2012, Number 2
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Ann Hepatol 2012; 11 (2)
Pegylated interferon-alpha2b plus ribavirin for the treatment of chronic hepatitis C virus genotype 4 infection in patients with normal serum ALT
Al-Ali J, Siddique I, Varghese R, Hasan F
Language: English
References: 37
Page: 186-193
PDF size: 98.78 Kb.
ABSTRACT
Background. Approximately one-third of patients with chronic hepatitis C virus infection have persistently
normal liver enzymes reflected by a normal serum alanine transaminase (ALT). Data with regards the efficacy
and safety of treatment in patients chronically infected with Hepatitis C virus genotype 4 and normal
serum ALT are limited.
Aim. To evaluate the efficacy and safety of peginterferon alfa-2b plus ribavirin combination
therapy in this population.
Material and methods. Twenty-two patients with chronic hepatitis C
virus genotype 4 infection were enrolled in an open-labeled, uncontrolled pilot study. All patients had
biopsy proven chronic hepatitis and persistently normal serum ALT levels. Patients were treated with subcutaneous
peginterferon alfa-2b at a dose of 1.5 µg/kg body weight once per week plus oral ribavirin (15
mg/kg/day) for 48 weeks. Patients were followed for 24 weeks post-treatment.
Results. Sixteen patients
out of twenty two completed the study (9 [40.9%] females, mean age 43.8 years). The ALT level were normal
in all patients, with a mean of 38.6 U/L. Sustained viral response was achieved in 13 patients (59%), 4
patients (18.1%) were non-responders and 2 patients (9%) relapsed while 1 patient had a viral breakthrough
during treatment. Two patients (9%) discontinued the treatment because of adverse events.
Conclusions.
Combination therapy of pegylated interferon-alpha2b and ribavirin is safe and resulted in a sustained virological
response in a significant number of patients with chronic Hepatitis C, genotype 4, and persistently
normal serum ALT.
REFERENCES
Abdel-Aziz F, Habib M, Mohamed MK, Abdel-Hamid M, Gamil F, Madkour S, Mikhail NN, et al. Hepatitis C (HCV) infection in a community in the Nile Delta: population description and HCV prevalence. Hepatology 2000; 32: 111-5.
Angelico M, Renganathan E, Gandin C, Fathy M, Profili MC, Refai W, De Santis A, et al. Chronic liver disease in the Alexandria governorate, Egypt: contribution of schistosomiasis and hepatitis virus infections. J Hepatol 1997; 26: 236-43.
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.
Zekri AR, Bahnassy AA, Ramadan AS, El-Bassuoni M, Badran A, Madwar MA. Hepatitis C virus genotyping versus serotyping in Egyptian patients. Infection 2001; 29: 24-6.
Fakeeh M, Zaki AM. Hepatitis C: prevalence and common genotypes among ethnic groups in Jeddah, Saudi Arabia. Am J Trop Med Hyg 1999; 6: 889-92.
Marcellin P, Lévy S, Erlinger S. Therapy of hepatitis C: patients with normal aminotransferase levels. Hepatology 1997; 26: 133S-136S.
Tassopoulos, NC. Treatment of patients with chronic hepatitis C and normal ALT levels. J Hepatol 1999; 31: 193-6.
Bacon BR. Treatment of patients with hepatitis C and normal serum aminotransferase levels. Hepatology 2002; 36: S179-S184.
Persico M, Persico E, Suozzo R, Conte S, De Seta M, Coppola L, Palmentieri B, et al. Natural history of hepatitis C virus carriers with persistently normal aminotransferase levels. Gastroenterology 2000; 118: 760-4.
Martinot-Peignoux M, Boyer N, Cazals-Hatem D, Pham BN, Gervais A, Le Breton V, Levy S, et al. Prospective study on anti-hepatitis C virus-positive patients with persistently normal serum alanine ansaminase with or without detectable serum hepatitis C virus RNA. Hepatology 2001; 34: 1000-5.
Cividini A, Rebucci C, Silini E, Mondelli MU. Is the natural history of hepatitis C virus carriers with normal aminotransferase really benign? Gastroenterology 2001; 121: 1526-7.
Puoti C, Magrini A, Stati T, Rigato P, Montagnese F, Rossi P, Aldegheri L, et al. Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels. Hepatology 1997; 26: 1393-8.
Hui CK, Belaye T, Montegrande K, Wright TL. A comparison in the progression of liver fibrosis in chronic hepatitis C between persistently normal and elevated transaminase. J Hepatol 2003; 38: 511-7.
Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004; 39: 1147-71.
Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195-206.
McHutchison JG, Everson GT, Gordon SC, Jacobson IM, Sulkowski M, Kauffman R, McNair L, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; 360: 1827-38.
Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology 1996; 24: 289-93.
Mathurin P, Moussalli J, Cadranel JF, Thibault V, Charlotte F, Dumouchel P, Cazier A, et al. Slow progression rate of fibrosis in hepatitis C virus patients with persistently normal alanine transaminase activity. Hepatology 1998; 27: 868-72.
