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World J Gastroenterol. Aug 28, 2014; 20(32): 11095-11115
Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11095
Post-liver transplant hepatitis C virus recurrence: An unresolved thorny problem
Alberto Grassi, Giorgio Ballardini
Alberto Grassi, Giorgio Ballardini, Internal Medicine and Hepatology Division, Department of Internal Medicine, “Infermi” Hospital, 47923 Rimini, Italy
Author contributions: Grassi A performed the literature review, analyzed and interpreted the data, drafted the manuscript, and approved the final version; Ballardini G critically reviewed the manuscript, assisted with the design of the paper, made corrections and revisions, and approved the final version.
Correspondence to: Alberto Grassi, MD, PhD, Internal Medicine and Hepatology Division, Department of Internal Medicine, “Infermi” Hospital, Viale Settembrini 2, 47923 Rimini, Italy. albgrassi@yahoo.com
Telephone: +39-541-705699 Fax: +39-541-705342
Received: December 27, 2013
Revised: February 15, 2014
Accepted: May 29, 2014
Published online: August 28, 2014
Processing time: 245 Days and 6 Hours
Abstract

Hepatitis C virus (HCV)-related cirrhosis represents the leading cause of liver transplantation in developed, Western and Eastern countries. Unfortunately, liver transplantation does not cure recipient HCV infection: reinfection universally occurs and disease progression is faster after liver transplant. In this review we focus on what happens throughout the peri-transplant phase and in the first 6-12 mo after transplantation: during this crucial period a completely new balance between HCV, liver graft, the recipient’s immune response and anti-rejection therapy is achieved that will deeply affect subsequent outcomes. Nearly all patients show an early graft reinfection, with HCV viremia reaching and exceeding pre-transplant levels; in this setting, histological assessment is essential to differentiate recurrent hepatitis C from acute or chronic rejection; however, differentiating the two patterns remains difficult. The host immune response (mainly cellular mediated) appears to be crucial both in the control of HCV infection and in the genesis of rejection, and it is also strongly influenced by immunosuppressive treatment. At present no clear immunosuppressive strategy could be strongly recommended in HCV-positive recipients to prevent HCV recurrence, even immunotherapy appears to be ineffective. Nonetheless it seems reasonable that episodes of rejection and over-immunosuppression are more likely to enhance the risk of HCV recurrence through immunological mechanisms. Both complete prevention of rejection and optimization of immunosuppression should represent the main goals towards reducing the rate of graft HCV reinfection. In conclusion, post-transplant HCV recurrence remains an unresolved, thorny problem because many factors remain obscure and need to be better determined.

Keywords: Hepatitis C virus; Liver transplantation; Hepatitis C antigens; Graft rejection; Immunosuppression

Core tip: Hepatitis C virus (HCV) graft reinfection universally occurs post-liver transplantation and disease progression is accelerated. Differentiating recurrent hepatitis from rejection is essential in this setting; however, differentiation of the two pathological patterns remains difficult. The host immune response appears to be crucial both in the control of HCV infection and in the genesis of rejection: complete prevention of rejection and optimization of immunosuppression should represent the main goals. A proper graft allocation seems to be crucial to realize an ideal donor-to-recipient matching; however, many factors remain obscure.