Histologic Findings of Advanced Fibrosis and Cirrhosis in Patients With Nonalcoholic Fatty Liver Disease Who Have Normal Aminotransferase Levels

and the NASH Clinical Research Network

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: Patients with nonalcoholic fatty liver disease (NAFLD) and normal aminotransferase levels may have advanced liver histology. We conducted a study to characterize the prevalence of and factors associated with advanced liver histology in patients with histologically characterized NAFLD and normal aminotransferase levels. METHODS: We evaluated 534 adults with biopsy-proven NAFLD and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <40U/L within 3 months of their liver biopsy. Histological phenotypes of primary interest were nonalcoholic steatohepatitis (NASH) with stage 2-3 fibrosis (NASH F2-3) and cirrhosis. Using multiple logistic regression models with Akaike's Information Criteria (AIC), we identified variables associated with these histological phenotypes. We developed and internally validated their clinical prediction models. RESULTS: The prevalence of NASH F2-F3 and cirrhosis was 19% and 7%, respectively. The best multiple regression AIC model for NASH F2-3 consisted of type 2 diabetes, white race, lower low-density lipoprotein, lower platelet count, higher AST/ALT ratio, higher serum triglycerides, and hypertension. The best AIC model for cirrhosis consisted of lower platelet count, lower AST/ALT ratio, higher body mass index, and female sex. The area under the receiver operator curves of the prediction models were 0.70 (95% confidence interval: 0.65-0.76) for detecting NASH-F2-3 and 0.85 (95% confidence interval: 0.77-0.92) for detecting cirrhosis. When models were fixed at maximum Youden's index, their positive and negative predictive values were 35% and 88% for NASH F2-F3 and 30% and 98% for cirrhosis, respectively. DISCUSSION: Clinically significant histological phenotypes are observed in patients with NAFLD and normal aminotransferase levels. Our models can assist the clinicians in excluding advanced liver histology in NAFLD patients with normal aminotransferase levels.

Original languageEnglish (US)
Pages (from-to)1626-1635
Number of pages10
JournalThe American Journal of Gastroenterology
Volume114
Issue number10
DOIs
StatePublished - Oct 1 2019

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Transaminases
Fibrosis
Aspartate Aminotransferases
Alanine Transaminase
Histology
Liver
Platelet Count
Phenotype
Non-alcoholic Fatty Liver Disease
Logistic Models
Confidence Intervals
Biopsy
LDL Lipoproteins
Type 2 Diabetes Mellitus
Triglycerides
Body Mass Index
Hypertension

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Histologic Findings of Advanced Fibrosis and Cirrhosis in Patients With Nonalcoholic Fatty Liver Disease Who Have Normal Aminotransferase Levels. / and the NASH Clinical Research Network.

In: The American Journal of Gastroenterology, Vol. 114, No. 10, 01.10.2019, p. 1626-1635.

Research output: Contribution to journalArticle

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title = "Histologic Findings of Advanced Fibrosis and Cirrhosis in Patients With Nonalcoholic Fatty Liver Disease Who Have Normal Aminotransferase Levels",
abstract = "OBJECTIVES: Patients with nonalcoholic fatty liver disease (NAFLD) and normal aminotransferase levels may have advanced liver histology. We conducted a study to characterize the prevalence of and factors associated with advanced liver histology in patients with histologically characterized NAFLD and normal aminotransferase levels. METHODS: We evaluated 534 adults with biopsy-proven NAFLD and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <40U/L within 3 months of their liver biopsy. Histological phenotypes of primary interest were nonalcoholic steatohepatitis (NASH) with stage 2-3 fibrosis (NASH F2-3) and cirrhosis. Using multiple logistic regression models with Akaike's Information Criteria (AIC), we identified variables associated with these histological phenotypes. We developed and internally validated their clinical prediction models. RESULTS: The prevalence of NASH F2-F3 and cirrhosis was 19{\%} and 7{\%}, respectively. The best multiple regression AIC model for NASH F2-3 consisted of type 2 diabetes, white race, lower low-density lipoprotein, lower platelet count, higher AST/ALT ratio, higher serum triglycerides, and hypertension. The best AIC model for cirrhosis consisted of lower platelet count, lower AST/ALT ratio, higher body mass index, and female sex. The area under the receiver operator curves of the prediction models were 0.70 (95{\%} confidence interval: 0.65-0.76) for detecting NASH-F2-3 and 0.85 (95{\%} confidence interval: 0.77-0.92) for detecting cirrhosis. When models were fixed at maximum Youden's index, their positive and negative predictive values were 35{\%} and 88{\%} for NASH F2-F3 and 30{\%} and 98{\%} for cirrhosis, respectively. DISCUSSION: Clinically significant histological phenotypes are observed in patients with NAFLD and normal aminotransferase levels. Our models can assist the clinicians in excluding advanced liver histology in NAFLD patients with normal aminotransferase levels.",
author = "{and the NASH Clinical Research Network} and Samer Gawrieh and Laura Wilson and Cummings, {Oscar W.} and Jeanne Clark and Rohit Loomba and Bilal Hameed and Abdelmalek, {Manal F.} and Srinivasan Dasarathy and Neuschwander-Tetri, {Brent A.} and Kris Kowdley and David Kleiner and Edward Doo and Tonascia, {James A} and Arun Sanyal and Naga Chalasani",
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AU - and the NASH Clinical Research Network

