title: Long-term leukocyte natural α-interferon and ribavirin treatment in hepatitis C virus recurrence after liver transplantation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Digestive Diseases and Internal Medicine, S. Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy.
authors: Mariarosa
authors: M
authors: Tamè
authors: Federica
authors: F
authors: Buonfiglioli
authors: Massimo
authors: M
authors: Del Gaudio
authors: Andrea
authors: A
authors: Lisotti
authors: Paolo
authors: P
authors: Cecinato
authors: Antonio
authors: A
authors: Colecchia
authors: Francesco
authors: F
authors: Azzaroli
authors: Antonietta
authors: A
authors: D'Errico
authors: Rosario
authors: R
authors: Arena
authors: Claudio
authors: C
authors: Calvanese
authors: Chiara
authors: C
authors: Quarneti
authors: Giorgio
authors: G
authors: Ballardini
authors: Antonio Daniele
authors: AD
authors: Pinna
authors: Giuseppe
authors: G
authors: Mazzella
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006085:Graft Survival / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects* / Q000401:mortality; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014775:Virus Activation
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D012254:Ribavirin
keywords: Hepatitis C recurrence; Hepatitis C virus; Interferon; Liver transplantation; Ribavirin
references: Am J Transplant. 2005 Aug;5(8):1909-13
references: 15996238
references: Liver Transpl. 2009 Jan;15(1):54-63
references: 19109834
references: Aliment Pharmacol Ther. 2008 Aug 15;28(4):450-7
references: 18549463
references: Gut. 2007 Feb;56(2):237-42
references: 16798778
references: Semin Liver Dis. 2011 Feb;31(1):71-81
references: 21344352
references: Gastroenterology. 2003 Mar;124(3):642-50
references: 12612903
references: J Clin Invest. 1995 May;95(5):2067-75
references: 7738174
references: Hepatology. 1997 Mar;25(3):658-63
references: 9049215
references: Gastroenterology. 1993 Sep;105(3):858-62
references: 7689520
references: J Hepatol. 2008 Aug;49(2):274-87
references: 18571272
references: Liver Transpl. 2004 Feb;10(2):199-207
references: 14762857
references: J Gastroenterol Hepatol. 2007 Dec;22(12):2135-42
references: 18031371
references: Liver Transpl. 2008 Dec;14(12):1766-77
references: 19025933
references: Liver Transpl. 2009 Jul;15(7):782-9
references: 19562715
references: Hepatology. 1995 Mar;21(3):730-4
references: 7533125
references: Liver Transpl. 2007 Jan;13(1):21-9
references: 17192906
references: N Engl J Med. 1996 Mar 28;334(13):815-20
references: 8596547
references: Hepatology. 2010 Feb;51(2):388-97
references: 19918980
references: J Viral Hepat. 2008 Oct;15(10):699-709
references: 18673428
references: J Hepatol. 2010 Oct;53(4):616-23
references: 20619475
references: Gastroenterology. 2007 May;132(5):1746-56
references: 17484872
references: J Hepatol. 2000 Apr;32(4):673-84
references: 10782918
references: Transplant Proc. 2003 Sep;35(6):2080-1
references: 14529846
references: Transplantation. 2001 Jan 27;71(2):261-6
references: 11213071
references: Gut. 2003 Feb;52(2):283-7
references: 12524414
references: Am J Transplant. 2006 Jul;6(7):1586-99
references: 16827859
references: Liver Int. 2012 Feb;32 Suppl 1:120-8
references: 22212582
references: J Gastroenterol Hepatol. 2005 Apr;20(4):577-82
references: 15836706
references: Liver Transpl. 2006 Nov;12(11):1673-81
references: 17031825
references: J Hepatol. 2011 Aug;55(2):245-64
references: 21371579
references: Hepatology. 1981 Sep-Oct;1(5):431-5
references: 7308988
references: J Hepatol. 2001 Nov;35(5):666-78
references: 11690716