المؤلفون: Lee, Brian P, Samur, Sumeyye, Dalgic, Ozden O, Bethea, Emily D, Lucey, Michael R, Weinberg, Ethan, Hsu, Christine, Rinella, Mary E, Im, Gene Y, Fix, Oren K, Therapondos, George, Han, Hyosun, Victor, David W, Voigt, Michael D, Eswaran, Sheila, Terrault, Norah A, Chhatwal, Jagpreet

المصدر: Gastroenterology. 157(2)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis, Liver Disease, Prevention, Transplantation, Substance Misuse, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Clinical Research, Alcoholism, Alcohol Use and Health, Organ Transplantation, Oral and gastrointestinal, Good Health and Well Being, Adult, Alcohol Abstinence, Alcohol Drinking, End Stage Liver Disease, Female, Hepatitis, Alcoholic, Humans, Life Expectancy, Liver Transplantation, Male, Middle Aged, Models, Biological, Prospective Studies, Risk Assessment, Severity of Illness Index, Survival Analysis, Time Factors, Time-to-Treatment, Treatment Outcome, Waiting Lists, 6-month rule, ACCELERATE-AH, Markov model, drinking, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics

الوصف: Background & aimsEarly liver transplantation (without requiring a minimum period of sobriety) for severe alcohol-associated hepatitis (AH) is controversial: many centers delay eligibility until a specific period of sobriety (such as 6 months) has been achieved. To inform ongoing debate and policy, we modeled long-term outcomes of early vs delayed liver transplantation for patients with AH.MethodsWe developed a mathematical model to simulate early vs delayed liver transplantation for patients with severe AH and different amounts of alcohol use after transplantation: abstinence, slip (alcohol use followed by sobriety), or sustained use. Mortality of patients before transplantation was determined by joint-effect model (based on Model for End-Stage Liver Disease [MELD] and Lille scores). We estimated life expectancies of patients receiving early vs delayed transplantation (6-month wait before placement on the waitlist) and life years lost attributable to alcohol use after receiving the liver transplant.ResultsPatients offered early liver transplantation were estimated to have an average life expectancy of 6.55 life years, compared with an average life expectancy of 1.46 life years for patients offered delayed liver transplantation (4.49-fold increase). The net increase in life expectancy from offering early transplantation was highest for patients with Lille scores of 0.50-0.82 and MELD scores of 32 or more. Patients who were offered early transplantation and had no alcohol use afterward were predicted to survive 10.85 years compared with 3.62 years for patients with sustained alcohol use after transplantation (7.23 life years lost). Compared with delayed transplantation, early liver transplantation increased survival times in all simulated scenarios and combinations of Lille and MELD scores.ConclusionsIn a modeling study of assumed carefully selected patients with AH, early vs delayed liver transplantation (6 months of abstinence from alcohol before transplantation) increased survival times of patients, regardless of estimated risk of sustained alcohol use after transplantation. These findings support early liver transplantation for patients with severe AH. The net increase in life expectancy was maintained in all simulated extreme scenarios but should be confirmed in prospective studies. Sustained alcohol use after transplantation significantly reduced but did not eliminate the benefits of early transplantation. Strategies are needed to prevent and treat posttransplantation use of alcohol.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6627q4vfTest

المؤلفون: Lee, Brian P, Mehta, Neil, Platt, Laura, Gurakar, Ahmet, Rice, John P, Lucey, Michael R, Im, Gene Y, Therapondos, George, Han, Hyosun, Victor, David W, Fix, Oren K, Dinges, Lisanne, Dronamraju, Deepti, Hsu, Christine, Voigt, Michael D, Rinella, Mary E, Maddur, Haripriya, Eswaran, Sheila, Hause, Jessica, Foley, David, Ghobrial, R Mark, Dodge, Jennifer L, Li, Zhiping, Terrault, Norah A

المصدر: Gastroenterology. 155(2)

