BACKGROUND.The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post-liver transplant (LT) remain poorly ...characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT.
METHODS.MEDLINE via PubMed, Embase, Scopus, and CINAHL were searched for studies from 2000 to 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale.
RESULTS.Seventeen studies representing 2378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of 2 studies that used imaging for outcome assessment. Seven studies evaluated occurrence of recurrent NAFLD/NASH, 3 evaluated de novo occurrence, and 7 evaluated both recurrent and de novo. In studies at generally high or moderate risk of bias, mean 1-, 3-, and ≥5-year incidence rates may be 59%, 57%, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; 53%, 57.4%, and 38% for recurrent NASH; and 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT body mass index (summarized odds ratio = 1.27) and hyperlipidemia were the most consistent predictors of outcomes.
CONCLUSIONS.There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, whereas de novo NASH occurs rarely. NAFLD/NASH after LT is associated with metabolic risk factors.
Metabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH ...is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the cornerstone of therapy. Real-world efficacy and sustainability of lifestyle interventions are low, however. Pharmacotherapy development for MASH is emerging with promising data from several agents with different mechanisms of action (MOAs) in phase 3 clinical trials. In this review, we highlight ongoing challenges and potential solutions in drug development for MASH and provide an overview of available data from emerging therapies across multiple MOAs.
Metabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide. In this review, Tincopa et al. highlight challenges and potential solutions in drug development for MASH. They cover current advances in pharmacotherapy for MASH, presenting promising data from several agents in the pipeline.
Introduction
In the setting of the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent forms of chronic liver disease worldwide. Approximately 25% of ...adults globally have NAFLD which includes those with NAFL, or simple steatosis, and individuals with nonalcoholic steatohepatitis (NASH) where inflammation, hepatocyte injury and potentially hepatic fibrosis are found in conjunction with steatosis. Individuals with NASH, particularly those with hepatic fibrosis, have higher rates of liver‐related and overall mortality, making this distinction of significant clinical importance. One of the core challenges in current clinical practice is identifying this subset of individuals with NASH without the use of liver biopsy, the gold standard for both diagnostics and staging disease severity. Identifying noninvasive biomarkers, an accurately measured and reproducible parameter, would aide in identifying patients eligible for NASH pharmacotherapy clinical trials and to help tailor intensity of monitoring required.
Methods, Results and Conclusions
In this review, we highlight both the currently available and novel diagnostic and interventional circulating biomarkers under investigation for NASH, underscoring their accuracy and limitations relevant to our patient population and current clinical practice.
One of the core challenges in NASH is the ability to accurately diagnose and stage individuals using non‐invasive methods. In this review, we highlight both the currently available and novel diagnostic and interventional circulating biomarkers under investigation for NASH, underscoring their accuracy and limitations relevant to our patient population and current clinical practice.
Identifying effective, feasible, low-cost interventions that promote sustainable lifestyle changes in nonalcoholic fatty liver disease (NAFLD) is a key unmet need. The aim of this study was to assess ...predictors of lifestyle practice patterns of NAFLD patients and evaluate the implementation of a mobile technology-based intervention. We prospectively enrolled adults with NAFLD (diagnosed by imaging or biopsy). Individuals with additional liver diseases or decompensated cirrhosis were excluded. Patient were randomized to usual care or a FitBit based program for 6-months. We obtained anthropometrics, labs, vibration controlled transient elastography (VCTE), health-related quality of life (HRQOL), physical activity, diet and motivation to change data. 70 patients were enrolled, 33% with cirrhosis. Median age was 52.1 years, 47% males, 83% white, body mass index 32.3, liver stiffness 7.6 kPa, controlled attenuation parameter 319 db/m, and 50% had diabetes. Baseline HRQOL was 5.4/7 and independently negatively correlated with level of concern about their disease and positively with physical function. Younger age was independently associated with unhealthy diets whereas diabetes was independently associated with unhealthy diets and higher VCTE kPa. 6-month follow-up data available on 31 patients showed trends in improvement in weight. In a cohort of NAFLD patients, we identified independent correlates of lifestyle behaviors and HRQOL. Implementation of interventions that improve physical function may improve HRQOL in NAFLD. Younger patients and those with diabetes appeared to have the greatest need for dietary interventions. Structured mobile technology lifestyle interventions using Fitbit and personalized coaching showed promise but require further validation with a focus on sustainability of intervention and improvement in outcomes.
Insulin resistance and altered energy metabolism is common in non-alcoholic fatty liver disease (NAFLD) and appears to also be associated with myocardial dysfunction. We aimed to evaluate prevalence, ...staging and clinical features correlated with NAFLD among patients with heart failure with preserved ejection fraction (HFpEF). Adults with HFpEF were prospectively enrolled. Demographic and clinical data were collected. NAFLD was defined based on liver biopsy, abdominal imaging or ICD-coding and the absence of other liver diseases. Descriptive, bivariate and multivariable analyses were performed. 181 patients were analyzed. The median age was 70 with 89% white, 59% female, median BMI 35.1, and 48% with diabetes. NAFLD was present in 27% of the full cohort and 50% of those with imaging. In patients with imaging, multivariable analysis identified diabetes (OR 3.38, 95% CI 1.29-8.88) and BMI (OR 1.11, 95% CI 1.04-1.19) as independent correlates of NAFLD. 54% of NAFLD patients had a NAFLD fibrosis score consistent with advanced fibrosis. Cirrhosis was present in 6.6% of patients overall and 11.5% with imaging. NAFLD patients had a higher frequency of advanced heart failure (75% vs 55%, p 0.01). NAFLD has a two-fold higher prevalence in HFpEF compared to the general population and is independently associated with BMI and diabetes. Patients with HFpEF and NAFLD also appeared to have more advanced fibrosis including cirrhosis suggesting a potential synergistic effect of cardiac dysfunction on fibrosis risk in NAFLD. This data supports consideration for evaluation of underlying liver disease in HFpEF patients.
