A Rare Case of Acute Viral Hepatitis A With Empyema and Acalculous Cholecystitis

INTRODUCTION

Hepatitis A virus (HAV) is the most common cause of acute hepatitis in children. It is one of the public health problems, particularly in low-income countries.^[1] Worldwide, an estimated 10 million people are infected with HAV annually.^[2] The incidence is associated with poor socioeconomic status and lack of access to safe water.^[3,4] While HAV typically presents with hepatic involvement, extrahepatic manifestations such as pleural effusion, ascites, and cholecystitis have been documented since 2000. However, the occurrence of empyema is rare in the paediatric population, representing ∼2% of HAV complications.^[5-7]

The pathophysiology of pleural involvement in HAV infection involves inflammatory cytokine-mediated serositis or immune complex deposition, leading to increased vascular permeability.^[8,9] The presence of exudative characteristics with elevated total leukocyte count should raise suspicion for secondary bacterial infection (empyema) rather than simple viral serositis. Full recovery occurs in 85% of the patients within three months. Mortality increases as age increases.^[10]

This report presents a comprehensive case of empyema with bacterial superinfection and acalculous cholecystitis complicating acute HAV infection in a 7-year-old child. The diagnosis was confirmed through serological testing and supported by laboratory workup, pleural fluid analysis, and imaging studies. Informed consent was obtained from the patient’s parent.

CASE REPORT

A 7-year-old male child presented to the paediatric emergency department with a five-day history of high-grade fever, vomiting, abdominal pain, and yellowish discolouration of skin and sclera. Associated features included anorexia, dark coloured urine, and fatigue. There was no history of recent travel, contact with HAV-infected patients, or ingestion of contaminated food. The patient was not previously vaccinated against hepatitis A.

On initial examination, the child appeared ill with clinical icterus. Vital signs revealed tachycardia and a respiratory rate of 28 breaths/min. Abdominal examination demonstrated tenderness in the right upper quadrant, liver palpable 5 cm below the right subcostal margin in the midclavicular line, firm edges, and tenderness present. Respiratory examination was initially normal with bilateral air entry equal and no adventitious sounds.

Complete blood count shows Hb 7.1 g/dL, total leukocyte count 50,000/μL (83/12/2/3/0), platelet count 4,06,000/μL, MCV 56.5 fL, MCH 14.8 pg, MCHC 26.2%, peripheral blood smear shows microcytic hypochromic anaemia with toxic granulations in neutrophils, consistent with severe acute infection.

Biochemical investigations like ALT 2073 IU/L, AST 3477 IU/L, ALP 600 IU/L, and GGT 285 IU/L, total serum bilirubin: 11.7 mg/dL, unconjugated bilirubin: 5.7 mg/dL, conjugated bilirubin 6.0 mg/dL, serum albumin: 2.9 g/dL, PT/INR 17.1/1.22, and CRP 35. The predominance of conjugated hyperbilirubinaemia together with markedly elevated liver enzymes is consistent with hepatocellular injury due to HAV infection. The elevated unconjugated fraction likely reflects reduced hepatic uptake due to hepatocellular dysfunction in the context of severe infection.

Serology for immunoglobulin M (IgM) anti-hepatitis A antibody was positive, while IgG anti-hepatitis A antibody was negative. Screening for tropical infections like leptospirosis, rickettsia, dengue, and malaria was negative. Initial Blood culture shows no growth after 48 h.

Abdominal ultrasonography revealed hepatomegaly with coarse parenchymal echogenicity consistent with liver parenchymal disease. The gallbladder was distended, measuring 9 mm in wall thickness without demonstrable stones, with positive Murphy’s sign on sonographic examination, confirming acalculous cholecystitis. No ascites was noted. The initial chest X-ray was normal [Figure 1].

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Figure 1: Chest radiographs of a 7-year-old male with acute Hepatitis A-associated empyema. L represents left side. (a) Chest X-ray (postero anterior view) demonstrating gross right-sided homogeneous opacification involving the right middle and lower zones with obliteration of the right costophrenic angle, rightward tracheal and mediastinal shift, and relative sparing of the right apex, consistent with a large right-sided pleural effusion. Blue arrow indicates homogenous opacification (i), (b) Post ICD insertion, showing interval reduction of the right-sided pleural effusion with improved aeration of the right lower zone and partial re-expansion of the right lung. Green arrow indicates ICD insertion (ii). Red arrow indicates partial re-expansion of right lung (iii). ICD: Intercostal drainage.

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Following admission, the patient showed initial symptomatic improvement with antipyretic, IV fluids, and vitamin K. However, on the 4^th day of admission, he developed an acute onset of respiratory distress with tachypnoea, subcostal and intercostal retractions, and oxygen desaturation. Repeat chest X-ray demonstrated gross right-sided pleural effusion involving the right middle and lower zones with displacement of the mediastinum, consistent with a large effusion. Bedside thoracic ultrasonography confirmed a large right-sided echogenic pleural collection, and an intercostal drain was inserted under ultrasound guidance.

Initial pleural fluid analysis showed pH 7.0, pale yellowish turbid appearance, total leukocyte count 8,500/μL with neutrophilic predominance, protein 3.9 g/dL (serum protein 5.2 g/dL; pleural-to-serum protein ratio >0.5), LDH 460 IU/L (serum LDH 620 IU/L; pleural-to-serum LDH ratio >0.6), and glucose 114 mg/dL. These biochemical parameters satisfied Light’s criteria for an exudate. Pleural fluid culture after 48 h isolated methicillin-sensitive Staphylococcus aureus (MSSA), sensitive to cloxacillin, cefazolin, and co-trimoxazole. Fluid cytology showed predominantly neutrophilic infiltrate consistent with acute bacterial infection, negative for malignancy. Screening for tuberculosis was negative.

The patient had initially been started on empirical broad-spectrum intravenous antibiotics comprising Cefotaxime 50 mg/kg/dose IV every 8 h and Amikacin 15 mg/kg/day IV once daily pending culture results. Following the culture and sensitivity report confirming MSSA, antibiotic therapy was rationalised and de-escalated to intravenous Cloxacillin 50 mg/kg/dose every 6 h to provide targeted MSSA coverage. Supportive Management in the form of IV fluids, vitamin K, fresh frozen plasma, Oxygen therapy titrated to maintain SpO2 >94%, Intercostal drain management with regular saline flushes and monitoring of output (initially 150–200 mL/day, tapering by day 10), and symptomatic management for fever and pain was given. Packed cell volume (PCV) transfusion of 10 mL/kg was administered on day 3 for symptomatic anaemia.^[5,6]

Repeat pleural fluid analysis after 48 hours of drainage and antibiotic therapy showed improvement with Pleural fluid TLC reduced to 3,200/μL, appearance clearing to serous, sterile repeat culture confirming effective antibiotic coverage, and pH normalised to 7.35. Repeat CBC also shows Hb 10.7g/dL, TLC 14,000/μL, Platelet count 8,00,000/μL, and CRP 4.5.

The pleural effusion gradually resolved over 10 days with progressive reduction in ICD output. The drain was removed on day 10 when output became minimal (<20 mL/day) and repeat imaging showed complete resolution of pleural effusion. Fever subsided by day 6, respiratory distress resolved, and oxygen support was weaned by day 8. The patient was discharged on day 12 in stable condition on oral supportive treatment. Follow-up outpatient assessment at 2 weeks showed complete clinical recovery with normalisation of liver enzymes and resolution of icterus.

No surgical intervention was required for acalculous cholecystitis.^[7] It resolved with supportive care, intravenous fluids, and antibiotics alone. Repeat abdominal ultrasound on day 8 showed resolution of gallbladder wall oedema with normalised wall thickness.

DISCUSSION

This case represents a complex presentation of acute hepatitis A infection complicated by bacterial empyema and acalculous cholecystitis, a combination that is exceptionally rare in paediatric patients.

