Published online Nov 8, 2015. doi: 10.4254/wjh.v7.i25.2610
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.
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.