Pradat P, Alberti A, Poynard T, Esteban JI, Weiland O, Marcellin P, Badalamenti S, et al. Predictive value of ALT levels for histologic findings in chronic hepatitis C: a European collaborative study. Hepatology 2002; 36: 973-7.
Rumi MG, De Filippi F, La Vecchia C, Donato MF, Gallus S, Del Ninno E, Colombo M. Hepatitis C reactivation in patients with chronic infection with genotypes 1b and 2c: a retrospective cohort study of 206 untreated patients. Gut 2005; 54: 402-6.
Ghany MG, Kleiner DE, Alter H, Doo E, Khokar F, Promrat K, Herion D, et al. Progression of fibrosis in chronic hepatitis C. Gastroenterology 2003: 124: 97-104.
Okanoue T, Makiyama A, Nakayama M, Sumida Y, Mitsuyoshi H, Nakajima T, Yasui K, et al. A follow-up study to determine the value of liver biopsy and need for antiviral therapy for hepatitis C virus carriers with persistently normal serum aminotransferase. J Hepatol 2005; 43: 599-605.
Persico M, Palmentieri B, Coppola L, Di Giacomo Russo G, De Marino F, De Sio I, Torella R. Occurrence of HCC in asymptomatic HCV-related chronic hepatitis. Dig Dis Sci 2002; 47: 2407-10.
Puoti C, Bellis L, Martellino F, Durola L, Spilabotti L, Dell’Unto O, Galossi A, et al. Occurrence of hepatocellular carcinoma in an apparently ‘healthy’ HCV patient. Eur J Gastroenterol Hepatol 2005; 17: 1263-4.
Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, Shiffman M, et al. Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels. Gastroenterology 2004; 127: 1724-32.
Puoti C, Pellicelli AM, Romano M, Mecenate F, Guarisco R, Barbarini G, Mazzoni E, et al. Treatment of hepatitis C virus carriers with persistently normal alanine aminotransferase levels with peginterferon alpha-2a and ribavirin: a multicentric study. Liver Int 2009; 29: 1479-84.
Hasan F, Asker H, Al-Khalid J, Al-Mekhaizeem K, Al-Shamali M, Siddique I, Al-Nakib B. Interferon-alpha in combination with ribavirin for the treatment of chronic hepatitis C in patients with persistently normal aminotransferase levels. Digestion 2002; 65: 127-30.
Hasan F, Asker H, Al-Khaldi J, Siddique I, Al-Ajmi M, Owaid S, Varghese R, et al. Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4. Am J Gastroenterol 2004; 99: 1733-7.
Alfaleh FZ, Hadad Q, Khuroo MS, Aljumah A, Algamedi A, Alashgar H, Al-Ahdal MN, et al. Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly infected with genotype 4. Liver Int 2004; 24: 568-74.
Kamal SM, El Tawil AA, Nakano T, He Q, Rasenack J, Hakam SA, Saleh WA, et al. Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response. Gut 2005; 54: 858-66.
El-Zayadi AR, Attia M, Barakat EM, Badran HM, Hamdy H, El-Tawil A, El-Nakeeb A, et al. Response of hepatitis C genotype-4 naïve patients to 24 weeks of Peg-interferonalpha2b/ ribavirin or induction-dose interferon-alpha2b/ ribavirin/amantadine: a non-randomized controlled study. Am J Gastroenterol 2005; 100: 2447-52.
Roulot D, Bourcier V, Grando V, Deny P, Baazia Y, Fontaine H, Bailly F, et al. Epidemiological characteristics and response to peginterferon plus ribavirin treatment of hepatitis C virus genotype 4 infection. J Viral Hepat 2007; 14: 460-7.
Moucari R, Ripault MP, Martinot-Peignoux M, Voitot H, Cardoso AC, Stern C, Boyer N, et al. Insulin resistance and geographical origin: major predictors of liver fibrosis and response to peginterferon and ribavirin in HCV-4. Gut 2009; 58: 1662-9.
Serfaty L, Chazouillères O, Pawlotsky JM, Andreani T, Pellet C, Poupon R. Interferon alfa therapy in patients with chronic hepatitis C and persistently normal aminotransferase activity. Gastroenterology 1996; 110: 291-5.
Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002; 137: 1-10.
Zeuzem S, Alberti A, Rosenberg W, Marcellin P, Diago M, Negro F, Prati D, et al. Review article: management of patients with chronic hepatitis C virus infection and “normal” alanine aminotransferase activity. Aliment Pharmacol Ther 2006; 24: 1133-49.
Yagura M, Tanaka A, Kamitsukasa H, Otsuka H, Kanno S, Aoyama T. Re-evaluation of the serum alanine aminotransferase upper normal limit in chronic hepatitis C patients. Intern Med 2010; 49: 525-8.