Pleural effusion as an extrahepatic manifestation of HAV infection is well-documented in the medical literature since 2000, though it remains uncommon.^[5,6] However, the distinction between simple pleural effusion (direct consequence of viral serositis) and bacterial empyema (secondary bacterial superinfection) is clinically critical and has significant implications for management and prognosis.

The biochemical profile of this patient showed a predominance of conjugated hyperbilirubinaemia (conjugated bilirubin 6.0 mg/dL versus unconjugated 5.7 mg/dL) in conjunction with markedly elevated transaminases (ALT 2,073 IU/L, AST 3,477 IU/L), which is consistent with hepatocellular injury from acute HAV infection. The elevated unconjugated fraction is best explained by reduced hepatic uptake of unconjugated bilirubin due to hepatocellular dysfunction in the context of severe systemic infection and sepsis. The microcytic hypochromic anaemia with haemoglobin of 7.1 g/dL represents pre-existing nutritional iron-deficiency anaemia (common in developing countries) that was further exacerbated by the acute illness. This constellation of findings underscores the severity of the systemic infection beyond isolated hepatitis.

While hepatocellular injury predominantly causes conjugated hyperbilirubinaemia, the presence of 50% unconjugated bilirubin can be explained by haemolysis secondary to severe systemic infection and sepsis, reduced hepatic uptake of unconjugated bilirubin due to hepatocellular dysfunction, and the microcytic hypochromic anaemia with haemoglobin of 8.2 g/dL representing pre-existing nutritional anaemia (common in developing countries), exacerbated by haemolysis from acute infection. This constellation of findings underscores the severity of the systemic infection beyond isolated hepatitis.

Concurrent acalculous cholecystitis in association with HAV infection has been documented in previous case reports since the year 2000 and represents secondary inflammation of the gallbladder wall. The elevated ALP (600 IU/L) and GGT (285 IU/L) support significant biliary involvement and inflammation. The absence of gallstones on ultrasound, combined with positive Murphy’s sign, acute clinical presentation, and biochemical evidence of biliary involvement, confirms the diagnosis of acalculous cholecystitis. No surgical intervention was required as the condition resolved with medical management, which aligns with current understanding that acalculous cholecystitis in the setting of viral hepatitis is typically self-limiting.

The pathophysiology of bacterial superinfection in HAV is likely multifactorial, including: immunosuppression from acute viral infection, reducing local and systemic immune responses; direct haematogenous seeding from bacteraemia; and environmental contamination given the patient’s socioeconomic circumstances, suggesting possible exposure to pathogenic organisms. While gastrointestinal translocation of Staphylococcus aureus is considered less likely given the organism’s typical habitat, skin or upper respiratory tract colonisation followed by haematogenous spread in the context of immune compromise represents a plausible route in this case.

The TLC of 50,000/μL in the setting of HAV infection prompted differential diagnostic consideration for hematologic malignancy and other infections. However, the culture of Staphylococcus aureus from pleural fluid clarified the aetiology as bacterial superinfection. This finding emphasises that markedly elevated TLC in paediatric HAV should trigger investigation for secondary bacterial infection rather than simple viral hepatitis, which typically presents with TLC <20,000/μL.

CONCLUSION

This case demonstrates a rare but significant complication of acute hepatitis A infection, bacterial empyema with concurrent acalculous cholecystitis in a paediatric patient. Key learning points include: pleural involvement in HAV can manifest as simple effusion or as empyema from secondary bacterial infection, comprehensive pleural fluid analysis including Gram stain, culture, biochemistry (protein, LDH, glucose, pH), and cytology is essential for accurate diagnosis and appropriate management, markedly elevated systemic TLC in HAV should alert clinicians to the possibility of bacterial superinfection and early recognition and aggressive antibiotic therapy with drainage intervention for empyema is critical for favourable outcomes.

This case emphasises that hepatitis A infection should remain in the differential diagnosis of pleural effusion/empyema in paediatric patients presenting with acute viral hepatitis, particularly in developing countries with limited access to vaccination programs. Awareness of such rare extrahepatic manifestations and their potential bacterial complications can facilitate early diagnosis, appropriate antimicrobial therapy, and timely drainage procedures, ensuring favourable clinical outcomes.