مصطلحات موضوعية: Substance Misuse, Clinical Research, Transplantation, Digestive Diseases, Prevention, Liver Disease, Alcoholism, Alcohol Use and Health, Chronic Liver Disease and Cirrhosis, Organ Transplantation, Hepatitis, Oral and gastrointestinal, Good Health and Well Being, Adult, Age Factors, Alcohol Abstinence, Alcohol Drinking, Female, Follow-Up Studies, Humans, Incidence, Liver Diseases, Alcoholic, Liver Transplantation, Male, Middle Aged, Patient Selection, Recurrence, Retrospective Studies, Risk Factors, Survival Analysis, Time Factors, Treatment Outcome, United States, Recidivism, Relapse, UNOS, Months, ACCELERATE-AH, Clinical Sciences, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology

الوصف: Background & aimsThe American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients.MethodsWe performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained.ResultsAmong 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P = .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P = .01).ConclusionsIn a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3wd6b2ftTest

المؤلفون: Flemming, Jennifer A, Kim, W Ray, Brosgart, Carol L, Terrault, Norah A

المصدر: Hepatology. 65(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Chronic Liver Disease and Cirrhosis, Organ Transplantation, Liver Cancer, Emerging Infectious Diseases, Infectious Diseases, Cancer, Digestive Diseases, Rare Diseases, Hepatitis - C, Liver Disease, Hepatitis - B, Hepatitis, Transplantation, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, Adult, Antiviral Agents, Cohort Studies, Dideoxyadenosine, End Stage Liver Disease, Female, Hepatitis B, Hepatitis C, Chronic, Humans, Liver Transplantation, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Preoperative Care, Quality Improvement, Registries, Retrospective Studies, Time Factors, Treatment Outcome, United States, Waiting Lists, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences

الوصف: Direct-acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait-listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait-listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End-Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003-2010), protease inhibitor (PI; 2011-2013), and direct-acting antiviral (DAA; 2014-2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (-17%; P = 0.002) and DAA eras (-24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all).ConclusionThe rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804-812).

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0sx1s1cqTest

المؤلفون: Verna, Elizabeth C, Saxena, Varun, Burton, James R, O’Leary, Jacqueline G, Dodge, Jennifer L, Stravitz, Richard T, Levitsky, Josh, Trotter, James F, Everson, Gregory T, Brown, Robert S, Terrault, Norah A

المصدر: Transplantation. 99(8)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis, Organ Transplantation, Liver Disease, Emerging Infectious Diseases, Chronic Liver Disease and Cirrhosis, Hepatitis - C, Digestive Diseases, Infectious Diseases, Clinical Research, Transplantation, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Antiviral Agents, Biomarkers, Cholestasis, Drug Therapy, Combination, Female, Genotype, Hepacivirus, Hepatitis C, Humans, Liver Cirrhosis, Liver Transplantation, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Oligopeptides, Proline, RNA, Viral, Recurrence, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, United States, Viral Load, CRUSH-C Consortium, Medical and Health Sciences, Surgery, Clinical sciences, Immunology

الوصف: BackgroundAntiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis.MethodsThe LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir- or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were SVR at 12 weeks (SVR12) and safety.ResultsForty-five patients with advanced fibrosis and 9 with cholestatic hepatitis (74% men, 57% genotype 1a, 63% previous nonresponders) were included. SVR12 occurred in 51% with advanced fibrosis and 44% with cholestatic hepatitis. Extended rapid virologic response was highly predictive of SVR12. Hispanic ethnicity (odds ratio, 0.16; P = 0.03), previous null/partial response (0.24; P = 0.02), IL28B genotype CC (7.0; P = 0.02), albumin (3.87; P = 0.03), platelet count (1.01; P = 0.02), and steroid use (0.21; P = 0.03) were associated with SVR12. Six (11%) patients died, and hepatic decompensation occurred in 22% with advanced fibrosis and 33% with cholestatic hepatitis. Albumin (0.02; P = 0.001), encephalopathy (12.0; P = 0.04) and Hispanic ethnicity (odds ratio, 6.17; P = 0.01) were associated with death or decompensation.ConclusionsFor LT recipients with recurrent advanced HCV and at greatest need of cure, protease inhibitor-based triple therapy achieved approximately 50% SVR12. However, there is significant risk of serious adverse events, arguing for earlier intervention. The availability of treatments with better efficacy and safety is of particular importance for posttransplant patients with advanced disease.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8gp2m329Test

