Emricasan (IDN-6556) Lowers Portal Pressure in Patients with Compensated Cirrhosis and Severe Portal Hypertension

Caspases play a central role in apoptosis, inflammation and fibrosis. They produce hemodynamically-active, pro-inflammatory microparticles that cause intrahepatic inflammation, vasoconstriction and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open-label study enrolled 23 subjects with compensated cirrhosis and PH (HVPG >5 mmHg). Emricasan 25 mg BID was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings.Median age was 59 (range 49-80); 70% were male. Cirrhosis etiologies were NASH and HCV. Subjects were Child class A (87%) with median MELD score of 8 (range 6-15). Twelve had severe PH (HVPG?12mmHg). Overall, there was no significant change in HVPG after emricasan (mean [SD] -1.1[4.57] mmHg). HVPG decreased significantly (mean [SD] -3.7[4.05] mmHg; p=0.003) in those with severe PH. 4/12 had a ?20% decrease; 8/12 had a ?10% decrease; and 2/12 HVPG decreased below 12mmHg. There were no significant changes in blood pressure or heart rate. AST/ALT decreased significantly in the entire group and in severe PH. Serum cCK18 and caspase-3/7 decreased significantly. Emricasan was well-tolerated. One subject discontinued for non-serious adverse events.Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH. An effect upon portal venous inflow is likely and concomitant decreases in AST/ALT suggest an intrahepatic anti-inflammatory effect

Gallstone Pancreatitis: A Common but Often Overlooked Cause of Abdominal Pain in Post-Liver-Transplant Patients

Introduction. In general population, gallstone pancreatitis is the most common cause of pancreatitis. However, there are very few literatures that address this topic in post-liver-transplant patients. Clinical Case. A 69-year-old female who had a liver transplant in 2015 due to hepatocellular carcinoma and nonalcoholic steatohepatitis (NASH) cirrhosis. She had a recent episode of acute cellular rejection that was treated with high dose methylprednisolone 1 week prior to admission. She presented with severe epigastric abdominal pain associated with nausea and vomiting. Her laboratory studies showed significantly elevated serum lipase, AST, and ALT from her baseline. She underwent urgent Endoscopic Ultrasound (EUS) with Endoscopic Retrograde Cholangiopancreatography (ERCP) that showed common bile duct stone that was extracted. Discussion. Biliary sludge and stones accounted for 22% of late onset acute pancreatitis after liver transplant. Corticosteroids have been identified as one of the potential causes of drug-induced pancreatitis. However, she is more likely to have gall stone pancreatitis since she also had dilated common bile duct and intrahepatic duct. In addition, there was CBD stone noted on ERCP. Conclusion. Acute gallstone associated pancreatitis after liver transplant is not uncommon. Patients generally have good outcomes. Further prospective studies are warranted

An extended treatment protocol with pegylated interferon and ribavirin for hepatitis C recurrence after liver transplantation

AIM: To evaluate the efficacy and tolerability of an extended treatment protocol and to determine the predictors of sustained virological response (SVR) after liver transplantation (LT)

Guillain-Barre syndrome associated with peginterferon alfa-2a for chronic hepatitis C: A case report

The recommended therapy for chronic hepatitis C (CHC) infection is the combination of a Pegylated interferon and Ribavirin. Almost all such patients on combination therapy experience one or more adverse events during the course of treatment. Significant neurological side effects are rare. A few cases of Bell’s Palsy, chronic inflammatory demyelinating polyneuropathy and even one case of acute demyelinating polyneuropathy with atypical features for Guillain-Barre syndrome (GBS) associated with Interferon therapy have been reported but no report of GBS with typical features has been published. We present a case report of typical GBS associated with Peginterferon alfa-2a and Ribavirin used for treatment of CHC infection

Emricasan (IDN-6556) Lowers Portal Pressure in Patients With Compensated Cirrhosis and Severe Portal Hypertension.

Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open-label study enrolled 23 subjects with compensated cirrhosis and PH (hepatic vein pressure gradient [HVPG] >5 mm Hg). Emricasan 25 mg twice daily was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings. Median age was 59 (range 49-80); 70% were male. Cirrhosis etiologies were nonalcoholic steatohepatitis and hepatitis C virus. Subjects were Child class A (87%) with a median Model for End-Stage Liver Disease score of 8 (range 6-15). Twelve had severe PH (HVPG ≥12 mm Hg). Overall, there was no significant change in HVPG after emricasan (mean [standard deviation, SD] -1.1 [4.57] mm Hg). HVPG decreased significantly (mean [SD] -3.7[4.05] mm Hg; P = 0.003) in those with severe PH: 4/12 had a ≥20% decrease, 8/12 had a ≥10% decrease, and 2/12 HVPG decreased below 12 mm Hg. There were no significant changes in blood pressure or heart rate. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased significantly in the entire group and in those with severe PH. Serum cleaved cytokeratin 18 and caspase-3/7 decreased significantly. Emricasan was well tolerated. One subject discontinued for nonserious adverse events. Conclusion: Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH; an effect upon portal venous inflow is likely, and concomitant decreases in AST/ALT suggest an intrahepatic anti-inflammatory effect