BACKGROUND & AIMS:Nonalcoholic steatohepatitis (NASH) is a leading cause of liver transplantation, and many trials are underway to evaluate potential therapies. The farnesoid X receptor ligand obeticholic acid in the NASH treatment trial evaluated the effects of obeticholic acid vs placebo on histologic response (defined as decrease in nonalcoholic fatty liver disease activity score [NAS] by ≥2, with no worsening of fibrosis); 45% of patients had a histologic response to obeticholic acid (25 mg), and 21% had a response to placebo (P < .01). We performed a secondary analysis of data from this trial to identify clinical parameters associated with a histologic response. METHODS: We used a logistic regression model with a stepwise selection procedure to identify baseline and early on-treatment factors associated with a histologic response at 72 weeks. Baseline demographics, liver histology, medical history, concomitant medications, cardiometabolic parameters, and serum biochemistry, as well as the changes over the course of the trial (at weeks 12 and 24), were evaluated as potential predictors of a histologic response. The model was cross-validated by a jackknife method, and performance was evaluated with the area under the receiver operating characteristic curve. RESULTS: The logistic regression model found that obeticholic acid treatment, baseline NAS > 5, baseline triglyceride level ≤ 154 mg/dL, baseline international normalized ratio ≤ 1, baseline aspartate aminotransferase level ≤ 49 U/L, and a decrease in alanine aminotransferase level at week 24 by 17 U/L or more, to be significantly associated with histologic response (area under the receiver operating characteristic curve, 0.83; 95% confidence interval, 0.77-0.89; P < .0001). CONCLUSIONS: In a secondary analysis of data from a clinical trial of obeticholic acid in patients with NASH, we identified routine clinical and laboratory parameters during the first 24 weeks of treatment (such as baseline NAS, triglyceride levels, and a decrease in alanine aminotransferase level) to significantly associate with histologic markers of response.
RCT Entities:
BACKGROUND & AIMS:Nonalcoholic steatohepatitis (NASH) is a leading cause of liver transplantation, and many trials are underway to evaluate potential therapies. The farnesoid X receptor ligand obeticholic acid in the NASH treatment trial evaluated the effects of obeticholic acid vs placebo on histologic response (defined as decrease in nonalcoholic fatty liver disease activity score [NAS] by ≥2, with no worsening of fibrosis); 45% of patients had a histologic response to obeticholic acid (25 mg), and 21% had a response to placebo (P < .01). We performed a secondary analysis of data from this trial to identify clinical parameters associated with a histologic response. METHODS: We used a logistic regression model with a stepwise selection procedure to identify baseline and early on-treatment factors associated with a histologic response at 72 weeks. Baseline demographics, liver histology, medical history, concomitant medications, cardiometabolic parameters, and serum biochemistry, as well as the changes over the course of the trial (at weeks 12 and 24), were evaluated as potential predictors of a histologic response. The model was cross-validated by a jackknife method, and performance was evaluated with the area under the receiver operating characteristic curve. RESULTS: The logistic regression model found that obeticholic acid treatment, baseline NAS > 5, baseline triglyceride level ≤ 154 mg/dL, baseline international normalized ratio ≤ 1, baseline aspartate aminotransferase level ≤ 49 U/L, and a decrease in alanine aminotransferase level at week 24 by 17 U/L or more, to be significantly associated with histologic response (area under the receiver operating characteristic curve, 0.83; 95% confidence interval, 0.77-0.89; P < .0001). CONCLUSIONS: In a secondary analysis of data from a clinical trial of obeticholic acid in patients with NASH, we identified routine clinical and laboratory parameters during the first 24 weeks of treatment (such as baseline NAS, triglyceride levels, and a decrease in alanine aminotransferase level) to significantly associate with histologic markers of response.
Authors: Giada Sebastiani; Keyur Patel; Vlad Ratziu; Jordan J Feld; Brent A Neuschwander-Tetri; Massimo Pinzani; Salvatore Petta; Annalisa Berzigotti; Peter Metrakos; Naglaa Shoukry; Elizabeth M Brunt; An Tang; Jeremy F Cobbold; Jean-Marie Ekoe; Karen Seto; Peter Ghali; Stéphanie Chevalier; Quentin M Anstee; Heather Watson; Harpreet Bajaj; James Stone; Mark G Swain; Alnoor Ramji Journal: Can Liver J Date: 2022-02-04
Authors: Samer Gawrieh; Laura A Wilson; Katherine P Yates; Oscar W Cummings; Eduardo Vilar-Gomez; Veeral Ajmera; Kris V Kowdley; William M Rosenberg; James Tonascia; Naga Chalasani Journal: Hepatol Commun Date: 2021-02-05
Authors: Yasser Fouad; Melissa Palmer; Minjun Chen; Arie Regev; Rajarshi Banerjee; Rob Myers; Robert Riccio; Richard Torstenson; Ramy Younes; Puneet S Arora; Henrik Landgren; Morten A Karsdal; Martin Blake; David A Shapiro; Hans-Juergen Gruss; Muhammad Y Sheikh; Dina Attia; Steven Bollipo; Alastair D Smith; Bradley Freilich; Robert G Gish; Detlef Schuppan Journal: J Clin Transl Hepatol Date: 2021-10-22
Authors: Rohit Loomba; Brent A Neuschwander-Tetri; Arun Sanyal; Naga Chalasani; Anna Mae Diehl; Norah Terrault; Kris Kowdley; Srinivasan Dasarathy; David Kleiner; Cynthia Behling; Joel Lavine; Mark Van Natta; Michael Middleton; James Tonascia; Claude Sirlin Journal: Hepatology Date: 2020-10-09 Impact factor: 17.425
Authors: Samer Gawrieh; Xiuqing Guo; Jingyi Tan; Marie Lauzon; Kent D Taylor; Rohit Loomba; Oscar W Cummings; Sreekumar Pillai; Pallav Bhatnagar; Kris V Kowdley; Katherine Yates; Laura A Wilson; Yii-Der Ida Chen; Jerome I Rotter; Naga Chalasani Journal: Hepatol Commun Date: 2019-11-03