Brief Article
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World J Gastroenterol. Aug 28, 2013; 19(32): 5278-5285
Published online Aug 28, 2013. doi: 10.3748/wjg.v19.i32.5278
Long-term leukocyte natural α-interferon and ribavirin treatment in hepatitis C virus recurrence after liver transplantation
Mariarosa Tamè, Federica Buonfiglioli, Massimo Del Gaudio, Andrea Lisotti, Paolo Cecinato, Antonio Colecchia, Francesco Azzaroli, Antonietta D’Errico, Rosario Arena, Claudio Calvanese, Chiara Quarneti, Giorgio Ballardini, Antonio Daniele Pinna, Giuseppe Mazzella
Mariarosa Tamè, Federica Buonfiglioli, Andrea Lisotti, Paolo Cecinato, Antonio Colecchia, Francesco Azzaroli, Rosario Arena, Claudio Calvanese, Chiara Quarneti, Giorgio Ballardini, Giuseppe Mazzella, Department of Digestive Diseases and Internal Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Massimo Del Gaudio, Antonio Daniele Pinna, Department of Liver and Multiorgan Transplant Unit, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Antonietta D’Errico, Department of Hematology, Oncology and Laboratory Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy
Author contributions: Tamè M and Buonfiglioli F contributed equally to this work; Mazzella G designed the research; Tamè M and Buonfiglioli F performed the research; Del Gaudio M and Colecchia A performed all liver biopsies; Mazzella G analyzed the data; Tamè M, Buonfiglioli F, Lisotti A and Azzaroli F wrote the paper; Cecinato P, Arena R and Calvanese C performed clinical follow-up of enrolled patients; D’Errico A evaluated liver histology; Quarneti C and Ballardini G contributed immunohistochemistry analysis; Pinna AD coordinated post-liver transplantation management.
Correspondence to: Federica Buonfiglioli, MD, Department of Digestive Diseases and Internal Medicine, S. Orsola-Malpighi Hospital, Via Massarenti, 9, 40138 Bologna, Italy. fedebuo82@yahoo.it
Telephone: +39-51-6363888 Fax: +39-51-6364112
Received: February 3, 2013
Revised: June 11, 2013
Accepted: July 4, 2013
Published online: August 28, 2013
Processing time: 205 Days and 16.3 Hours
Abstract

AIM: To evaluate the effect of long-term treatment with leukocyte natural α-interferon (ln-α-IFN) plus ribavirin (RBV).

METHODS: Forty-six patients with hepatitis C virus (HCV) recurrence received 3 MU three times a week of ln-α-IFN plus RBV for 1 mo; then, patients with good tolerability (n = 30) were switched to daily IFN administration, while the remaining were treated with the same schedule. Patients have been treated for 12 mo after viral clearance while non-responders (NR) entered in the long-term treatment group. Liver biopsies were planned at baseline, 1 year after sustained virological response (SVR) and at 36 mo after start of therapy in NR. MedCalc software package was used for statistical analysis.

RESULTS: About 16.7% of genotype 1-4 and 70% of genotype 2-3 patients achieved SVR. Nine patients withdrew therapy because of non-tolerance or non-compliance. A significant improvement in serum biochemistry and histological activity was observed in all SVR patients and long-term treated; 100% of patients with SVR achieved a histological response (fibrosis stabilization or improvement) with a significant reduction in mean staging value (from 2.1 to 1.0; P = 0.0031); histological response was observed in 84% of long-term treated patients compared to 57% of drop-out. Six patients died during the entire study period (follow-up 40.6 ± 7.7 mo); of them, 5 presented with severe HCV recurrence on enrollment. Diabetes (OR = 0.38, 95%CI: 0.08-0.59, P = 0.01), leukopenia (OR = 0.54, 95%CI: 0.03-0.57, P = 0.03) and severe HCV recurrence (OR = 0.51, 95%CI: 0.25-0.69, P = 0.0003) were variables associated to survival. Long-term treatment was well tolerated; no patients developed rejection or autoimmune disease.

CONCLUSION: Long-term treatment improves histology in SVR patients and slows disease progression also in NR, leading to a reduction in liver decompensation, graft failure and liver-related death.

Keywords: Hepatitis C virus; Hepatitis C recurrence; Interferon; Ribavirin; Liver transplantation

Core tip: Recurrent hepatitis C virus hepatitis is associated with a significant increase in morbidity and mortality of transplanted patients; biochemical and necro-inflammatory improves in transplanted patients who achieved a virological response after a course of antiviral treatment. Although the relative small sample size of our study, we demonstrated the efficacy of long-term antiviral treatment on disease progression despite the virological response, without significant side effects.