Immunosuppression, Liver Injury and Post-transplant HCV Recurrence

S. Ciesek; H. Wedemeyer

Disclosures

J Viral Hepat. 2012;19(1):1-8. 

In This Article

Abstract and Introduction

Abstract

Hepatitis C virus (HCV) infection is a major cause for liver transplantation worldwide. Still, HCV re-infection of the graft occurs in almost all cases. Most liver transplant recipients experience episodes of graft hepatitis associated with fibrosis progression and graft failure. Clinical management of graft hepatitis can be challenging as in addition to rejection and HCV-induced hepatitis various other factors might be involved including toxic liver injury, steatohepatitis, ischaemic bile duct lesions or infections with other pathogens. Treatment options are often contradictory for different causes of graft hepatitis, and the role of distinct immunosuppressive drugs has been discussed controversially. Corticosteroids increase the infectivity of HCV by altering expression levels of entry factors and other immunosuppressive agents may have diverse effects on HCV replication and fibrosis progression. Interferon alpha-therapy of hepatitis C shows limited efficacy and tolerability in liver transplant recipients and may also cause rejection. In this review we summarize the current knowledge on mechanisms of liver injury in post-transplant hepatitis C, discuss the pros and cons of immunosuppressive agents in this specific setting and describe potential novel approaches to prevent HCV reinfection.

Introduction

Around 160 million people are chronically infected with the hepatitis C virus (HCV), representing 2.2% of the world population.[1,2] The geographic distribution of HCV-infected individuals varies largely between 0.1% in Northern Europe and up to 20% in Egypt.[3–6] HCV is a highly variable enveloped RNA virus that infects hepatocytes. Based on sequence analyses, HCV can be grouped into seven different genotypes and more than 100 subtypes within the Flaviviridae family.[7,8]

Patients with acute HCV infection stay asymptomatic in the majority of cases and fail to clear the virus spontaneously.[9,10] Chronic hepatitis C can lead to hepatic inflammation, fibrosis, cirrhosis (10–20%) and hepatocellular carcinoma (HCC; 1–4% per year in cirrhotic patients).[4,9,11] Until 2011 the standard of care for chronic HCV infection has been combination therapy with pegylated interferon alpha (PEGIFN-α) and ribavirin inducing a sustained virological response (SVR), i.e. HCV RNA negativity 6 months after completion of therapy,[12] in 40–50% of patients infected with the most prevalent HCV genotype 1.[13,14] Successful treatment is associated with an improved clinical long-term outcome even though HCC can still develop in cirrhotic patients after HCV has been eliminated.[11,15] Very recently, two inhibitors of the HCV NS3/4A protease, boceprevir and telaprevir have been approved for the treatment of chronic hepatitis C. Triple therapy with a protease inhibitor, PEG-IFNa and ribavirin has substantially improved response rates now approaching 70%-80% for HCV genotype 1 infection.[16]

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