“
“Clinical Autophagy activator perspectives in hepatology aims to engage two experts with opinions supporting differing perspectives on the management of a case. Typically, the case represents an area of debate or evolving practice in clinical hepatology. The case described by Dr. Reddy provides an opportunity to discuss the benefits and risks of using a direct-acting antiviral as

part of a treatment regimen for aggressive post–liver transplant (LT) hepatitis C. A 54-year-old white man was diagnosed in 1995 with hepatitis C virus (HCV) infection genotype 1 (GT1), acquired from a blood transfusion in 1975. Between 1996 and 2002, the patient underwent three courses of treatment for HCV infection. He took traditional interferon (IFN) in 1996 for 6 months, IFN and ribavirin (RBV) for 7 months in 1998, and, last, pegylated interferon alfa-2b (PEG-IFN) and RBV in 2002. Unfortunately, he did not achieve viral clearance with any of these treatments. Over time, he had progressive liver disease and a liver biopsy revealed cirrhosis in 2003. His condition continued to decline with the development of complications of portal hypertension that included esophageal varices, mild hepatic encephalopathy, and ascites. In April 2007, the patient underwent a live donor

LT, receiving a right lobe from his son. His post-transplant course was complicated by recurrent HCV infection Selleckchem Palbociclib and the development of chronic active hepatitis and bridging fibrosis. In June 2009, he began treatment for recurrent infection with PEG-IFN and

RBV. The patient achieved a rapid virologic response, but relapsed after 48 weeks of treatment. A repeat biopsy performed in January 2011 demonstrated the development of cirrhosis. His IL28B genotype is C/T. Subsequently, when protease inhibitors became available, the decision was made to administer boceprevir as a part of a 48-week triple therapy (TT) regimen. A 4-week lead-in phase of PEG-IFN plus RBV (800 mg) was started, after which boceprevir Phloretin was added. TT was administered for 32 weeks, after which boceprevir was discontinued and PEG-IFN and RBV alone were administered for 12 weeks. Within the first 8 weeks of therapy, the patient’s HCV RNA was detectable, but not quantifiable. At week 12, HCV RNA was not detectable. The dose of tacrolimus was reduced because of the known drug-drug interactions (DDIs) between the calcineurin inhibitor (CNI) and boceprevir, and the level of tacrolimus was monitored closely with dosage alterations occurring when necessary. Adverse events (AEs) of therapy included fatigue, anemia, and syncope, requiring hospital admission. Anemia was managed with RBV dose reduction, erythropoietin-stimulating agent (ESA), and blood transfusion. Details of the course of his therapy, including management of his tacrolimus levels and dosage, are presented in Fig. 1.