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Cited by 46Liver Disease Diagnosis and TreatmentAlcohol Consumption and Health EffectsLiver Diseases and Immunity

Lifestyle modifications for nonalcohol-related fatty liver disease: a network meta-analysis

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Buzzetti, Elena, Linden, Audrey, Best, Lawrence MJ, Madden, Angela M, Roberts, Danielle, Chase, Thomas J G, Freeman, Suzanne C, Cooper, Nicola J, Sutton, Alex J, Fritche, Dominic, Milne, Elisabeth Jane, Wright, Kathy, Pavlov, Chavdar S, Davidson, Brian R, Tsochatzis, Emmanuel, Gurusamy, Kurinchi Selvan·2021·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd013156.pub2PMC PMC6516973
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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.

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  • In a Cochrane systematic review of RCTs in people with MASLD, data were sparse regarding the effects of lifestyle interventions on any clinical outcome (death, liver-related complications, and liver cancer).

    “In a Cochrane systematic review of RCTs in people with MASLD, with follow-up periods of 2 -24 months, data were sparse regarding the effects of lifestyle interventions on any clinical outcome (death, liver-related complications, and liver cancer). 295”

    From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [295]

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Cited by

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Authors
Buzzetti, E., Linden, A., Best, L. M., Madden, A. M., Roberts, D., Chase, T. J. G., Freeman, S. C., Cooper, N. J., Sutton, A. J., Fritche, D., Milne, E. J., Wright, K., Pavlov, C. S., Davidson, B. R., Tsochatzis, E., & Gurusamy, K. S.
Affiliations
  • The Royal Free Hospital (GB)
  • University of Hertfordshire (GB)
  • University College London (GB)
  • Homerton University Hospital (GB)
  • University of Leicester (GB)
  • Coventry University (GB)
  • Copenhagen University Hospital (DK)
  • Sechenov University (RU)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2021-06-11
Volume
2021
Issue
6
Pages
CD013156-CD013156
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd013156.pub2
PMC
PMC6516973
OpenAlex
W4211099393
Cited by
46
References
1
Citations by year
2026: 1 · 2025: 6 · 2024: 13 · 2023: 12 · 2022: 7 · 2021: 4 · 2020: 1 · 2018: 2
FWCI
1.37
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • University of Hertfordshire Research Archive (University of Hertfordshire) (acceptedVersion)
  • Pure (Coventry University) (submittedVersion, other-oa)
  • University of Hertfordshire Research Archive (University of Hertfordshire) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
Funders
  • National Institute for Health and Care Research (project number 14/178/29, 16/114/17, 14/178/29)
  • Gentofte Hospital
  • Universiteit Stellenbosch
  • Rigshospitalet
  • Region Hovedstaden
  • Copenhagen Trial Unit, Centre for Clinical Intervention Research
  • Evidence Synthesis Programme
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
non-alcoholic fatty liver disease, lifestyle intervention, physical activity, dietary intervention, weight loss, nonalcoholic steatohepatitis, liver cirrhosis, hepatocellular carcinoma, liver transplantation, treatment efficacy and safety, comparative effectiveness, risk of bias, patient-reported outcomes, quality of life, anxiety, sleep disorders, fatigue
MeSH terms
Network Meta-Analysis, Bayes Theorem, Follow-Up Studies, Humans, Life Style, Time Factors, Exercise, Bias, Odds Ratio, Randomized Controlled Trials as Topic, Caloric Restriction, Diet, Mediterranean, Diet, Carbohydrate-Restricted, Resistance Training, Non-alcoholic Fatty Liver Disease

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