Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Double-Blind Study of Timolol (A Nonselective Beta-Adrenergic Blocker) vs Placebo to Prevent Complications of Hepatic Portal Hypertension in Patients With Cirrhosis
Brief Summary: The purpose of this study is to learn whether timolol is useful in preventing or delaying the appearance of gastroesophageal varices, a complication that may develop in the future as a consequence of liver disease. Cirrhosis causes an increased resistance of blood flowing through the liver. This leads to an increased pressure in the portal vein (the vein that takes blood to your liver). High portal pressure is responsible for the appearance of complications of chronic liver disease such as varices and variceal bleeding (bleeding from veins in your esophagus). Timolol belongs to a group of medications called beta-blockers. Beta-blockers decrease high portal pressure and previous studies have shown that beta-blocker pills are useful in preventing bleeding from varices in patients who already have varices. A more desirable effect would be if these pills could prevent not only bleeding from varices but the appearance of varices (and therefore of bleeding).


Options:
A: Inclusion Criteria:

* Patients with Non Cirrhotic Portal Hypertension (NCPH) presenting to our Liver Diseases Follow-up Clinic with history of hemetemesis and/or malena within the past 6 weeks and proven to have esophageal varices as the bleeding source on upper GI endoscopy

Exclusion Criteria:

* A history of surgery for portal hypertension
* Patients already on a EST, EVL, or glue injection program before presenting to our hospital
* Patients already on beta blockers for primary prophylaxis of variceal bleed
* Severe cardiopulmonary or renal disease
* Bradycardia (basal heart rate, \<50 beats per minute \[bpm\]) or complete heart block
* A history of severe side effects or contraindications to β- blockers, like bronchial asthma, diabetes mellitus, heart failure, peripheral vascular disease, prostatic hypertrophy, or arterial hypotension (systolic blood pressure \<90 mm Hg)
* Refusal to give informed written consent to participate in the trial
* Patients bleeding from gastric varices or Portal Hypertensive Gastropathy (PHG).
* Patients who had a failure of primary hemostasis during acute bleed were also excluded.
B: Inclusion Criteria:

* All patients with UGI bleeding (blood in the esophagus, stomach, or duodenum) who enter the emergency room or develop bleeding while in the hospital or are transferred from nearby hospitals and are suspected of having cirrhosis and BEV will be eligible for consideration (all comers).
* Those who are shown to have the findings of cirrhosis and esophageal varices that:

  * Are seen to be actively bleeding;
  * Have an adherent clot;
  * Have no other associated lesion that could reasonably account for bleeding of that magnitude (such as large gastric or duodenal varices, GU, DU, etc)
* Require 2 or more units of blood transfusion, will be included in the study.

Exclusion Criteria:

* None
C: Inclusion Criteria:

* Liver biopsy compatible with cirrhosis.
* Absence of gastroesophageal varices.
* An increased hepatic venous pressure gradient (HVPG) (6mmHg).
* Age over 18 and below 76 years.
* Informed, written consent.
* Absence of exclusion criteria.

Exclusion Criteria:

* Presence of ascites that requires specific treatment (diuretics, paracentesis, peritoneo-venous shunt, etc).
* Proven hepatocellular carcinoma by radiological or histological criteria.
* Splenic or portal vein thrombosis by Doppler-ultrasound.
* Presence of any concurrent disease that is expected to decrease life expectancy to less than one year.
* Patients taking diuretics, beta-blockers, clonidine, prazosin, nitrates, molsidomine and any drug which may have an effect on splanchnic hemodynamics/portal pressure.
* Patients participating in other pharmacological randomized clinical trials.
* Patients with primary biliary cirrhosis and primary sclerosing cholangitis will also be excluded since these entities have a slower progression of the disease, are usually enrolled in other clinical trials and are transplanted at an earlier stage.
* Contraindications to beta-blockers: asthma, COPD with positive broncoconstrictive test, heart failure, A-V block, aortic valve stenosis, organic psychosis, insulin-dependent diabetes, hypersensitivity to beta-blockers.
* Women who are pregnant, nursing or of childbearing potential and who are not using oral or mechanical contraception.
D: Inclusion Criteria:

* All patients with UGI bleeding who are shown to have the findings of cirrhosis and esophagogastric varices or portal hypertensive gastropathy and require 2 or more units of blood transfusion will be included.

Exclusion Criteria:

* None

Answer: C