Predictive factors of anemia during sofosbuvir and ribavirin therapy for genotype 2 chronic hepatitis C patients.
anemia
estimated glomerular filtration rate
hepatitis C virus
inosine triphosphatase
Journal
Hepatology research : the official journal of the Japan Society of Hepatology
ISSN: 1386-6346
Titre abrégé: Hepatol Res
Pays: Netherlands
ID NLM: 9711801
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
14
11
2018
revised:
05
03
2019
accepted:
07
04
2019
pubmed:
23
4
2019
medline:
23
4
2019
entrez:
23
4
2019
Statut:
ppublish
Résumé
Sofosbuvir (SOF) and ribavirin (RBV) combination therapy has improved the sustained virologic response (SVR) rate and shortened the treatment duration for patients with chronic hepatitis C virus (HCV) genotype 2 infection. Ribavirin-induced hemolytic anemia is one of the most troublesome side-effects of SOF/RBV therapy; however, factors associated with this condition have not been fully elucidated. We aimed to identify a safer way to complete treatment with SOF/RBV therapy by examining factors related to RBV-induced hemolytic anemia and identifying patients who did not develop anemia. Two hundred and one patients with genotype 2 chronic hepatitis C treated with SOF/RBV therapy were studied. Significant factors associated with the decline in hemoglobin (Hb) levels from the baseline were analyzed. The SVR rate was 96.5% (194 out of 201 patients) based on intent-to-treat analysis. In multivariate analysis, inosine triphosphatase (ITPA) gene variation (P < 0.0001) and estimated glomerular filtration rate (eGFR) (0.001) were significantly associated with a decrease in Hb levels less than 2 g/dL. All patients were divided into four groups by ITPA and eGFR at baseline, and we identified patients with ITPA CA/AA and eGFR >75 as a group that did not develop anemia. The results presented here suggest that patients with ITPA CA/AA and eGFR >75 had no reduction in Hb levels during the treatment with SOF/RBV in HCV genotype 2-infected patients. Adding RBV to direct-acting antiviral therapy might not be problematic in certain patients, at least in terms of the occurrence of anemia.
Types de publication
Journal Article
Langues
eng
Pagination
853-859Informations de copyright
© 2019 The Japan Society of Hepatology.
Références
Kiyosawa K, Sodeyama T, Tanaka E et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology 1990; 12: 671-675.
Niederau C, Lange S, Heintges T et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology 1998; 28: 1687-1695.
Yoshida H, Tateishi R, Arakawa Y et al. Benefit of interferon therapy in hepatocellular carcinoma prevention for individual patients with chronic hepatitis C. Gut 2004; 53: 425-430.
George SL, Bacon BR, Brunt EM, Mihindukulasuriya KL, Hoffmann J, di Bisceglie AM. Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients. Hepatology 2009; 49: 729-738.
Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61: S45-S57.
Shiffman ML, Suter F, Bacon BR et al. Peginterferon α-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med 2007; 357: 124-134.
Sato K, Hashizume H, Yamazaki Y et al. Response-guided peginterferon-α-2b plus ribavirin therapy for chronic hepatitis C patients with genotype 2 and high viral loads. Heptol Res 2012; 42: 854-863.
Jacobson IM, Gordon SC, Kowdley KV et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013; 368: 1867-1877.
Lawitz E, Mangia A, Wyles D et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368: 1878-1887.
Zeuzem S, Dusheiko GM, Salupere R et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014; 370: 1993-2001.
Foster GR, Pianko S, Brown A et al. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-α in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection. Gastroenterology 2015; 149: 1462-1470.
Welzel TM, Nelson DR, Morelli G et al. Effectiveness and safety of sofosbuvir plus ribavirin for the treatment of HCV genotype 2 infection: results of the real-world, clinical practice HCV-TARGET study. In: Gut. 66, 2017; 1844-1852.
Akahane T, Kurosaki M, Itakura J et al. Real-world efficacy and safety of sofosbuvir + ribavirin for hepatitis C genotype 2: a nationwide multicenter study by the Japanese Red Cross Liver Study Group. Hepatol Res 2019; 149: 264-270.
Fellay J, Thompson AJ, Ge D et al. ITPA gene variants protect against anemia in patients treated for chronic hepatitis C. Nature 2010; 464: 405-408.
Ochi H, Maekawa T, Abe H et al. ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy - a genomewide study of Japanese HCV virus patients. Gastroenterology 2010; 139: 1190-1197.
Marsh S, King CR, Ahluwalia R, McLeod HL. Distribution of ITPA P32T alleles in multiple world populations. J Hum Genet 2004; 49: 579-581.
Suzuki F, Suzuki Y, Akuta N et al. Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir. Hepatology 2011; 53: 415-421.
Akamatsu S, Hayes CN, Tsuge M et al. Ribavirin dose reduction during telaprevir/ribavirin/peg-interferon therapy overcomes the effect of the ITPA gene polymorphism. J Viral Hepat 2015; 22: 166-174.
Morio K, Imamura M, Kawakami Y et al. Effects of ITPA polymorphism on decrease of hemoglobin during simeprevir, peg-interferon, and ribavirin combination treatment for chronic hepatitis C. Hepatol Res 2016; 46: 1256-1263.
Murakawa M, Asahina Y, Nagata H et al. ITPA gene variation and ribavirin-induced anemia in patients with genotype 2 chronic hepatitis C treated with sofosbuvir plus ribavirin. Hepatol Res 2017; 47: 1212-1218.
Ohnishi Y, Tanaka T, Ozaki K et al. A high-throughput SNP typing system for genome-wide association studies. Genet 2001; 46: 471-477.
Oze T, Hiramatsu N, Kurashige N et al. Early decline of hemoglobin correlates with progression of ribavirin-induced hemolytic anemia during interferon plus ribavirin combination therapy in patients with chronic hepatitis C. J Gastroenterol 2006; 41: 862-872.
Bruchfeld A, Lindahl K, Schvarcz R, Ståhle L. Dosage of ribavirin in patients with hepatitis C should be based on renal function: a population pharmacokinetic analysis. Ther Drug Monit 2002; 24: 701-708.