What is the approach to managing hepatitis in the pediatric age group?

Approach to Hepatitis in Pediatric Age Group

The approach to pediatric hepatitis requires systematic evaluation to determine etiology (viral, autoimmune, metabolic), assess disease severity and chronicity, initiate appropriate monitoring protocols, and make evidence-based treatment decisions that prioritize prevention of cirrhosis, hepatocellular carcinoma, and acute liver failure.

Initial Assessment and Risk Stratification

Immediate Red Flags Requiring Emergency Evaluation

• Coagulopathy, hypoglycemia, or encephalopathy indicate potential acute liver failure and mandate immediate specialist consultation or emergency evaluation 1
• Ascites or signs of portal hypertension require urgent assessment 1
• Unexplained clinical jaundice, particularly conjugated hyperbilirubinemia in infants (possible biliary atresia), necessitates prompt intervention 1

Essential History and Physical Examination

• Document family history of liver disease, hepatocellular carcinoma, or metabolic disorders 1
• Record maternal and neonatal history, medication exposures, and ethnicity for hepatitis B/C risk stratification 1
• Calculate BMI and examine for hepatosplenomegaly, ascites, and stigmata of chronic liver disease 1

Initial Laboratory Workup

Core Diagnostic Panel

• Comprehensive metabolic panel including ALT, AST, alkaline phosphatase, GGT, total and direct bilirubin, albumin, glucose, and prothrombin time/INR 1
• Viral hepatitis screening: hepatitis B surface antigen, hepatitis C antibody 1
• Autoimmune markers: immunoglobulin G and autoantibodies (ANA, ASMA, anti-LKM1) 1
• Determine enzyme pattern (hepatocellular vs. cholestatic) to guide further testing 1

Age-Specific Considerations

• In very young or non-overweight children, test for monogenic causes including Wilson's disease, fatty acid oxidation defects, carnitine metabolism disorders, peroxisomal disorders, lysosomal storage diseases, and cystic fibrosis 1
• In overweight/obese children ≥10 years, consider non-alcoholic fatty liver disease as primary differential 1

Etiology-Specific Management

Chronic Hepatitis B

Monitoring Protocol

• Physical examination and measurement of serum ALT and HBeAg/anti-HBe levels every 6 months 2
• In HBeAg-positive patients with persistently elevated ALT, monitor every 3 months for at least one year 2
• In HBeAg-negative patients, measure ALT and HBV DNA every 4 months within the first year to rule out HBeAg-negative hepatitis 2
• After confirming inactive carrier status (normal ALT and HBV DNA <2000 IU/ml), monitor every 6 months 2
• Full blood count and liver function tests yearly 2
• HCC surveillance with liver ultrasound every 6-12 months depending on fibrosis stage 2
• Lifetime follow-up is warranted even for inactive carriers due to risk of cirrhosis, HCC, and reactivation 2

Treatment Criteria

• Consider antiviral treatment if ALT >1.5 times laboratory ULN or >60 IU/L (whichever is lower) 2
• Antivirals should be considered for children with elevated ALT for at least 6 months (12 months if HBeAg-negative) to avoid treating spontaneous HBeAg seroconversion 2
• HBV DNA threshold of 2000 IU/ml is appropriate for children 2
• Histologic assessment (liver biopsy) is recommended before treatment to evaluate degree of inflammation and fibrosis stage 2
• Treatment is more likely to succeed with at least moderate necroinflammation or moderate fibrosis 2
• Family history of HCC may warrant treatment even with mild histological changes 2

Antiviral Selection

• For children ≥12 years with hepatitis B, tenofovir is preferred due to lower resistance rates 3, 4
• For children <12 years, entecavir may be considered 3
• Nucleoside analogs (lamivudine, entecavir, or tenofovir depending on age) can be considered for hepatitis B-related fulminant hepatic failure, though efficacy in acute setting remains unproven 5

Acute Viral Hepatitis with Fulminant Hepatic Failure

Supportive Care

• Restrict fluid therapy to 50-60% of maintenance volume (Holliday-Segar formula) to prevent fluid overload and worsening edema 5, 3
• Use isotonic maintenance fluids to reduce hyponatremia risk; avoid lactate buffer solutions in severe liver dysfunction 5, 3
• Monitor fluid balance, electrolytes (especially sodium), and glucose levels daily 5, 3
• Avoid NSAIDs and aspirin due to increased bleeding risk from coagulopathy 5, 3

Virus-Specific Treatment

• For suspected herpes virus-related acute liver failure, immediate acyclovir treatment is required and patient should be placed on liver transplant list 5
• For hepatitis A, C, and E, management is primarily supportive as no specific antiviral therapy has proven effective in acute setting 5
• In immunocompromised children with viral hepatitis, consider prophylactic nucleoside analogs to prevent reactivation 5

Autoimmune Hepatitis

Diagnostic Approach

• Low serum titers of autoantibodies are common in children with NAFLD and do not necessarily indicate autoimmune hepatitis 1
• Higher autoantibody titers, particularly with markedly elevated aminotransferases and elevated globulin, should prompt liver biopsy 1
• Liver biopsy is indicated when diagnosis remains unclear after non-invasive testing, multiple diagnoses are possible, or before starting potentially hepatotoxic medications 1

Treatment Considerations

• For autoimmune hepatitis presenting with fulminant failure, glucocorticoid therapy (prednisone/prednisolone up to 2 mg/kg daily) may be considered, but should not delay transplant evaluation 5
• Timely immunosuppressive therapy improves prognosis and decreases need for liver transplantation 6

Common Pitfalls to Avoid

• Do not assume transient elevation without investigation, as most abnormalities persist and warrant etiologic workup 1
• Do not overlook extrahepatic causes including muscle injury, cardiovascular disease, and medications 1
• Do not misinterpret isolated elevated ferritin as hemochromatosis, as this commonly reflects dysmetabolic iron overload in NAFLD 1
• Do not delay referral in children—threshold for specialist consultation should be lower than in adults 1
• Avoid hypotonic fluids which increase hyponatremia risk 3
• Avoid fluid overload which can exacerbate ascites and edematous states 3

Follow-Up Strategy

• For identified chronic liver disease, annual monitoring is recommended 1
• For viral hepatitis, monitor liver function tests every 3 months during acute phase, then at least yearly during follow-up 3, 1
• Regular ultrasound surveillance every 6-12 months depending on disease severity 3
• Educate parents about warning signs requiring immediate medical attention: worsening jaundice, abdominal distension, mental status changes, unusual bleeding, persistent vomiting, and fever 5