Retrospective Cohort Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 8, 2015; 7(25): 2610-2618
Published online Nov 8, 2015. doi: 10.4254/wjh.v7.i25.2610
Histopathological differences utilizing the nonalcoholic fatty liver disease activity score criteria in diabetic (type 2 diabetes mellitus) and non-diabetic patients with nonalcoholic fatty liver disease
Bharat K Puchakayala, Siddharth Verma, Pushpjeet Kanwar, John Hart, Raghavendra R Sanivarapu, Smruti R Mohanty
Bharat K Puchakayala, Siddharth Verma, Pushpjeet Kanwar, Raghavendra R Sanivarapu, Smruti R Mohanty, Center for Liver Diseases, Division of Gastroenterology and Hepatology, New York Methodist Hospital at Weill Cornell Medical College, Brooklyn, NY 11215, United States
John Hart, Department of Pathology, University of Chicago Medical Center, Chicago, IL 60637, United States
Author contributions: Study concept, design, data collection and supervision by Mohanty SR; analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content shared between Puchakayala BK (major contribution), Verma S and Kanwar P; initial statistical analysis performed by University of Chicago statistician and secondary analysis with review was performed by Matt Briggs, consultant statistician at New York Methodist Hospital; liver biopsy slides analysed by Hart J at University of Chicago; secondary analysis of data, formulation of tables and review of manuscript by Sanivarapu RR.
Institutional review board statement: Noted under methods section of manuscript. This study was approved by the Institutional Review Board at University of Chicago Medical Center.
Informed consent statement: Noted under methods section of manuscript. There was no identifiable data in this study and informed consent was waived by University of Chicago Medical Center Institutional Review Board.
Conflict-of-interest statement: We do not have any commercial relationships (i.e., consultancies, patent-licensing agreements) or any conflicting interests (including but not limited to commercial, personal, political, intellectual, or religious interests) that might pose a conflict of interest in connection with the submitted manuscript.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at Consent from participants was not obtained as the presented data is anonymized and risk of identification is nil.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Smruti R Mohanty, MD, MS, FACP, Center for Liver Diseases, Division of Gastroenterology and Hepatology, New York Methodist Hospital at Weill Cornell Medical College, 506 Sixth Street, 3rd Floor, Brooklyn, NY 11215, United States.
Telephone: +1-718-7805898 Fax: +1-718-7803478
Received: April 16, 2015
Peer-review started: April 18, 2015
First decision: June 3, 2015
Revised: September 23, 2015
Accepted: October 20, 2015
Article in press: October 27, 2015
Published online: November 8, 2015

AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease (NAFLD) in patients with and without type 2 diabetes mellitus (T2DM) using updated nonalcoholic steatohepatitis clinical research network (NASH-CRN) grading system.

METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2DM. This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author. The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison. The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist. The updated criteria for type 2 diabetes have been utilized for analysis. Background data of patients with NASH and NAFLD has been included. The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.

RESULTS: Patients with NAFLD and T2DM were significantly older (49.9 vs 43.0, P < 0.01), predominantly female (71.4 vs 56.3, P < 0.02), had higher rate of metabolic syndrome (88.7 vs 36.4, P < 0.01), had significantly higher aspartate transaminase (AST)/alanine transaminase (ALT) ratio (0.94 vs 0.78, P < 0.01) and Fib-4 index (1.65 vs 1.06, P < 0.01) as markers of NASH, showed higher mean NAFLD activity score (3.5 vs 3.0, P = 0.03) and higher mean fibrosis score (1.2 vs 0.52, P < 0.01) compared to patients with NAFLD without T2DM. Furthermore, advanced fibrosis (32.5 vs 12.0, P < 0.01) and ballooning (27.3 vs 13.3, P < 0.01) was significantly higher among patients with NAFLD and T2DM compared to patients with NAFLD without T2DM. On multivariate analysis, T2DM was independently associated with NASH (OR = 3.27, 95%CI: 1.43-7.50, P < 0.01) and advanced fibrosis (OR = 3.45, 95%CI: 1.53-7.77, P < 0.01) in all patients with NAFLD. There was a higher rate of T2DM (38.1 vs 19.4, P < 0.01) and cirrhosis (8.3 vs 0.0, P = 0.01) along with significantly higher mean Bilirubin (0.71 vs 0.56, P = 0.01) and AST (54.2 vs 38.3, P < 0.01) and ALT (78.7 vs 57.0, P = 0.01) level among patients with NASH when compared to patients with steatosis alone. The mean platelet count (247 vs 283, P < 0.01) and high-density lipoprotein cholesterol level (42.7 vs 48.1, P = 0.01) was lower among patients with NASH compared to patients with steatosis.

CONCLUSION: Patients with NAFLD and T2DM tend to have more advanced stages of NAFLD, particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2DM.

Keywords: Non-alcoholic steatohepatitis, Non-alcoholic fatty liver disease, Advanced fibrosis, Non-alcoholic fatty liver disease activity score, Type 2 diabetes, Liver biopsy

Core tip: This retrospective cohort study shows that type 2 diabetes mellitus (T2DM) is a reliable predictor for both nonalcoholic steatohepatitis (NASH) and advanced fibrosis. Patients with nonalcoholic fatty liver disease (NAFLD) and uncontrolled T2DM tend to have advanced fibrosis and higher rate of ballooning histologically. It is important to recognize the differences between composite NAS and individual histological features while interpreting liver biopsies among NAFLD patients. Early diagnosis of NASH and advanced fibrosis in patients with NAFLD has important clinical significance especially to prevent further progression of liver disease to cirrhosis, hepatocellular carcinoma and other related complications. Thus, optimization of risk factors for NAFLD such as metabolic syndrome, uncontrolled T2DM and dyslipidemia is of paramount importance.