Introduction:
Hepatitis A virus (HAV) is a positive-strand RNA virus of the
picornaviridae family. It may affect individuals at any age, from
infancy to maturity. The majority of children afflicted are
asymptomatic, with just 30% developing symptomatic hepatitis, whereas
80% of adults exposed have clinical signs and symptoms of hepatitis(1). Hepatitis A, unlike hepatitis B and C, does not
cause chronic liver damage and normally cures in approximately two
months (2). The majority of viral hepatitis A
transmission occurs through the feco-oral route. The most common form of
transmission is food-borne transmission. Hepatitis A outbreaks have
happened in the past across the world and are assumed to have a cyclical
recurrence pattern (3). Most of the children infected
are asymptomatic but symptoms can range from mild to severe. Most common
symptoms are fever, diarrhea, anorexia, abdominal pain, jaundice. Adults
are more often symptomatic than children and are more prone to develop
complications.
Host immune response to HAV results in cellular death. An excessive
immune response can lead to severe hepatitis and can rarely cause
fulminant hepatitis (4). Complications include
”cholestatic hepatitis, relapsing hepatitis, autoimmune hepatitis,
Fulminant hepatic failure, acute kidney injury and other extrahepatic
manifestations”. Rare Extrahepatic manifestations include anemia, acute
pancreatitis, neuritis, pleural and pericardial effusion, myocarditis.
The infection can lead to fulminant hepatitis and death in some patients(5). After recovery, it provides a lifelong immunity
There is no specific treatment for Hepatitis A. Supportive treatment is
usually provided and the patient completely recovers from the disease
most of the time within 2 months to 6 months. In some patients, it can
lead to fulminant hepatic failure, severe extrahepatic manifestation and
even death.
Hepatitis A leading to pericarditis, myocarditis, and pleural or
pericardial effusion has been reported in the literature but is
extremely rare (6,7). Cases of complete heart block
following infectious hepatitis have been published (8)and myocarditis following viral infection can lead to complete heart
block (9,10). Complete heart block secondary to
amoebic hepatitis and measles are also reported in the literature(11,12) but we have not found any case report of
complete heart block secondary to hepatitis A in the literature.
Case Report:
An 8 years old female child, presented to emergency with complaints of
high-grade fever for seven days and yellow discoloration of the body and
sclera for 3 days associated with vomiting and abdominal pain. On
examination, she was pale, had a heart rate of 54 beats/min, a feeble
pulse, respiratory rate of 35/min, and blood pressure was not
recordable. Normal lung sounds and normal heart sounds with bradycardia.
She was afebrile on presentation; blood glucose level was 122 mg/dl. She
was immediately admitted to the High Dependency Unit of Pediatrics, and
then to the Pediatric Intensive care Unit (PICU)
Lab investigations were ordered. Leukocytes were normal. The patient had
raised ALT levels (995U/L), and raised bilirubin levels 6.6mg/dl. The
patient had Sodium levels at 126mEq/L, potassium levels at 4.8 mEq/L and
Calcium levels at 7.8mg/dl. The patient had raised hepatitis A (HAV) IgM
levels. She was primarily diagnosed as a case of acute viral hepatitis
due to the hepatitis A virus (HAV). Cardiac enzymes were found raised.
CPK at 812 U/L, CKMB at 122 U/L and LDH at 1264U/L. (table 1)
Supplemental oxygen was initiated. Electrolytes were corrected
immediately and IV calcium was administered. She was clinically
suspected to be a case of viral myocarditis secondary to acute viral
hepatitis.
Abdominal ultrasound showed pericholecystic edema, normal-sized liver,
mild abdominal and pelvic ascites and mild bilateral pleural effusion on
chest USG. Chest X-ray was done which showed pleural effusion on the
right side with a blunt costophrenic angle and cardiomegaly. (Figure 1).
ECG was done, which showed complete AV dissociation with a fixed atrial
rate of 13 bpm and fixed ventricular rate of 46 bpm and varying PR
intervals. (Figure 2) The patient was managed in cardiology, and a
temporary Pacemaker (TPM) was placed immediately. The patient was
medically managed with atropine and dopamine.
