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