Center for Liver Diseases and Transplantation

Pumpkin Center, NC, United States

Center for Liver Diseases and Transplantation

Pumpkin Center, NC, United States
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Noell B.C.,Center for Liver Diseases and Transplantation | Besur S.V.,Center for Liver Diseases and Transplantation | De Lemos A.S.,Center for Liver Diseases and Transplantation
Drug Design, Development and Therapy | Year: 2015

The availability of direct-acting antiviral (DAA) therapy has launched a new era in the management of chronic hepatitis C. Sofosbuvir, a uridine nucleotide analog that inhibits the hepatitis C RNA-dependent RNA polymerase, is the backbone of chronic hepatitis C therapy. Acting at the catalytic site of the polymerase, sofosbuvir is highly potent in suppressing viral replication and has a high genetic barrier to resistance. Sofosbuvir is effective across all hepa­titis C genotypes, and is a mainstay of interferon-free combination therapy. In Phase II and III studies, genotype 1 patients who took sofosbuvir in combination with another DAA such as the NS3-4A protease inhibitor, simeprevir, or the NS5A replication complex inhibitors, ledipasvir or daclatasvir, achieved a sustained virologic response rate of over 90%. Harvoni®, a combination tablet of sofosbuvir and ledipasvir, dosed once daily is recommended for 24 weeks for treatment-experienced genotype 1 patients with cirrhosis, but 12 weeks of therapy is sufficient for all other populations. While genotype 2 (12 weeks or 16 weeks) and treatment-naïve genotype 3 patients (24 weeks) have excellent response rates with sofosbuvir and ribavirin, treatment-experienced cirrhotic genotype 3 patients may need the addition of another DAA such as daclatasvir. Sofos­buvir is efficacious in special populations such as HIV–hepatitis C virus-coinfected patients and liver transplant recipients and has already made a profound impact in these groups. Since it is renally eliminated, patients with advanced kidney disease or on dialysis must await dosing recommendations. Sofosbuvir-based regimens appear to be well tolerated with headache and fatigue being the most common side effects. The opportunity to cure patients with hepatitis C with sofosbuvir combination therapy is likely to change the future for our patients, particularly if the emphasis shifts to identifying those patients unaware that they are infected and providing affordable access to treatment. © 2015 Noell et al.

Zamor P.J.,Center for Liver Diseases and Transplantation | Russo M.W.,Center for Liver Diseases and Transplantation
Current Opinion in Cardiology | Year: 2011

PURPOSE OF REVIEW: To discuss recent data on statins in patients with elevated liver tests. RECENT FINDINGS: As a result of the obesity epidemic in Western societies, conditions associated with metabolic syndrome are increasing, including nonalcoholic fatty liver disease (NAFLD). Because most patients with metabolic syndrome have indications for statins, clinicians will be confronted with prescribing statins to patients with elevated liver tests. Statins are associated with elevations in aminotransferases in up to 3% of treated patients, but statins rarely lead to serious drug-induced liver injury (DILI), chronic liver disease, or acute liver failure. Data have emerged demonstrating that not only are statins well tolerated to use in most patients with elevated liver tests but also they may have a beneficial therapeutic effect in treating the underlying liver disease. Studies demonstrate that statins may increase response rates of antiviral therapy for hepatitis C. In a study of 437 patients with moderate elevations in baseline aminotransferases, patients on statins were more likely to have a decline in aminotransferases compared with untreated patients. SUMMARY: Data support using statins in patients with elevated liver tests, especially patients with NAFLD, who may be at particularly high risk for cardiovascular disease. © 2011 Lippincott Williams & Wilkins, Inc.

DeLemos A.S.,Center for Liver Diseases and Transplantation | Schmeltzer P.A.,Center for Liver Diseases and Transplantation | Russo M.W.,Center for Liver Diseases and Transplantation
World Journal of Gastroenterology | Year: 2014

End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5B polymerase inhibitors and NS5A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients. © 2014 Baishideng Publishing Group Inc. All rights reserved.

Delemos A.S.,Center for Liver Diseases and Transplantation | Foureau D.M.,Carolinas Medical Center | Jacobs C.,Carolinas Medical Center | Ahrens W.,Carolinas Medical Center | And 2 more authors.
Seminars in Liver Disease | Year: 2014

Drug-induced liver injury (DILI) with features of autoimmunity (AI) represents an important category of hepatotoxicity due to medication exposure. Drugs repeatedly associated with AI-DILI include diclofenac, α-methyl DOPA, hydralazine, nitrofurantoin, minocycline, and more recently statins and anti-TNF-α agents. Usually, symptoms of acute liver injury occur within a few months after initiation of a culprit medication, but a longer latency period is possible. Like idiopathic autoimmune hepatitis, circulating autoantibodies and a hypergammaglobulinemia are frequently present in sera from patients with AI-DILI. If performed, a liver biopsy should demonstrate interface hepatitis with a prominent plasma cell infiltrate. The severity of AI-DILI is variable, but a complete resolution after withdrawal of the offending medication is the expectation. A response to corticosteroid therapy supports the diagnosis, whereas a lack of recurrence of symptoms or signs following corticosteroid cessation distinguishes AI-DILI from idiopathic autoimmune hepatitis. Copyright © 2014 by Thieme Medical Publishers, Inc.

DeLemos A.S.,Center for Liver Diseases and Transplantation | Chung R.T.,Harvard University
Trends in Molecular Medicine | Year: 2014

An exciting paradigm shift is occurring in the treatment of hepatitis C virus (HCV). We now have the capacity to specifically target therapy to HCV proteins, and thereby directly interrupt the viral life cycle. The first direct-acting antivirals (DAAs), the NS3-4A serine protease inhibitors boceprevir and telaprevir, improved the rate of sustained virologic response (SVR), but their toxicities combined with PEG-IFN and RBV limited their overall efficacy. Sofosbuvir, a nucleotide HCV polymerase inhibitor, is now available and offers better tolerability and efficacy across all HCV genotypes. The next phase of therapy will be combining several classes of DAAs without IFN in order to make sustained clearance of hepatitis C deliverable to a much larger number of infected individuals. © 2014 Elsevier Ltd.

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