Browsing by Author "Terrault, Norah A."

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    Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)
    (Wiley, 2022) Brandman, Danielle; Boyle, Marie; McPherson, Stuart; Van Natta, Mark L.; Sanyal, Arun J.; Kowdley, Kris; Neuschwander-Tetri, Brent; Chalasani, Naga; Abdelmalek, Manal F.; Terrault, Norah A.; McCullough, Art; Bettencourt, Ricki; Caussy, Cyrielle; Kleiner, David E.; Behling, Cynthia; Tonascia, James; Anstee, Quentin M.; Loomba, Rohit; Members of the Nonalcoholic Steatohepatitis Clinical Research Network; Medicine, School of Medicine
    Background and aims: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD. Methods: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort. Results: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89). Conclusions: This cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher-risk patients maintain access to specialty care.
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    Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study
    (Elsevier, 2023-08) Huang, Daniel Q.; Wilson, Laura A.; Behling, Cynthia; Kleiner, David E.; Kowdley, Kris V.; Dasarathy, Srinivasan; Amangurbanova, Maral; Terrault, Norah A.; Diehl, Anna Mae; Chalasani, Naga; Neuschwander-Tetri, Brent A.; Sanyal, Arun J.; Tonascia, James; Loomba, Rohit; Medicine, School of Medicine
    Background & Aims There are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis progression in people with T2DM compared with people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies. Methods This study included 447 adult participants (64% were female) with NAFLD who had paired liver biopsies more than 1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis in participants with T2DM compared with participants without T2DM. Results The mean (SD) age and body mass index (calculated as weight in kilograms divided by the square of the height in meters) were 50.9 (11.5) years and 34.7 (6.3), respectively. The median time between biopsies was 3.3 years (interquartile range, 1.8–6.1 years). Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4 years (24% vs 20%), 8 years (60% vs 50%), and 12 years (93% vs 76%) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95% CI, 1.17–2.43; P = .005). The cumulative incidence of fibrosis regression by ≥1 stage was similar in participants with T2DM compared with participants without T2DM (P = .24). Conclusions In this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we found that fibrosis progressed faster in participants with T2DM compared with participants without T2DM. These data have important implications for clinical practice and trial design.
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    Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease
    (Elsevier, 2015-09) Charlton, Michael; Everson, Gregory T.; Flamm, Steven L.; Kumar, Princy; Landis, Charles; Brown, Robert S., Jr.; Fried, Michael W.; Terrault, Norah A.; O'Leary, Jacqueline G.; Vargas, Hugo E.; Kuo, Alexander; Schiff, Eugene; Sulkowski, Mark S.; Gilroy, Richard; Watt, Kymberly D.; Brown, Kimberly; Kwo, Paul; Pungpapong, Surakit; Korenblat, Kevin M.; Muir, Andrew J.; Teperman, Lewis; Fontana, Robert J.; Denning, Jill; Arterburn, Sarah; Dvory-Sobol, Hadas; Brandt-Sarif, Theo; Pang, Phillip S.; McHutchison, John G.; Reddy, K. Rajender; Afdhal, Nezam; Department of Medicine, IU School of Medicine
    Background & Aims There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease. Methods In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12). Results We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%–89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%–98% of patients without cirrhosis or with compensated cirrhosis, by 85%−88% of patients with moderate hepatic impairment, by 60%–75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation. Conclusion The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation.
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    Validation of the accuracy of the FAST™ score for detecting patients with at-risk nonalcoholic steatohepatitis (NASH) in a North American cohort and comparison to other non-invasive algorithms
    (PLOS, 2022) Woreta, Tinsay A.; Van Natta, Mark L.; Lazo, Mariana; Krishnan, Arunkumar; Neuschwander-Tetri, Brent A.; Loomba, Rohit; Diehl, Anna Mae; Abdelmalek, Manal F.; Chalasani, Naga; Gawrieh, Samer; Dasarathy, Srinivasan; Vuppalanchi, Raj; Siddiqui, Mohammad S.; Kowdley, Kris V.; McCullough, Arthur; Terrault, Norah A.; Behling, Cynthia; Kleiner, David E.; Fishbein, Mark; Hertel, Paula; Wilson, Laura A.; Mitchell, Emily P.; Miriel, Laura A.; Clark, Jeanne M.; Tonascia, James; Sanyal, Arun J.; NASH Clinical Research Network; Medicine, School of Medicine
    Background and aims: Management of patients with NASH who are at elevated risk of progressing to complications of cirrhosis (at-risk NASH) would be enhanced by an accurate, noninvasive diagnostic test. The new FAST™ score, a combination of FibroScan® parameters liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) and aspartate aminotransferase (AST), has shown good diagnostic accuracy for at-risk NASH (area-under-the-Receiver-Operating-Characteristic [AUROC] = 0.80) in European cohorts. We aimed to validate the FAST™ score in a North American cohort and show how its diagnostic accuracy might vary by patient mix. We also compared the diagnostic performance of FAST™ to other non-invasive algorithms for the diagnosis of at-risk NASH. Methods: We studied adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from the multicenter NASH Clinical Research Network (CRN) Adult Database 2 (DB2) cohort study. At-risk-NASH was histologically defined as definite NASH with a NAFLD Activity Score (NAS) ≥ 4 with at least 1 point in each category and a fibrosis stage ≥ 2. We used the Echosens® formula for FAST™ from LSM (kPa), CAP (dB/m), and AST (U/L), and the FAST™-based Rule-Out (FAST™ ≤ 0.35, sensitivity = 90%) and Rule-In (FAST™ ≥ 0.67, specificity = 90%) zones. We determined the following diagnostic performance measures: AUROC, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV); these were calculated for the total sample and by subgroups of patients and by FibroScan® exam features. We also compared the at-risk NASH diagnostic performance of FAST™ to other non-invasive algorithms: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) index, and AST to platelet ratio index (APRI). Results: The NASH CRN population of 585 patients was 62% female, 79% white, 14% Hispanic, and 73% obese; the mean age was 51 years. The mean (SD) AST and ALT were 50 (37) U/L and 66 (45) U/L, respectively. 214 (37%) had at-risk NASH. The AUROC of FAST™ for at-risk NASH in the NASH CRN study population was 0.81 (95% CI: 0.77, 0.84. Using FAST™-based cut-offs, 35% of patients were ruled-out with corresponding NPV = 0.90 and 27% of patients were ruled-in with corresponding PPV = 0.69. The diagnostic accuracy of FAST™ was higher in non-whites vs. whites (AUROC: 0.91 vs 0.78; p = 0.001), and in patients with a normal BMI vs. BMI > 35 kg/m2 (AUROC: 0.94 vs 0.78, p = 0.008). No differences were observed by other patient characteristics or FibroScan® exam features. The FAST™ score had higher diagnostic accuracy than other non-invasive algorithms for the diagnosis of at-risk NASH (AUROC for NFS, FIB-4, and APRI 0.67, 0.73, 0.74, respectively). Conclusion: We validated the FAST™ score for the diagnosis of at-risk NASH in a large, multi-racial population in North America, with a prevalence of at-risk NASH of 37%. Diagnostic performance varies by subgroups of NASH patients defined by race and obesity. FAST™ performed better than other non-invasive algorithms for the diagnosis of at-risk NASH.