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3. Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study

Author

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, Allende, Daniela, Bellar, Annette, Dasarathy, Jaividhya, Welch, Nicole, Yerrapothu, Rahul, Bashir, Mustafa, Guy, Cynthia, Kopping, Mariko, Piercy, Dawn, Suzuki, Ayako, Tawadrou, Naglaa, Cruz, Mandy, Cummings, Oscar W, Garrison, Lisa, Gawrieh, Samer, Samala, Niharika, Vuppalanchi, Raj, Carpenter, Danielle, Cattoor, Theresa, Freebersyser, Janet, Angkanaworakul, Pannapat, Berihun, Achashman, Buysse, Andrew, Dorrian, Theresa, Gulati, Breanna, Liu, Kevin, Misic, Sandra, Sohal, Adam, Vuong, Joseph, Ajmera, Veeral, Madamba, Egbert, Middleton, Michael S, Richards, Lisa, Singh, Seema, Sirlin, Claude, Gill, Ryan, Hameed, Bilal, Awe, Remilekun, Olvera, Daisy, Terrault, Norah, Yuan, Liyun, Yeh, Matthew, Albhaisi, Somaya, Asgharpour, Amon, Boyett, Sherry, Contos, Melissa J, Luketic, Velimir AC, Schlosser, Jolene, Siddiqui, Mohammad S, Adamo, Peggy, Belt, Patricia, Clark, Jeanne M, DeSanto, Jennifer M, Meinert, Jill, Miriel, Laura, Mitchell, Emily P, Shade, Carrie, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Van Natta, Mark L, Wagoner, Annette, Woreta, Tinsay, and Yates, Katherine P

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis, Liver Disease, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Clinical Research, Diabetes, Obesity, Metabolic and endocrine, Good Health and Well Being, Adult, Humans, Female, Male, Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2, Cohort Studies, Liver Cirrhosis, Biopsy, Nonalcoholic Steatohepatitis, NAFLD, Cirrhosis, Type 2 Diabetes Mellitus, NASH Clinical Research Network, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsThere 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.MethodsThis 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.ResultsThe 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).ConclusionsIn 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.

Published
2023

4. Differential fuel utilization in liver transplant recipients and its relationship with non‐alcoholic fatty liver disease

Author

Siddiqui, Mohammad S, Patel, Samarth, Forsgren, Mikael, Bui, Anh T, Shen, Steve, Syed, Taseen, Boyett, Sherry, Chen, Shanshan, Sanyal, Arun J, Wolver, Susan, Kirkman, Danielle, Celi, Francesco S, and Bhati, Chandra S

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Liver Disease, Hepatitis, Chronic Liver Disease and Cirrhosis, Obesity, Transplantation, Prevention, Nutrition, Digestive Diseases, Oral and gastrointestinal, Metabolic and endocrine, Carbohydrates, Humans, Liver Cirrhosis, Liver Transplantation, Non-alcoholic Fatty Liver Disease, carbohydrates, energy expenditure, fatty acids, liver transplantation, metabolic flexibility, non-alcoholic steatohepatitis, Gastroenterology & Hepatology, Clinical sciences
Abstract

Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT).MethodsPatients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation).ResultsThe two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p

Published
2022

6. 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

Author

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, and Sanyal, Arun J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Liver Disease, Chronic Liver Disease and Cirrhosis, Women's Health, Obesity, Hepatitis, Clinical Research, 4.2 Evaluation of markers and technologies, Oral and gastrointestinal, Adult, Algorithms, Biopsy, Cohort Studies, Female, Fibrosis, Humans, Liver, Liver Cirrhosis, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Severity of Illness Index, NASH Clinical Research Network, General Science & Technology
Abstract

Background and aimsManagement 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.MethodsWe 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).ResultsThe 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).ConclusionWe 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.

