- Email: [email protected]
Hepatitis C virus (HCV) reactivation during fingolimod treatment for relapsing and remitting multiple sclerosis
Author’s Accepted Manuscript Hepatitis C Virus (HCV) reactivation during fingolimod treatment for relapsing and remitting multiple sclerosis Asako Tagawa, Tomoko Ogawa, Syuichi Tetsuka, Mieko Otsuka, Ritsuo Hashimoto, Hiroyuki Kato, Katsuyoshi Ando, Hiroki Tanabe www.elsevier.com/locate/msard
PII: DOI: Reference:
S2211-0348(16)30131-6 http://dx.doi.org/10.1016/j.msard.2016.08.003 MSARD450
To appear in: Multiple Sclerosis and Related Disorders Received date: 9 March 2016 Revised date: 1 August 2016 Accepted date: 4 August 2016 Cite this article as: Asako Tagawa, Tomoko Ogawa, Syuichi Tetsuka, Mieko Otsuka, Ritsuo Hashimoto, Hiroyuki Kato, Katsuyoshi Ando and Hiroki Tanabe, Hepatitis C Virus (HCV) reactivation during fingolimod treatment for relapsing and remitting multiple sclerosis, Multiple Sclerosis and Related Disorders, http://dx.doi.org/10.1016/j.msard.2016.08.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Hepatitis C Virus (HCV) reactivation during fingolimod treatment for relapsing and remitting multiple sclerosis
Asako Tagawa 1, Tomoko Ogawa 1, Syuichi Tetsuka 1, Mieko Otsuka 1 , Ritsuo Hashimoto 1, Hiroyuki Kato 1, Katsuyoshi Ando 2, Hiroki Tanabe 2
1 Departments
of Neurology, International University of Health and Welfare
Hospital, 537-3, Iguchi Nasushiobara City, Tochigi, 329-2763, Japan 2 Departments
of Gastroenterology, International University of Health and
Welfare Hospital, 537-3, Iguchi Nasushiobara City, Tochigi, 329-2763, Japan
Email: [email protected]
Abstract We here report a case involving a 38-year-old female with relapsing and remitting multiple sclerosis who developed reactivation of hepatitis C virus (HCV) during administration of fingolimod for 16 months. She had been previously treated for chronic hepatitis C with pegylated interferon and
ribavirin, and kept an undetectable HCV-RNA state for more than 4 years before fingolimod starting.
Although the increased risk for viral reactivation,
for example of herpes zoster virus and varicella-zoster virus, during fingolimod treatment is known, this is, to our knowledge, the first case report of HCV reappearance.
KewWords
fingolimod, multiple sclerosis, hepatitis C virus, reactivation
1. Introduction Multiple
sclerosis
(MS)
is
a
relapsing
and
remitting
inflammatory
demyelinating disease. In recent years, several disease modifying drugs have been widely used for preventing relapse of inflammation. Fingolimod has been approved as the first oral drug for relapsing and remitting multiple sclerosis (RRMS). It functionally antagonizes sphingosine 1-phosphate receptor-1 (S1P1) on T cells and consequently inhibits S1P/S1P1-dependent C-C chemokine receptor type 7 (CCR7)+ naïve and central memory T cells exporting from secondary lymphoid organs (Mehling et al., 2008). Fingolimod has been also shown to attenuate the antiviral immune response in MS patients (Ricklin et a., 2013).
Some cases of viral reactivation, such as due to
varicella-zoster virus (McNamara et al., 2013), Epstein-Barr virus (Marrone et al., 2014), herpes simplex virus (HSV-1) (Pfender et al., 2015) have been reported during fingolimod treatment.
In recent, a case of progressive
multifocal leukoencephalopathy (PML) under fingolimod administration prior with other immunosuppressant other than natalizumab has been reported (Gyang et al, 2016). Concerning hepatitis virus, although the host immune reaction under fingolimod treatment remains unknown, the Japanese Guideline for the Management for Multiple Sclerosis emphasizes the us e of fingolimod with extreme caution for hepatitis virus-positive patients. Reactivation of hepatitis B virus (HBV) while using an immunosuppressive agent might occur, as outlined in the Japan Society of Hepatology Guidelines for the Management of Hepatitis B Virus Infection 2015. In contrast, hepatitis
C virus (HCV) reactivation is very uncommon (Marrero et al., 2014). Of note, to date, there has been no report of HCV reactivation in a patient with successful treatment for chronic hepatitis, that is, undetectable HCV-RNA for more than 4 years, during fingolimod administration. Here, for the first time, we report a unique case involving a patient with RRMS who developed HCV reactivation during fingolimod treatment.
