Sorafenib for Hepatopulmonary Syndrome

Inclusion Criteria: * Diagnosis of HPS: 1. AaPO2 ≥ 15 mm Hg (≥ 20 mm Hg for age \> 64 yrs) 2. Intrapulmonary shunting 3. Absence of significant restriction (TLC \< 70%) or obstruction (FEV1 \< 80% \& FEV1/FVC \< 70%) 4. Presence of cirrhosis/hepatic fibrosis and/or portal hypertension * Child-Pugh class A or B liver disease * Platelet count ≥ 30 ×10e9 per liter * Hemoglobin ≥ 8.5 g per deciliter * International normalized ratio ≤ 2.3 * Albumin ≥ 2.8 g per deciliter * Total bilirubin ≤ 5 mg per deciliter * Alanine aminotransferase and aspartate aminotransferase ≤ 5 times the upper limit of the normal range * Serum creatinine ≤ 1.5 times the upper limit of the normal range and not receiving dialysis * Negative pregnancy test (for women of childbearing potential) at both screening and baseline visits. Post-menopausal women (defined as no menses for one year) and surgically sterilized women are not required to undergo a pregnancy test. * Subjects (men and women) of childbearing potential must agree to use medically acceptable contraception beginning at the signing of the Informed Consent Form until at least 14 days after the last dose of study drug. * Age ≥ 21 years * Ability to provide informed consent Exclusion Criteria: * Recent chronic heavy alcohol consumption * Enrollment in a clinical trial or concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 28 days of screening visit * Current hepatic encephalopathy * Active infection * Diagnosis of portopulmonary hypertension * WHO Class IV functional status * Congenital long-QT syndrome * Subjects who have used strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, phenobarbital, St. John's Wort \[Hypericum perforatum\], dexamethasone at a dose of greater than 16 mg daily, or rifampin \[rifampicin\], and/or rifabutin) within 28 days before randomization * Subjects who are currently taking Coumadin®(warfarin) * Active or clinically significant cardiac disease, including: 1. Active coronary artery disease 2. Unstable angina (anginal symptoms at rest), new-onset angina within 12 weeks before randomization, or myocardial infarction within 24 weeks before randomization * Liver or other solid organ transplant recipients * Expectation of liver transplant within four months of randomization * Hepatocellular carcinoma that does not meet all of the following criteria: 1. Single lesion ≤ 3 cm documented by LIRADS criteria 2. Complete response to ablative therapy (TACE, RFA, alcohol ablation) using the modified RECIST criteria one month after therapy with no more than two treatments 3. No other lesions develop after initiation of HCC therapy * Uncontrolled hypertension (systolic pressure \>140 mm Hg or diastolic pressure \> 90 mm Hg on repeated measurement) despite optimal medical management. * Any hemorrhage/bleeding event of NCI-Common Toxicity Criteria for Adverse Effects v4.0 Grade 3 or higher within 4 weeks before randomization * Presence of a non-healing wound, non-healing ulcer, or bone fracture * Women who are pregnant or breast-feeding * Major surgery 28 days prior to randomization * Subjects with any previously untreated or concurrent cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed. All cancer treatments (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form). * Inability to comply with the protocol and/or not willing or not available for follow-up assessments