Abstract/Text
BACKGROUND. NAFLD ranges from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). The natural history of NAFLD and the optimal strategy to identify subjects with progressive liver disease are unclear. Objectives. To assess the evidence in: (1) natural history of NAFLD; and (2) non-invasive methods to differentiate NAFLD histological subtypes. DESIGN AND SETTING. Among 4185 articles published on MEDLINE, Cochrane Library, EMBASE, Pubmed, national and International meeting abstracts through July 2010, 40 articles assessing the natural history of NAFLD and 32 articles evaluating the diagnostic accuracy of non-invasive tests against liver biopsy (LB) were included. MEASUREMENTS. Two reviewers retrieved articles and evaluated study quality by appropriate scores. Main outcomes were pooled using random- or fixed-effects models. RESULTS. NAFLD has an increased overall mortality (OR: 1.57, 95% CI: 1.18-2.10), deriving from liver-related and cardiovascular disease, and a 2-fold risk of diabetes. Compared to SS, NASH has a higher liver-related (OR for NASH: 5.71, 2.31-14.13; OR for NASH with advanced fibrosis: 10.06, 4.35-23.25), but not cardiovascular mortality (OR: 0.91, 0.42-1.98). Three non-invasive methods received independent validation: pooled AUROC, sensitivity and specificity of cytokeratin-18 for NASH are 0.82 (0.78-0.88), 0.78 (0.64-0.92), 0.87 (0.77-0.98). For NASH with advanced fibrosis, pooled AUROC, sensitivity and specificity of NAFLD fibrosis score and Fibroscan are 0.85 (0.80-0.93), 0.90 (0.82-0.99), 0.97 (0.94-0.99) and 0.94 (0.90-0.99), 0.94 (0.88-0.99) and 0.95 (0.89-0.99). CONCLUSIONS. NAFLD warrants screening for cardio-metabolic risk and for progressive liver disease. The combination of three noninvasive tests with LB may optimally individuate patients with NASH, with or without advanced fibrosis.
F M Finucane, S J Sharp, L R Purslow, K Horton, J Horton, D B Savage, S Brage, H Besson, E De Lucia Rolfe, A Sleigh, H J Martin, A Aihie Sayer, C Cooper, U Ekelund, S J Griffin, N J Wareham
The effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial.
Diabetologia. 2010 Apr;53(4):624-31. doi: 10.1007/s00125-009-1641-z. Epub 2010 Jan 6.
Abstract/Text
AIMS/HYPOTHESIS: We sought to determine the effect of an aerobic exercise intervention on clustered metabolic risk and related outcomes in healthy older adults in a single-centre, explanatory randomised controlled trial.
METHODS: Participants from the Hertfordshire Cohort Study (born 1931-1939) were randomly assigned to 36 supervised 1 h sessions on a cycle ergometer over 12 weeks or to a non-intervention control group. Randomisation and group allocation were conducted by the study co-ordinator, using a software programme. Those with prevalent diabetes, unstable ischaemic heart disease or poor mobility were excluded. All data were collected at our clinical research facility in Cambridge. Components of the metabolic syndrome were used to derive a standardised composite metabolic risk score (zMS) as the primary outcome. Trial status: closed to follow-up.
RESULTS: We randomised 100 participants (50 to the intervention, 50 to the control group). Mean age was 71.4 (range 67.4-76.3) years. Overall, 96% of participants attended for follow-up measures. There were no serious adverse events. Using an intention-to-treat analysis, we saw a non-significant reduction in zMS in the exercise group compared with controls (0.07 [95% CI -0.03, 0.17], p = 0.19). However, the exercise group had significantly decreased weight, waist circumference and intrahepatic lipid, with increased aerobic fitness and a 68% reduction in prevalence of abnormal glucose metabolism (OR 0.32 [95% CI 0.11-0.92], p = 0.035) compared with controls. Results were similar in per-protocol analyses.
CONCLUSIONS/INTERPRETATION: Enrolment in a supervised aerobic exercise intervention led to weight loss, increased fitness and improvements in some but not all metabolic outcomes. In appropriately screened older individuals, such interventions appear to be safe.
TRIAL REGISTRATION: Controlled-trials.com ISRCTN60986572
FUNDING: Medical Research Council.
Abstract/Text
BACKGROUND AND AIM: Non-alcoholic fatty liver disease associated with insulin resistance is the most common cause of abnormal liver tests in clinical practice. To date, practical and effective strategies to improve the metabolic profile of this large group of patients have not been well characterised. We sought to assess the effect at 3 months of a behavior change-based lifestyle intervention on the metabolic profile of patients characterised by elevated liver enzymes.