Case report A 38-year-old woman developed sensory and motor disturbance on the left upper and lower limbs in September 2010. The symptoms spontaneously remitted. However, spastic gait on the left lower extremities and urinary disturbance appeared in March 2011, and she hence consulted our hospital. She had a history of chronic HCV genotype 2 hepatitis C, for which she achieved a HCV-RNA clearance after treatment with pegylated interferon and ribavirin for 24 weeks. At the first examination, her Expanded Disability Status Scale (EDSS) was 3.5. Brain and spinal cord T2 magnetic resonance imaging revealed multiple high-signal lesions in the periventricular white matter and cervical and thoracic spinal cord (Figure). Serological examination revealed positive anti-HCV antibody (titer, 8.70). However, no HCV-RNA or liver dysfunction was observed. No other abnormality was seen on serological examination. Serum anti-aquaporin 4 antibody, examined with a cell-based assay, was negative. On cerebrospinal fluid examination, the immunoglobulin G index was found to be elevated to 0.86. Consequently, she was diagnosed with RRMS, and interferon-β1b (Betaferon®) treatment was started. However, we stopped interferon-β1b treatment 10 months later because of a continuous
high fever after the injection and a skin reaction. As a result, daily oral administration of fingolimod 0.5 mg (Gilenya®) was started on April, 2013. At this time, her EDSS score was 4.0. Serum HCV-RNA was not detected and her liver function was normal. Her clinical course had been stable for 14 months after fingolimod starting, except for a mild relapse on the upper cervical cord 5 months after starting fingolimod, which spontaneously remitted. However, she was obliged to stop medication for 1 month because she could not attend our hospital temporarily from family reason.
Then, we restart administration of
Gilenya® at 16 months after the initial induction.
From the restarting period,
mild liver dysfunction began to be observed, and her aspartate transaminase and alanine transaminase levels were elevated to 197 IU/l and 348 IU/l, respectively. Her serum HCV-RNA was positive (5.2 logIU/ml) and the HCV core protein was elevated to 508 fmol/L. The viral genotype was group 2, which was same type as that initially detected, suggesting viral reactivation. The serum anti-mitochondrial, anti-hemagglutinin, and anti-HBV antibodies were negative.
Other
virus
infections
such
as
Epstein-Barr
virus
and
cytomegalovirus were also excluded. Consequently, fingolimod administration was stopped, but liver dysfunction and HCV-RNA positivity were observed for more than 6 months after the discontinuation, indicating persistence of chronic hepatitis. Treatment with sofosbuvir for 12 months and ribavirin for 13 months could successfully induced HCV-RNA clearance, and her liver function was recovered. However, a relapse of the upper cervical cord occurred within one year after stopping fingolimod and her EDSS score deteriorated to 6.0.
Discussion
To our knowledge, this is the first report of a patient with successfully treated chronic hepatitis C and a HCV-RNA undetectable state for several years in whom HCV-RNA reappeared and the liver function worsened during fingolimod administration for RRMS. Reactivation of HCV is uncommon compared with that of HBV (Marrero et al., 2014). In recent years, combination of pegylated interferon and ribavirin treatment has been shown to successfully induce an sustained serological response (SVR), that is, undetectable HCV-RNA for more than six months’ duration in HCV-positive patients 7,8 . However, in 2014, HCV-RNA recurrence was observed in 19% of patients who achieved a treatment-induced viral suppression, and the risk for reactivation of HCV following immunosuppressive therapy has been reported (Grebely et al., 2014). Rituximab, cytarabine, and etoposide are the most commonly used agents preceding HCV reactivation (Marrero et al., 2014; Watanabe et al., 2013). However, many patients with HCV reactivation during with these agents were simultaneously treated with corticosteroids (Watanabe et al., 2013).
From a
study examining the chemotherapy-related HCV reactivation, more than 50% of 33 patients had mild to moderate ALT elevation after 2-3 weeks after the withdrawal of chemotherapy (Zuckerman et al., 1998).
Similarly, in our case,
mild liver dysfunction was began to be observed from 1 month after discontinuation of fingolimod.