Published
2022

7. Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study

Author

Allende, Daniela, Bellar, Annette, Dasarathy, Jaividhya, Dasarathy, Srinivasan, Welch, Nicole, Yerrapothu, Rahul, Bashir, Mustafa, Diehl, Anna Mae, Guy, Cynthia, Kopping, Mariko, Piercy, Dawn, Suzuki, Ayako, Tawadrou, Naglaa, Chalasani, Naga, Cruz, Mandy, Cummings, Oscar W., Garrison, Lisa, Gawrieh, Samer, Samala, Niharika, Vuppalanchi, Raj, Carpenter, Danielle, Cattoor, Theresa, Freebersyser, Janet, Neuschwander-Tetri, Brent A., Angkanaworakul, Pannapat, Berihun, Achashman, Buysse, Andrew, Dorrian, Theresa, Gulati, Breanna, Kowdley, Kris V., Liu, Kevin, Misic, Sandra, Sohal, Adam, Vuong, Joseph, Ajmera, Veeral, Behling, Cynthia, Loomba, Rohit, Madamba, Egbert, Middleton, Michael S., Richards, Lisa, Singh, Seema, Sirlin, Claude, Gill, Ryan, Hameed, Bilal, Awe, Remilekun, Olvera, Daisy, Terrault, Norah, Yuan, Liyun, Yeh, Matthew, Albhaisi, Somaya, Asgharpour, Amon, Boyett, Sherry, Contos, Melissa J., Luketic, Velimir A.C., Sanyal, Arun J., Schlosser, Jolene, Siddiqui, Mohammad S., Kleiner, David E., Adamo, Peggy, Belt, Patricia, Clark, Jeanne M., DeSanto, Jennifer M., Meinert, Jill, Miriel, Laura, Mitchell, Emily P., Shade, Carrie, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Tonascia, James, Van Natta, Mark L., Wagoner, Annette, Wilson, Laura A., Woreta, Tinsay, Yates, Katherine P., Huang, Daniel Q., Amangurbanova, Maral, and Terrault, Norah A.

Published
2023
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8. Hepatic, Extra-hepatic Outcomes and Causes of Mortality in NAFLD – An Umbrella Overview of Systematic Review of Meta-Analysis

Author

Xiao, Jieling, Ng, Cheng Han, Chan, Kai En, Fu, Clarissa, Tay, Phoebe, Yong, Jie Ning, Lim, Wen Hui, Tan, Darren Jun Hao, Syn, Nicholas, Wong, Zhen Yu, Tseng, Michael, Chew, Nicholas, Huang, Daniel Q., Dan, Yock Yong, Wong, Vincent Wai-Sun, Loomba, Rohit, Siddiqui, Mohammad S., Sanyal, Arun J., Noureddin, Mazen, and Muthiah, Mark D.

Published
2023
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9. A Pilot Genome‐Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH

Author

Gawrieh, Samer, Guo, Xiuqing, Tan, Jingyi, Lauzon, Marie, Taylor, Kent D, Loomba, Rohit, Cummings, Oscar W, Pillai, Sreekumar, Bhatnagar, Pallav, Kowdley, Kris V, Yates, Katherine, Wilson, Laura A, Chen, Yii‐Der Ida, Rotter, Jerome I, Chalasani, Naga, Allende, Daniela, Dasarathy, Srinivasan, McCullough, Arthur J, Penumatsa, Revathi, Dasarathy, Jaividhya, Lavine, Joel E, Abdelmalek, Manal F, Bashir, Mustafa, Buie, Stephanie, Diehl, Anna Mae, Guy, Cynthia, Kigongo, Christopher, Kopping, Mariko, Malik, David, Piercy, Dawn, Ragozzino, Linda, Sandrasegaran, Kumar, Vuppalanchi, Raj, Brunt, Elizabeth M, Cattoor, Theresa, Carpenter, Danielle, Freebersyser, Janet, King, Debra, Lai, Jinping, Neuschwander, Brent A, Siegner, Joan, Stewart, Susan, Torretta, Susan, Wriston, Kristina, Gonzalez, Maria Cardona, Davila, Jodie, Jhaveri, Manan, Mukhtar, Nizar, Ness, Erik, Poitevin, Michelle, Quist, Brook, Soo, Sherilynn, Ang, Brandon, Behling, Cynthia, Bhatt, Archana, Middleton, Michael S, Sirlin, Claude, Akhter, Maheen F, Bass, Nathan M, Brandman, Danielle, Gill, Ryan, Hameed, Bilal, Maher, Jacqueline, Terrault, Norah, Ungermann, Ashley, Yeh, Matthew, Boyett, Sherry, Contos, Melissa J, Kirwin, Sherri, Luketic, Velimir AC, Puri, Puneet, Sanyal, Arun J, Schlosser, Jolene, Siddiqui, Mohammad S, Yost‐Schomer, Leslie, Fowler, Kathryn, Kleiner, David E, Doo, Edward C, Hall, Sherry, Hoofnagle, Jay H, Robuck, Patricia R, Sherker, Averell H, Torrance, Rebecca, Belt, Patricia, Clark, Jeanne M, Dodge, John, Donithan, Michele, Isaacson, Milana, Lazo, Mariana, Meinert, Jill, Miriel, Laura, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Tonascia, James, Natta, Mark L, Wagoner, Annette, and Yamada, Goro

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Liver Disease, Digestive Diseases, Clinical Trials and Supportive Activities, Human Genome, Hepatitis, Clinical Research, Genetics, Chronic Liver Disease and Cirrhosis, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, NASH Clinical Research Network, Clinical sciences
Abstract

