المؤلفون: Feld, Jordan J, King, Wendy C, Ghany, Marc G, Chang, Kyong-Mi, Terrault, Norah, Perrillo, Robert P, Khalili, Mandana, Hinerman, Amanda S, LA. Janssen, Harry, Lok, Anna S, Network, Hepatitis B Research

المصدر: Clinical Gastroenterology and Hepatology. 21(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Hepatitis - B, Prevention, Hepatitis, Chronic Liver Disease and Cirrhosis, Infectious Diseases, Clinical Trials and Supportive Activities, Clinical Research, Liver Disease, Good Health and Well Being, Adult, Male, Humans, Aged, Female, Hepatitis B, Chronic, Hepatitis B virus, Hepatitis B e Antigens, Cohort Studies, Cross-Sectional Studies, Hepatitis B Surface Antigens, Alanine Transaminase, DNA, Viral, Immune Tolerance, Chronic HBV Infection, Immune Active, Immunotolerant, Phase Transition, Hepatitis B Research Network, Gastroenterology & Hepatology, Clinical sciences

الوصف: Background & aimsMost patients in the immunotolerant (IT) phase of chronic hepatitis B (CHB) transition to the immune active (IA-hepatitis B surface antigen [HBeAg]+) phase by early adulthood. We examined characteristics of adults in the IT vs IA-HBeAg+ phase and rate of transition from IT to other phases of CHB, with a focus on those ≥40 years.MethodsDemographic, clinical, and virologic characteristics of participants in the Hepatitis B Research Network adult cohort study with IT CHB (alanine aminotransferase ≤1.5 × upper limit of normal, hepatitis B virus DNA >107 IU/mL) were compared by age category, and to those with IA-HBeAg+ CHB in cross-sectional analysis. This study received institutional review board approval at all participating centers.ResultsOf 107 adult IT participants, 52 (48%) were

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1z80b9x1Test
https://escholarship.org/content/qt1z80b9x1/qt1z80b9x1.pdfTest

المؤلفون: Loomba, Rohit, Neuschwander‐Tetri, Brent A, Sanyal, Arun, Chalasani, Naga, Diehl, Anna Mae, Terrault, Norah, Kowdley, Kris, Dasarathy, Srinivasan, Kleiner, David, Behling, Cynthia, Lavine, Joel, Van Natta, Mark, Middleton, Michael, Tonascia, James, Sirlin, Claude, Network, for the NASH Clinical Research

المصدر: Hepatology. 72(4)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Clinical Research, Clinical Trials and Supportive Activities, Liver Disease, Hepatitis, Chronic Liver Disease and Cirrhosis, Biomedical Imaging, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Oral and gastrointestinal, Adipose Tissue, Adult, Aged, Chenodeoxycholic Acid, Double-Blind Method, Female, Humans, Liver, Magnetic Resonance Imaging, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Protons, Weight Loss, NASH Clinical Research Network, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences

الوصف: Background and aimsEmerging data from a single-center study suggests that a 30% relative reduction in liver fat content as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) from baseline may be associated with histologic improvement in nonalcoholic steatohepatitis (NASH). There are limited multicenter data comparing an active drug versus placebo on the association between the quantity of liver fat reduction assessed by MRI-PDFF and histologic response in NASH. This study aims to examine the association between 30% relative reduction in MRI-PDFF and histologic response in obeticholic acid (OCA) versus placebo-treated patients in the FLINT (farnesoid X receptor ligand obeticholic acid in NASH trial).Approach and resultsThis is a secondary analysis of the FLINT trial including 78 patients with MRI-PDFF measured before and after treatment along with paired liver histology assessment. Histologic response was defined as a 2-point improvement in nonalcoholic fatty liver disease activity score without worsening of fibrosis. OCA (25 mg orally once daily) was better than placebo in improving MRI-PDFF by an absolute difference of -3.4% (95% confidence interval [CI], -6.5 to -0.2%, P value = 0.04) and relative difference of -17% (95% CI, -34 to 0%, P value = 0.05). The optimal cutoff point for relative decline in MRI-PDFF for histologic response was 30% (using Youden's index). The rate of histologic response in those who achieved less than 30% decline in MRI-PDFF versus those who achieved a 30% or greater decline in MRI-PDFF (MRI-PDFF responders) relative to baseline was 19% versus 50%, respectively. Compared with MRI-PDFF nonresponders, MRI-PDFF responders demonstrated both a statistically and clinically significant higher odds 4.86 (95% CI, 1.4-12.8, P value