Small quantities of HCV-RNA may persist in
the liver tissue, macrophages, and monocytes in the peripheral blood even after adequate treatment (Redkiwski et al, 2005).
Such continuous viral
presence can persistently affect the cellular and humoral immune responses, and
acute
inflammation
can
occur
under
the
administration
of
immunosuppressive agents. Fingolimod blocks the egression of lymphocytes
from the lymphoid tissue to the blood circulation by leading to a marked reduction of CCR7+ naïve and central memory T cells and a relative increase of effector memory T cells, which are regarded as the main T-cell population for the control of viral reactivation (Ricklin et al., 2013). However, they reported that the absolute number of CD4+ effector memory T cells was reduced in fingolimod-treated patients. In their investigation, varicella zoster virus- and Epstein-Barr virus-specific interferon-γ-producing T cells were reduced, and viral DNA in the saliva was observed in some patients, indicating subclinical reactivation (McNamara et al., 2013).
In an in vitro investigation using
genotype 2a HCV-infected cells, Ciesek et al.
showed that addition of
fingolimod to the cell culture reduced replication of HCV-RNA (Ciesek et al., 2008). However, clinical investigations examining the relevance of fingolimod in terms of HCV reactivation have been not reported. Our case emphasizes that, when treating RRMS patients with fingolimod, the possibility for HCV appearance should be kept in mind, even in cases where treatment-induced HCV-RNA clearance has been previously achieved.
Acknowledgement We thank Dr. Fujihara K and Dr. Ichiro Nakashima of Department of Neurology, Tohoku University School of Medicine for examining the serum anti-aquaporin-4 antibody.
Conflict of interest statement The authors declare there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial sectors.
References Ciesek S, Steinmann E, et al., 2008. The Suppressive Effect That Myriocin Has on Hepatitis C Virus RNA Replication Is Independent of Inhibition of Serine Palmitoyl Transferase.
J Infec Dis. 198, 1-3.
Grebely J, Pham ST, Matthews GV, et al., 2012.
Hepatitis C virus reinfection
and superinfection among treated and untreated participants with recent infection. Hepatology. 55, 1058-1069. Gyang TV, Hamel J, et al, 2016.
Fingolimod-associated PML in a patient with
prior immunosuppression. Neurology. 86,1843-1845. Marrero LB, Pyrsopoulos N., 2014.
Hepatitis B and Hepatitis C Reactivation
in the Biological Era. J Clin Transl Hepatol. 2, 240-246. Marrone A, Signoriello E, et al., 2014. Epstein Barr virus infection reactivation as a possible trigger of primary biliary cirrhosis-like syndrome in a patient with multiple sclerosis in the course of fingolimod treatment. Infez Med. 22,331-336. McNamara PH, Redmond JM, et al., 2013. Varicella-zoster virus encephalitis and
vasculopathy
in
a
patient
treated
with
fingolimod.
Neurology.81,306-311. Mehling M, Brinkmann V, et al., 2008.
FTY720 therapy exerts differential
effects on T cell subsets in multiple sclerosis. Neurology. 71, 1261-1267. Pfender N, Jelcic I, et al., 2015. Reactivation of herpesvirus under fingolimod:
a case of severe herpes simplex encephalitis. Neurology. 84, 2377-2378. Redkiwski M, Gallegos-Orozco JF, et al., 2005. Persistence of Hepatitis C Virus in Patients Successfully Treated for Chronic Hepatitis C. Hepatology. 41,106-114. Ricklin
ME,
Lorscheider
J,
et
al.,
2013.
T-cell
response
against
virecella-zoster virus in fingolimod-treated MS patients. Neurology. 81,1-8. Watanabe T, Tanaka Y., 2013. Reactivation of hepatitis virus following immunomodulating systemic chemotherapy. Zuckerman E, Zuckerman T, et al., 1998.
Hepatol Res. 43, 113-121.
Liver dyysfuntion in a patients
infected with hepatitis C virus undergoing chemotherapy for hematologic malignancies.
Cancer. 83, 1224-1230.
Figure Legend Brain (a,b) and cervical (c,d) magnetic resonance image at the first examination. (a) T2-weighted image shows periventricular high intensity area. (b) This periventricular lesion revealed low signal black hole on T1-weghited image. (c) Multiple high signal areas were observed in cervical spinal cord on T2 -whighet image. (d) Axial T2-weighted image revealed widely spread high signal areas on the cervical cord.
Highlights
・We present a case of HCV reactivation during fingolimod treatment for RRMS.