A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome-wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 had multiple single nucleotide polymorphisms (SNPs) with suggestive association (P

Published
2019

13. Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage

Author

Siddiqui, Mohammad Shadab, Yamada, Goro, Vuppalanchi, Raj, Van Natta, Mark, Loomba, Rohit, Guy, Cynthia, Brandman, Danielle, Tonascia, James, Chalasani, Naga, Neuschwander-Tetri, Brent, Sanyal, Arun J, Allende, Daniela, Dasarathy, Srinivasan, McCullough, Arthur J, Penumatsa, Revathi, Dasarathy, Jaividhya, Lavine, Joel E, Abdelmalek, Manal F, Bashir, Mustafa, Buie, Stephanie, Diehl, Anna Mae, Kigongo, Christopher, Kopping, Mariko, Malik, David, Piercy, Dawn, Cummings, Oscar W, Gawrieh, Samer, Ragozzino, Linda, Sandrasegaran, Kumar, Brunt, Elizabeth M, Cattoor, Theresa, Carpenter, Danielle, Freebersyser, Janet, King, Debra, Lai, Jinping, Neuschwander-Tetri, Brent A, Siegner, Joan, Stewart, Susan, Torretta, Susan, Wriston, Kristina, Gonzalez, Maria Cardona, Davila, Jodie, Jhaveri, Manan, Kowdley, Kris V, Mukhtar, Nizar, Ness, Erik, Poitevin, Michelle, Quist, Brook, Soo, Sherilynn, Ang, Brandon, Behling, Cynthia, Bhatt, Archana, Middleton, Michael S, Sirlin, Claude, Akhter, Maheen F, Bass, Nathan M, Gill, Ryan, Hameed, Bilal, Maher, Jacqueline, Terrault, Norah, Ungermann, Ashley, Yeh, Matthew, Boyett, Sherry, Contos, Melissa J, Kirwin, Sherri, Luketic, Velimir AC, Puri, Puneet, Schlosser, Jolene, Siddiqui, Mohammad S, Yost-Schomer, Leslie, Fowler, Kathryn, Kleiner, David E, Doo, Edward C, Hall, Sherry, Hoofnagle, Jay H, Lee, Jessica J, Robuck, Patricia R, Sherker, Averell H, Torrance, Rebecca, Belt, Patricia, Clark, Jeanne M, Dodge, John, Donithan, Michele, Hallinan, Erin, Isaacson, Milana, Lazo, Mariana, Meinert, Jill, Miriel, Laura, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, and Van Natta, Mark L

Subjects
Clinical Research, Chronic Liver Disease and Cirrhosis, Liver Disease, Digestive Diseases, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Good Health and Well Being, Adult, Alanine Transaminase, Aspartate Aminotransferases, Biopsy, Disease Progression, Female, Humans, Liver, Liver Cirrhosis, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Platelet Count, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Severity of Illness Index, Nonalcoholic Steatohepatitis, Diagnostic, Prognostic, Scoring System Comparison, NASH Clinical Research Network, Clinical Sciences, Gastroenterology & Hepatology
Abstract

Background & aimsNoninvasive methods are needed to determine disease stage in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the diagnostic performance of several widely available fibrosis models for the assessment of hepatic fibrosis in patients with NAFLD.MethodsWe performed a retrospective analysis of data from individuals enrolled in the NIDDK NASH Clinical Research Network, from 2004 through 2018. Using biopsy as the reference standard, we determined the diagnostic performance of the aspartate aminotransferase (AST):platelet ratio (APRI), FIB-4, ratio of AST:alanine aminotransferase (ALT) and the NAFLD fibrosis score (NFS) in a cross-sectional study of 1904 subjects. The ability of these models to detect changes in fibrosis stage was assessed in a longitudinal data set of 292 subjects with 2 biopsies and accompanying laboratory data. Outcomes were detection of fibrosis of any stage (stages 0-4), detection of moderate fibrosis (stages 0-1 vs 2-4), and detection of advanced fibrosis (stages 0-2 vs 3-4). Diagnostic performance was evaluated using the C-statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) analyses.ResultsIn the cross-sectional study, FIB-4 and NFS outperformed other non-invasive models for detecting advanced fibrosis; the C-statistics were 0.80 for FIB-4 and 0.78 for NFS. In the longitudinal study, 216 patients had non-advanced fibrosis at baseline and 35 patients progressed to advanced fibrosis after median follow up of 2.6 years. After we adjusted for fibrosis stage and model score at initial biopsy, change in APRI, FIB-4, and NFS were significantly associated with change in fibrosis. A unit change in APRI, FIB-4, or NFS was associated with changes in fibrosis stage of 0.33 (95% CI, 0.20-0.45; P < .001), 0.26 (95% CI, 0.15-0.37; P < .001), and 0.19 (95% CI, 0.07-0.31; P = .002), respectively. The cross-validated C-statistic for detecting progression to advanced fibrosis for APRI was 0.82 (95% CI, 0.74-0.89), for FIB-4 was 0.81 (95% CI, 0.73-0.81), and for NFS was 0.80 (95% CI, 0.71-0.88).ConclusionsIn a combined analysis of data from 2 large studies, we found that FIB-4, APRI, and NFS can detect advanced fibrosis and fibrosis progression in patients with NAFLD.

