A Phase 1, Open-Label Study of Intravenous Sildenafil in Patients With Cirrhosis

Subjects will be eligible for the study if they meet the following inclusion criteria:

1. Cirrhosis. Diagnosis of cirrhosis will be based on either liver biopsy OR clinical
characteristics (e.g. history of ascites or encephalopathy or esophageal varices or
gastric varices or splenomegaly or spider angioma or any clinical sign of portal
hypertension/cirrhosis), laboratory (e.g. history of thrombocytopenia or history of
APRI (Reference: Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA,
Conjeevaram HS, Lok AS. A simple noninvasive index can predict both significant
fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology
2003;38:518-26) [Aspartate aminotransferase (AST) to platelet ratio index] score
consistent with cirrhosis or history of abnormal liver function tests) and abdominal
imaging (Magnetic Resonance Imaging or Computed Tomography or ultrasound of the
abdomen) data

2. CTP Class B or C cirrhosis

3. Age 18 years or older at the time of enrollment

4. Variceal screening with an upper endoscopy within 1 year before enrollment

5. Renal dysfunction [GFR ≥ 15 and < 60 ml/min/1.73m2 estimated by 6-variable MDRD
equation (Reference: Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S,
Kusek JW, Van Lente F. Using standardized serum creatinine values in the modification
of diet in renal disease study equation for estimating glomerular filtration rate. Ann
Intern Med 2006;145:247-54)]

6. Hemoglobin level ≥ 8 mg/dl within 4 weeks before enrollment

7. Serum sodium level ≥ 125 mmol/L within 4 weeks before enrollment

Subjects will be excluded if they have any of the following:

1. Inability to provide informed consent

2. Women who are pregnant, breast-feeding, or contemplating pregnancy

3. Treatment with organic nitrates, ritonavir, erythromycin, saquinavir, ketoconazole,
itraconazole, cimetidine, bosentan, rifampin, Sildenafil or any other PDE-5
inhibitors, alpha-blockers, and anticoagulants within 7 days before enrollment

4. Hypersensitivity or allergy to Sildenafil or any component of Sildenafil

5. Previous reaction to PDE-5 inhibitors including, but not limited to Sildenafil,
Vardenafil, Tadalafil, Avanafil (Myocardial infarction, ventricular arrhythmia, sudden
cardiac death, cerebrovascular hemorrhage, transient ischemic attack, stroke,
transient global amnesia, subarachnoid and intracerebral hemorrhages, seizure,
recurrence in seizures, pulmonary hemorrhage, sudden decrease of hearing, loss of
hearing, anxiety, prolonged erection, priapism, ocular redness, ocular burning,
diplopia, temporary vision loss/decreased vision, ocular swelling, ocular pressure,
increased intraocular pressure, retinal problems in the eye, vitreous detachment,
vitreous traction, paramacular edema, non-arteritic anterior ischemic optic
neuropathy)

6. History of untreated severe left ventricular outflow obstruction (e.g. aortic
stenosis, idiopathic hypertrophic subaortic stenosis)

7. History of pulmonary veno-occlusive disease

8. History of unstable angina, myocardial infarctus, life-threatening arrhythmia or
stroke within 6 months before enrollment

9. History of retinitis pigmentosa

10. Anatomical deformation of the penis (Peyronie's disease, angulation, cavernosal
fibrosis)

11. History of sickle cell anemia, multiple myeloma or leukemia

12. Renal failure treated with dialysis

13. Cognitive impairment based on IRB "evaluation to sign consent form"

14. Transjugular intrahepatic porto-systemic shunt placement

15. Previous kidney or liver transplantation