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In Reply

Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

We much appreciate the comments by Ennishi et al on our report.¹ They raised several issues about the relationship of rituximab, chemotherapy, hepatitis C virus (HCV) reactivation, and liver dysfunction.

We agree that monitoring HCV RNA levels before and after the first cycle of chemotherapy can provide better understanding of the impact of chemotherapy and rituximab on chronic HCV patients. However, those data are unavailable due to this patient's economic condition. Though Besson et al² reported higher incidence of liver dysfunction in HCV patients during chemotherapy, most toxicities were grade one or two, and the majority of patients could follow the protocols without delay or reduced dosage of chemotherapy. A similar result was also reported by Visco et al.³ Contrary to those studies, the elevated transaminase level lasted almost 2 months, which caused our patient to withdraw from the scheduled chemotherapy.

The relationship between rituximab and HCV reactivation has been explored in several reports. In one case study, HCV RNA increased within 2 weeks after the first dose of rituximab and decreased about 20 weeks later.⁴ Meanwhile, The transaminase level fluctuated during this episode of HCV reactivation. Though one report showed elevated HCV viral load without synchronized abnormal liver function after the weekly rituximab regimen,⁵ our patient did experience HCV-associated hepatic injury that was confirmed by liver biopsy with Metavir score of histologic activity three and fibrosis four.

Fong et al⁶ reported that prednisone can increase HCV RNA but decrease transaminase levels in patients with chronic HCV. Henry et al⁷ discovered that prednisone did not affect replication of HCV in vitro. Therefore, the influence of human immune response to HCV is still uncertain. In comparison to HBV-infected patients, chemotherapy-associated hepatic events are less common in HCV patients. Our patient developed increment of HCV viral load and hepatic dysfunction when being treated by corticosteroid inclusion–chemotherapy and rituximab. Consequently, the incidence and severity of HCV-related hepatic dysfunction should be reconsidered in the rituximab era.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Hsieh CY, Huang HH, Lin CY, et al: Rituximab-Induced Hepatitis C Virus Reactivation After Spontaneous Remission in Diffuse Large B-Cell Lymphoma. J Clin Oncol 26:2584-2586, 2008[Free Full Text]

2. Besson C, Canioni D, Lepage E, et al: Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive patients in LNH 93 and LNH 98 Groupe d’Etude des Lymphomes de l’Adulte programs. J Clin Oncol 24:953-960, 2006[Abstract/Free Full Text]

3. Visco C, Arcaini L, Brusamolino E, et al: Distinctive natural history in hepatitis C virus positive diffuse large B-cell lymphoma: Analysis of 156 patients from northern Italy. Ann Oncol 17:1434-1440, 2006[Abstract/Free Full Text]

4. Lake-Bakaar G, Dustin L, McKeating J, et al: Hepatitis C virus and alanine aminotransferase kinetics following B-lymphocyte depletion with rituximab: Evidence for a significant role of humoral immunity in the control of viremia in chronic HCV liver disease. Blood 109:845-846, 2007[Free Full Text]

5. Aksoy S, Abali H, Kilickap S, et al: Accelerated hepatitis C virus replication with rituximab treatment in a non-Hodgkin's lymphoma patient. Clin Lab Haematol 28:211-214, 2006[CrossRef][Medline]

6. Fong TL, Valinluck B, Govindarajan S, et al: Short-term prednisone therapy affects aminotransferase activity and hepatitis C virus RNA levels in chronic hepatitis C. Gastroenterology 107:196-199, 1994[Medline]

7. Henry SD, Metselaar HJ, van Dijck J, et al: Impact of steroids on hepatitis C virus replication in vivo and in vitro. Ann N Y Acad Sci 1110:439-447, 2007[CrossRef][Medline]

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