Published
2019

14. Vibration-Controlled Transient Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease

Author

Siddiqui, Mohammad S, Vuppalanchi, Raj, Van Natta, Mark L, Hallinan, Erin, Kowdley, Kris V, Abdelmalek, Manal, Neuschwander-Tetri, Brent A, Loomba, Rohit, Dasarathy, Srinivasan, Brandman, Danielle, Doo, Edward, Tonascia, James A, Kleiner, David E, Chalasani, Naga, Sanyal, Arun J, and Network, NASH Clinical Research

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Clinical Research, Liver Disease, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Oral and gastrointestinal, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Elasticity Imaging Techniques, Fatty Liver, Female, Humans, Liver Cirrhosis, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Prospective Studies, ROC Curve, Severity of Illness Index, Young Adult, NAFLD, Fibroscan, VCTE, Vibration Controlled Transient Elastography, Controlled Attenuation Parameter, Fibrosis, Steatosis, NASH Clinical Research Network, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background & aimsVibration-controlled transient elastography (VCTE), which measures liver stiffness, has become an important tool for evaluating patients with nonalcoholic fatty liver disease (NAFLD). We aimed to determine the diagnostic accuracy of VCTE in detection of NAFLD in a multicenter cohort of patients.MethodsWe performed a prospective study of 393 adults with NAFLD who underwent VCTE within 1 year of liver histology analysis (median time, 49 d; interquartile range, 25-78 d), from July 1, 2014, through July 31, 2017. Liver stiffness measurement (LSM) cut-off values for pairwise fibrosis stage and controlled attenuation parameter cut-off values for pairwise steatosis grade were determined using cross-validated area under the receiver operating characteristics curve (AUROC) analyses. Diagnostic statistics were computed at a sensitivity fixed at 90% and a specificity fixed at 90%.ResultsLSM identified patients with advanced fibrosis with an AUROC of 0.83 (95% CI, 0.79- 0.87) and patients with cirrhosis with an AUROC of 0.93 (95% CI, 0.90-0.97). At a fixed sensitivity, a cut-off LSM of 6.5 kPa excluded advanced fibrosis with a negative predictive value of 0.91, and a cut-off LSM of 12.1 kPa excluded cirrhosis with a negative predictive value of 0.99. At a fixed specificity, LSM identified patients with advanced fibrosis with a positive predictive value of 0.71 and patients with cirrhosis with a positive predictive value of 0.41. Controlled attenuation parameter analysis detected steatosis with an AUROC of 0.76 (95% CI, 0.64-0.87). In contrast, the VCTE was less accurate in distinguishing lower fibrosis stages, higher steatosis grades, or the presence of NASH.ConclusionsIn a prospective study of adults with NAFLD, we found VCTE to accurately distinguish advanced vs earlier stages of fibrosis, using liver histology as the reference standard.

Published
2019

15. Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial

Author

Harrison, Stephen A, Abdelmalek, Manal F, Neff, Guy, Gunn, Nadege, Guy, Cynthia D, Alkhouri, Naim, Bashir, Mustafa R, Freilich, Bradley, Kohli, Anita, Khazanchi, Arun, Sheikh, Muhammad Y, Leibowitz, Mark, Rinella, Mary E, Siddiqui, Mohammad S, Kipnes, Mark, Moussa, Sam E, Younes, Ziad H, Bansal, Meena, Baum, Seth J, Borg, Brian, Ruane, Peter J, Thuluvath, Paul J, Gottwald, Mildred, Khan, Mujib, Chen, Charles, Melchor-Khan, Liza, Chang, William, DePaoli, Alex M, Ling, Lei, and Lieu, Hsiao D

Published
2022
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16. Liver transplant recipients have worse metabolic body phenotype compared with matched non‐transplant controls.

