Effects of Weight Loss on Portal Pressure in Patients With Overweight/Obesity and Cirrhosis
Condition: Compensated Cirrhosis; Obesity
MeSH terms: Liver Cirrhosis; Obesity; Overweight; Weight Loss; Fibrosis
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Diet + exercise
Intervention type(s): Behavioral
Intervention description(s): Program of dietary counselling by dietists, who will periodically follow-up the patient to achieve weight loss; moreover a fitness professional will instruct and train the patients twice a week to enhance their physical activity. A step counter will be also given to all participants and daily step count will be recorded. The duration of diet+exercise is 4 months from baseline HVPG measurement.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Obesity; Portal hypertension; Cirrhosis; Diet; Exercise