المؤلفون: Dirchwolf, Melisa, Dodge, Jennifer L, Gralla, Jane, Bambha, Kiran M, Nydam, Trevor, Hung, Kenneth W, Rosen, Hugo R, Feng, Sandy, Terrault, Norah A, Biggins, Scott W

المصدر: Liver Transplantation. 21(8)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Organ Transplantation, Chronic Liver Disease and Cirrhosis, Hepatitis - C, Digestive Diseases, Emerging Infectious Diseases, Infectious Diseases, Liver Disease, Hepatitis, Transplantation, Good Health and Well Being, Adult, Age Factors, Decision Support Techniques, Donor Selection, End Stage Liver Disease, Female, Graft Survival, Hepatitis C, Humans, Likelihood Functions, Liver Transplantation, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Proportional Hazards Models, Reproducibility of Results, Risk Assessment, Risk Factors, Time Factors, Tissue Donors, Treatment Outcome, United States, Surgery, Clinical sciences

الوصف: Donor age has become the dominant donor factor used to predict graft failure (GF) after liver transplantation (LT) in hepatitis C virus (HCV) recipients. The purpose of this study was to develop and validate a model of corrected donor age (CDA) for HCV LT recipients that transforms the risk of other donor factors into the scale of donor age. We analyzed all first LT recipients with HCV in the United Network for Organ Sharing (UNOS) registry from January 1998 to December 2007 (development cohort, n = 14,538) and January 2008 to December 2011 (validation cohort, n = 7502) using Cox regression, excluding early GF ( 8 hours and -1 year/hour

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/25m9x0nnTest

المؤلفون: Campos-Varela, Isabel, Lai, Jennifer C, Verna, Elizabeth C, O’Leary, Jacqueline G, Stravitz, R Todd, Forman, Lisa M, Trotter, James F, Brown, Robert S, Terrault, Norah A

المصدر: Transplantation. 99(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Emerging Infectious Diseases, Digestive Diseases, Hepatitis, Prevention, Chronic Liver Disease and Cirrhosis, Liver Disease, Transplantation, Infectious Diseases, Genetics, Hepatitis - C, Organ Transplantation, Good Health and Well Being, Adult, Aged, Antiviral Agents, Chi-Square Distribution, Disease Progression, Female, Genotype, Graft Survival, Hepacivirus, Hepatitis C, Chronic, Humans, Kaplan-Meier Estimate, Liver Cirrhosis, Liver Transplantation, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, RNA, Viral, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, United States, Viral Load, Consortium to Study Health Outcomes in HCV Liver Transplant Recipients, Medical and Health Sciences, Surgery, Clinical sciences, Immunology

الوصف: BackgroundIn nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear.MethodsUsing the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined.ResultsAmong 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1.ConclusionRisk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/49r6n7jkTest

المؤلفون: Burton, James R, O’Leary, Jacqueline G, Verna, Elizabeth C, Saxena, Varun, Dodge, Jennifer L, Stravitz, Richard T, Levitsky, Joshua, Trotter, James F, Everson, Gregory T, Brown, Robert S, Terrault, Norah A

المصدر: Journal of Hepatology. 61(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Digestive Diseases, Organ Transplantation, Hepatitis - C, Liver Disease, Transplantation, Chronic Liver Disease and Cirrhosis, Emerging Infectious Diseases, Infectious Diseases, Hepatitis, Clinical Research, Genetics, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adult, Aged, Cohort Studies, Drug Therapy, Combination, Female, Genotype, Hepacivirus, Hepatitis C, Humans, Interferon-alpha, Male, Middle Aged, Oligopeptides, Polyethylene Glycols, Proline, Protease Inhibitors, RNA, Viral, Recombinant Proteins, Retrospective Studies, Ribavirin, Treatment Outcome, United States, Telaprevir, Boceprevir, Antiviral therapy, Interferon, Public Health and Health Services, Gastroenterology & Hepatology, Clinical sciences