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الوصول الحر: https://escholarship.org/uc/item/57t3875sTest

المؤلفون: Di Bisceglie, Adrian M, King, Wendy C, Lisker‐Melman, Mauricio, Khalili, Mandana, Belle, Steven H, Feld, Jordan J, Ghany, Marc G, Janssen, Harry LA, Lau, Daryl, Lee, William M, Ling, Simon C, Cooper, Stewart, Rosenthal, Philip, Schwarz, Kathleen B, Sterling, Richard K, Teckman, Jeffrey H, Terrault, Norah, Network, the Hepatitis B Research

المصدر: Journal of Viral Hepatitis. 26(7)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Chronic Liver Disease and Cirrhosis, Hepatitis, Hepatitis - B, Genetics, Clinical Research, Digestive Diseases, Infectious Diseases, Liver Disease, 4.2 Evaluation of markers and technologies, 2.1 Biological and endogenous factors, Detection, screening and diagnosis, Aetiology, Infection, Good Health and Well Being, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Child, Preschool, DNA, Viral, Female, Genotype, Hepatitis B e Antigens, Hepatitis B virus, Hepatitis B, Chronic, Humans, Infant, Male, Middle Aged, Population Groups, Public Health Surveillance, Seroepidemiologic Studies, Viral Load, Young Adult, e antigen, hepatitis B, natural history, Hepatitis B Research Network, Microbiology, Medical Microbiology, Gastroenterology & Hepatology, Clinical sciences, Medical microbiology

الوصف: Hepatitis B e antigen (HBeAg) is an important serological marker of hepatitis B virus (HBV) infection and is associated with higher levels of viraemia, increased risk of infectivity to others and increased risk of hepatocellular carcinoma. We analysed HBeAg status in a large cohort of adults and children enrolled in Cohort Studies of the Hepatitis B Research Network, long-term natural history studies of chronic HBV infection. A cross-sectional analysis examined factors associated with HBeAg positivity, including demographic and virologic data, across the age spectrum. Among 2241 enrolled participants who met criteria for this analysis, 825 (37%) were seropositive for HBeAg. The prevalence of HBeAg was lower in those with older age, ranging from 85% among those up to 10 years of age to only 12% among those older than 50 years. In addition to age, both race and HBV genotype were independently associated with HBeAg positivity. There was a significant interaction between age and race; the prevalence of HBeAg was significantly higher among Asians > 10-30 years old vs Whites or Blacks who were >10 to 30 years old and those infected with HBV genotype C. Conversely, the presence of the basal core promoter and precore variants was associated with significantly lower prevalence of HBeAg, even when adjusted for age, race and genotype. These data will provide a better understanding of factors associated with seropositivity for HBeAg and may lead to better strategies for preventing HBV infection and broader indications for antiviral therapy.

