IMPORTANCE Nonalcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide and is associated with obesity. Weight loss may improve biomarkers of liver disease, but its implications have not been systematically reviewed and quantified. OBJECTIVE To estimate the association of weight loss interventions with biomarkers of liver disease in NAFLD. DATA SOURCES MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and Web of Science databases along with 3 trial registries were searched from inception through January 2019. STUDY SELECTION Randomized clinical trials of people with NAFLD were included if they compared any intervention aiming to reduce weight (behavioral weight loss programs [BWLPs], pharmacotherapy, and surgical procedures) with no or lower-intensity weight loss intervention. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. DATA EXTRACTION AND SYNTHESIS Two independent reviewers screened the studies, extracted the data, and assessed the risk of bias using the Cochrane tool. Pooled mean differences or odds ratios (ORs) were obtained from random-effects meta-analyses. MAIN OUTCOMES AND MEASURES Blood, radiologic, and histologic biomarkers of liver disease. RESULTS Twenty-two studies with 2588 participants (with a mean [SD] age of 45 [14] years and with approximately 66% male) were included. Fifteen studies tested BWLPs, 6 tested pharmacotherapy, and 1 tested a surgical procedure. The median (interquartile range) intervention duration was 6 (3-8) months. Compared with no or lower-intensity weight loss interventions, more-intensive weight loss interventions were statistically significantly associated with greater weight change (-3.61 kg; 95% CI,-5.11 to-2.12; I 2 = 95%). Weight loss interventions were statistically significantly associated with improvements in biomarkers, including alanine aminotransferase (-9.81 U/L; 95% CI,-13.12 to-6.50; I 2 = 97%), histologically or radiologically measured liver steatosis (standardized mean difference:-1.48; 95% CI,-2.27 to-0.70; I 2 = 94%), histologic NAFLD activity score (-0.92; 95% CI,-1.75 to-0.09; I 2 = 95%), and presence of nonalcoholic steatohepatitis (OR, 0.14; 95% CI, 0.04-0.49; I 2 = 0%). No statistically significant change in histologic liver fibrosis was found (-0.13; 95% CI,-0.54 to 0.27; I 2 = 68%). Twelve studies were at high risk of bias in at least 1 domain. In a sensitivity analysis of the 3 trials at low risk of bias, the estimates and precision of most outcomes did not materially change. CONCLUSIONS AND RELEVANCE The trials, despite some heterogeneity, consistently showed evidence of the association between weight loss interventions and improved biomarkers of liver disease in NAFLD in the short to medium term, although evidence on long-term health outcomes was limited. These findings appear to support the need to change the clinical guidelines and to recommend formal weight loss programs for people with NAFLD.

BackgroundSystematic reviews suggest school-based mindfulness training (SBMT) shows promise in promoting student mental health.ObjectiveThe My Resilience in Adolescence (MYRIAD) Trial evaluated the effectiveness and cost-effectiveness of SBMT compared with teaching-as-usual (TAU).MethodsMYRIAD was a parallel group, cluster-randomised controlled trial. Eighty-five eligible schools consented and were randomised 1:1 to TAU (43 schools, 4232 students) or SBMT (42 schools, 4144 students), stratified by school size, quality, type, deprivation and region. Schools and students (mean (SD); age range=12.2 (0.6); 11–14 years) were broadly UK population-representative. Forty-three schools (n=3678 pupils; 86.9%) delivering SBMT, and 41 schools (n=3572; 86.2%) delivering TAU, provided primary end-point data. SBMT comprised 10 lessons of psychoeducation and mindfulness practices. TAU comprised standard social-emotional teaching. Participant-level risk for depression, social-emotional-behavioural functioning and well-being at 1 year follow-up were the co-primary outcomes. Secondary and economic outcomes were included.FindingsAnalysis of 84 schools (n=8376 participants) found no evidence that SBMT was superior to TAU at 1 year. Standardised mean differences (intervention minus control) were: 0.005 (95% CI −0.05 to 0.06) for risk for depression; 0.02 (−0.02 to 0.07) for social-emotional-behavioural functioning; and 0.02 (−0.03 to 0.07) for well-being. SBMT had a high probability of cost-effectiveness (83%) at a willingness-to-pay threshold of £20 000 per quality-adjusted life year. No intervention-related adverse events were observed.ConclusionsFindings do not support the superiority of SBMT over TAU in promoting mental health in adolescence.Clinical implicationsThere is need to ask what works, for whom and how, as well as considering key contextual and implementation factors.Trial registrationCurrent controlled trials ISRCTN86619085. This research was funded by the Wellcome Trust (WT104908/Z/14/Z and WT107496/Z/15/Z).

BackgroundPreventing mental health problems in early adolescence is a priority. School-based mindfulness training (SBMT) is an approach with mixed evidence.ObjectivesTo explore for whom SBMT does/does not work and what influences outcomes.MethodsThe My Resilience in Adolescence was a parallel-group, cluster randomised controlled trial (K=84 secondary schools; n=8376 students, age: 11–13) recruiting schools that provided standard social–emotional learning. Schools were randomised 1:1 to continue this provision (control/teaching as usual (TAU)), and/or to offer SBMT (‘.b’ (intervention)). Risk of depression, social–emotional–behavioural functioning and well-being were measured at baseline, preintervention, post intervention and 1 year follow-up. Hypothesised moderators, implementation factors and mediators were analysed using mixed effects linear regressions, instrumental variable methods and path analysis.FindingsSBMT versus TAU resulted in worse scores on risk of depression and well-being in students at risk of mental health problems both at post intervention and 1-year follow-up, but differences were small and not clinically relevant. Higher dose and reach were associated with worse social–emotional–behavioural functioning at postintervention. No implementation factors were associated with outcomes at 1-year follow-up. Pregains−postgains in mindfulness skills and executive function predicted better outcomes at 1-year follow-up, but the SBMT was unsuccessful to teach these skills with clinical relevance.SBMT as delivered in this trial is not indicated as a universal intervention. Moreover, it may be contraindicated for students with existing/emerging mental health symptoms.Clinical implicationsUniversal SBMT is not recommended in this format in early adolescence. Future research should explore social−emotional learning programmes adapted to the unique needs of young people.