Liver Cirrhoses
Conditions
Keywords
Cirrhosis, Variceal Bleeding, Non-selective beta blocker, Intestinal Permeability, Gene expression, Bacterial translocation
Brief summary
This study seeks to investigate whether non-selective beta blocker treatment decreases intestinal permeability in cirrhotic patients by altering the expression of genes encoding intercellular junction proteins.
Detailed description
There is evidence that the non-selective beta-blocker (NSBB) propranolol reduces intestinal permeability and decreases bacterial translocation in cirrhotic patients, independent of hemodynamic effects on portal pressure. The mechanism by which this decrease in intestinal permeability and bacterial translocation occurs has not been established. Among the proposed mechanisms are: modification of splanchnic hemodynamics, increased gastrointestinal motility, and immunological properties of nonselective beta blockade. It is not known, however, if beta-blocker treatment decreases intestinal permeability by altering the expression of genes encoding intercellular junction proteins. This study seeks to investigate this question to improve understanding of the mechanism by which beta-blockers work in primary and secondary prophylaxis of variceal hemorrhage.
Interventions
DRUGPropanolol
Sponsors
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* \> 18 years * Diagnosis of cirrhosis of any etiology or severity as established by the treating physician (biopsy, biochemical, imaging) * High risk gastroesophageal varices, that is those with medium/large varices or any size varices with red wale signs * Scheduled appointment for endoscopic ligation as previously ordered by the treating physician * Signed informed consent * Ability to keep return appointments
Exclusion criteria
* Beta blocker treatment within 1 month prior to study period * Antibiotic treatment during or within 1 month prior to study period * Prebiotic or probiotic treatment during or within 1 month before study period * Current immunosuppressive treatment * Patients with active infectious process * Patients with portal thrombosis * Patients with hepatocellular carcinoma * Patients with intestinal surgical shunts * Patients with chronic diarrhea or documented celiac disease * Patients with chronic renal failure (KDOQI: ≤ 3) * Patients with allergy or absolute contraindication for the use of nonselective beta blockers (asthma, significant heart block, systolic BP \<90 mm Hg, basal HR \<55, refractory ascites)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intestinal permeability | Baseline and after 4 weeks of propranolol treatment | Evaluate and compare intestinal permeability using studies evaluating the absorption of three orally administered sugars (sucrose, mannitol and lactulose) in patients with cirrhosis before and after treatment with propranolol for 1 month. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expression of genes related to intestinal mucosal integrity | Baseline and after 4 weeks of propranolol treatment | Evaluate and compare the expression of mRNA of the genes for zona occludens 1 (ZO1), occludin, claudin-1 and 2 in gastric and duodenal mucosal tissue of patients with cirrhosis, before and after treatment with propranolol for 1 month. |
| Presence of intercellular junction proteins by immunohistochemistry | Baseline and after 4 weeks of propranolol treatment | Evaluate and compare the presence of intercellular junction proteins by immunohistochemistry in gastric and duodenal mucosa of patients with cirrhosis before and after treatment with propranolol for 1 month. |
| Serum inflammatory markers | Baseline and after 4 weeks of propranolol treatment | Compare serum proinflammatory cytokines and lipopolysaccharide levels in patients with cirrhosis before and after treatment with propranolol for 1 month. |
Countries
Mexico
Contacts
Primary ContactAldo Torre Delgadillo, MD
Backup ContactJonathan Manuel Aguirre Valadez, MD
Outcome results
None listed