Unravelling the Mystery: Acute Hepatitis of Unknown Origin in Children

Sara D. Artta^*
*Correspondence: Sara D. Artta, Department of Microbiology and Immunology, Bambino Gesù Children’s Hospital, Rome, Italy, Email:

Keywords

Pediatric hepatitis • Unknown etiology • Multidisciplinary approach

Introduction

Acute hepatitis in children encompasses a spectrum of liver inflammation, ranging from mild, self-limiting illness to severe, life-threatening disease. While viral, autoimmune, metabolic, and toxic etiologies are commonly implicated, a subset of cases presents a diagnostic dilemma, characterized by an unknown origin of hepatitis. This manuscript aims to explore the complexities of acute hepatitis of unknown origin in children, highlighting the challenges in diagnosis and management [1].

Literature Review

Children with acute hepatitis of unknown origin often present with nonspecific symptoms such as fatigue, anorexia, jaundice, and abdominal pain. Laboratory evaluation typically reveals elevated liver enzymes, including Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), along with derangements in bilirubin levels. In severe cases, coagulopathy and hepatic encephalopathy may develop, necessitating urgent medical attention. In addition to the nonspecific symptoms mentioned, children with acute hepatitis of unknown origin may exhibit signs of systemic illness, such as fever and malaise. Fatigue can be profound, significantly impacting daily activities and quality of life. Anorexia and weight loss are common due to the associated nausea and abdominal discomfort. Jaundice, evident by yellowing of the skin and sclerae, indicates impaired bilirubin metabolism and is often accompanied by dark urine and pale stools.

Laboratory findings typically demonstrate elevated liver enzymes, reflecting hepatocellular injury. ALT and AST levels are notably elevated, exceeding several times the upper limit of normal. Bilirubin levels may be elevated, with a predominance of conjugated bilirubin in hepatocellular injury. In severe cases, coagulopathy may manifest as prolonged Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT), predisposing to bleeding complications [2]. Hepatic encephalopathy, characterized by altered mental status, confusion, and coma, may develop in advanced cases, warranting immediate medical intervention to prevent life-threatening complications such as hepatic failure and cerebral edema. Early recognition of these clinical features is crucial for timely diagnosis and intervention in children with acute hepatitis of unknown origin.

Discussion

The diagnostic workup for acute hepatitis of unknown origin in children involves a systematic approach to identify potential etiologies while ruling out common causes. History-taking, physical examination, and serological testing for viral hepatitis, autoimmune markers, and metabolic disorders are essential initial steps. Advanced imaging modalities such as ultrasound, Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) may be utilized to assess liver morphology and detect structural abnormalities.

Further diagnostic evaluation may include liver biopsy, particularly in cases where the etiology remains elusive despite initial investigations. Liver biopsy provides histopathological assessment of hepatic architecture and inflammation, aiding in the diagnosis of specific etiologies such as autoimmune hepatitis, metabolic liver diseases, or infiltrative disorders. Additionally, molecular diagnostic techniques, including Polymerase Chain Reaction (PCR) assays and Next-Generation Sequencing (NGS), may be employed to detect viral nucleic acids or genetic mutations associated with liver disease. Serological testing for specific antibodies, such as Anti-Mitochondrial Antibodies (AMA) and Anti-Smooth Muscle Antibodies (ASMA), assists in diagnosing autoimmune liver diseases. Collaborative consultation with pediatric hepatologists, infectious disease specialists, and genetic counselors facilitates comprehensive evaluation and management planning, ensuring timely diagnosis and appropriate intervention in children with acute hepatitis of unknown origin [3].

The differential diagnosis for acute hepatitis of unknown origin in children is broad and includes infectious, autoimmune, genetic, and neoplastic conditions. Hepatitis viruses, including hepatitis A, B, and E, should be promptly excluded, along with other viral pathogens such as Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV). Autoimmune hepatitis, Wilson's disease, alpha-1 antitrypsin deficiency, and drug-induced liver injury are among the myriad of etiologies to consider. Additionally, genetic conditions like alpha-1 antitrypsin deficiency and Wilson's disease present with hepatocellular injury and may manifest with concomitant extrahepatic features [4]. Neoplastic etiologies, including hepatoblastoma and lymphoma, require consideration, particularly in cases with atypical clinical features or rapid disease progression. Rare metabolic disorders such as glycogen storage diseases and mitochondrial disorders can also present with acute hepatitis-like symptoms. A thorough evaluation, including genetic testing, imaging studies, and histopathological examination, is essential to delineate the underlying etiology and guide appropriate management in children with acute hepatitis of unknown origin.

Management of acute hepatitis of unknown origin in children focuses on supportive care, addressing symptoms, and preventing complications while awaiting further diagnostic clarity. Hospitalization may be warranted for close monitoring and initiation of intravenous fluids, nutritional support, and symptomatic treatment. Consultation with pediatric hepatologists, infectious disease specialists, and rheumatologists may be beneficial for optimizing care and guiding diagnostic investigations.

In hospitalized children with acute hepatitis of unknown origin, close monitoring of liver function tests, coagulation parameters, and mental status is essential to detect any deterioration and intervene promptly. Intravenous fluids correct dehydration and electrolyte imbalances, while nutritional support ensures adequate caloric intake and promotes liver regeneration [5,6]. Symptomatic treatment for pruritus, nausea, and pain improves patient comfort and overall well-being. Consultation with subspecialists, including pediatric hepatologists for expert guidance on liver-related issues, infectious disease specialists for targeted antimicrobial therapy if indicated, and rheumatologists for evaluation of autoimmune etiologies, facilitates comprehensive management and diagnostic investigations. Collaboration with the interdisciplinary team, including nurses, dietitians, and pharmacists, ensures coordinated care and optimal outcomes for children with acute hepatitis of unknown origin. Regular reassessment and adjustment of management strategies based on evolving clinical and diagnostic findings are crucial to achieving favorable outcomes in these patients.

Conclusion

Acute hepatitis of unknown origin in children presents a diagnostic conundrum, necessitating a thorough evaluation and multidisciplinary approach. Advancements in diagnostic techniques, including next-generation sequencing and biomarker discovery, hold promise for elucidating the underlying etiologies of this enigmatic condition. Collaborative efforts between clinicians, researchers, and families are essential for unraveling the mystery of acute hepatitis of unknown origin and improving outcomes for affected children.

Acknowledgement

None.

Conflict of Interest

None.

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