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الوصول الحر: https://escholarship.org/uc/item/1rx2359pTest

المؤلفون: Lim, Joseph K, Liapakis, Ann Marie, Shiffman, Mitchell L, Lok, Anna S, Zeuzem, Stefan, Terrault, Norah A, Park, James S, Landis, Charles S, Hassan, Mohamed, Gallant, Joel, Kuo, Alexander, Pockros, Paul J, Vainorius, Monika, Akushevich, Lucy, Michael, Larry, Fried, Michael W, Nelson, David R, Ben-Ari, Ziv, Group, HCV-TARGET Study

المصدر: Clinical Gastroenterology and Hepatology. 16(11)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Chronic Liver Disease and Cirrhosis, Hepatitis, Emerging Infectious Diseases, Hepatitis - C, Digestive Diseases, Clinical Research, Infectious Diseases, Liver Disease, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Antiviral Agents, Benzimidazoles, Drug Therapy, Combination, Drug-Related Side Effects and Adverse Reactions, Europe, Female, Fluorenes, Genotype, Hepacivirus, Hepatitis C, Chronic, Humans, Liver Cirrhosis, Longitudinal Studies, Male, Middle Aged, North America, Prospective Studies, Ribavirin, Sofosbuvir, Sustained Virologic Response, Treatment Outcome, Young Adult, Real World, Viral Hepatitis, Therapy, HCV-TARGET, HCV-TARGET Study Group, Gastroenterology & Hepatology, Clinical sciences

الوصف: BACKGROUND & AIMS:We aimed to evaluate the safety and effectiveness of 12 or 24 weeks treatment with ledipasvir and sofosbuvir, with or without ribavirin, in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis in routine clinical practice. Patients were followed in a multi-center, prospective, observational cohort study (HCV-TARGET). METHODS:We collected data from 667 treatment-experienced adults with chronic genotype 1 HCV infection who began treatment with ledipasvir and sofosbuvir, with or without ribavirin, from 2011 through September 15, 2016, according to the regional standards of care, at academic (n = 39) and community (n = 18) centers in the United States, Canada, Germany, and Israel. Information was collected from medical records and abstracted into a unique centralized data core. Independent monitors systematically reviewed data entries for completeness and accuracy. Demographic, clinical, adverse event, and virologic data were collected every 12 weeks during treatment and during the follow-up period. The primary efficacy endpoint was sustained virologic response, defined as a level of HCV RNA below the lower limit of quantification or undetectable at a minimum 64 days after the end of treatment (SVR12). The per-protocol population (n = 610) was restricted to patients who completed 12 or 24 weeks of treatment (±2 weeks) and had final virologic outcomes available. RESULTS:The per-protocol analysis revealed that 579 patients (93.8%) achieved an SVR12, including 50/51 patients who received ledipasvir and sofosbuvir for 12 weeks (98%), 384/408 patients who received ledipasvir and sofosbuvir for 24 weeks (94.1%), 68/70 patients who received ledipasvir and sofosbuvir with ribavirin for 12 weeks (97.1%), and 57/60 patients who received ledipasvir and sofosbuvir with ribavirin for 24 weeks (95%). On multivariate analysis, neither treatment duration nor the addition of ribavirin was associated with SVR12. Compensated cirrhosis (odds ratio [OR] compared to decompensated cirrhosis, 2.41; 95% CI, 1.16-5.02), albumin ≥ 3.5 g/dL (OR, 3.15; 95% CI 1.46-6.80), or total bilirubin ≤ 1.2 mg/dL (OR 3.34; 95% CI, 1.59-7.00) were associated with SVR12. CONCLUSIONS:In an analysis of safety and effectiveness data from the HCV-TARGET study, we found treatment with ledipasvir and sofosbuvir, with or without ribavirin, to be effective and well tolerated by treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis. There were no significant differences in rate of SVR12 among patients treated with ledipasvir and sofosbuvir for 12 or 24 weeks, with or without ribavirin. Patients with decompensated cirrhosis appear to benefit from the addition of ribavirin or extension of ledipasvir and sofosbuvir treatment to 24 weeks. ClinicalTrials.gov no: NCT10474811.

