Skip to main content
Top
Published in: Digestive Diseases and Sciences 6/2011

01-06-2011 | Original Article

Treatment of Genotype 4 Hepatitis C Recurring After Liver Transplantation Using a Combination of Pegylated Interferon Alfa-2a and Ribavirin

Authors: Waleed Al-hamoudi, Hazem Mohamed, Faisal Abaalkhail, Yaser Kamel, Nasser Al-Masri, Naglaa Allam, Saleh Alqahtani, Mohammed Al-Sofayan, Hatem Khalaf, Mohammed Al-Sebayel, Ahmed Al-jedai, Ayman Abdo

Published in: Digestive Diseases and Sciences | Issue 6/2011

Login to get access

Abstract

Background

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and tends to be more aggressive. Data on post-transplant HCV genotype 4 treatment is scarce. The aim of this study is to assess the safety and efficacy of pegylated interferon alpha-2a (PEG-IFN) in combination with ribavirin in the treatment of recurrent HCV genotype 4 after LT.

Methods

Twenty-five patients infected with HCV genotype 4 were treated with PEG-IFN alpha-2a at a dose of 180 μg/week in addition to 800 mg/day of ribavirin (the dose was adjusted within the tolerated range of 400–1,200 mg). Pretreatment liver biopsies were obtained from all patients. Biochemical and virological markers were assessed before, during, and after treatment.

Results

Twenty-two patients (88%) achieved an early virological response (EVR) (12 patients tested negative for HCV-RNA). Fifteen (60%) and 14 patients (56%) achieved an end of treatment virological response (ETVR) and a sustained virological response (SVR), respectively. Five patients had advanced pretreatment liver fibrosis. Pretreatment ALT was elevated in 24 patients (96%). The most common adverse effects were flu-like symptoms and cytopenia. Eighteen patients (72%) required erythropoietin alpha and/or granulocyte-colony stimulating factor as a supportive measure. One patient developed severe rejection complicated by sepsis, renal failure, and death. Other adverse effects included depression, mild rejection, impotence, itching, and vitiligo.