・This is the first case report of HCV reappearance under fingolimod administration.
・HCV recurrence after successful anti-viral treatment is uncommon.
・When using fingolimod, possibility for HCV reactivation should be kept in mind
PII: DOI: Reference:
S2211-0348(16)30131-6 http://dx.doi.org/10.1016/j.msard.2016.08.003 MSARD450
To appear in: Multiple Sclerosis and Related Disorders Received date: 9 March 2016 Revised date: 1 August 2016 Accepted date: 4 August 2016 Cite this article as: Asako Tagawa, Tomoko Ogawa, Syuichi Tetsuka, Mieko Otsuka, Ritsuo Hashimoto, Hiroyuki Kato, Katsuyoshi Ando and Hiroki Tanabe, Hepatitis C Virus (HCV) reactivation during fingolimod treatment for relapsing and remitting multiple sclerosis, Multiple Sclerosis and Related Disorders, http://dx.doi.org/10.1016/j.msard.2016.08.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Hepatitis C Virus (HCV) reactivation during fingolimod treatment for relapsing and remitting multiple sclerosis
Asako Tagawa 1, Tomoko Ogawa 1, Syuichi Tetsuka 1, Mieko Otsuka 1 , Ritsuo Hashimoto 1, Hiroyuki Kato 1, Katsuyoshi Ando 2, Hiroki Tanabe 2
1 Departments
of Neurology, International University of Health and Welfare
Hospital, 537-3, Iguchi Nasushiobara City, Tochigi, 329-2763, Japan 2 Departments
of Gastroenterology, International University of Health and
Welfare Hospital, 537-3, Iguchi Nasushiobara City, Tochigi, 329-2763, Japan
Email: [email protected]
Abstract We here report a case involving a 38-year-old female with relapsing and remitting multiple sclerosis who developed reactivation of hepatitis C virus (HCV) during administration of fingolimod for 16 months. She had been previously treated for chronic hepatitis C with pegylated interferon and
ribavirin, and kept an undetectable HCV-RNA state for more than 4 years before fingolimod starting.
Although the increased risk for viral reactivation,
for example of herpes zoster virus and varicella-zoster virus, during fingolimod treatment is known, this is, to our knowledge, the first case report of HCV reappearance.
KewWords
fingolimod, multiple sclerosis, hepatitis C virus, reactivation
1. Introduction Multiple
sclerosis
(MS)
is
a
relapsing
and
remitting
inflammatory
demyelinating disease. In recent years, several disease modifying drugs have been widely used for preventing relapse of inflammation. Fingolimod has been approved as the first oral drug for relapsing and remitting multiple sclerosis (RRMS). It functionally antagonizes sphingosine 1-phosphate receptor-1 (S1P1) on T cells and consequently inhibits S1P/S1P1-dependent C-C chemokine receptor type 7 (CCR7)+ naïve and central memory T cells exporting from secondary lymphoid organs (Mehling et al., 2008). Fingolimod has been also shown to attenuate the antiviral immune response in MS patients (Ricklin et a., 2013).
Some cases of viral reactivation, such as due to
varicella-zoster virus (McNamara et al., 2013), Epstein-Barr virus (Marrone et al., 2014), herpes simplex virus (HSV-1) (Pfender et al., 2015) have been reported during fingolimod treatment.
In recent, a case of progressive
multifocal leukoencephalopathy (PML) under fingolimod administration prior with other immunosuppressant other than natalizumab has been reported (Gyang et al, 2016). Concerning hepatitis virus, although the host immune reaction under fingolimod treatment remains unknown, the Japanese Guideline for the Management for Multiple Sclerosis emphasizes the us e of fingolimod with extreme caution for hepatitis virus-positive patients. Reactivation of hepatitis B virus (HBV) while using an immunosuppressive agent might occur, as outlined in the Japan Society of Hepatology Guidelines for the Management of Hepatitis B Virus Infection 2015. In contrast, hepatitis
C virus (HCV) reactivation is very uncommon (Marrero et al., 2014). Of note, to date, there has been no report of HCV reactivation in a patient with successful treatment for chronic hepatitis, that is, undetectable HCV-RNA for more than 4 years, during fingolimod administration. Here, for the first time, we report a unique case involving a patient with RRMS who developed HCV reactivation during fingolimod treatment.