On the third day of admission, oxygen saturation dropped further low to
77%. On examination, the patient was tachypneic, apprehensive, severely
distressed, with nasal flaring, pulse was not palpable and there was
generalized puffiness along with pedal edema. There were bilateral
crepitations in the lower zone; the abdomen was distended and tendered
along with the firm liver. ABGs were ordered, which showed a Blood pH of
7.49, HCO3 of 13.7 mEq/L, PCo2 of 17.9 mm Hg, and PO2 of 84 mm Hg. The
Patient was shifted to CPAP and was considered at risk of cardiogenic
shock. The patient was managed with inotropes. Dobutamine, rivaroxaban
in lower doses and furosemide (0.5mg/kg) were added to the treatment
regimen. The patient died on the fourth day of admission (DOA) due to
cardiogenic shock. The case timeline is shown in figure 3
Discussion:
The patient had no history of any cardiovascular disease and was
admitted to the pediatric ICU as a case of acute viral hepatitis with
secondary or associated cardiac involvement, with clinically diagnosed
myocarditis and complete heart block. The patient was strongly suspected
of complete heart block due to viral myocarditis secondary to acute
viral hepatitis due to HAV which is a very rare complication of HAV
infection. The child had not been diagnosed with any congenital cardiac
anomaly or congenital heart block. She had never been hospitalized
before it. She never had any apparent cardiac risk and the family
history was negative for any cardiomyopathy.
HAV infection is most of the time asymptomatic but can lead to fulminant
hepatitis in some cases and some extra-hepatic manifestations like
myocarditis (13). Mechanism leading to myocarditis in
HAV infection is not known but it is believed that the immune response
to infected cell play a central role in myocarditis(13). WHO has reported that around 7134 people died
from hepatitis A worldwide in 2016. USA (CDC) reported around 12474
cases of hepatitis A in 2018.
Myocarditis-induced heart block has been reported in the literature(14). Viral pathogens are the leading cause of
myocarditis. Myocarditis due to COVID-19 has been one of the dangerous
complications of COVID-19 (15,16). Other infectious
causes of myocarditis reported in the literature include measles,
amoebic hepatitis, Lyme disease, herpes, coxsackie, adenovirus etc(17,18). Cases of viral myocarditis present with
abnormal ECG and raised cardiac markers. Definite diagnostic
investigations usually required in these cases are echocardiography,
cardiac MRI, and endomyocardial biopsy but the critical condition, need
of a pacemaker and limited resources often makes it difficult to
properly investigate a case of myocarditis. One should be cautious of
myocarditis secondary to HAV infection and the patient must be screened
with the help of cardiac markers in case the patient develops
hypotension. Clinically suspected cases should be investigated at the
earliest, and cases should be managed with supplemental oxygen and
inotrope therapy (19). Temporary Pacemaker and
automatic implantable cardioverter-defibrillator (AICD) should be
considered at the earliest. The use of a ventricular assist device is
beneficial and should be offered considering the deteriorating condition
of a patient and to those at risk of cardiogenic shock. Complete heart
block due to myocarditis can be managed with pacemaker implantation but
persistent low blood pressure even after installation of a pacemaker (as
in this case) increases the risk of mortality in the child(20).
The cardiac MRI and myocardial biopsy are investigations of choice to
diagnose myocarditis (21). Clinical picture of
cardiomegaly and deranged cardiac enzymes without any ischemic
manifestations raise clinical suspicion of myocarditis. We were not able
to get a cardiac MRI of the patient because of the critical condition of
the patient and the necessity of pacemaker; we had clinically diagnosed
the patient as a case of viral myocarditis, leading to a complete heart
block.
Conclusion:
Acute viral hepatitis caused by the hepatitis A virus can be complicated
by complete heart block secondary to viral myocarditis and may
necessitate the installation of a temporary pacemaker (TPM) and can also
lead to death due to cardiogenic shock. Specialized pediatric cardiac
care is necessary to timely diagnose the condition. Close monitoring of
the deteriorating cardiac condition of the child is important to prevent
death. It is important to timely consider cardiac complications of
symptomatic HAV infections, and consider early shifting of patients to
Mechanical Circulatory Support.
Abbreviations: Hepatitis A virus (HAV), Temporary pace-maker
(TPM), Electrocardiograph (ECG), Atrioventricular dissociation (AV
dissociation), Pediatric Intensive Care unit (PICU), Alanine
Transaminase (ALT), Aspartate aminotransferase (AST), Creatine
Phosphokinase (CPK), Creatine Kinase myocardial Band (CK-MB), Lactate
dehydrogenase (LDH), Continuous positive airway pressure (CPAP), Day of
Admission (DOA)