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الوصول الحر: https://escholarship.org/uc/item/0sg8z5mvTest

المؤلفون: Huang, Annsa C, Mehta, Neil, Dodge, Jennifer L, Yao, Francis Y, Terrault, Norah A

المصدر: Hepatology. 68(2)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis, Digestive Diseases, Organ Transplantation, Liver Disease, Transplantation, Cancer, Rare Diseases, Chronic Liver Disease and Cirrhosis, Hepatitis - C, Liver Cancer, Clinical Research, Infectious Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Aged, Antiviral Agents, Carcinoma, Hepatocellular, Cohort Studies, Female, Hepacivirus, Hepatitis C, Humans, Incidence, Liver, Liver Cirrhosis, Liver Neoplasms, Liver Transplantation, Male, Middle Aged, Neoplasm Recurrence, Local, Patient Dropouts, Propensity Score, Retrospective Studies, Risk Factors, Waiting Lists, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences

الوصف: Whether direct-acting antivirals (DAAs) increase the risk of hepatocellular carcinoma (HCC) recurrence after tumor-directed therapy is controversial. We sought to determine the impact of DAA therapy on HCC recurrence after local-regional therapy (LRT) and waitlist dropout among liver transplant (LT) candidates with HCC. We performed a retrospective cohort study of 149 LT candidates with hepatitis C virus (HCV) and HCC at a single center from 2014 through 2016. Cumulative incidence of HCC recurrence post-LRT and waitlist dropout was estimated by the DAA group. Factors associated with each outcome were evaluated using competing risks regression. A propensity score stabilized inverse probability weighting approach was used to account for differences in baseline characteristics between groups. The no DAA group (n = 87) had more severe cirrhosis and lower rates of complete radiologic tumor response after LRT than those treated with DAA (n = 62) but had similar alpha-fetoprotein and tumor burden at listing. Cumulative incidence of HCC recurrence within 1 year of complete response after LRT was 47.0% in the DAA group and 49.8% in the no DAA group (P = 0.93). In adjusted competing risk analysis using weighted propensity score modeling, risk of HCC recurrence was similar in the DAA group compared to those without DAA (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.58-1.42; P = 0.67). Patients treated with DAAs had lower risk of waitlist dropout due to tumor progression or death compared to the no DAA group in adjusted weighted analysis (HR, 0.30; 95% CI 0.13-0.69; P = 0.005).ConclusionIn LT candidates with HCV and HCC with initial complete response to LRT, DAA use is not associated with increased risk of HCC recurrence but rather is associated with reduced risk of waitlist dropout due to tumor progression or death. (Hepatology 2018).

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الوصول الحر: https://escholarship.org/uc/item/9k19p9j9Test

المؤلفون: Yang, Ju Dong, Abdelmalek, Manal F, Guy, Cynthia D, Gill, Ryan M, Lavine, Joel E, Yates, Katherine, Klair, Jagpal, Terrault, Norah A, Clark, Jeanne M, Unalp-Arida, Aynur, Diehl, Anna Mae, Suzuki, Ayako, Dasarathy, Srinivasan, Dasarathy, Jaividhya, Hawkins, Carol, McCullough, Arthur J, Pagadala, Mangesh, Pai, Rish, Sargent, Ruth, Bashir, Mustafa, Buie, Stephanie, Guy, Cynthia, Kigongo, Christopher, Pan, Yi-Ping, Piercy, Dawn, Chalasani, Naga, Cummings, Oscar W, Gawrieh, Samer, Ghabril, Marwan, Marri, Smitha, Ragozzino, Linda, Sandrasegaran, Kumar, Vuppalanchi, Raj, King, Debra, Osmack, Pat, Siegner, Joan, Stewart, Susan, Neuschwander-Tetri, Brent A, Torretta, Susan, Ang, Brandon, Behling, Cynthia, Bhatt, Archana, Loomba, Rohit, Middleton, Michael, Patton, Heather, Sirlin, Claude, Aouizerat, Bradley, Bass, Nathan M, Brandman, Danielle, Ferrell, Linda D, Gill, Ryan, Hameed, Bilal, Ramos, Claudia, Terrault, Norah, Ungermann, Ashley, Atla, Pradeep, Croft, Brandon, Garcia, Rebekah, Garcia, Sonia, Sheikh, Muhammad, Singh, Mandeep, Boyett, Sherry, Carucci, Laura, Contos, Melissa J, Kraft, Kenneth, Luketic, Velimir AC, Puri, Puneet, Sanyal, Arun J, Schlosser, Jolene, Siddiqui, Mohhamad S, Wolford, Ben, Ackermann, Sarah, Cooney, Shannon, Coy, David, Gelinas, Katie, Kowdley, Kris V, Lee, Maximillian, Pierce, Tracey, Mooney, Jody, Nelson, James E, Shaw, Cheryl, Siddique, Asma, Wang, Chia, Brunt, Elizabeth M, Fowler, Kathryn, Kleiner, David E, Grave, Gilman D, Doo, Edward C, Hoofnagle, Jay H, Robuck, Patricia R, Sherker, Averell, Belt, Patricia, Donithan, Michele, Hallinan, Erin, Isaacson, Milana