AU - Gawrieh, Samer

AU - Wilson, Laura

AU - Cummings, Oscar W.

AU - Clark, Jeanne

AU - Loomba, Rohit

AU - Hameed, Bilal

AU - Abdelmalek, Manal F.

AU - Dasarathy, Srinivasan

AU - Neuschwander-Tetri, Brent A.

AU - Kowdley, Kris

AU - Kleiner, David

AU - Doo, Edward

AU - Tonascia, James A

AU - Sanyal, Arun

AU - Chalasani, Naga

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N2 - OBJECTIVES: Patients with nonalcoholic fatty liver disease (NAFLD) and normal aminotransferase levels may have advanced liver histology. We conducted a study to characterize the prevalence of and factors associated with advanced liver histology in patients with histologically characterized NAFLD and normal aminotransferase levels. METHODS: We evaluated 534 adults with biopsy-proven NAFLD and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <40U/L within 3 months of their liver biopsy. Histological phenotypes of primary interest were nonalcoholic steatohepatitis (NASH) with stage 2-3 fibrosis (NASH F2-3) and cirrhosis. Using multiple logistic regression models with Akaike's Information Criteria (AIC), we identified variables associated with these histological phenotypes. We developed and internally validated their clinical prediction models. RESULTS: The prevalence of NASH F2-F3 and cirrhosis was 19% and 7%, respectively. The best multiple regression AIC model for NASH F2-3 consisted of type 2 diabetes, white race, lower low-density lipoprotein, lower platelet count, higher AST/ALT ratio, higher serum triglycerides, and hypertension. The best AIC model for cirrhosis consisted of lower platelet count, lower AST/ALT ratio, higher body mass index, and female sex. The area under the receiver operator curves of the prediction models were 0.70 (95% confidence interval: 0.65-0.76) for detecting NASH-F2-3 and 0.85 (95% confidence interval: 0.77-0.92) for detecting cirrhosis. When models were fixed at maximum Youden's index, their positive and negative predictive values were 35% and 88% for NASH F2-F3 and 30% and 98% for cirrhosis, respectively. DISCUSSION: Clinically significant histological phenotypes are observed in patients with NAFLD and normal aminotransferase levels. Our models can assist the clinicians in excluding advanced liver histology in NAFLD patients with normal aminotransferase levels.

AB - OBJECTIVES: Patients with nonalcoholic fatty liver disease (NAFLD) and normal aminotransferase levels may have advanced liver histology. We conducted a study to characterize the prevalence of and factors associated with advanced liver histology in patients with histologically characterized NAFLD and normal aminotransferase levels. METHODS: We evaluated 534 adults with biopsy-proven NAFLD and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <40U/L within 3 months of their liver biopsy. Histological phenotypes of primary interest were nonalcoholic steatohepatitis (NASH) with stage 2-3 fibrosis (NASH F2-3) and cirrhosis. Using multiple logistic regression models with Akaike's Information Criteria (AIC), we identified variables associated with these histological phenotypes. We developed and internally validated their clinical prediction models. RESULTS: The prevalence of NASH F2-F3 and cirrhosis was 19% and 7%, respectively. The best multiple regression AIC model for NASH F2-3 consisted of type 2 diabetes, white race, lower low-density lipoprotein, lower platelet count, higher AST/ALT ratio, higher serum triglycerides, and hypertension. The best AIC model for cirrhosis consisted of lower platelet count, lower AST/ALT ratio, higher body mass index, and female sex. The area under the receiver operator curves of the prediction models were 0.70 (95% confidence interval: 0.65-0.76) for detecting NASH-F2-3 and 0.85 (95% confidence interval: 0.77-0.92) for detecting cirrhosis. When models were fixed at maximum Youden's index, their positive and negative predictive values were 35% and 88% for NASH F2-F3 and 30% and 98% for cirrhosis, respectively. DISCUSSION: Clinically significant histological phenotypes are observed in patients with NAFLD and normal aminotransferase levels. Our models can assist the clinicians in excluding advanced liver histology in NAFLD patients with normal aminotransferase levels.

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