Background
Lifestyle modification is currently the only treatment for nonalcoholic fatty liver disease (NAFLD). The most effective way to motivate behavior change in this population is not well ...understood.
Aims
The aims of this study were to characterize the association between patient disease knowledge, attitudes, and behaviors and to determine the impact of an educational intervention.
Methods
Adults with NAFLD had the following assessed before and after an educational intervention: (1) disease knowledge; (2) health-related quality of life (HRQOL); (3) physical activity; (4) diet; (5) stages of change; and (6) clinical variables.
Results
Median age of the cohort (
N
= 248) was 53.5, 46% were male, 85% were white, and median body mass index was 33.9. Forty-eight percentage had nonalcoholic steatohepatitis, and 28% had cirrhosis. The median correct knowledge score was 73.6%, median Chronic Liver Disease Questionnaire-NAFLD was 5.2/7, and diet score was 7/16 (higher indicating unhealthy diets). The cohort was sedentary at baseline, with 46% and 60% in active phases of change for nutrition and physical activity, respectively. Fifty-six (22%) had all three high-risk behaviors (sedentary, poor diet scores, low stage of change), which was independently associated with depression. The educational intervention improved diet scores, HRQOL, stages of change, and weight.
Conclusions
Despite good disease knowledge, NAFLD participants were sedentary and 1/4 had high-risk lifestyle behaviors. An educational intervention had positive impacts on clinical outcomes, though effect size was small. Pairing educational interventions with targeted interventions to motivate behavior change can improve care for patients with NAFLD.
Background and Aims
Lifestyle modification is the main treatment for nonalcoholic fatty liver disease (NAFLD), but remains challenging to implement. The aim of this pilot was to assess the ...acceptability and feasibility of a mobile-technology based lifestyle program for NAFLD patients.
Methods
We enrolled adult patients with NAFLD in a 6-month mobile-technology based program where participants received a FitBit with weekly tailored step count goals and nutritional assessments. Anthropometrics, hepatic and metabolic parameters, Fibroscan, physical function and activity, and health-related quality of life measures were obtained at enrollment and month 6. Semi-structured exit interviews were conducted to assess patient’s experience with the program.
Results
40 (63%) eligible patients were enrolled. Median age was 52.5 with 53% males, 93% whites, 43% with diabetes and median BMI 33.9. On baseline Fibroscan, 59% had F0-2 fibrosis and 70% had moderate-severe steatosis. 33 patients completed the study. Median percentage of days with valid FitBit data collection was 91. 4 patients increased and maintained, 19 maintained, and 8 increased but subsequently returned to baseline weekly step count. 59% of patients reported Fitbit was easy to use and 66% felt step count feedback motivated them to increase their activity. Roughly 50% of patients had reduction in weight, triglycerides and Fibroscan liver stiffness, and 75% had improvement in controlled attenuation parameter and physical function.
Conclusions
A 6-month mobile-technology based pilot lifestyle intervention was feasible and acceptable to NAFLD patients. The program promoted physical activity and was associated with improvement in clinical parameters in some patients.
ObjectiveDespite clear evidence that weight loss via nutritional and physical activity changes improves histological outcomes in non-alcoholic fatty liver disease (NAFLD), many patients struggle to ...implement and maintain these health behaviour changes. The aim of this study was to characterise disease knowledge, attitudes and behaviours among persons with NAFLD and to identify the factors driving these health behaviours and perceptions.DesignWe conducted semistructured interviews among patients with NAFLD. We used purposeful sampling to enroll equivalent percentages based on age and sex, and enrolled approximately one-third of patients with cirrhosis to capture those perspectives. Interviews were conducted until thematic saturation was achieved. Transcripts were coded using NVivo software to identify themes and subthemes.ResultsA total of 29 patient interviews were completed. Ambiguity about the diagnosis and aetiology of their liver disease was a key theme, though the vast majority of patients were aware that weight loss via nutrition and exercise was the primary therapy. Most patients were asymptomatic, diagnosed incidentally, and reported low level of concern regarding their diagnosis. The primary barriers and facilitators to health behaviour change were the presence of social support, competing medical comorbidities and low motivation to change behaviours.ConclusionsAlthough patients are aware that lifestyle interventions are the primary therapy for NAFLD, there is a gap in knowledge about the condition. The presence of social support and competing medical comorbidities were the most consistent facilitators and barriers to lifestyle change. Tailoring treatment recommendations to provide relevant disease education, specific nutrition and exercise regimens, and personalised approaches based on specific individual barriers and facilitators will likely aid in uptake and maintenance of first-line therapy for NAFLD.
First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications.1,2 Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has ...been associated with improvement in hepatic inflammation and fibrosis.3 The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.
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