المصدر: Clinical Gastroenterology and Hepatology. 15(1)

مصطلحات موضوعية: Reproductive Medicine, Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Liver Disease, Contraception/Reproduction, Prevention, Hepatitis, Estrogen, Chronic Liver Disease and Cirrhosis, Aging, Good Health and Well Being, Adolescent, Adult, Aged, Cross-Sectional Studies, Female, Histocytochemistry, Hormones, Humans, Male, Menopause, Middle Aged, Non-alcoholic Fatty Liver Disease, Reproduction, Risk Factors, Sex Factors, United States, Young Adult, Gender Differences, Fibrosis, Risk Factor Analysis., Nonalcoholic Steatohepatitis Clinical Research Network, Risk Factor Analysis, Gastroenterology & Hepatology, Clinical sciences

الوصف: Background & aimsSex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation.MethodsWe collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress.ResultsPremenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P < .01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P < .05).ConclusionsBeing a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress.

الوصول الحر: https://escholarship.org/uc/item/7h29p34cTest

المؤلفون: Khalili, Mandana, Shuhart, Margaret C, Lombardero, Manuel, Feld, Jordan J, Kleiner, David E, Chung, Raymond T, Terrault, Norah A, Lisker-Melman, Mauricio, Sanyal, Arun, Lok, Anna S, Network, for the Hepatitis B Research

المصدر: Diabetes Care. 41(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, Liver Disease, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Clinical Research, Hepatitis, Hepatitis - B, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adolescent, Adult, Aged, Alanine Transaminase, Aspartate Aminotransferases, Cohort Studies, Female, Hepatitis B, Chronic, Humans, Liver Cirrhosis, Male, Metabolic Syndrome, Middle Aged, North America, Platelet Count, Prevalence, United States, Young Adult, Hepatitis B Research Network, Harvard Consortium, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences

الوصف: ObjectiveMetabolic syndrome (MS) is prevalent and is associated with adverse outcomes of liver disease. We evaluated the prevalence of MS and its influence on alanine aminotransferase (ALT) levels and fibrosis, as estimated by the aspartate aminotransferase-to-platelet ratio index (APRI), in a large, multiethnic North American cohort with chronic hepatitis B (HBV) infection.Research design and methodsAdults with chronic HBV from 21 centers within the U.S. and Canada were evaluated at baseline and for up to 5 years (median 3.7 years) of follow-up. MS was defined as the presence of at least three of five criteria including waist circumference, blood pressure, glucose, triglyceride, and HDL levels.ResultsAnalysis included 777 participants, of whom 171 (22%) had MS. Participants with MS (vs. those without MS) were older (median age 54.4 vs. 40.2 years), more often male (61% vs. 51%), and born in the U.S./Canada or had immigrated >20 years ago (60% vs. 43%). MS was not associated with ALT or APRI at baseline. Upon adjusted multivariable analysis of serial ALT values, ALT was significantly higher (mean 12%; P = 0.02) among those with MS at baseline and even higher (mean 19%; P = 0.003) among those with persistent MS compared with those with persistent absence of MS. MS was not associated with serial APRI on follow-up.ConclusionsMS was prevalent in this HBV cohort and was independently associated with higher ALT levels longitudinally. These findings highlight the importance of screening for MS and the potential for MS to influence ALT and its interpretation in the context of HBV treatment decisions.

