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Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years
  1. Vincent Wai-Sun Wong1,2,
  2. Grace Lai-Hung Wong1,2,
  3. Paul Cheung-Lung Choi3,
  4. Anthony Wing-Hung Chan3,
  5. Mia Ka-Po Li1,2,
  6. Hoi-Yun Chan1,2,
  7. Angel Mei-Ling Chim1,2,
  8. Jun Yu1,2,
  9. Joseph Jao-Yiu Sung1,2,
  10. Henry Lik-Yuen Chan1,2
  1. 1Department of Medicine and Therapeutics, The Chinese University of Hong Kong
  2. 2Institute of Digestive Disease, The Chinese University of Hong Kong
  3. 3Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong
  1. Correspondence to Professor Henry L-Y Chan, Department of Medicine and Therapeutics, 9/F, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong; hlychan{at}


Background Patients with non-alcoholic steatohepatitis (NASH) have increased mortality and liver-related complications. In contrast, simple steatosis is considered benign and non-progressive.

Objective To investigate disease progression in patients with different degrees of non-alcoholic fatty liver disease (NAFLD) activity.

Design Prospective longitudinal hospital-based cohort study.

Patients Fifty-two patients (age 44±9 years) with biopsy-proven NAFLD had liver biopsies repeated at month 36.

Results Among 13 patients with simple steatosis at baseline, 2 (15%) had a normal liver at month 36, 3 (23%) continued to have simple steatosis, 5 (39%) developed borderline NASH and 3 (23%) developed NASH. Among 22 patients with borderline NASH at baseline, 4 (18%) had simple steatosis and 13 (59%) had borderline NASH at month 36, while 5 (23%) developed NASH. Among 17 patients with NASH at baseline, 10 (59%) continued to have NASH and 6 (35%) had borderline NASH at month 36. Only 1 (6%) patient regressed to simple steatosis. Overall, 14 (27%) patients had fibrosis progression, 25 (48%) had static disease, and 13 (25%) had fibrosis regression. Reduction in body mass index and waist circumference was independently associated with non-progressive disease activity and fibrosis. The baseline serum levels and month 36 changes in adiponectin, tumour necrosis factor α, interleukin 6 and leptin were not associated with disease progression. Serum cytokeratin-18 fragment level reflected disease activity and its change correlated with the change in NAFLD activity score (R=0.51, p<0.001).

Conclusions Patients with simple steatosis may still develop NASH and fibrosis progression. Weight reduction is associated with non-progressive disease. All patients with NAFLD should undergo periodic assessment and lifestyle modification.

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  • Funding The Chinese University of Hong Kong, Shatin, Hong Kong, China.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Chinese University Clinical Research Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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