Author

Bhati, Chandra, Kirkman, Danielle, Forsgren, Mikael F, Kamal, Hiba, Khan, Hiba, Boyett, Sherry, Leinhard, Olof Dahlqvist, Linge, Jennifer, Patel, Vaishali, Patel, Samarth, Wolver, Susan, and Siddiqui, Mohammad S

Subjects
ABDOMINAL adipose tissue, ADIPOSE tissues, BODY composition, MAGNETIC resonance imaging, BODY mass index
Abstract

Background and Aim: Quantification of body compartments, particularly the interaction between adipose tissue and skeletal muscle, is emerging as novel a biomarker of metabolic health. The present study evaluated the impact of liver transplant (LT) on body compartments. Methods: Totally 66 adult LT recipients were enrolled in whom body compartments including visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), muscle fat infiltration (MFI), fat‐free muscle volume (FFMV), and liver fat (LF) were quantified via whole body magnetic resonance imaging (MRI). To provide non‐LT comparison, each LT recipient was matched to at least 150 non‐LT controls for same sex, age, and body mass index (BMI) from the UK Biobank registry. Results: LT recipients (vs matched non‐LT controls) had significantly higher subcutaneous (13.82 ± 5.47 vs 12.10 ± 5.10 L, P < 0.001) and visceral fat (7.59 ± 3.75 vs 6.72 ± 3.06 L, P = 0.003) and lower LF (5.88 ± 7.14 vs 8.75 ± 6.50%, P < 0.001) and muscle volume (11.69 ± 2.95 vs 12.12 ± 2.90 L, P = 0.027). In subgroup analysis, patients transplanted for metabolic dysfunction‐associated steatohepatitis (MASH) cirrhosis (vs non‐MASH cirrhosis) had higher ASAT, VAT, and MFI. A trend toward higher LF content was noted; however, this did not reach statistical significance (6.90 ± 7.35 vs 4.04 ± 6.23%, P = 0.189). Finally, compared with matched non‐LT controls, patients transplanted for MASH cirrhosis had higher ASAT and VAT; however, FFMV and MFI were similar. Conclusion: Using non‐LT controls, the current study established the higher‐than‐expected adiposity burden among LT recipients, which is even higher among patients transplanted for MASH cirrhosis. These findings provide data needed to design future studies developing radiomics‐based risk‐stratification strategies in LT recipients. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Performance characteristics of vibration‐controlled transient elastography for evaluation of nonalcoholic fatty liver disease

Author

Vuppalanchi, Raj, Siddiqui, Mohammad S, Van Natta, Mark L, Hallinan, Erin, Brandman, Danielle, Kowdley, Kris, Neuschwander‐Tetri, Brent A, Loomba, Rohit, Dasarathy, Srinivas, Abdelmalek, Manal, Doo, Edward, Tonascia, James A, Kleiner, David E, Sanyal, Arun J, Chalasani, Naga, and Network, for the NASH Clinical Research

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Liver Disease, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Good Health and Well Being, Adult, Aged, Biopsy, Needle, Body Mass Index, Databases, Factual, Elasticity Imaging Techniques, Female, Humans, Immunohistochemistry, Logistic Models, Male, Middle Aged, Multivariate Analysis, Non-alcoholic Fatty Liver Disease, Obesity, Observer Variation, Retrospective Studies, Risk Assessment, Severity of Illness Index, Task Performance and Analysis, Vibration, NASH Clinical Research Network, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences
Abstract

Vibration-controlled transient elastography estimates liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), which are noninvasive assessments of hepatic fibrosis and steatosis, respectively. However, prior vibration-controlled transient elastography studies reported high failure rates in patients with nonalcoholic fatty liver disease. We examined the performance characteristics of the FibroScan 502 Touch with two probes, medium (M+) and extra large (XL+), in patients with nonalcoholic fatty liver disease in a multicenter setting. A total of 1,696 exams were attempted in 992 patients (body mass index, 33.6 ± 6.5 kg/m2 ) with histologically confirmed nonalcoholic fatty liver disease. Simultaneous assessment of LSM and CAP was performed using the FibroScan 502 Touch with an automatic probe selection tool. Testing was conducted twice in patients by either a single operator (87%) or two operators (13%). Failure was defined as the inability to obtain a valid examination. An examination was considered unreliable if LSM interquartile range/median was >30%. Significant disagreement between two readings was defined as >95% limits of agreement between two readings. A total of 1,641 examinations yielded valid results with a failure rate of 3.2% (55/1,696). The proportion of unreliable scans for LSM was 3.9%. The proportion of unreliable scans with operator experience in the top quartile (≥59 procedures) was significantly lower than that in the lower three quarters combined (1.6% versus 4.7%, P = 0.02 by Fisher's exact test). The significant disagreement between first and second readings for LSM and CAP when obtained back to back was 18% and 11%, respectively.ConclusionVibration-controlled transient elastography for estimation of LSM and CAP can be successfully deployed in a multicenter setting with low failure (3.2%) and high reliability (>95%) rates and high reproducibility. (Hepatology 2018;67:134-144).

