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Severe thrombocytopenia in a patient with inosine triphosphatase (ITPA)-CC genotype caused by pegylated interferon (IFN)-?-2a with ribavirin therapy: a case report.

ABSTRACT: Pegylated interferon combined with ribavirin treatment is an effective therapy for chronic hepatitis C viral infection. However, pegylated interferon combined with ribavirin is associated with various adverse reactions. Severe thrombocytopenia is a life-threatening side effect of interferon therapy that can lead to bleeding. It is generally understood that the inosine triphosphatase-CC genotype does not have a significantly lower reduction by pegylated interferon combined with ribavirin in the mean platelet counts compared with the AA/CA genotype. We report a case of severe thrombocytopenia that developed in a patient with chronic hepatitis C treated with pegylated interferon combined with ribavirin in spite of having the inosine triphosphatase-CC genotype.A 57-year-old female had been diagnosed as having HCV infection in 2008. The inosine triphosphatase gene showed one single nucleotide polymorphism (rs1127354) C/C (major homozygous) and the IL28B gene showed single nucleotide polymorphism (rs8099917 T/T, rs11881222 T/T) (major homozygous). The patient was treated with pegylated interferon 180 ?g once a week combined with ribavirin 600 mg per day from April 2011. The hepatitis c virus ribonucleic acid turned negative 9 weeks after treatment with pegylated interferon combined with ribavirin. During the therapy, the platelet count remained above 8.0?×?10(4)/?l for about 9 months. In January 2012, the platelet count was 6.8?×?10(4)/?l. In February 2012, the 44th week from the beginning of the treatment, a sudden decrease in the platelet count to 0.8?×?10(4)/?l was observed. After prednisolone was administered, the platelet count increased. Finally the platelet count had risen above normal range.We should pay careful attention in the differential diagnosis for patients with the inosine triphosphatase-CC genotype because, although rare, severe thrombocytopenia could occur.

SUBMITTER: Jiang W

PROVIDER: S-EPMC3995698 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Severe thrombocytopenia in a patient with inosine triphosphatase (ITPA)-CC genotype caused by pegylated interferon (IFN)-α-2a with ribavirin therapy: a case report.

Jiang Weimin W Hidaka Hisashi H Nakazawa Takahide T Kitagawa Hiroyuki H Koizumi Wasaburo W

BMC research notes 20140312

<h4>Background</h4>Pegylated interferon combined with ribavirin treatment is an effective therapy for chronic hepatitis C viral infection. However, pegylated interferon combined with ribavirin is associated with various adverse reactions. Severe thrombocytopenia is a life-threatening side effect of interferon therapy that can lead to bleeding. It is generally understood that the inosine triphosphatase-CC genotype does not have a significantly lower reduction by pegylated interferon combined with ...[more]

PMID: 24621321

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Project description:Patients receiving therapy for chronic hepatitis C virus (HCV) infection frequently experience cytopenias and weight loss. We retrospectively assessed the pharmacodynamic effects of pegylated interferon (PEG-IFN) alfa-2a and ribavirin by evaluating the relationship between changes in hematologic parameters, body weight, and virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of PEG-IFN alfa-2a and ribavirin therapy were pooled from four phase 3/4 trials. Maximum decreases in hemoglobin level, neutrophil count, platelet count, and weight during therapy were assessed according to virologic response category (sustained virologic response [SVR], relapse, breakthrough, and nonresponder) and race/ethnicity. Of 1,778 patients analyzed, more than half were male, non-Hispanic Caucasian, and infected with HCV genotype 1; had a baseline HCV RNA >800,000; and had alanine aminotransferase levels ?3 × the upper limit of normal. Virologic responders (SVR, relapse, and breakthrough) experienced greater maximum decreases from baseline in hemoglobin level, neutrophil count, platelet count, and weight compared with nonresponders; however, no clear trend was observed between SVR, relapse, and breakthrough. After adjusting for drug exposure and treatment duration, only decreases in neutrophil count remained associated with virologic response. Significantly greater declines in neutrophil (P < 0.0001) and platelet (P < 0.005) count were observed at weeks 4, 12, and 24 of therapy in virologic responders compared with nonresponders. This difference between responders and nonresponders was also observed among racial/ethnic groups, although statistical significance was not consistent across all groups.This post hoc analysis of HCV patients treated with PEG-IFN alfa-2a and ribavirin shows that maximum decreases from baseline in hematologic parameters and weight loss were associated with virologic response. However, after adjusting for drug exposure and accounting for duration of therapy, only neutropenia was independently associated with virologic response.

Project description:To investigate the safety and efficacy of a Hansenula-derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection.Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group?I?included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at www.ClinicalTrials.gov (NCT02027493).Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well.Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.

Dataset Information

Severe thrombocytopenia in a patient with inosine triphosphatase (ITPA)-CC genotype caused by pegylated interferon (IFN)-?-2a with ribavirin therapy: a case report.

Publications

Severe thrombocytopenia in a patient with inosine triphosphatase (ITPA)-CC genotype caused by pegylated interferon (IFN)-α-2a with ribavirin therapy: a case report.

Similar Datasets

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