Conclusions

Post-transplant treatment with pegylated interferon alpha-2a and ribavirin achieved SVR in 56% of liver transplant recipients with chronic HCV genotype 4 infection. The combination was relatively safe and exhibited a low rate of treatment withdrawal.
Literature
1.
go back to reference Gane EJ, Portmann BC, Naoumov NV, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med. 1996;334:815–820.PubMedCrossRef Gane EJ, Portmann BC, Naoumov NV, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med. 1996;334:815–820.PubMedCrossRef
2.
go back to reference Samuel D, Forns X, Berenguer M, et al. Report of the monothematic EASL conference on liver transplantation for viral hepatitis (Paris, France, January 12–14, 2006). J Hepatol. 2006;45(1):127–143. Samuel D, Forns X, Berenguer M, et al. Report of the monothematic EASL conference on liver transplantation for viral hepatitis (Paris, France, January 12–14, 2006). J Hepatol. 2006;45(1):127–143.
3.
go back to reference Prieto M, Berenguer M, Rayón JM, et al. High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes. Hepatology. 1999;29:250–256.PubMedCrossRef Prieto M, Berenguer M, Rayón JM, et al. High incidence of allograft cirrhosis in hepatitis C virus genotype 1b infection following transplantation: relationship with rejection episodes. Hepatology. 1999;29:250–256.PubMedCrossRef
4.
go back to reference Firpi RJ, Abdelmalek MF, Soldevila-Pico C, et al. Combination of interferon alfa-2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C. Liver Transpl. 2002;8:1000–1006.PubMedCrossRef Firpi RJ, Abdelmalek MF, Soldevila-Pico C, et al. Combination of interferon alfa-2b and ribavirin in liver transplant recipients with histological recurrent hepatitis C. Liver Transpl. 2002;8:1000–1006.PubMedCrossRef
5.
go back to reference De Vera ME, Smallwood GA, Rosado K, et al. Interferon-alpha and ribavirin for the treatment of recurrent hepatitis C after liver transplantation. Transplantation. 2001;71:678–686.PubMedCrossRef De Vera ME, Smallwood GA, Rosado K, et al. Interferon-alpha and ribavirin for the treatment of recurrent hepatitis C after liver transplantation. Transplantation. 2001;71:678–686.PubMedCrossRef
6.
go back to reference Gopal DV, Rabkin JM, Berk BS, et al. Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin. Liver Transpl. 2001;7:181–190.PubMedCrossRef Gopal DV, Rabkin JM, Berk BS, et al. Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin. Liver Transpl. 2001;7:181–190.PubMedCrossRef
7.
go back to reference Kamal SM. Hepatitis C genotype 4 therapy: increasing options and improving outcomes. Liver Int. 2009;29:39–48.PubMedCrossRef Kamal SM. Hepatitis C genotype 4 therapy: increasing options and improving outcomes. Liver Int. 2009;29:39–48.PubMedCrossRef
8.
go back to reference Nguyen MH, Keeffe EB. Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6. Clin Gastroenterol Hepatol. 2005;3:S97–S101.PubMedCrossRef Nguyen MH, Keeffe EB. Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6. Clin Gastroenterol Hepatol. 2005;3:S97–S101.PubMedCrossRef
9.
go back to reference Abdel-Aziz F, Habib M, Mohamed MK, et al. Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence. Hepatology. 2000;32:111–115.PubMedCrossRef Abdel-Aziz F, Habib M, Mohamed MK, et al. Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence. Hepatology. 2000;32:111–115.PubMedCrossRef
10.
go back to reference Ray SC, Arthur RR, Carella A, Bukh J, Thomas DL. Genetic epidemiology of hepatitis C virus throughout Egypt. J Infect Dis. 2000;182:698–707.PubMedCrossRef Ray SC, Arthur RR, Carella A, Bukh J, Thomas DL. Genetic epidemiology of hepatitis C virus throughout Egypt. J Infect Dis. 2000;182:698–707.PubMedCrossRef
11.
go back to reference Shobokshi OA, Serebour FE, Skakni L, Al-Saffy YH, Ahdal MN. Hepatitis C genotypes and subtypes in Saudi Arabia. J Med Virol. 1999;58:44–48.PubMedCrossRef Shobokshi OA, Serebour FE, Skakni L, Al-Saffy YH, Ahdal MN. Hepatitis C genotypes and subtypes in Saudi Arabia. J Med Virol. 1999;58:44–48.PubMedCrossRef
12.
go back to reference Xu L-Z, Larzul D, Delaporte E, Br′echot C, Kremsdorf D. Hepatitis C virus genotype 4 is highly prevalent in central Africa (Gabon). J Gen Virol. 1994;75:2393–2398.PubMedCrossRef Xu L-Z, Larzul D, Delaporte E, Br′echot C, Kremsdorf D. Hepatitis C virus genotype 4 is highly prevalent in central Africa (Gabon). J Gen Virol. 1994;75:2393–2398.PubMedCrossRef
13.
go back to reference Nicot F, Legrand-Abravanel F, Sandres-Saune K, et al. Heterogeneity of hepatitis C virus genotype 4 strains circulating in south-western France. J Gen Virol. 2005;86:107–114.PubMedCrossRef Nicot F, Legrand-Abravanel F, Sandres-Saune K, et al. Heterogeneity of hepatitis C virus genotype 4 strains circulating in south-western France. J Gen Virol. 2005;86:107–114.PubMedCrossRef
14.