Published
2018

21. Immune Activation Mediates the Association of Advanced Hepatic Fibrosis With Adverse Outcomes in Patients With Coronary Artery Disease

Author

Jain, Vardhmaan, primary, Mehta, Anurag, additional, Lee, Terence B., additional, Liu, Chang, additional, Chew, Nicholas W. S., additional, Ko, Yi‐An, additional, Gold, Matthew E., additional, Gold, Daniel A., additional, Vatsa, Nishant, additional, Desai, Shivang R., additional, Kim, Jonathan H., additional, Rahbar, Alireza, additional, Haroun, Yazan, additional, Ejaz, Kiran, additional, Hayek, Salim S., additional, Siddiqui, Mohammad S., additional, Salloum, Fadi N., additional, Sperling, Laurence S., additional, Sanyal, Arun J., additional, and Quyyumi, Arshed A., additional

Published
2023
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23. Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage

Author

Allende, Daniela, Dasarathy, Srinivasan, McCullough, Arthur J., Penumatsa, Revathi, Dasarathy, Jaividhya, Lavine, Joel E., Abdelmalek, Manal F., Bashir, Mustafa, Buie, Stephanie, Diehl, Anna Mae, Guy, Cynthia, Kigongo, Christopher, Kopping, Mariko, Malik, David, Piercy, Dawn, Chalasani, Naga, Cummings, Oscar W., Gawrieh, Samer, Ragozzino, Linda, Sandrasegaran, Kumar, Vuppalanchi, Raj, Brunt, Elizabeth M., Cattoor, Theresa, Carpenter, Danielle, Freebersyser, Janet, King, Debra, Lai, Jinping, Neuschwander-Tetri, Brent A., Siegner, Joan, Stewart, Susan, Torretta, Susan, Wriston, Kristina, Gonzalez, Maria Cardona, Davila, Jodie, Jhaveri, Manan, Kowdley, Kris V., Mukhtar, Nizar, Ness, Erik, Poitevin, Michelle, Quist, Brook, Soo, Sherilynn, Ang, Brandon, Behling, Cynthia, Bhatt, Archana, Loomba, Rohit, Middleton, Michael S., Sirlin, Claude, Akhter, Maheen F., Bass, Nathan M., Brandman, Danielle, Gill, Ryan, Hameed, Bilal, Maher, Jacqueline, Terrault, Norah, Ungermann, Ashley, Yeh, Matthew, Boyett, Sherry, Contos, Melissa J., Kirwin, Sherri, Luketic, Velimir A.C., Puri, Puneet, Sanyal, Arun J., Schlosser, Jolene, Siddiqui, Mohammad S., Yost-Schomer, Leslie, Fowler, Kathryn, Kleiner, David E., Doo, Edward C., Hall, Sherry, Hoofnagle, Jay H., Lee, Jessica J., Robuck, Patricia R., Sherker, Averell H., Torrance, Rebecca, Belt, Patricia, Clark, Jeanne M., Dodge, John, Donithan, Michele, Hallinan, Erin, Isaacson, Milana, Lazo, Mariana, Meinert, Jill, Miriel, Laura, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Tonascia, James, Van Natta, Mark L., Wagoner, Annette, Wilson, Laura A., Yamada, Goro, Yates, Katherine, Siddiqui, Mohammad Shadab, Van Natta, Mark, and Neuschwander-Tetri, Brent

Published
2019
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25. Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children

