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World J Gastroenterol. Mar 21, 2014; 20(11): 2810-2824
Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.2810
Histopathological evaluation of recurrent hepatitis C after liver transplantation: A review
Francesco Vasuri, Deborah Malvi, Elisa Gruppioni, Walter F Grigioni, Antonia D’Errico-Grigioni
Francesco Vasuri, Deborah Malvi, Elisa Gruppioni, Walter F Grigioni, Antonia D’Errico-Grigioni, “F. Addarii” Institute of Oncology and Transplantation Pathology, S. Orsola-Malpighi Hospital, Bologna University, 40138 Bologna, Italy
Author contributions: Vasuri F and Malvi D reviewed the literature, wrote the paper and contributed to the images; Gruppioni E reviewed the literature concerning reverse transcription-polymerase chain reaction methods in hepatitis C virus recipients and wrote the relevant paragraph; Grigioni WF and D’Errico-Grigioni A designed the review and revised it critically; all authors approved the final version of the manuscript and its contents.
Correspondence to: Walter F Grigioni, MD, “F. Addarii” Institute of Oncology and Transplant Pathology, S. Orsola-Malpighi Hospital, Bologna University, V.le Ercolani 4/2, 40138 Bologna, Italy. franco.grigioni@aosp.bo.it
Telephone: +39-51-6364546 Fax: +39-51-6364403
Received: September 23, 2013
Revised: November 8, 2013
Accepted: December 12, 2013
Published online: March 21, 2014
Abstract

Although the morphological features of hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) have been well established in the last decades, the differential diagnosis still represents a challenge for the pathologist, especially early recurrent hepatitis C vs mild acute cellular rejection. The present review focuses on the role of the pathologist and the pathology laboratory in the management of recipients with recurrent hepatitis C, the usefulness of early and late post-OLT liver biopsies, and the potential role of ancillary techniques (immunohistochemistry and reverse transcription-polymerase chain reaction, RT-PCR). The English literature on the topic is reviewed, focusing on the histopathology, the immunohistochemistry and the use of RT-PCR on HCV-positive post-OLT biopsies. The different histopathological illustrations of early and chronic recurrent hepatitis C are presented, with special focus on the main differential diagnoses and those features with prognostic relevance (cholestasis above all). The usefulness of ancillary techniques are discussed, especially HCV RNA quantitation by RT-PCR. Finally, the usefulness of long-term protocol biopsies is addressed: their usefulness for the study of allograft disease progression is clear, but their meaning in the long term is still debated. The significance of plasma cell infiltrate in HCV-positive allografts, the prognostic weight of graft steatosis, and the impact of donor age in recurrent hepatitis C also represent additional open issues.

Keywords: Hepatitis C virus, Histopathology, Immunohistochemistry, Orthotopic liver transplantation, Recurrent hepatitis C, Polymerase chain reaction

Core tip: Recently, tissue hepatitis C virus (HCV) RNA quantitation by means of reverse transcription-polymerase chain reaction has been largely used in the early post-orthotopic liver transplantation (OLT) phases, especially in the differential diagnosis of recurrent hepatitis C vs mild acute rejection, replacing immunohistochemistry in some laboratories. Nevertheless, the importance of tissue HCV RNA quantitation in the long post-OLT term has not been clarified yet. The suitability and usefulness of protocol biopsies are still debated: protocol biopsies may be necessary in order to answer other open questions, such as the significance of plasma cell infiltrate in HCV-positive allografts, the prognostic weight of HCV-induced steatosis, and the impact of donor age in recurrent hepatitis C.