Effects of Weight Loss on Portal Pressure in Patients With Overweight/Obesity and Cirrhosis

Phase 2

Completed

• Conditions: Compensated Cirrhosis; Obesity
• Interventions: Behavioral: Diet + exercise

• Registration Number: NCT01409356
• Lead Sponsor: Hospital Clinic of Barcelona

Brief Summary

Overweight/obesity is increasing both in the general population and in patients with cirrhosis. In compensated patients with cirrhosis increased BMI is a risk factor for clinical decompensation independent of liver function and portal pressure. Nonetheless, patients with cirrhosis and obesity show a progressive increase in portal pressure, which might explain their increased risk of complications. Since obesity is a potentially modifiable risk factor, we designed this proof-of-concept study to assess the effects of weight loss (obtained by 4 months of diet and exercise) on portal pressure in patients with compensated cirrhosis and overweight/obesity.

Detailed Description

Overweight and obesity markedly increase the risk of appearance and progression of most chronic diseases, including chronic liver diseases. In the general population obesity is constantly and dramatically raising, and represents a global epidemics. In a study including both European and American patients, our group reported that in patients with compensated cirrhosis overweight/obesity is very frequently observed (55% OW, 15% OB in Spanish patients; \> 50% OB in USA patients), being the figure similar to that of general population. Moreover, this study demonstrated that the increase in body mass index (BMI) is a risk factor for the development of decompensation of cirrhosis, independent of portal pressure and liver function (Berzigotti et al. Hepatology 2011). We also observed that included patients with cirrhosis and obesity showed a significant increase of portal pressure (estimated through hepatic venous pressure gradient measurement-HVPG), which was not found in OW or normal weight patients. This suggests that the mechanism inducing decompensation in obese patients with cirrhosis might be mediated by an increase in portal pressure, even if no data are available in this population to support this hypothesis. It is well known that in obesity the adipose tissue acquires a pro-inflammatory phenotype leading to increased release of IL-1, IL-6 and TNF-alfa and many other pro-fibrogenic cytokines and hormones, which might mediate also an increase in portal pressure.

Given these observation, and given the potential reversibility of OW/OB, we hypothesise that weight loss (obtained by diet and exercise) might effectively reduce the HVPG in patients with compensated cirrhosis and OW/OB, so reducing their risk to progression. We designed this proof-of-concept study to confirm this hypothesis.

Study Timeline

• Study First Submitted: 2011-08-03
• Study First Submitted QC: 2011-08-03
• Study First Posted: 2011-08-04
• Study Start: 2011-10
• Primary Completion: 2014-02
• Study Completion: 2014-12
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-17
• Last Update Posted: 2015-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Age: 18-75 years
• Compensated liver cirrhosis (diagnosed by biopsy or clear clinical, laboratory and imaging data), of any etiology; patients who presented decompensation due to gastroesophageal variceal hemorrhage can also be included if hemorrhage a) occurred > 3 months before inclusion AND b) has been treated with drugs+band ligation AND c) no other decompensations occurred simultaneously.
• HVPG > 5 mmHg
• BMI > 26 Kg/m2
• Absence of gastroesophageal varices or small esophageal varices OR large varices only if the patient is already on treatment with beta-blockers since at least 6 weeks.
• In case of presence of systemic arterial hypertension and/or diabetes, patients can be included if the treatment of these condition is stable for at least 3 months

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diet+Exercise	Diet + exercise	Program of weight loss through diet+exercise (=intervention)

Primary Outcome Measures

Name	Time	Method
HVPG change	4 months	The effects of weight loss on portal pressure will be assessed by measuring the HVPG at baseline and after 4 months of diet+exercise in the included patients.

Secondary Outcome Measures

Name	Time	Method
Hepatic function	4 months	The effects of weight loss on liver function will be estimated by assessing standard liver tests and indocyanine green clearance at baseline and after 4 months of diet+exercise
Serum markers of fibrosis, angiogenesis, endothelial dysfunction and oxidative stress	4 months	The effects of weight loss on Serum markers of fibrosis, angiogenesis, endothelial dysfunction and oxidative stress will be assessed by extracting adequate blood samples at baseline and after 4 months of diet+exercise
Body adiposity changes	4 months	Changes in BMI and body fat% will be assessed by measuring body weight and % of fat at baseline and after 4 months of diet + exercise.

Trial Locations

Locations (6)

Hospital Clinic; 🇪🇸 Barcelona, Spain

Hospital Vall D'Hebron; 🇪🇸 Barcelona, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Puerta de Hierro; 🇪🇸 Madrid, Spain

Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain