirin. We collected demographic, clinical, treatment response, and laboratory data from patients and tested their associations with patient outcomes at 36 weeks. The primary outcome was factors associated with reduction of CPT score to class A., Results: The presence of ascites or encephalopathy, serum level of albumin <3.5 g/dL or alanine aminotransferase <60 U/L, and body mass index >25 kg/m 2 were associated with an increased risk of not achieving a reduction in CPT to class A, independent of sustained viral response to therapy. Serum level of albumin <2.8 g/dL and abnormal level of bilirubin were associated with an increased risk of liver transplantation or death. We developed a scoring system based on 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated significantly with patient outcomes, which we called the "BE3A score." For patients with scores of 4-5, the hazard ratio for reduction of CPT score to class A was 52.3 (95% confidence interval, 15.2-179.7)., Conclusions: We identified 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated with a reduction of CPT score to class A in patients with hepatitis C virus-associated decompensated cirrhosis receiving DAA therapy. We developed a predictive score using these factors, called the BE3A score, which can be used as a shared decision-making tool, quantifying the potential benefits of DAA therapy for patients with decompensated cirrhosis., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Elbasvir-grazoprevir is indicated for chronic hepatitis C virus (HCV) genotypes 1 and 4., Aim: To evaluate the utilization and outcomes of chronic HCV patients treated with elbasvir-grazoprevir in the United States., Methods: We conducted a retrospective cohort study of adults treated with elbasvir-grazoprevir with or without ribavirin for chronic HCV genotypes 1 or 4 infection. Data were collected from healthcare providers and specialty pharmacies through Innervation Platform, a proprietary, cloud-based disease management program from Trio Health. The primary endpoint was per protocol sustained virological response 12 weeks post-treatment (SVR12)., Results: Among 470 patients treated in 2016, 95% had HCV genotype 1 infection, 80% (373/468) were HCV treatment naïve and 70% (327/468) had non-cirrhotic disease. Almost 3 quarters (73%) of patients received care in community practices. The majority (89%) of patients received elbasvir-grazoprevir for 12 weeks. Per protocol SVR12 rates were 99% (396/402) for HCV genotype 1 and 95% (21/22) for HCV genotype 4. Among patients with Stage 4 or 5 chronic kidney diseases, 99% (113/114) achieved SVR12. In univariate analyses, variables significantly associated with per protocol SVR12 for the entire sample were therapy duration (P = 0.001), treatment experience (P = 0.016), and cirrhosis status (P = 0.001). However, among HCV genotype 1 patients, no variables were significant. Intent-to-treat SVR12 rates were 89% (396/447) for HCV genotype 1 and 91% (21/23) for HCV genotype 4., Conclusion: Elbasvir-grazoprevir is highly effective, and in this 2016 cohort, its use was predominantly in patients with HCV genotype 1 and as a 12-week therapy without ribavirin., (© 2018 John Wiley & Sons Ltd.)