Tuesday, April 5, 2011

Acute pericarditis due to pegylated interferon alpha therapy for chronic HCV hepatitis - Case report

ISSN 1471-230X

Article type Case report
Submission date 5 December 2010
Acceptance date 31 March 2011
Publication date 31 March 2011

Article URL http://www.biomedcentral.com/1471-230X/11/30

Case report
Acute pericarditis due to pegylated interferon alpha therapy for chronic HCV hepatitis - Case report

Cristina Popescu , Victoria Arama and Smaranda Gliga

BMC Gastroenterology 2011, 11:30doi:10.1186/1471-230X-11-30
Published: 31 March 2011

Abstract (provisional)

Cardiotoxicity due to interferon therapy was reported only in small case series or case reports. The most frequent cardiac adverse effects related to interferon are arrhythmias and ischemic manifestations. The cardiomyopathy and pericarditis are rare but can be life threatening. The predisposing factors for interferon cardiotoxicity were described only for ischemic manifestations and arrhythmias.

Case presentation
The authors report a case of pericarditis due to alpha interferon therapy for chronic hepatitis C, in a young woman without previous cardiac pathology. The clinical manifestations started during the 7-th month of interferon treatment. The cessation of interferon was necessary. After interferon discontinuation the patient recovered, with complete resolution of pericarditis. The patient scored 9 points on the Naranjo ADR probability scale, indicating a very probable association between pericarditis and interferon administration.

If a patient receiving interferon therapy complains of chest pain of sudden onset, a cardiac ultrasound should be performed in order to rule out pericarditis. We point out the possibility of an infrequent but severe adverse effect of interferon therapy.


Pegylated interferon plus ribavirin represents the gold standard therapy for hepatitis C virus
(HCV) but various side effects may occur, limiting its efficacy [1, 2]. Although some of these
adverse effects are rarely reported, their severity can be higher than expected, sometimes leading
to a life-threatening event. The diversity of the described adverse effects may increase because
of the high number of patients who receive treatment for HCV hepatitis. Their monitoring and
reporting is important in order to facilitate subsequent recognition of similar cases.
We report a case of acute pericarditis without tamponade which was correlated with pegylated
interferon alpha 2a treatment for chronic HCV hepatitis.


A 38-year-old white female, without previous cardiac pathology, was being monitored and
treated for chronic HCV hepatitis, genotype I virus. She was started on a combination treatment
with peginterferon alpha 2a (180μg weekly) and ribavirin (1000mg daily, according to her body
weight). The patient had complete early virologic response (HCV-RNA was undetectable at 12
weeks of treatment). In the first seven months of treatment no severe side effects (hematologic,
endocrine, ophthalmic or autoimmune) were observed.

In the 7th month of treatment the patient accused chest pain, dry cough, fatigue, dyspnea, without
fever and she presented herself to the emergency room.
On physical examination we found: tachypnea (22-24/min), tachycardia (96/min), a blood
pressure of 100/70 mmHg with pulmonary and abdominal examination within the normal limits.

Cardiac examination revealed a third heart sound over the precordium as well as muffled cardiac
sounds. The pulmonary X-ray was normal and the ECG showed no specific repolarisation
abnormalities. Trans-thoracic cardiac ultrasonography revealed a pericardial effusion without
tamponade. Laboratory data revealed: mild leukopenia, anemia, thrombocytopenia (which didn’t
need reduction of interferon or ribavirin doses), minor biological inflammatory syndrome (CRP
– 17mg/l). The hepatic enzymes were normal, HCV-RNA was undetectable, serological tests for
viruses and bacteria which could have explained the pericarditis were negative: ECHO,
Coxsackie, adenovirus, influenza virus, parainfluenza virus, EBV, CMV, HIV, Mycoplasma
pneumoniae, Chlamydia pneumoniae, Rickettsia spp, Legionella pneumophila, Borrelia
burgdorferii. Serological tests for viruses remained negative for the following 2 weeks.

Quantiferon TB gold was negative. The patient didn’t receive antimycobacterial medication. The
ASO titer was in the normal range. Autoimmune tests were performed, with negative antinuclear
factor, anti-DNA antibodies, p ANCA, c ANCA, anti-mitochondrial antibody, anti-Ro
and anti-La antibodies and negative cryoglobulinemia. Thyroid function tests were normal, and
anti tyreo-peroxidase antibodies were absent.

