Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: Guidelines for referral in NAFLD

Jessica Bazick, Michele Donithan, Brent A. Neuschwander-Tetri, David Kleiner, Elizabeth M. Brunt, Laura Wilson, Ed Doo, Joel Lavine, James A Tonascia, Rohit Loomba

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. RESEARCH DESIGN AND METHODS: This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. RESULTS: The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 6 ±.8 kg/m2, respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with an AUROC of 0.80 (95% CI 0.76-0.85, P <0.001). The specificity, sensitivity, NPV, and PPV were 90.0%, 57%, 75.1%, and 80.2%, respectively, and the model correctly classified 76.6% of patients as having advanced fibrosis. Results remained consistent for both models in the validation cohort. The proposed model performed better than the NAFLD fibrosis score in detecting advanced fibrosis. CONCLUSIONS: Routinely available clinical variables can be used to quantify the likelihood of NASH or advanced fibrosis in adult diabetic patients with NAFLD. The clinical models presented can be used to guide clinical decision making about referrals of patients with diabetes and NAFLD to hepatologists.

Original languageEnglish (US)
Pages (from-to)1347-1355
Number of pages9
JournalDiabetes Care
Volume38
Issue number7
DOIs
StatePublished - Jul 1 2015

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Fibrosis
Referral and Consultation
Guidelines
ROC Curve
Non-alcoholic Fatty Liver Disease
Aspartate Aminotransferases
Alanine Transaminase
Type 2 Diabetes Mellitus
Alkaline Phosphatase
Sensitivity and Specificity
Serum Globulins
International Normalized Ratio
Waist-Hip Ratio
Ferritins
Platelet Count
Hematocrit
Bilirubin
Hispanic Americans
Serum Albumin
Liver Cirrhosis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Bazick, J., Donithan, M., Neuschwander-Tetri, B. A., Kleiner, D., Brunt, E. M., Wilson, L., ... Loomba, R. (2015). Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: Guidelines for referral in NAFLD. Diabetes Care, 38(7), 1347-1355. https://doi.org/10.2337/dc14-1239

Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD : Guidelines for referral in NAFLD. / Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A.; Kleiner, David; Brunt, Elizabeth M.; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James A; Loomba, Rohit.

In: Diabetes Care, Vol. 38, No. 7, 01.07.2015, p. 1347-1355.

Research output: Contribution to journalArticle

Bazick, J, Donithan, M, Neuschwander-Tetri, BA, Kleiner, D, Brunt, EM, Wilson, L, Doo, E, Lavine, J, Tonascia, JA & Loomba, R 2015, 'Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD: Guidelines for referral in NAFLD', Diabetes Care, vol. 38, no. 7, pp. 1347-1355. https://doi.org/10.2337/dc14-1239
Bazick, Jessica ; Donithan, Michele ; Neuschwander-Tetri, Brent A. ; Kleiner, David ; Brunt, Elizabeth M. ; Wilson, Laura ; Doo, Ed ; Lavine, Joel ; Tonascia, James A ; Loomba, Rohit. / Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD : Guidelines for referral in NAFLD. In: Diabetes Care. 2015 ; Vol. 38, No. 7. pp. 1347-1355.
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author = "Jessica Bazick and Michele Donithan and Neuschwander-Tetri, {Brent A.} and David Kleiner and Brunt, {Elizabeth M.} and Laura Wilson and Ed Doo and Joel Lavine and Tonascia, {James A} and Rohit Loomba",
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T1 - Clinical model for NASH and advanced fibrosis in adult patients with diabetes and NAFLD

T2 - Guidelines for referral in NAFLD

AU - Bazick, Jessica

AU - Donithan, Michele

AU - Neuschwander-Tetri, Brent A.

AU - Kleiner, David

AU - Brunt, Elizabeth M.

AU - Wilson, Laura

AU - Doo, Ed

AU - Lavine, Joel

AU - Tonascia, James A

AU - Loomba, Rohit

PY - 2015/7/1

Y1 - 2015/7/1

N2 - OBJECTIVE: Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. RESEARCH DESIGN AND METHODS: This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. RESULTS: The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 6 ±.8 kg/m2, respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with an AUROC of 0.80 (95% CI 0.76-0.85, P <0.001). The specificity, sensitivity, NPV, and PPV were 90.0%, 57%, 75.1%, and 80.2%, respectively, and the model correctly classified 76.6% of patients as having advanced fibrosis. Results remained consistent for both models in the validation cohort. The proposed model performed better than the NAFLD fibrosis score in detecting advanced fibrosis. CONCLUSIONS: Routinely available clinical variables can be used to quantify the likelihood of NASH or advanced fibrosis in adult diabetic patients with NAFLD. The clinical models presented can be used to guide clinical decision making about referrals of patients with diabetes and NAFLD to hepatologists.

AB - OBJECTIVE: Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. RESEARCH DESIGN AND METHODS: This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. RESULTS: The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 6 ±.8 kg/m2, respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with an AUROC of 0.80 (95% CI 0.76-0.85, P <0.001). The specificity, sensitivity, NPV, and PPV were 90.0%, 57%, 75.1%, and 80.2%, respectively, and the model correctly classified 76.6% of patients as having advanced fibrosis. Results remained consistent for both models in the validation cohort. The proposed model performed better than the NAFLD fibrosis score in detecting advanced fibrosis. CONCLUSIONS: Routinely available clinical variables can be used to quantify the likelihood of NASH or advanced fibrosis in adult diabetic patients with NAFLD. The clinical models presented can be used to guide clinical decision making about referrals of patients with diabetes and NAFLD to hepatologists.

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