Case report A 38-year-old woman developed sensory and motor disturbance on the left upper and lower limbs in September 2010. The symptoms spontaneously remitted. However, spastic gait on the left lower extremities and urinary disturbance appeared in March 2011, and she hence consulted our hospital. She had a history of chronic HCV genotype 2 hepatitis C, for which she achieved a HCV-RNA clearance after treatment with pegylated interferon and ribavirin for 24 weeks. At the first examination, her Expanded Disability Status Scale (EDSS) was 3.5. Brain and spinal cord T2 magnetic resonance imaging revealed multiple high-signal lesions in the periventricular white matter and cervical and thoracic spinal cord (Figure). Serological examination revealed positive anti-HCV antibody (titer, 8.70). However, no HCV-RNA or liver dysfunction was observed. No other abnormality was seen on serological examination. Serum anti-aquaporin 4 antibody, examined with a cell-based assay, was negative. On cerebrospinal fluid examination, the immunoglobulin G index was found to be elevated to 0.86. Consequently, she was diagnosed with RRMS, and interferon-β1b (Betaferon®) treatment was started. However, we stopped interferon-β1b treatment 10 months later because of a continuous
high fever after the injection and a skin reaction. As a result, daily oral administration of fingolimod 0.5 mg (Gilenya®) was started on April, 2013. At this time, her EDSS score was 4.0. Serum HCV-RNA was not detected and her liver function was normal. Her clinical course had been stable for 14 months after fingolimod starting, except for a mild relapse on the upper cervical cord 5 months after starting fingolimod, which spontaneously remitted. However, she was obliged to stop medication for 1 month because she could not attend our hospital temporarily from family reason.
Then, we restart administration of
Gilenya® at 16 months after the initial induction.
From the restarting period,
mild liver dysfunction began to be observed, and her aspartate transaminase and alanine transaminase levels were elevated to 197 IU/l and 348 IU/l, respectively. Her serum HCV-RNA was positive (5.2 logIU/ml) and the HCV core protein was elevated to 508 fmol/L. The viral genotype was group 2, which was same type as that initially detected, suggesting viral reactivation. The serum anti-mitochondrial, anti-hemagglutinin, and anti-HBV antibodies were negative.
Other
virus
infections
such
as
Epstein-Barr
virus
and
cytomegalovirus were also excluded. Consequently, fingolimod administration was stopped, but liver dysfunction and HCV-RNA positivity were observed for more than 6 months after the discontinuation, indicating persistence of chronic hepatitis. Treatment with sofosbuvir for 12 months and ribavirin for 13 months could successfully induced HCV-RNA clearance, and her liver function was recovered. However, a relapse of the upper cervical cord occurred within one year after stopping fingolimod and her EDSS score deteriorated to 6.0.
Discussion
To our knowledge, this is the first report of a patient with successfully treated chronic hepatitis C and a HCV-RNA undetectable state for several years in whom HCV-RNA reappeared and the liver function worsened during fingolimod administration for RRMS. Reactivation of HCV is uncommon compared with that of HBV (Marrero et al., 2014). In recent years, combination of pegylated interferon and ribavirin treatment has been shown to successfully induce an sustained serological response (SVR), that is, undetectable HCV-RNA for more than six months’ duration in HCV-positive patients 7,8 . However, in 2014, HCV-RNA recurrence was observed in 19% of patients who achieved a treatment-induced viral suppression, and the risk for reactivation of HCV following immunosuppressive therapy has been reported (Grebely et al., 2014). Rituximab, cytarabine, and etoposide are the most commonly used agents preceding HCV reactivation (Marrero et al., 2014; Watanabe et al., 2013). However, many patients with HCV reactivation during with these agents were simultaneously treated with corticosteroids (Watanabe et al., 2013).
From a
study examining the chemotherapy-related HCV reactivation, more than 50% of 33 patients had mild to moderate ALT elevation after 2-3 weeks after the withdrawal of chemotherapy (Zuckerman et al., 1998).
Similarly, in our case,
mild liver dysfunction was began to be observed from 1 month after discontinuation of fingolimod.
Small quantities of HCV-RNA may persist in
the liver tissue, macrophages, and monocytes in the peripheral blood even after adequate treatment (Redkiwski et al, 2005).