go back to reference Fernandez-Arcas N, Lopez-Siles J, Trapero S, et al. High prevalence of hepatitis C virus subtypes 4c and 4d in Malaga (Spain): phylogenetic and epidemiological analyses. J Med Virol. 2006;78:1429–1435.PubMedCrossRef Fernandez-Arcas N, Lopez-Siles J, Trapero S, et al. High prevalence of hepatitis C virus subtypes 4c and 4d in Malaga (Spain): phylogenetic and epidemiological analyses. J Med Virol. 2006;78:1429–1435.PubMedCrossRef
15.
go back to reference Koshy A, Marcellin P, Martinot M, Madda JP. Improved response to ribavirin interferon combination compared with interferon alone in patients with type 4 chronic hepatitis C without cirrhosis. Liver. 2000;20:335–339.PubMedCrossRef Koshy A, Marcellin P, Martinot M, Madda JP. Improved response to ribavirin interferon combination compared with interferon alone in patients with type 4 chronic hepatitis C without cirrhosis. Liver. 2000;20:335–339.PubMedCrossRef
16.
go back to reference Alfaleh FZ, Hadad Q, Khuroo MS, et al. Peginterferon a-2b plus ribavirin compared with interferon a-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly infected with genotype 4. Liver Int. 2004;24:568–574.PubMedCrossRef Alfaleh FZ, Hadad Q, Khuroo MS, et al. Peginterferon a-2b plus ribavirin compared with interferon a-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly infected with genotype 4. Liver Int. 2004;24:568–574.PubMedCrossRef
17.
go back to reference Kamal S, Kamary S, Shardell M, et al. Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: the role of rapid and early virologic response. Hepatology. 2007;46:1732–1740.PubMedCrossRef Kamal S, Kamary S, Shardell M, et al. Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: the role of rapid and early virologic response. Hepatology. 2007;46:1732–1740.PubMedCrossRef
18.
go back to reference Mudawi H, Helmy A, Kamel Y, et al. Recurrence of hepatitis C virus genotype 4 infection following orthotopic liver transplantation: natural history and predictors of outcome. Ann Saudi Med. 2009;29:91–97.PubMedCrossRef Mudawi H, Helmy A, Kamel Y, et al. Recurrence of hepatitis C virus genotype 4 infection following orthotopic liver transplantation: natural history and predictors of outcome. Ann Saudi Med. 2009;29:91–97.PubMedCrossRef
19.
go back to reference Sugo H, Balderson GA, Crawford DH, et al. The influence of viral genotypes and rejection episodes on the recurrence of hepatitis C after liver transplantation. Surg Today. 2003;33:421–425.PubMedCrossRef Sugo H, Balderson GA, Crawford DH, et al. The influence of viral genotypes and rejection episodes on the recurrence of hepatitis C after liver transplantation. Surg Today. 2003;33:421–425.PubMedCrossRef
20.
go back to reference Wali MH, Heydtmann M, Harrison RF, Gunson BK, Mutimer DJ. Outcome of liver transplantation for patients infected by hepatitis C, including those infected by genotype 4. Liver Transpl. 2003;9:796–804.PubMedCrossRef Wali MH, Heydtmann M, Harrison RF, Gunson BK, Mutimer DJ. Outcome of liver transplantation for patients infected by hepatitis C, including those infected by genotype 4. Liver Transpl. 2003;9:796–804.PubMedCrossRef
21.
go back to reference Zeuzem S. Heterogeneous virologic response rates to interferon-based therapy in patients with chronic hepatitis C: who responds less well? Ann Intern Med. 2004;140:370–381.PubMed Zeuzem S. Heterogeneous virologic response rates to interferon-based therapy in patients with chronic hepatitis C: who responds less well? Ann Intern Med. 2004;140:370–381.PubMed
22.
go back to reference Dinges S, Morard I, Heim M, et al. Pegylated interferon-alpha2a/ribavirin treatment of recurrent hepatitis C after liver transplantation. Transpl Infect Dis. 2009;11:33–39.PubMedCrossRef Dinges S, Morard I, Heim M, et al. Pegylated interferon-alpha2a/ribavirin treatment of recurrent hepatitis C after liver transplantation. Transpl Infect Dis. 2009;11:33–39.PubMedCrossRef
23.
go back to reference Xirouchakis E, Triantos C, Manousou P, et al. Pegylated-interferon and ribavirin in liver transplant candidates and recipients with HCV cirrhosis: systematic review and meta-analysis of prospective controlled studies. J Viral Hepat. 2008;15:699–709.PubMedCrossRef Xirouchakis E, Triantos C, Manousou P, et al. Pegylated-interferon and ribavirin in liver transplant candidates and recipients with HCV cirrhosis: systematic review and meta-analysis of prospective controlled studies. J Viral Hepat. 2008;15:699–709.PubMedCrossRef
Metadata
Title
Treatment of Genotype 4 Hepatitis C Recurring After Liver Transplantation Using a Combination of Pegylated Interferon Alfa-2a and Ribavirin
Authors
Waleed Al-hamoudi
Hazem Mohamed
Faisal Abaalkhail
Yaser Kamel
Nasser Al-Masri
Naglaa Allam
Saleh Alqahtani
Mohammed Al-Sofayan
Hatem Khalaf
Mohammed Al-Sebayel
Ahmed Al-jedai
Ayman Abdo
Publication date
01-06-2011
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 6/2011
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-010-1526-5

Other articles of this Issue 6/2011

Digestive Diseases and Sciences 6/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine