Standardisation of diet and exercise in clinical trials of NAFLD-NASH: Recommendations from the Liver Forum.

Lifestyle modification is the foundation of treatment recommendations for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The design of clinical trials in NASH may be impeded by the lack of a systematic approach to identify and evaluate how lifestyle changes and/or modifications influence clinical trial outcomes and associated endpoints. Furthermore, there are additional uncertainties regarding the methods that can be utilised to better characterise and quantify lifestyle variables - which can influence disease activity and alter trial endpoints - to allow for comparisons of trial outcomes across different phases of research and/or within drug-classes. This summary by the Liver Forum's Standard of Care Working Group reviews currently available clinical data, identifies the barriers and challenges associated with the standard of care in NAFLD/NASH clinical trials, defines available assessments of lifestyle changes, and proposes approaches to better understand and define the influence of diet and exercise on NASH treatment in the context of different pharmacologic interventions. The ultimate objective is to propose tangible solutions which enable investigators, sponsors, and regulatory authorities to meaningfully interpret clinical trial outcomes and the impact of lifestyle modification on such outcomes as they pertain to phase I-IV clinical trials.

Effectiveness of two physical activity programs on non-alcoholic fatty liver disease. a randomized controlled clinical trial.

Introduction: To estimate the effectiveness of two physical activity programs on NAFLD. Methods: Participants come from a survey conducted in southern Italy. Subjects with moderate or severe NAFLD were invited to participate. After giving informed consent, they completed a questionnaire, underwent ultrasonography and anthropometric measurements. Then they were randomized an Aerobic or a Combined Exercise program and followed up for six months. The first group followed a program of moderate aerobic activity lasting 30 minutes, 5 days per week. The second group did aerobic training with the addition of muscle training involving the large muscle groups, stimulating them to make more intense efforts, for a duration of 60 minutes, at least, 3 days a week. Compliance with the programs was measured. A mixed linear model was applied to the data. Results: Compliance with Aerobic Exercise was homogeneous and increased over time. Combined Program compliance was equal to 100%. There was no significant difference in the NAFLD mean score by treatment at baseline and after six months. However, there was a significant reduction in the NAFLD mean score for treatments after six months. The NAFLD measured score was reduced by 22% in the Aerobic treatment group when confronted with the other program. In the Combined program, after 6 months, results showed to be less effective than the Aerobic Exercise in reducing the NAFLD score. Conclusion: An aerobic exercise program is a realistic intervention which could be included as a part of primary prevention of several chronic diseases.

Introducción: Estimar la eficiencia de dos programas de actividad física sobre la NAFLD Métodos: Sujetos con NAFLD moderada o severa que habían participado a un estudio de pobación en el sur de Italia fueron invitados a participar. Fue completado un cuestionario, se tomaron medidas antropométricas y se realizó una ecografia hepática. Cada participante proveyó el consenso informato. Los participantes fueron aleatorizados a un programa aerobico (actividad aerobica moderada per 30 minutos, 5 veces a la semana) o un programa mixto (aerobico más entrenamiento de la fuerza de los grandes grupos musculares, 60 minutos, tres veces a la semana). Fue medida la adherencia a los programas y se aplicó un modelo linear mixto a los datos. Resultados: El programa aerobico tuvo muy buena adherencia y esta aumentó con el tiempo mientras el programa mixto tuvo 100% de adherencia. No hubo diferencias estadísticamente significativas en el score de NAFLD al enrolamiento, mientras hubo diferencias estadísticamente significativas en el score medio de NAFLD después de 6 meses pero el score en el grupo del programa aerobico tuvo una reducción del 22% más intensa que el programa mixto. Este último programa por lo tanto se ha mostrado menos efectivo que el programa aerobico. Conclusión: Un programa de actividad física aerobica es un tratamiento realístico que podría ser efectuado no solo para la NAFLD sino también como prevención primaria de otras enfermedades crónicas.

Text messaging approach improves weight loss in patients with nonalcoholic fatty liver disease: A randomized study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease. The only effective treatment is 7%-10% weight loss. Mobile technology is increasingly used in weight management. This study was performed to evaluate the effects of text messaging intervention on weight loss in patients with NAFLD. METHODS: Thirty well-defined NAFLD patients (mean age 52 years, 67% females, mean BMI 38) were randomized 1:1 to control group: counselling on healthy diet and exercise, or intervention group: text messages in addition to healthy life style counselling. NAFLD text messaging program sent weekly messages for 22 weeks on healthy life style education. Primary outcome was change in weight. Secondary outcomes were changes in liver enzymes and lipid profile. RESULTS: Intervention group lost an average of 6.9 lbs. (P = .03) compared to gain of 1.8 lbs. in the control group (P = .45). Intervention group also showed a decrease in ALT level (-12.5 IU/L, P = .035) and improvement in serum triglycerides (-28 mg/dL, P = .048). There were no changes in the control group on serum ALT level (-6.1 IU/L, P = .46) and on serum triglycerides (-20.3 mg/dL P = .27). Using one-way analysis of variance, change in outcomes in intervention group compared to control group was significant for weight (P = .02) and BMI (P = .02). CONCLUSIONS: Text messaging on healthy life style is associated with reduction in weight in NAFLD patients. Larger studies are suggested to examine benefits on liver histology, and assess long-term impact of this approach in patients with NAFLD.

[The prospects for the application of the natural and preformed therapeutic factors in the treatment of non-alcoholic fatty liver disease]. / Perspektivy primeneniya prirodnykh i preformirovannykh lechebnykh faktorov v terapii bol'nykh nealkogol'noi zhirovoi bolezn'yu pecheni.

UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is one of the most widespread diffuse liver pathologies among the patients over 40 years of age. The available algorithms for the pharmacological treatment of this disease do not always ensure the desirable results which makes their further development and improvement with the use of natural and preformed physical factors an important priority. AIM: The objective of the present study was to evaluate the effectiveness of the internal course of mineral waters of different balneological types and a bischofite aqueous solution for the treatment of the patients presenting with NAFLD. PATIENTS AND METHODS: A total of 120 patients with non-alcoholic fatty liver disease were examined and treated with the use of the anamnestic, clinical, biochemical and immunochemical methods as well as sonographic studies of the digestive system and the statistical analysis. RESULTS: The data on the effectiveness of the use of mineral waters of different balneological types and a bischofite aqueous solution in the treatment of NAFLD are presented. It is shown that the use of an aqueous solution of bischofite improves the clinical course of the underlying disease (p<0.05), concomitant diseases of the biliary tract (p<0.02) and irritable bowl syndrome complicated by constipation (p<0.003); also, it improves the functional state of the liver and the blood lipid profile (p<0.02) and significantly reduces insulin resistance (p<0.01), primarily due to the reduction of hyperinsulinemia (p<0.01). Using the mineral waters with the predominance of sulfates can improve the clinical course of liver diseases (p<0.01), biliary tract and intestines (p<0.02), normalize the functional state of the liver including that in the patients with non-alcoholic steatohepatitis (p<0.05,) significantly improve the blood lipid profile (p<0.02) due to the substantial improvement of disordered carbohydrate metabolism including that in the patients suffering from type 2 diabetes mellitus (p<0.05). The application of mineral waters with the elevated content of hydrocarbons improves the clinical course of NAFLD with the concomitant esophagogastroduodenal pathology (p<0.001) and simultaneously reduces the severity of insulin resistance due to the lowering of the level of hyperinsulinemia (p<0.001). Moreover, the mineral water-based therapy improves tolerance to carbohydrates, in the first place in the patients with type 2 diabetes mellitus (p<0.01), and restores the background lipid profile (p<0.05). CONCLUSION: The studies has demonstrated the high efficiency of the non-pharmacological treatment resulting in the multifaceted and oppositely directional influence on the patients presenting with non-alcoholic fatty liver disease. The possibility of the differentiated application of mineral water and an aqueous solution of bischofite for the treatment of this pathology is confirmed depending on the stage of the disease, the severity of metabolic disorders, the presence of a concomitant pathology of the digestive system, type 2 diabetes mellitus, and hypertension.