Emricasan, an Oral Caspase Inhibitor, in Subjects With NASH Cirrhosis and Severe Portal Hypertension

Inclusion Criteria: * Male or female subjects 18 years or older, able to provide written informed consent and able to understand and willing to comply with the requirements of the study. * Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.) * Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event * Severe portal hypertension defined as HVPG ≥12 mmHg * Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must be on a stable dose for at least 3 months prior to Day 1 * Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug Exclusion Criteria: * Evidence of severe decompensation * Severe hepatic impairment defined as a Child-Pugh score ≥10 * ALT (alanine transaminase) \> 3 times upper limit of normal (ULN) or AST (aspartate transaminase) \>5 times ULN during screening * Estimated creatinine clearance \<30 mL/min * Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure * Known portal vein thrombosis * Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy * Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters * Alpha-fetoprotein \>50 ng/mL * History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of \>500 msec * History of or active malignancies, other than those successfully treated with curative intent and believed to be cured * Prior liver transplant * Change in diabetes medications or vitamin E within 3 months of screening * Uncontrolled diabetes mellitus (HbA1c \>9%) within 3 months of screening * Significant systemic or major illness other than liver disease * HIV infection * Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening * If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding * Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1