Such continuous viral
presence can persistently affect the cellular and humoral immune responses, and
acute
inflammation
can
occur
under
the
administration
of
immunosuppressive agents. Fingolimod blocks the egression of lymphocytes
from the lymphoid tissue to the blood circulation by leading to a marked reduction of CCR7+ naïve and central memory T cells and a relative increase of effector memory T cells, which are regarded as the main T-cell population for the control of viral reactivation (Ricklin et al., 2013). However, they reported that the absolute number of CD4+ effector memory T cells was reduced in fingolimod-treated patients. In their investigation, varicella zoster virus- and Epstein-Barr virus-specific interferon-γ-producing T cells were reduced, and viral DNA in the saliva was observed in some patients, indicating subclinical reactivation (McNamara et al., 2013).
In an in vitro investigation using
genotype 2a HCV-infected cells, Ciesek et al.
showed that addition of
fingolimod to the cell culture reduced replication of HCV-RNA (Ciesek et al., 2008). However, clinical investigations examining the relevance of fingolimod in terms of HCV reactivation have been not reported. Our case emphasizes that, when treating RRMS patients with fingolimod, the possibility for HCV appearance should be kept in mind, even in cases where treatment-induced HCV-RNA clearance has been previously achieved.
Acknowledgement We thank Dr. Fujihara K and Dr. Ichiro Nakashima of Department of Neurology, Tohoku University School of Medicine for examining the serum anti-aquaporin-4 antibody.
Conflict of interest statement The authors declare there is no conflict of interest.
Funding This research received no specific grant from any funding agency in the public, commercial sectors.
References Ciesek S, Steinmann E, et al., 2008. The Suppressive Effect That Myriocin Has on Hepatitis C Virus RNA Replication Is Independent of Inhibition of Serine Palmitoyl Transferase.
J Infec Dis. 198, 1-3.
Grebely J, Pham ST, Matthews GV, et al., 2012.
Hepatitis C virus reinfection
and superinfection among treated and untreated participants with recent infection. Hepatology. 55, 1058-1069. Gyang TV, Hamel J, et al, 2016.
Fingolimod-associated PML in a patient with
prior immunosuppression. Neurology. 86,1843-1845. Marrero LB, Pyrsopoulos N., 2014.
Hepatitis B and Hepatitis C Reactivation
in the Biological Era. J Clin Transl Hepatol. 2, 240-246. Marrone A, Signoriello E, et al., 2014. Epstein Barr virus infection reactivation as a possible trigger of primary biliary cirrhosis-like syndrome in a patient with multiple sclerosis in the course of fingolimod treatment. Infez Med. 22,331-336. McNamara PH, Redmond JM, et al., 2013. Varicella-zoster virus encephalitis and
vasculopathy
in
a
patient
treated
with
fingolimod.
Neurology.81,306-311. Mehling M, Brinkmann V, et al., 2008.
FTY720 therapy exerts differential
effects on T cell subsets in multiple sclerosis. Neurology. 71, 1261-1267. Pfender N, Jelcic I, et al., 2015. Reactivation of herpesvirus under fingolimod:
a case of severe herpes simplex encephalitis. Neurology. 84, 2377-2378. Redkiwski M, Gallegos-Orozco JF, et al., 2005. Persistence of Hepatitis C Virus in Patients Successfully Treated for Chronic Hepatitis C. Hepatology. 41,106-114. Ricklin
ME,
Lorscheider
J,
et
al.,
2013.
T-cell
response
against
virecella-zoster virus in fingolimod-treated MS patients. Neurology. 81,1-8. Watanabe T, Tanaka Y., 2013. Reactivation of hepatitis virus following immunomodulating systemic chemotherapy. Zuckerman E, Zuckerman T, et al., 1998.
Hepatol Res. 43, 113-121.
Liver dyysfuntion in a patients
infected with hepatitis C virus undergoing chemotherapy for hematologic malignancies.
Cancer. 83, 1224-1230.
Figure Legend Brain (a,b) and cervical (c,d) magnetic resonance image at the first examination. (a) T2-weighted image shows periventricular high intensity area. (b) This periventricular lesion revealed low signal black hole on T1-weghited image. (c) Multiple high signal areas were observed in cervical spinal cord on T2 -whighet image. (d) Axial T2-weighted image revealed widely spread high signal areas on the cervical cord.
Highlights
・We present a case of HCV reactivation during fingolimod treatment for RRMS.
・This is the first case report of HCV reappearance under fingolimod administration.
・HCV recurrence after successful anti-viral treatment is uncommon.
・When using fingolimod, possibility for HCV reactivation should be kept in mind