The antiviral medication was stopped and the patient received ibuprofen. The symptoms
disappeared and the pericardial effusion resolved in 15 days.
Because the patient was infected with genotype 1 virus and detection of HCV-RNA at 4 weeks
of treatment was not performed (in order to confirm a rapid virological response), the antiviral
treatment was restarted only with pegylated interferon. After the first dose of interferon
administration symptoms reappeared. The echocardiography showed an increase of pericardial
fluid (at 24 hours after interferon administration). The antiviral medication was stopped again
with rapid recovery.

Six months after discontinuation of treatment, the HCV-RNA was undetectable (the patient had
sustained virologic response).
The correlation of pericarditis with interferon administration was appreciated, for the presented
case using the Naranjo ADR probability scale, which summed up 9 points, indicating a very
probable association (table 1) [3].


Interferon plays an essential role in the mechanisms of defense against infections, being
produced by a variety of cells. Until now two types of interferon have been identified: type I
(alpha and beta interferon), which blocks the translation and viral replication and type II (gamma
interferon), which initiates the synthesis of chemical substances with antiviral properties. [4] On
top of the positive effects, the administration of interferon can be associated with many
unwanted adverse effects because of the destruction of uninfected cells. The prevalence of life
threatening complications during the interferon treatment is less then 1%. The cardio toxicity of
interferon has been even rarely reported, only in small series of patients, and often just in isolated
cases. [5] Among the three types of interferon, the alpha interferon is the most cardio toxic,
followed by beta and gamma interferon.

The mechanism through which interferon is cardio toxic has not been clearly demonstrated
[6, 7], but it is presumed that at least two factors are implicated: the deterioration of endothelial
cells inducing the overlay of immune complexes at this level; and stimulation of TNF alpha, IL
2, IL 6, IL 1 release, that influence the vasopressor response.

The most common cardio toxic clinical effects of interferon are: arrhythmias- 58 %, acute
coronary syndrome- 21 %, cardiomiopathies-12 % and other manifestations - 9 % (including
pericarditis) [5]. There are no described predisposing factors for interferon cardio toxicity.  
Acute pericarditis is determined by a multitude of causes: infectious, neoplastic, uremia,
autoimmune, traumatic, drug induced. Concerning drug toxicity, there have been reported cases
of acute pericarditis after the administration of: hydralazine, procainamide, izoniazid,
phenylbutazone, dantrolene, doxorubicin, penicillin, these situations being extremely rare.

Interferon is not cited by the ESC Guidelines on the Diagnosis and Management of Pericardial
Diseases [8] as one of the causes of drug induced pericarditis.
Acute pericarditis, as a consequence of interferon treatment is extremely rare. So far, very few
cases of pericarditis related to administration of interferon have been reported; some of these
patients received interferon for neoplastic diseases such as melanoma or acute leukemia [9, 10].
The role of ribavirin in the pathogenesis of pericarditis could be considered. In our case, we
restarted only interferon therapy (after two weeks of discontinuation), which concluded in the
reappearance of pericardial effusion.

Six cases of pericarditis due to interferon alpha have been reported in patients with chronic HCV
hepatitis. Three of these patients had an underlying pathology that could explain the pericarditis:
Sikole et al. reported a case of pericarditis among hemodialysis patients receiving interferon for
hepatitis C [11], Suarez A et al described a case of pericarditis in a patient with cryoglobulinemia
[12], Boonen et al. reported a case of pericarditis during the treatment of chronic HCV hepatitis
as part of a lupus-like syndrome, with clinical manifestations of auto-immune pathologies [13].
Recently Kazuahi Nishio et al described a case of pericarditis related to pegylated interferon
therapy for HCV hepatitis. This patient had positive anti-DNA and anti-ds DNA IgM antibodies
[14]. The case of pericarditis reported by Gressens B et al in conjunction with the
administration of interferon occurred four months after stopping the treatment [15].
We are reporting a very rare adverse effect of pegylated interferon treatment- acute toxic
pericarditis, this being the second case observed in a patient with no underlying pathology,
described in the medical literature. The first case was reported by Wisniewski B et al; pericarditis
occurred in this case after the first dose of interferon. [16]

In summary, we report a patient without any history of cardiac disease who developed
pericarditis after interferon treatment. Reappearance of symptoms when the antiviral treatment
was restarted indicates a strong correlation between drug and adverse effects [3]. The effect of
the virus itself is quite unlikely (undetectable HCV-RNA). The clinical and biological markers of
a possible associated autoimmune pathology were absent. We excluded a viral or bacterial
(including tuberculosis) etiology of pericarditis.


We consider that in a patient receiving interferon, pericarditis must be evoked if the patient
accuses sudden chest pain. It is of most importance that a cardiac ultrasound should be
performed in a situation like this.

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