Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials
Open accessAbstract
Aims/hypothesis Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH): NAFLD causes an increased risk of cardiovascular disease, diabetes and liver-related complications (the latter confined to NASH). The effect of proposed treatments on liver disease, glucose metabolism and cardiovascular risk in NAFLD is unknown. We reviewed the evidence for the management of liver disease and cardio-metabolic risk in NAFLD. Methods Publications through November 2011 were systematically reviewed by two authors. Outcomes evaluated though standard methods were: histological/radiological/biochemical features of NAFLD, variables of glucose metabolism and cardiovascular risk factors. Seventy-eight randomised trials were included (38 in NASH, 40 in NAFLD): 41% assessed post-treatment histology, 71% assessed glucose metabolism and 88% assessed cardiovascular risk factors. Lifestyle intervention, thiazolidinediones, metformin and antioxidants were most extensively evaluated. Results Lifestyle-induced weight loss was safe and improved cardio-metabolic risk profile; a weight loss ≥7% improved histological disease activity, but was achieved by <50% patients. Statins and polyunsaturated fatty acids improved steatosis, but their effects on liver histology are unknown. Thiazolidinediones improved histological disease activity, glucose, lipid and inflammatory variables and delayed fibrosis progression. Pioglitazone also improved blood pressure. Weight gain (up to 4.8%) was common. Antioxidants yielded mixed histological results: vitamin E improved histological disease activity when administered for 2 years, but increased insulin resistance and plasma triacylglycerols. Conclusions/interpretation Weight loss is safe, and improves liver histology and cardio-metabolic profile. For patients not responding to lifestyle intervention, pioglitazone improves histological disease activity, slows fibrosis progression and extensively ameliorates cardio-metabolic endpoints. Further randomised controlled trials (RCTs) of adequate size and duration will assess long-term safety and efficacy of proposed treatments on clinical outcomes.
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Weight loss of ≥7% is generally safe and improves liver histology and cardiometabolic profile in NAFLD patients.
“a large systemic review and meta‐analysis have shown that weight loss (≥7%) generally is safe and improves liver histology and cardiometabolic profile in NAFLD patients [30].”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [30]
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- Authors
- Musso, G., Cassader, M., Rosina, F., & Gambino, R.
- Affiliations
- Ospedale Humanitas Gradenigo (IT)
- University of Turin (IT)
- Corresponding author
- Musso, G.
- ORCID
- Venue
- Diabetologia
- Published
- 2012-01-27
- Volume
- 55
- Issue
- 4
- Pages
- 885-904
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2157338541
- Cited by
- 661
- References
- 16
- Citations by year
- 2026: 11 · 2025: 29 · 2024: 40 · 2023: 49 · 2022: 63 · 2021: 59 · 2020: 58 · 2019: 54 · 2018: 43 · 2017: 41 · 2016: 51 · 2015: 47 · 2014: 42 · 2013: 48 · 2012: 23
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Regione Piemonte
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, NAFLD treatment, lifestyle intervention, weight loss, thiazolidinediones, pioglitazone, metformin, antioxidants, vitamin E, statins, polyunsaturated fatty acids, glucose metabolism, cardiovascular risk, insulin resistance, liver fibrosis, steatosis, liver histopathology
- MeSH terms
- Cardiovascular Diseases, Fatty Liver, Glucose, Humans, Liver Diseases, Risk, Randomized Controlled Trials as Topic
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