A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver

J Hepatol. 2013 Sep;59(3):550-6. doi: 10.1016/j.jhep.2013.04.027. Epub 2013 May 9.


Background & aims: Disease progression in non-alcoholic fatty liver disease (NAFLD) is not well understood and there is controversy about whether non-alcoholic fatty liver (NAFL, i.e., steatosis alone or with mild inflammation not qualifying for steatohepatitis) can evolve towards steatohepatitis (NASH) with fibrosis.

Methods: We reviewed 70 patients with untreated NAFLD and with two biopsies performed more than one year apart. Clinical and biological data were recorded at the time of both biopsies. Alcohol consumption did not change during follow-up.

Results: Initially 25 patients had NAFL and 45 had NASH and/or advanced fibrosis. After a mean follow-up of 3.7 years (s.d. 2.1), 16 NAFL patients developed NASH, eight with severe ballooning and six with bridging fibrosis on the follow-up biopsy. Patients with mild lobular inflammation or any degree of fibrosis were at higher risk of progression than those with steatosis alone. Those with unambiguous disease progression were older and had worsening of their metabolic risk factors (higher weight and more diabetes at baseline and during follow-up). In the whole cohort, ballooning progression and bridging fibrosis often occurred together and co-existed with a reduction in ALT, higher weight gain, and a higher incidence of diabetes during follow-up.

Conclusions: A substantial proportion of patients with NAFL can progress towards well-defined NASH with bridging fibrosis, especially if metabolic risk factors deteriorate. Even mild inflammation or fibrosis could substantially increase the risk of progression when compared to steatosis alone. Current monitoring practices of these patients should be revised.

Keywords: ALT; AST; BMI; Fibrosis; GGT; HOMA-IR; Insulin resistance; Liver biopsy; NAFLD; NAFLD activity score; NAS; NASH; Steatohepatitis; Steatosis; alanine aminotransferase; aspartate aminotransferase; body mass index; gammaglutamyltranspaptidase; homeostasis model assessment; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / metabolism
  • Biopsy
  • Disease Progression
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Fatty Liver / pathology*
  • Female
  • Fibrosis
  • Follow-Up Studies
  • Humans
  • Insulin Resistance
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Retrospective Studies
  • Risk Factors


  • Alanine Transaminase