Author

Abrams, Stephanie H., Barlow, Sarah, Himes, Ryan, Krisnamurthy, Rajesh, Maldonado, Leanel, Mahabir, Rory, Carr, April, Bernstein, Kimberlee, Bramlage, Kristin, Cecil, Kim, DeVore, Stephanie, Kohli, Rohit, Lake, Kathleen, Podberesky, Daniel, Towbin, Alex, Xanthakos, Stavra, Allende, Daniela, Dasarathy, Srinivasan, McCullough, Arthur J., Pagadala, Mangesh, Pai, Rish, Winston, Cha'Ron, Behr, Gerald, Lavine, Joel E., Lefkowitch, Jay H., Mencin, Ali, Reynoso, Elena, Abdelmalek, Manal F., Bashir, Mustafa, Buie, Stephanie, Diehl, Anna Mae, Guy, Cynthia, Kigongo, Christopher, Malik, David, Pan, Yi-Ping, Piercy, Dawn, Kopping, Mariko, Thrasher, Tyler, Alazraki, Adina, Cleeton, Rebecca, Cordero, Maria, Hernandez, Albert, Karpen, Saul, Munos, Jessica Cruz, Raviele, Nicholas, Vos, Miriam, Bozic, Molly, Chalasani, Naga, Cummings, Oscar W., Gawrieh, Samer, Klipsch, Ann, Molleston, Jean P., Ragozzino, Emily, Ragozzino, Linda, Sandrasegaran, Kumar, Subbarao, Girish, Vuppalanchi, Raj, Walker, Laura, Kafka, Kimberly, Scheimann, Ann, Ito, Joy, Fishbein, Mark H., Mohammad, Saeed, Rigsby, Cynthia, Sharda, Lisa, Whitington, Peter F., Cattoor, Theresa, Derdoy, Jose, Freebersyser, Janet, Jain, Ajay, King, Debra, Lai, Jinping, Osmack, Pat, Siegner, Joan, Stewart, Susan, Neuschwander-Tetri, Brent A., Torretta, Susan, Wriston, Kristina, Assadian, Fereshteh, Barone, Vanessa, Gonzalez, Maria Cardona, Davila, Jodie, Fix, Oren, Hennessey, Kelly Anne, Kowdley, Kris V., Lopez, Kacie, Ness, Erik, Poitevin, Michelle, Procaccini, Nicholas, Quist, Brook, Saddic, Alana, Wiseman, Cara, Yeh, Matthew, Baker, Susan S., Lopez-Graham, Diana, Williams, Sonja, Zhu, Lixin, Africa, Jonathan, Ang, Brandon, Awai, Hannah, Behling, Cynthia, Bhatt, Archana, Bross, Craig, Collins, Jennifer, Durelle, Janis, Harlow, Kathryn, Loomba, Rohit, Middleton, Michael, Newton, Kimberly, Paiz, Melissa, Schwimmer, Jeffrey B., Sirlin, Claude, Ugalde-Nicalo, Patricia, Villarreal, Mariana Dominguez, Aouizerat, Bradley, Bass, Nathan M., Brandman, Danielle, Courtier, Jesse, Ferrell, Linda D., Feier, Natasha, Gill, Ryan, Hameed, Bilal, Langlois, Camille, Maher, Jacqueline, Perito, Emily Rothbaum, Ramos, Claudia, Rosenthal, Philip, Terrault, Norah, Tsai, Patrika, Ungermann, Ashley, Atla, Pradeep, Croft, Brandon, Garcia, Rebekah, Garcia, Sonia, Sheikh, Muhammad, Singh, Mandeep, Cooper, Kara, Horslen, Simon, Hsu, Evelyn, Murray, Karen, Otto, Randolph, Young, Melissa, Boyett, Sherry, Carucci, Laura, Contos, Melissa J., Kirwin, Sherri, Kraft, Kenneth, Luketic, Velimir A.C., Puri, Puneet, Sanyal, Arun J., Schlosser, Jolene, Siddiqui, Mohammad S., Brunt, Elizabeth M., Fowler, Kathryn, Kleiner, David E., Brown, Sherry, Doo, Edward C., Hoofnagle, Jay H., Robuck, Patricia R., Sherker, Averell, Torrance, Rebecca, Belt, Patricia, Clark, Jeanne M., Donithan, Michele, Hallinan, Erin, Isaacson, Milana, May, Kevin P., Miriel, Laura, Sternberg, Alice, Tonascia, James, Van Natta, Mark, Wilson, Laura, Yates, Katherine, Newton, Kimberly P., Feldman, Haruna S., and Chambers, Christina D.

Published
2017
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28. Examining the interim proposal for name change to steatotic liver disease in the US population

Author

Ng, Cheng Han, primary, Chan, Kai En, additional, Muthiah, Mark, additional, Tan, Caitlyn, additional, Tay, Phoebe, additional, Lim, Wen Hui, additional, Tan, Darren Jun Hao, additional, Fu, Clarissa Elysia, additional, Yong, Jie Ning, additional, Wong, Zhen Yu, additional, Koh, Benjamin, additional, Chew, Nicholas WS, additional, Syn, Nicholas, additional, Huang, Daniel Q., additional, Young Dan, Yock, additional, Siddiqui, Mohammad S., additional, Sanyal, Arun J., additional, and Noureddin, Mazen, additional

Published
2023
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32. Symptom Domain Groups of the Patient-Reported Outcomes Measurement Information System Tools Independently Predict Hospitalizations and Re-hospitalizations in Cirrhosis

Author

Patidar, Kavish R., Thacker, Leroy R., Wade, James B., White, Melanie B., Gavis, Edith A., Fagan, Andrew, Sterling, Richard K., Fuchs, Michael, Siddiqui, Mohammad S., Matherly, Scott, Stravitz, Richard T., Sanyal, Arun J., Puri, Puneet, Luketic, Velimir A., and Bajaj, Jasmohan S.