METHODS: A total of 152 patients with elevated liver enzymes, central obesity and a range of metabolic risk factors were randomised to either a moderate- (6 sessions/10 weeks) or low-intensity (3 sessions/4 weeks) lifestyle counselling intervention or control group.
RESULTS: There was improvement in all metabolic risk factors in the moderate-intensity group, versus a smaller number of changes in the low-intensity intervention group and no change in any metabolic risk factors in control subjects. Reduction in liver enzymes was greatest in the moderate-intensity intervention group and least in the control group. The likelihood of elevated alanine aminotransferase (ALT) levels in both the moderate and low-intensity groups was reduced by over 70% compared to controls. The proportion of subjects achieving weight loss (>or= 2%) was significantly higher in the moderate-intensity intervention group (66%) versus the low-intensity intervention group (39%; P < 0.05) and controls (29%; P < 0.001).
CONCLUSIONS: Moderate and even low-intensity lifestyle counselling interventions targeting improvement in physical activity and nutritional behaviors and modest weight loss are a practical and effective method for improving the health of patients with elevated liver enzymes and a range of metabolic risk factors.
Abstract/Text
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming a wide spread liver disease. The present recommendations for treatment are not evidence-based. Some of them are various weight reduction measures with diet, exercise, drug, or surgical therapy.
OBJECTIVES: To assess the benefits and harms of intended weight reduction for patients with NAFLD.
SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, PubMed, EMBASE, Science Citation Index Expanded, Chinese Biomedicine Database, and ClinicalTrials.gov until February 2011.
SELECTION CRITERIA: We included randomised clinical trials evaluating weight reduction with different measures versus no intervention or placebo in NAFLD patients.
DATA COLLECTION AND ANALYSIS: We extracted data independently. We calculated the odds ratio (OR) for dichotomous data and calculated the mean difference (MD) for continuous data, both with 95% confidence intervals (CI).
MAIN RESULTS: The review includes seven trials; five on aspects of lifestyle changes (eg, diet, physical exercise) and two on treatment with a weight reduction drug 'orlistat'. In total, 373 participants were enrolled, and the duration of the trials ranged from 1 month to 1 year. Only one trial on lifestyle programme was judged to be of low risk of bias. We could not perform meta-analyses for the main outcomes as they were either not reported or there were insufficient number of trials for each outcome to be meta-analysed. We could meta-analyse the available data for body weight and body mass index only. Adverse events were poorly reported.
AUTHORS' CONCLUSIONS: The sparse data and high risk of bias preclude us from drawing any definite conclusion on lifestyle programme or orlistat for treatment of NAFLD. Further randomised clinical trials with low risk of bias are needed to test the beneficial and harmful effects of weight reduction for NAFLD patients. The long-term prognosis of development of fibrosis, mortality, and quality of life should be studied.
Abstract/Text
BACKGROUND & AIMS: Weight loss in overweight or obese individuals results in marked improvement or resolution of hypertension, diabetes mellitus, and hyperlipidemia. However, the overall effect of weight loss on nonalcoholic fatty liver disease (NAFLD) remains unclear. This systematic review and meta-analysis is an effort to explore the effect of weight loss after bariatric surgical procedures on NAFLD.
METHODS: We performed an electronic literature search of published articles on bariatric surgery and liver histology since inception to September of 2007. Primary outcome measures were improvement and/or resolution in the 3 components of NAFLD (steatosis, steatohepatitis, and fibrosis) after bariatric surgery-induced weight loss. A pooled proportion of patients with improvement or resolution was calculated for steatosis, steatohepatitis, and fibrosis using a random effects model. Heterogeneity among the studies was assessed using the I(2) (inconsistency) statistic and subgroup analyses.
RESULTS: A total of 15 studies (766 paired liver biopsies) were selected for final data extraction. The percentage reduction in mean body mass index after bariatric surgeries ranged from 19.11 to 41.76. The pooled proportion of patients with improvement or resolution in steatosis was 91.6% (95% confidence interval [CI], 82.4%-97.6%), in steatohepatitis was 81.3% (95% CI, 61.9%-94.9%), in fibrosis was 65.5% (95% CI, 38.2%-88.1%), and for complete resolution of nonalcoholic steatohepatitis was 69.5 (95% CI, 42.4%-90.8%).
CONCLUSIONS: Steatosis, steatohepatitis, and fibrosis appear to improve or completely resolve in the majority of patients after bariatric surgery-induced weight loss.