الوصف: Background & aimsNS3/4A protease inhibitors, boceprevir or telaprevir, combined with peginterferon and ribavirin was the standard treatment for HCV genotype 1 and remains the only available direct antiviral drug based therapy in some countries. Efficacy and safety data in liver transplant recipients are limited.MethodsThis was a retrospective cohort study of 81 patients with genotype 1 HCV treated with boceprevir (10%) or telaprevir (90%) plus peginterferon and ribavirin at 6 US transplant centers (53% stage 3-4/4 fibrosis, 57% treatment experienced). The primary end point was undetectable HCV RNA 12 weeks after treatment completion (SVR12).ResultsThe intent-to-treat SVR12 rate was 63% (51/81). Patients with an extended rapid virologic response, (undetectable HCV RNA at 4 and 12 weeks after starting boceprevir or telaprevir), had a higher rate of SVR12 than all other patients (85% vs. 15%, p

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/74g8r7b9Test

المؤلفون: Terrault, Norah A, Stravitz, R Todd, Lok, Anna SF, Everson, Greg T, Brown, Robert S, Kulik, Laura M, Olthoff, Kim M, Saab, Sammy, Adeyi, Ovedele, Argo, Curtis K, Everhart, Jay E, Rodrigo, Del R, Group, the A2ALL Study

المصدر: Hepatology. 59(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Chronic Liver Disease and Cirrhosis, Hepatitis, Emerging Infectious Diseases, Clinical Research, Organ Transplantation, Women's Health, Hepatitis - C, Infectious Diseases, Digestive Diseases, Liver Disease, Transplantation, Good Health and Well Being, Adult, Disease Progression, Female, Follow-Up Studies, Graft Rejection, Hepatitis C, Humans, Liver Transplantation, Living Donors, Male, Middle Aged, Prospective Studies, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, Time Factors, Tissue Donors, Treatment Outcome, A2ALL Study Group, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences

الوصف: UnlabelledDonor factors influence hepatitis C virus (HCV) disease severity in liver transplant (LT) recipients. Living donors, because they are typically young and have short cold ischemic times, may be advantageous for HCV-infected patients. Among HCV-infected patients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) surviving >90 days and followed for a median 4.7 years, advanced fibrosis (Ishak stage ≥3) and graft loss were determined. The 5-year cumulative risk of advanced fibrosis was 44% and 37% in living donor LT (LDLT) and deceased donor LT (DDLT) patients (P = 0.16), respectively. Aspartate aminotransferase (AST) activity at LT (hazard ratio [HR] = 1.38 for doubling of AST, P = 0.005) and biliary strictures (HR = 2.68, P = 0.0001) were associated with advanced fibrosis, but LDLT was not (HR = 1.11, 95% confidence interval [CI] 0.73-1.69, P = 0.63). The 5-year unadjusted patient and graft survival probabilities were 79% and 78% in LDLT, and 77% and 75% in DDLT (P = 0.43 and 0.32), with 27% and 20% of LDLT and DDLT graft losses due to HCV (P = 0.45). Biliary strictures (HR = 2.25, P = 0.0006), creatinine at LT (HR = 1.74 for doubling of creatinine, P = 0.0004), and AST at LT (HR = 1.36 for doubling of AST, P = 0.004) were associated with graft loss, but LDLT was not (HR = 0.76, 95% CI: 0.49-1.18, P = 0.23).ConclusionDonor type does not affect the probability of advanced fibrosis or patient and graft survival in HCV-infected recipients. Thus, while LDLT offers the advantage of shorter wait times, there is no apparent benefit for HCV disease progression. Biliary strictures have a negative effect on HCV fibrosis severity and graft survival, and a high AST at LT may be an important predictor of fibrosis risk post-LT.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4570q884Test
https://escholarship.org/content/qt4570q884/qt4570q884.pdfTest

المؤلفون: Shores, Nathan J, Dodge, Jennifer L, Feng, Sandy, Terrault, Norah A

المصدر: Hepatology. 58(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Hepatitis, Infectious Diseases, Liver Disease, Hepatitis - C, Organ Transplantation, Chronic Liver Disease and Cirrhosis, Transplantation, Emerging Infectious Diseases, Good Health and Well Being, Adolescent, Adult, Black or African American, Age Factors, Aged, Child, Female, Follow-Up Studies, Graft Rejection, Hepacivirus, Hepatitis C, Humans, Liver Transplantation, Male, Middle Aged, Prevalence, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Survival Rate, Tissue Donors, Treatment Outcome, Young Adult, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences

الوصف: UnlabelledAfrican American (AA) liver transplant (LT) recipients with hepatitis C virus (HCV) have higher rates of graft loss than other racial/ethnic groups. The Donor Risk Index (DRI) predicts graft loss but is neither race- nor disease-specific and may not be optimal for assessing donor risk for AA HCV-positive LT recipients. We developed a DRI for AA with HCV with the goal of enhancing graft loss predictions. All U.S. HCV-positive adult AA first deceased donor LTs surviving ≥30 days from March 2002 to December 2009 were included. A total of 1,766 AA LT recipients were followed for median 2.8 (interquartile range [IQR] 1.3-4.9) years. Independent predictors of graft loss were donor age (40-49 years: hazard ratio [HR] 1.54; 50-59 years: HR 1.80; 60+ years: HR 2.34, P 8 hours, P = 0.03). Importantly, the negative effect of increasing donor age on graft and patient survival among AAs was attenuated by receipt of an AA donor. A new donor risk model for AA (AADRI-C) consisting of donor age, race, and CIT yielded 1-year, 3-year, and 5-year predicted graft survival rates of 91%, 77%, and 68% for AADRI 2.44. In the validation dataset, AADRI-C correctly reclassified 27% of patients (net reclassification improvement P = 0.04) compared to the original DRI.ConclusionAADRI-C identifies grafts at higher risk of failure and this information is useful for risk-benefit discussions with recipients. Use of AA donors allows consideration of older donors.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8pp4s7wfTest

المؤلفون: Everson, Gregory T, Terrault, Norah A, Lok, Anna S, Rodrigo, Del R, Brown, Robert S, Saab, Sammy, Shiffman, Mitchell L, Al‐Osaimi, Abdullah MS, Kulik, Laura M, Gillespie, Brenda W, Everhart, James E, Study, and the Adult‐to‐Adult Living Donor Liver Transplantation Cohort

المصدر: Hepatology. 57(5)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Sexually Transmitted Infections, Clinical Research, HIV/AIDS, Digestive Diseases, Emerging Infectious Diseases, Organ Transplantation, Clinical Trials and Supportive Activities, Patient Safety, Hepatitis, Transplantation, Liver Disease, Infectious Diseases, Hepatitis - C, Chronic Liver Disease and Cirrhosis, Prevention, Comparative Effectiveness Research, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Antiviral Agents, Dose-Response Relationship, Drug, Drug Therapy, Combination, End Stage Liver Disease, Female, Genotype, Hepacivirus, Hepatitis C, Chronic, Humans, Interferon alpha-2, Interferon-alpha, Liver Transplantation, Male, Middle Aged, Polyethylene Glycols, Preoperative Care, Recombinant Proteins, Recurrence, Ribavirin, Treatment Outcome, Adult-to-Adult Living Donor Liver Transplantation Cohort Study, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences

الوصف: UnlabelledHepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized, controlled trial to test the efficacy and safety of pretransplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-α2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or Model for End-Stage Liver Disease upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n = 44/2/1) were randomized 2:1 to treatment (n = 31) or untreated control (n = 16); HCV G2/3 (n=32) were assigned to treatment. Overall, 59 were treated and 20 were not. Peg-IFN-α2b, starting at 0.75 μg/kg/week, and RBV, starting at 600 mg/day, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pretransplant sustained virologic response and post-transplant virologic response (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR (P = 0.29); per-protocol values were 13 (22%) and 0 (0%) (P = 0.03). Among treated G1/4/6 patients, 23 of 30 received transplant, of whom 22% had pTVR; among treated G2/3 patients 21 of 29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for 16 weeks, respectively (P = 0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% versus 55%; P = 0.30), but the number of SAEs per patient was higher in the treated group (2.7 versus 1.3; P = 0.003).ConclusionPretransplant treatment with Peg-IFN-α2b/RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with >16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9d64q2whTest
https://escholarship.org/content/qt9d64q2wh/qt9d64q2wh.pdfTest