Clinical trial NCT01409356: Effects of Weight Loss on Portal Pressure in Patients With Overweight/Obesity and Cirrhosis
Official title: Effects of Weight Loss on Portal Pressure in Patients With Compensated Cirrhosis and Overweight/Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Compensated Cirrhosis
Obesity
Keywords: Obesity
Portal hypertension
Cirrhosis
Diet
Exercise
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
Collaborators: name: Consorcio Centro de Investigación Biomédica en Red (CIBER)
First posted: 2011-08-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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:

Primary outcomes:
measure: HVPG change
timeFrame: 4 months
Secondary outcomes:
measure: Hepatic function
timeFrame: 4 months
measure: Serum markers of fibrosis, angiogenesis, endothelial dysfunction and oxidative stress
timeFrame: 4 months
measure: Body adiposity changes
timeFrame: 4 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: Universitario Ramón y Cajal
Study officials:
affiliation: Hospital Clinic and CIBERehd
name: Jaime Bosch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berzigotti A, Albillos A, Villanueva C, Genesca J, Ardevol A, Augustin S, Calleja JL, Banares R, Garcia-Pagan JC, Mesonero F, Bosch J; Ciberehd SportDiet Collaborative Group. Effects of an intensive lifestyle intervention program on portal hypertension in patients with cirrhosis and obesity: The SportDiet study. Hepatology. 2017 Apr;65(4):1293-1305. doi: 10.1002/hep.28992. Epub 2017 Mar 6.