Nonalcoholic Steatohepatitis: A 9-Year Follow Up Cohort Study

Abstract

Background and aim: Non-alcoholic fatty liver disease (NAFLD) may progress to severe liver fibrosis and cirrhosis. A limited number of studies with a long follow up assessed fibrosis progression and related predictors in untreated patients with a histological diagnosis of NAFLD. This study aims to investigate rate and predictors of NAFLD progression.

Methods: For 9 (2-16.7) years, we followed up a cohort of patients histologically diagnosed. Disease progression was defined by a composite endpoint as evidence of cirrhosis in patients without cirrhosis at baseline, evidence of de novo occurrence of cirrhosis complications, histologically established worsening of stage 1 of fibrosis or increase of 20% in liver stiffness by transient elastography in patients rejecting a second liver biopsy.

Results: A total of 91 patients were enrolled. Of them, 31 had NAFL and 60 NASH. A second liver biopsy was performed in 22 NASH patients and in 4 NAFL. Disease progression was observed in 38.5% NASH and in 12.0% NAFL (p = 0.034). Patients with portal inflammation had a higher risk of progression (66.7% vs 26%, p = 0.021). High triglycerides levels, advanced fibrosis at baseline and the duration of follow-up predict disease progression (p = 0.021; OR = 6.93, 95% CI 1.33-36.08, p = 0.43; OR 8.37; 95% CI 1.07-65.58 and p = 0.034; OR = 0.88; 95% CI 0.78-0.99, respectively).

Conclusions: Our results reinforce the evidence that, in the absence of pharmacologic treatment, NASH progresses in about 40% of patients. Liver biopsy is the only mean to discriminate NAFL from NASH. The prognostic role of portal inflammation needs to be explored in larger series.

Keywords: NASH; cirrhosis; fibrosis; liver histology; non-invasive diagnosis.

Figure 1

Study flow chart showing the number of patients initially included, the number of subjects lost to follow up and the number of patients with paired biopsies. (NAFLD = Non-Alcoholic fatty liver disease; NASH = Non-alcoholic steatohepatitis).

Figure 2

Fibrosis changes in 26 patients undergone a second liver biopsy. The first column indicates the number of patients with different fibrosis stages at baseline, the second the correstonding numbers at the follow up liver biopsy.

Figure 3

(A) NASH with severe steatosis and moderate portal inflammation (arrow) at presentation (H&E; original magnification 1.2×; insert original magnification 40×. (B) The same patient showed cirrhosis in the follow up biopsy performed 4 years later (Van Gieson’s stain; original magnification 2.5×).

Figure 4

(A) Moderate steatosis with minimal lobular inflammation at presentation (H&E; original magnification 2.5×); (B) same patient 15 years later did not show any fibrosis progression (Van Gieson’s stain; original magnification 2.5×).