Introduction

Hepatitis A virus (HAV) is a positive-stranded Ribonucleic acid (RNA) virus that is stable at moderate temperatures and low pH, allowing for prolonged survival in the environment and fecal–oral transmission. It is known to circulate among children, especially in developing countries due to poor hygiene and lack of sanitation [1]. Although hepatitis A is usually asymptomatic or presents with mild symptoms in children, extrahepatic manifestations and, particularly, pleural effusions are rare [2, 3]. The first case of pleural effusion caused by hepatitis A as underlying infection was described as early as 1971 by Gross and Gerding [4], but this association has been scarcely reported in medical literature, with no more than 20 cases [5]. We provide herein a comprehensive literature review of 20 published cases and also report a new case, to clarify this rare entity.

Case presentation

A previously healthy 5-year-old middle eastern boy with no known history of any medical diseases presented to the emergency department with jaundice and scleral icterus, in addition to dark-colored urine, abdominal pain and distention, and slight shortness of breath beginning 4 days previously after contact history with individuals having acute hepatitis A symptoms.

He had no previous history of traveling, blood transfusion, bleeding, or previous medical, drug, or surgical treatment.

Upon presentation, during physical examination, the patient had high fever (39 °C), abdominal distention, hepatomegaly with normal spleen size, unilateral basal right-sided decreased breathing sound and dullness, as well as tachycardia and tachypnea. The rest of the examination was normal, including normal mental status.

The patient was admitted, and laboratory investigations were carried out (Tables 1, 2). HAV serology testing was positive. Chest x-ray showed unilateral right-sided pleural effusion. Chest contrast computed tomography (CT) scan delineated right effusion with significant lung collapse, plus negligible amount on the left side and clear left lung field (Figs. 1, 2). Abdominal sonography and abdominal–pelvic CT scan identified hepatomegaly and ascites. Echocardiography was free of any abnormality.

Table 1 Laboratory analysis
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Table 2 Liver biochemical markers tracing during hospital stay
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Fig. 1
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Chest x-ray showing right-sided pleural effusion

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Fig. 2
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Computed tomography showing right-sided pleural effusion

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Our patient was diagnosed with HAV acute hepatitis associated with right-side pleural effusion and ascites, confirmed by CT scan. Treatment consisted of supportive parenteral fluid and carbohydrate-enriched diet, while no diuretics or antibiotics were used. The patient was discharged on day 4 after significant improvement, achieving full clinical and biochemical recovery 5 days postdischarge with normal liver function tests and normal lung and abdominal imaging.

Discussion

Acute hepatitis caused by hepatitis A virus infection can manifest with a variety of symptoms and severities. One important factor is age, as disease severity is inversely proportional to age, with more than 80% of children having a less severe course and complete recovery within 3 months, usually being asymptomatic and anicteric. However, severity and mortality rates increase with advancing age [6].

Onset of symptoms follows a mean incubation period of approximately 30 days. Common signs and symptoms include fever, jaundice, fatigue, abdominal pain, nausea, and emesis.

Infectivity and viral shedding last from the beginning of the incubation period until 1 week after jaundice resolution, during which the virus is capable of fecal–oral spread [7].

HAV acute hepatitis may be associated with many complications, including:

  1. 1.

    Intrahepatic: such as cholestatic hepatitis, relapsing hepatitis, and autoimmune hepatitis. Rarely, hepatitis A can progress to acute liver failure.

  2. 2.

    Extrahepatic manifestations are infrequently reported in HAV acute hepatitis (6.4–8%) and may include: urticarial and maculopapular rash, acute kidney injury, autoimmune hemolytic anemia, aplastic anemia, acute pancreatitis, mononeuritis, reactive arthritis, Guillain–Barre syndrome and pleural or pericardial effusion, ascites, glomerulonephritis, polyarteritis nodosa, cryoglobulinemia, and thrombocytopenia [2, 3, 8].

Among those complications, pleural effusion is an extremely rare co-occurring condition that is scarcely reported in literature. The exact mechanism is unknown and could be multifactorial. There are many theories regarding the suspected pathogenesis of this entity:

  1. 1.

    Kurt et al. suggested direct viral invasion of pleura, immune complex deposition, or inflammatory response as probable cause, since HAV ribonucleic acid was found in the pleural fluid of a HAV viral hepatitis patient by polymerase chain reaction [9].

  2. 2.

    Dhakal et al. postulated that copresenting ascites could contribute to the pleural effusion via small diaphragmatic defects or diaphragmatic lymphatics [5, 10].

  3. 3.

    Also, a decrease in the plasma oncotic pressure as well as a transient rise of the pressure in the portal vein and/or lymphatics due to compression by the hepatic sinusoids may be a contributory factor in some cases developing ascites and pleural effusion [5, 11].

Tables 3 and 4 present a comprehensive review of available published cases of HAV with pleural effusion. All 20 patients were diagnosed by positive serum anti-HAV IgM antibodies and pleural effusion on imaging studies, regardless of the underlying nature of effusion (transudative or exudative). Most patients were from the pediatric population with average age of 9 years 8 months, while 80% (16 patients) were younger than 12 years old, with a male-to-female ratio of 9:11. Most patients presented with usual symptoms of acute hepatitis including fever, vomiting, abdominal pain, jaundice, icterus, and fatigue. Also, abdominal and chest examination revealed hepatomegaly, abdominal distention, chest dullness, and decreased airway entry and normal mental status in all patients. Laboratory testing showed an average of 3.1 albumin g/dl, with average total and direct bilirubin of 5.2 and 4 mg/dl respectively. Chest x-ray, ultrasonography, and in some patients computerized tomography or magnetic resonance imaging all generally showed similar results: most patients had right-sided (ten patients) or bilateral pleural effusion (nine patients), while one case had effusion on the left side. Also, the majority copresented with hepatomegaly (16 patients) and ascites (14 patients). Finally, thickened gallbladder wall was seen in only three patients. Moreover, pleural fluid analysis mostly showed a transudative nature of the effusion, while one patient had exudative effusion resulting from Salmonella paratyphi A superinfection, and one case had chylothorax, but pleural fluid analysis was carried out in a limited number of patients (nine).

Table 3 Literature review
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Table 4 Literature review
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All patients were managed supportively. Furthermore, no invasive additional treatments were used in five cases, including intravenous fluids, vitamin K, oral lactulose, and antibiotics prophylactically for bacterial superinfection [12, 14], while thoracostomy and chest tube insertion were only needed in one patient of chylothorax [13].

Of these patients, 95% (19 out of 20 patients) had complete recovery and resolution of pleural effusion and ascites, while one patient (5% of patients) suffered from fulminant liver failure and refractory intracranial pressure increase leading to death 2 weeks after diagnosis [14]

HAV infection is usually self-limited and does not progress to a chronic or latent state, being managed supportively, and the same applies to associated pleural effusions. Pleural effusions do not change the prognosis or require any invasive treatment.

Conclusion

Pleural effusion is a benign, rare, extrahepatic complication of HAV acute hepatitis, mostly present in juveniles as early right-sided effusion. It resolves spontaneously with supportive management. Thus, further invasive procedures would only complicate this self-resolving benign condition and should be minimized.