title: Systematic review: Current evidence in non-alcoholic fatty liver disease lacks relevance to patients with advanced fibrosis.
abstract: OBJECTIVE
  Epidemiological data have shown that individuals with advanced fibrosis are at greatest risk of premature morbidity in non-alcoholic fatty liver disease (NAFLD). Individuals included in clinical trials are often highly selected to remove confounding factors, but selection can introduce bias and limit external validity. We examined the external validity of trials in NAFLD by examining characteristics of participants in observational studies (OS) and randomized controlled trials (RCT) in NAFLD.
  
  
  METHODS
  A systematic review was performed with structured literature searches for relevant OS and RCT using PubMed and Ovid Embase (1948-2016). Identified studies were screened for inclusion by the authors and data extracted. Study populations were compared using t-tests to compare means and variances, in each case weighted by the size of individual studies. Dichotomous data were compared by Chi-squared test.
  
  
  RESULTS
  In total, 148 studies were included: 67 RCT and 81 OS including data from 44 860 individuals. Fifteen RCT participants differed from individuals in OS with regard to age, body mass index, prevalence of Diabetes mellitus, and gender (P < 0.001 in each case). The most pronounced differences were seen between RCT participants and patients with advanced fibrosis. Comorbid conditions prevalent among individuals with NAFLD were frequent exclusion criteria in RCT.
  
  
  CONCLUSIONS
  The characteristics of participants in randomized controlled trials differ to those of the wider population of individuals with NAFLD. These differences may reduce the utility of trial data to individuals with NAFLD at greatest risk of death.
authors: Centre for Liver Research, University of Birmingham, Birmingham, UK.
authors: Richard
authors: http://orcid.org/0000-0003-4888-8670
authors: R
authors: Parker
authors: Statistics Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
authors: James
authors: J
authors: Hodson
authors: Leeds Institute for Data Analysis, University of Leeds, Leeds, UK.
authors: Ian A C
authors: IAC
authors: Rowe
mesh_terms: D000367:Age Factors; D015992:Body Mass Index; D016009:Chi-Square Distribution; D015897:Comorbidity; D016206:Databases, Bibliographic; D003920:Diabetes Mellitus; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology / Q000628:therapy*; D064887:Observational Studies as Topic; D010361:Patients; D016032:Randomized Controlled Trials as Topic; D012306:Risk
keywords: non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; systematic review