title: Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study.
abstract: BACKGROUND
  There is no consensus on the treatment of pediatric nonalcoholic fatty liver disease (NAFLD). However, in a small pilot study conducted in 10 children, metformin has been proposed to be effective.
  
  
  OBJECTIVE
  We aimed to determine the effect of metformin in addition to lifestyle intervention/modification in children with NAFLD.
  
  
  METHODS
  Overweight or obese children aged 9 to 18 years with biopsy-proven NAFLD or nonalcoholic steatohepatitis were enrolled in an observational pilot study, initially planned for 12 months, which aimed to estimate the effect of metformin on liver enzymes. The study was extended to 24 months to estimate outcomes on liver histology. All subjects received lifestyle intervention (nutritional counseling and a physical exercise regimen) and metformin 1.5 g/d (MET group). To serve as the control in this study, we selected a control group from a separate but parallel study (N=30) that had identical inclusion criteria on the use of antioxidants in NAFLD. End points were changes in liver enzymes and histology. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment of IR (HOMA-IR) and liver biopsy was determined by the NAFLD activity score (NAS).
  
  
  RESULTS
  Sixty patients were assessed for inclusion in this study. However, 2 patients in the MET group dropped out of the study during the first year because they relocated abroad, and 1 patient in the control group refused follow-up after 12 months. Thus, study data is based on the findings in the 57 remaining patients. Alanine aminotransferase significantly improved from baseline with decreasing body weight in both groups (MET: 35 [range, 21-43] to 32 [20-46] U/L; control: 66 [28-121] to 33 [14-45] U/L; P<or=0.01). HOMA-IR significantly improved in both groups from baseline with decreasing body weight as well (MET: 1.4 [range, 0.5-5.11] to 1.3 [0.13-4.21]; control: 2.29 [0.86-5.76] to 1.5 [0.70-4.23]; P<or=0.01). Steatosis was reduced in both the MET (P=0.02) and control (P=0.02) groups as well as ballooning (both, P=0.008). Lobular inflammation improved from baseline in the MET group (P=0.003). The NAS score decreased from baseline (both, P=0.001), but no significant changes in fibrosis were detected.
  
  
  CONCLUSIONS
  In this small, 24-month observational study, metformin did not appear more effective than lifestyle intervention in ameliorating levels of aminotransferases, steatosis, and liver histology in these children with NAFLD.
authors.affiliation: Liver Unit, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
authors.forename: Melania
authors.initials: M
authors.lastname: Manco
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciampalini
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
authors.forename: Rita
authors.initials: R
authors.lastname: Devito
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.forename: Matilde
authors.initials: M
authors.lastname: Marcellini
authors.forename: Giulio
authors.initials: G
authors.lastname: Marchesini
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D015992:Body Mass Index; D002648:Child; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D010865:Pilot Projects; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase