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Impact of Weight Loss in Cirrhosis With Obesity and MAFLD

Not Applicable
Recruiting
Conditions
Obesity
Liver Cirrhosis
Interventions
Other: Weight loss
Registration Number
NCT05104541
Lead Sponsor
Institute of Liver and Biliary Sciences, India
Brief Summary

Nutrition therapy is the cornerstone of medical therapy in patients with cirrhosis. 70% compensated patients with Chronic Liver Disease (CLD) are overweight or obese. Obesity in CLD augments decompensation, plausibly through increase in portal pressure. Moreover, the cardiometabolic risk factors are increased with increase in body weight, obesity also has an impact on the already compromised health-related quality of life of patients with CLD. Most feasible, safe, and widely used method of management of obesity is life-style modifications. Hypocaloric with normal to high protein diet along with moderate-intensity exercises have been practiced for weight reduction.

These kinds of dietary changes reduce body weight and may bring about favourable changes in the body composition (reduce the body fat percentage but at the same time preserving the lean body mass). Weight loss in obese patients with CLD would in turn improve the clinical outcome, reduce the hepatic complications, moreover weight loss may also improve health related quality of life, and other prognostic markers of the disease like fibroscan along with improvement in the associated metabolic derangements in patients with CLD. There is no Indian data in this context. Thus, through this trial, investigator would be able to ascertain an appropriate lifestyle-related non- intervention regimen that helps in the management of obesity in patients with cirrhosis. Not only that the baseline information of these obese patients with CLD would give us an idea or the profile of the body composition in terms of muscularity, adiposity, sarcopenic obesity (if any), of these patients with CLD.

Detailed Description

Liver disease is one of the main causes of hospital admissions worldwide and the 12th leading cause of mortality in many countries. Among all etiologies (toxic-metabolites, viral, autoimmune, and genetic disorders), nonalcoholic fatty liver disease (NAFLD) features as the most common cause, with increasing prevalence attributed to the epidemic of metabolic syndrome. According to the World Health Organization, in 2014, more than 30% of the United States population were obese and more than 60% overweight. Furthermore, 15% of all Western population and 35% of patients with obesity will develop steatohepatitis (NASH). Hence world over obesity is on a rise, the prevalence of obesity has consistently risen since past four decades in both genders. Indian similar scenario is seen not only in the urban but also in the rural population. This pandemic disease is attributed to both the increased amounts of processed foods high in fructose, sodium, and saturated fats, and the increasingly sedentary lifestyle. Obesity is considered a chronic state of low-grade inflammation, being associated with complications such as metabolic syndrome, type 2 diabetes, hypertension, and cardiovascular disease. It has also been linked with increased risks of certain cancers, such as colon, breast, breast, endometrium, kidney, esophagus, stomach, pancreas, and gallbladder. The combination of obesity, insulin resistance, and NASH is also thought to increase the risk of Hepatocellular Carcinoma (HCC). Most of all obesity in cirrhotics accelerates decompensation plausibly through an increase in portal hypertension. The risk of first clinical decompensation of cirrhosis is approximately three times higher in obese cirrhotics compared to those with normal weight. There are innumerable randomized controlled trials examining the role of various kinds of weight-loss diets and regimens in NAFLD patients, namely Mediterranean diets, Ornish diets, south beach diets, Atkins diets, Zone diet, weight watcher's diets, etc. However, once cirrhosis sets in or is diagnosed the concept of malnutrition akin to undernutrition is the prime consideration in a patient which baffles the physicians. The nutritional guidelines either European Society of Parenteral and Enteral Nutrition (ESPEN) or American Society of Parenteral and Enteral Nutrition (ASPEN) have always focused on a high calorie and a high protein diet in cirrhosis. These guidelines have not even touched upon the topic of obesity in cirrhosis. Moreover, for decades, investigator have been obsessed with the idea of protein restriction in patients with cirrhosis. In the recent past, our attention is drawn towards the other end of the spectrum of malnutrition i.e. obesity, which has been steadily on the rise world over and cirrhotics are no exception. Obesity is associated with poor survival, severe hepatic decompensation, poor post-transplantation outcomes as well as greater difficulty in liver transplantation, and also higher non-response to antiviral therapy in patients with cirrhosis. Hence weight reduction is the standard of care in such patients. A few studies have examined the role of a monitored exercise program including resistance training including cycle ergometric exercises have been shown to favorably change the body composition but none have been done in obese cirrhotics with the aim of weight loss. At the same time, low-calorie and even very-low-calorie ketogenic diets have been tried in obese cirrhosis and published as case series. Based on the magnitude of the problem of obesity in CLD and its detrimental impact on the clinical outcome investigator propose to assess the impact of weight loss with low calorie, high protein diet and moderate physical activity (lifestyle modifications- a non-pharmacological strategy) on liver fibrosis, body composition changes, functional capacity, clinical outcome in obese cirrhotics in this study.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
96
Inclusion Criteria
  • Adult patients between 18 and 65 years.
  • Obese cirrhotics of any etiology.
  • BMI > 30
Exclusion Criteria
  • Patients with oChild B (8,9) and C oMELD>20

    • High-risk varices
    • HPS/ pleural effusion
    • Alcoholic Hepatitis
    • Chronic Kidney Disease, cardiac, neurological diseases
    • HCC
    • Pregnancy
    • Unwilling patients

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Intervention ArmWeight lossIn addition to standard pharmacological treatment this group would receive diet comprising of 20-25 kcal and 1.2gm protein per kg ideal body weight per day. The total distribution of the calories would be as 55-60% from carbohydrates, 25% from protein, and 20% from fat. The diet would be explained to the patient with the help of individual diet charts.
Primary Outcome Measures
NameTimeMethod
Number of Patients with change in liver fibrosis with 10% weight loss in 3 months in an obese patient with CLD.3 months
Secondary Outcome Measures
NameTimeMethod
Effect of weight loss (10%) in three months on Insulin resistance (HOMA- IR)3 months

Insulin resistance will be measured at baseline and at 3 months

Effect of weight loss (10%) in three months on blood sugar levels as a component of metabolic syndrome3 months

Blood sugar levels will be noted at baseline and at 3 months

Effect of weight loss (10%) in three months on metabolic syndrome3 months

Components of metabolic syndrome will be noted at baseline and at 3 months

Effect of weight loss (10%) in three months on anthropometric mid arm muscle circumference (MAMC)3 months

Mid amr muscle circumference (MAMC) will be measured at baseline and at the end of three months

Effect of weight loss (10%) in three months on anthropocentric tricep fold thickness (TSF)3 months

Tricep fold thickness (TSF) will be measured at baseline and at the end of three months

Effect of weight loss (10%) in three months on Pro inflammatory marker -IL-63 months

Pro inflammatory marker will be noted at baseline and at 3 months

Effect of weight loss (10%) in three months on anthropometric Mid upper arm circumference (MUAC)3 months

Mid upper arm circumference (MUAC) will be measured at baseline and at the end of three months

Effect of weight loss (10%) in three months on Triglyceride levels3 months

Triglyceride levels will be measured at baseline and at 3 months

Effect of weight loss (10%) in three months on central obesity as a component of metabolic syndrome3 months

Central obesity will be noted at baseline and at 3 months

Effect of weight loss (10%) in three months on high density lipoprotein (HDL) as a component of metabolic syndrome3 months

High density lipoprotein (HDL)metabolic syndrome will be noted at baseline and at 3 months

Effect of weight loss (10%) in three months on body composition- bio electrical impedance3 months

Body composition by bioelectrical impedance will be measured at baseline and at the end of three months

Effect of weight loss (10%) in three months on Anti inflammatory marker -Adiponectin3 months

Anti inflammatory marker (Adiponectin) will be noted at baseline and at 3 months

Effect of weight loss (10%) in three months on Pro inflammatory marker- (Tumor Necrosis Factor) TNF-alpha3 months

Pro inflammatory marker will be noted at baseline and at 3 months

Effect of weight loss (10%) in three months on functional capacity3 months

Functional capacity will be measured by hand grip dyanamometer at baseline and at the end of three months

Trial Locations

Locations (1)

Institute of Liver and Biliary Sciences

🇮🇳

New Delhi, Delhi, India

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