Published
2017
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33. Hepatic, Extra-hepatic Outcomes and Causes of Mortality in NAFLD – An Umbrella Overview of Systematic Review of Meta-Analysis

Author

Xiao, Jieling, primary, Ng, Cheng Han, additional, Chan, Kai En, additional, Fu, Clarissa, additional, Tay, Phoebe, additional, Yong, Jie Ning, additional, Lim, Wen Hui, additional, Tan, Darren Jun Hao, additional, Syn, Nicholas, additional, Wong, Zhen Yu, additional, Tseng, Michael, additional, Chew, Nicholas, additional, Huang, Daniel Q., additional, Dan, Yock Yong, additional, Wong, Vincent Wai-Sun, additional, Loomba, Rohit, additional, Siddiqui, Mohammad S., additional, Sanyal, Arun J., additional, Noureddin, Mazen, additional, and Muthiah, Mark D., additional

Published
2022
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34. Readmission rates and risk factors associated with emergency surgeries

Author

Siddiqui, Mohammad S., primary, Albawardi, Abdulkarim A., additional, Alqahtani, Meshari S., additional, Almarshadi, Jamal A., additional, Alanazi, Thamer A., additional, Alshammari, Fahad H., additional, Almalki, Marwan T., additional, Mohamed, Dalal A., additional, Alamoudi, Osama O., additional, Almalky, Ayman J., additional, and Alobaidi, Ahmed E., additional

Published
2022
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36. Meta-analysis of the Placebo and Nocebo effects associated with Placebo treatment in randomized trials of lipid-lowering therapies

Author

Chin, Yip H, primary, Lim, Oliver, additional, Lin, Chaoxing, additional, Chan, Yu Y, additional, Kong, Gwyneth, additional, Ng, Cheng H, additional, Chong, Bryan, additional, Syn, Nicholas, additional, Chan, Kai E, additional, Muthiah, Mark D, additional, Siddiqui, Mohammad S, additional, Wang, Jiong-Wei, additional, Figtree, Gemma, additional, Chan, Mark Y, additional, and Chew, Nicholas W S, additional

Published
2022
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40. Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease

Author

Siddiqui, Mohammad S., Patel, Samarth, Forsgren, Mikael, Bui, Anh T., Shen, Steve, Syed, Taseen, Boyett, Sherry, Chen, Shanshan, Sanyal, Arun J., Wolver, Susan, Kirkman, Danielle, Celi, Francesco S., Bhati, Chandra S., Siddiqui, Mohammad S., Patel, Samarth, Forsgren, Mikael, Bui, Anh T., Shen, Steve, Syed, Taseen, Boyett, Sherry, Chen, Shanshan, Sanyal, Arun J., Wolver, Susan, Kirkman, Danielle, Celi, Francesco S., and Bhati, Chandra S.

Abstract

Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). Methods Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). Results The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. Conclusion Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT., Funding Agencies|CTSA awardUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS) [KL2TR002648]; National Center for Advancing Translational SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Advancing Translational Sciences (NCATS)

Published
2022
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45. Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: Implications for the gut-liver-brain axis

Author

Ahluwalia, Vishwadeep, Wade, James B., Heuman, Douglas M., Hammeke, Thomas A., Sanyal, Arun J., Sterling, Richard K., Stravitz, R. Todd, Luketic, Velimir, Siddiqui, Mohammad S., Puri, Puneet, Fuchs, Michael, Lennon, Micheal J., Kraft, Kenneth A., Gilles, HoChong, White, Melanie B., Noble, Nicole A., and Bajaj, Jasmohan S.

Published
2014
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50. Derivation and Validation of a Model to Predict Clinically Significant Portal Hypertension Using Transient Elastography and FIB-4

Author

Banini, Bubu A., primary, Patel, Samarth, additional, Yu, Jonathan W., additional, Kang, Le, additional, Bailey, Christopher, additional, Strife, Brian J., additional, Siddiqui, Mohammad S., additional, Patel, Vaishali, additional, Matherly, Scott C., additional, Lee, Hannah, additional, Lewis, Shawn, additional, Cherian, Reena, additional, Stravitz, Richard T., additional, Luketic, Velimir, additional, Sanyal, Arun J., additional, and Sterling, Richard K., additional

Published
2022
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