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الوصول الحر: https://escholarship.org/uc/item/7046s9zqTest

المؤلفون: Terrault, Norah A, Zeuzem, Stefan, Di Bisceglie, Adrian M, Lim, Joseph K, Pockros, Paul J, Frazier, Lynn M, Kuo, Alexander, Lok, Anna S, Shiffman, Mitchell L, Ari, Ziv Ben, Akushevich, Lucy, Vainorius, Monika, Sulkowski, Mark S, Fried, Michael W, Nelson, David R, Group, HCV-TARGET Study

المصدر: Gastroenterology. 151(6)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Emerging Infectious Diseases, Digestive Diseases, Hepatitis, Clinical Trials and Supportive Activities, Chronic Liver Disease and Cirrhosis, Clinical Research, Liver Disease, Infectious Diseases, Hepatitis - C, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Antiviral Agents, Benzimidazoles, Bilirubin, Drug Therapy, Combination, Female, Fluorenes, Genotype, Hepacivirus, Hepatitis C, Chronic, Humans, Liver Cirrhosis, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Proton Pump Inhibitors, Ribavirin, Risk Factors, Serum Albumin, Sofosbuvir, Sustained Virologic Response, Time Factors, Treatment Failure, Uridine Monophosphate, Young Adult, DAA, NS5A Inhibitor, NS5B Inhibitor, Antiviral, HCV-TARGET Study Group, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics

الوصف: Background & aimsThe combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9766f44bTest

المؤلفون: Saxena, Varun, Nyberg, Lisa, Pauly, Marypat, Dasgupta, Aditi, Nyberg, Anders, Piasecki, Barbara, Winston, Bradley, Redd, Jacquelyn, Ready, Joanna, Terrault, Norah A

المصدر: Hepatology. 62(3)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Liver Disease, Hepatitis, Clinical Research, Digestive Diseases, Chronic Liver Disease and Cirrhosis, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Infection, Good Health and Well Being, Aged, Analysis of Variance, Antiviral Agents, Case-Control Studies, Drug Therapy, Combination, Female, Follow-Up Studies, Hepacivirus, Hepatitis C, Humans, Liver Cirrhosis, Logistic Models, Male, Middle Aged, Multivariate Analysis, Patient Safety, Reference Values, Retrospective Studies, Ribavirin, Risk Assessment, Severity of Illness Index, Simeprevir, Sofosbuvir, Treatment Outcome, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences

الوصف: UnlabelledRisks and benefits of simeprevir plus sofosbuvir (SIM+SOF) in patients with advanced cirrhosis are unknown. We assessed the safety and sustained virological responses (SVR) of SIM+SOF with and without ribavirin (RBV) in patients with Child-Pugh (CP)-B/C versus CP-A cirrhosis and compared to matched untreated controls. This study was of a multicenter cohort of adults with hepatitis C virus genotype 1 and cirrhosis treated with SIM+SOF with/without RBV for 12 weeks. Controls were matched on treatment center, age, CP class, and Model for End-Stage Liver Disease (MELD) score. Of 160 patients treated with SIM+SOF with/without RBV, 35% had CP-B/C and 64% had CP-A, with median baseline MELD 9 (interquartile range, 8-11). Sustained virological response at week 12 (SVR12) was achieved by 73% of CP-B/C versus 91% of CP-A (P

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الوصول الحر: https://escholarship.org/uc/item/4zm8p3m6Test

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.

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