eprintid: 10129575 rev_number: 25 eprint_status: archive userid: 608 dir: disk0/10/12/95/75 datestamp: 2021-06-15 10:45:48 lastmod: 2024-10-26 14:08:56 status_changed: 2021-06-15 10:45:48 type: article metadata_visibility: show creators_name: Buzzetti, E creators_name: Linden, A creators_name: Best, LM creators_name: Madden, AM creators_name: Roberts, D creators_name: Chase, TJG creators_name: Freeman, SC creators_name: Cooper, NJ creators_name: Sutton, AJ creators_name: Fritche, D creators_name: Milne, EJ creators_name: Wright, K creators_name: Pavlov, CS creators_name: Davidson, BR creators_name: Tsochatzis, E creators_name: Gurusamy, KS title: Lifestyle modifications for nonalcohol-related fatty liver disease: a network meta-analysis ispublished: pub subjects: RFH divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G91 divisions: D16 divisions: G85 note: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. abstract: BACKGROUND: The prevalence of nonalcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases the risks of liver cirrhosis, hepatocellular carcinoma, and requirement for liver transplantation. There is uncertainty surrounding the relative benefits and harms of various lifestyle interventions for people with NAFLD. OBJECTIVES: To assess the comparative benefits and harms of different lifestyle interventions in the treatment of NAFLD through a network meta-analysis, and to generate rankings of the different lifestyle interventions according to their safety and efficacy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or status) in people with NAFLD, whatever the method of diagnosis, age, and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS: We planned to perform a network meta-analysis with OpenBUGS using Bayesian methods and to calculate the differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios (RaRs) with 95% credible intervals (CrIs) based on an available-participant analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. However, the data were too sparse for the clinical outcomes. We therefore performed only direct comparisons (head-to-head comparisons) with OpenBUGS using Bayesian methods. MAIN RESULTS: We included a total of 59 randomised clinical trials (3631 participants) in the review. All but two trials were at high risk of bias. A total of 33 different interventions, ranging from advice to supervised exercise and special diets, or a combination of these and no additional intervention were compared in these trials. The reference treatment was no active intervention. Twenty-eight trials (1942 participants) were included in one or more comparisons. The follow-up ranged from 1 month to 24 months. The remaining trials did not report any of the outcomes of interest for this review. The follow-up period in the trials that reported clinical outcomes was 2 months to 24 months. During this short follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. This is probably because of the very short follow-up periods. It takes a follow-up of 8 years to 28 years to detect differences in mortality between people with NAFLD and the general population. It is therefore unlikely that differences by clinical outcomes will be noted in trials with less than 5 years to 10 years of follow-up. In one trial, one participant developed an adverse event. There were no adverse events in any of the remaining participants in this trial, or in any of the remaining trials, which seemed to be directly related to the intervention. AUTHORS' CONCLUSIONS: The evidence indicates considerable uncertainty about the effects of the lifestyle interventions compared with no additional intervention (to general public health advice) on any of the clinical outcomes after a short follow-up period of 2 months to 24 months in people with nonalcohol-related fatty liver disease. Accordingly, high-quality randomised clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (a study design in which multiple interventions are trialed within large longitudinal cohorts of participants to gain efficiencies and align trials more closely to standard clinical practice), comparing aerobic exercise and dietary advice versus standard of care (exercise and dietary advice received as part of national health promotion). The reason for the choice of aerobic exercise and dietary advice is the impact of these interventions on indirect outcomes which may translate to clinical benefit. The outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource use measures including costs of intervention and decreased healthcare use after a minimum follow-up of eight years, to find meaningful differences in the clinically important outcomes. date: 2021-06-11 date_type: published official_url: http://dx.doi.org/10.1002/14651858.CD013156.pub2 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1870774 doi: 10.1002/14651858.CD013156.pub2 lyricists_name: Best, Lawrence lyricists_name: Davidson, Brian lyricists_name: Gurusamy, Kurinchi lyricists_name: Linden, Audrey lyricists_name: Roberts, Danielle lyricists_name: Tsochatzis, Emmanouil lyricists_id: LMJBE89 lyricists_id: BRDAV24 lyricists_id: GURUS55 lyricists_id: ALIND73 lyricists_id: DROBE40 lyricists_id: ETSOC40 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Cochrane Database of Systematic Reviews volume: 6 article_number: CD013156 event_location: England citation: Buzzetti, E; Linden, A; Best, LM; Madden, AM; Roberts, D; Chase, TJG; Freeman, SC; ... Gurusamy, KS; + view all <#> Buzzetti, E; Linden, A; Best, LM; Madden, AM; Roberts, D; Chase, TJG; Freeman, SC; Cooper, NJ; Sutton, AJ; Fritche, D; Milne, EJ; Wright, K; Pavlov, CS; Davidson, BR; Tsochatzis, E; Gurusamy, KS; - view fewer <#> (2021) Lifestyle modifications for nonalcohol-related fatty liver disease: a network meta-analysis. Cochrane Database of Systematic Reviews , 6 , Article CD013156. 10.1002/14651858.CD013156.pub2 <https://doi.org/10.1002/14651858.CD013156.pub2>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10129575/1/Buzzetti_et_al-2021-Cochrane_Database_of_Systematic_Reviews.pdf