What are the treatment options for patients with gastroenteritis and hepatitis?

Treatment of Gastroenteritis and Hepatitis

Gastroenteritis Management

Oral rehydration therapy is the first-line treatment for gastroenteritis with mild-to-moderate dehydration, and IV azithromycin 500 mg daily for 2-5 days is the preferred antibiotic for severe bacterial gastroenteritis, particularly when dysentery or fluoroquinolone-resistant pathogens are suspected. 1

Initial Assessment and Supportive Care

• Assess dehydration severity to determine oral versus intravenous rehydration needs 2, 3
• Oral rehydration solution (ORS) is as effective as IV therapy for mild-to-moderate dehydration and should be the first-line approach 4, 3
• For every 25 children treated with ORT, only one will fail and require IV therapy 3
• Antiemetics (ondansetron) can improve ORS tolerance and decrease hospitalization rates, though not routinely recommended for all cases 4

Antibiotic Therapy for Bacterial Gastroenteritis

When antibiotics are indicated:

• IV azithromycin 500 mg daily for 2-5 days is first-line for severe bacterial gastroenteritis with dysentery or incapacitating watery diarrhea 1
• Alternative regimen: Single 1-gram dose or 500 mg daily for 3 days 1
• Azithromycin is superior to fluoroquinolones in areas with high resistance, showing 100% clinical cure rates for Campylobacter versus treatment failures with fluoroquinolones 1
• Effective against Campylobacter, Shigella, enteroinvasive E. coli, Aeromonas, Plesiomonas, and Yersinia 1

Pathogen-Specific Considerations

• Exclude C. difficile and perform stool cultures before initiating immunosuppression in all suspected cases 5
• CMV gastroenteritis: Ganciclovir 5 mg/kg IV twice daily for 2-3 weeks, followed by maintenance therapy 5
• Rotavirus enteritis: Consider nitazoxanide 7.5 mg/kg twice daily orally 5
• Adenovirus enteritis: Cidofovir 5 mg/kg IV once weekly for 2 weeks, then weekly maintenance 5

Treatment Algorithm

1. Mild-moderate dehydration: ORS as first-line 4, 3
2. Severe dehydration or treatment failure: IV rehydration 3
3. Dysentery or severe symptoms: IV azithromycin 500 mg daily 1
4. Suspected fluoroquinolone resistance: Azithromycin preferred 1
5. Transition to oral therapy when clinical improvement occurs (typically 2-5 days) 1

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Hepatitis Management

For immune checkpoint inhibitor (ICI) hepatitis Grade 3 or higher (AST/ALT >5× ULN or total bilirubin >3× ULN), permanently discontinue the ICI and initiate methylprednisolone 1-2 mg/kg/day with urgent gastroenterology consultation. 5

Grading and Initial Management

Grade 1 (AST/ALT 1-3× ULN or bilirubin 1-1.5× ULN):

• Continue ICI with close monitoring 5
• Monitor liver chemistries 1-2 times weekly 5
• No treatment required 5

Grade 2 (AST/ALT >3-5× ULN or bilirubin >1.5-3× ULN):

• Hold ICI temporarily 5
• Discontinue potentially hepatotoxic medications 5
• If no improvement after 3-5 days, administer prednisone 0.5-1 mg/kg/day 5
• Obtain gastroenterology consultation 5

Grade 3 (AST/ALT >5-20× ULN or bilirubin >3-10× ULN):

• Permanently discontinue ICI 5
• Urgent gastroenterology/hepatology consultation 5
• Methylprednisolone 1-2 mg/kg/day until symptoms improve to Grade 1, then taper over 4-6 weeks 5
• Consider hospitalization and liver biopsy 5
• If inadequate response after 3-5 days, add second-line agents: azathioprine, mycophenolate mofetil, or tacrolimus 5

Grade 4 (AST/ALT >20× ULN or bilirubin >10× ULN or hepatic decompensation):

• Immediate hospitalization at tertiary care center 5, 6
• Permanently discontinue ICI 5
• Methylprednisolone 2 mg/kg/day 5
• Early contact with transplant center 6
• If no 50% drop in transaminases within 3 days, initiate azathioprine, mycophenolate mofetil, or tacrolimus 5

Critical Diagnostic Workup

Before initiating steroids:

• Viral hepatitis panel (hepatitis B surface antigen, core antibody, surface antibody; hepatitis C antibody) 5
• Liver function tests: AST, ALT, alkaline phosphatase, total bilirubin 5
• Cross-sectional imaging (CT/MRI) if elevated alkaline phosphatase or bilirubin to exclude biliary obstruction 5
• Liver biopsy should be considered for Grade 2 or higher before starting glucocorticoids to maximize diagnostic utility 5
• Rule out drug-induced liver injury, alcohol history, iron studies, thromboembolic events, liver metastases 5

Important Caveats

• Infliximab is contraindicated for hepatic immune-related adverse events due to idiosyncratic liver toxicity risk 5
• Monitor INR closely as INR ≥1.5 with any mental status changes defines acute liver failure requiring immediate ICU admission 6
• Assess for hepatic encephalopathy as altered mental status with INR ≥1.5 requires immediate hospitalization 6
• Patients with both ICI-related hepatitis and colitis require systemic immunosuppressants (prednisone plus mycophenolate) rather than infliximab 5

Hospitalization Criteria for Any Hepatitis

Immediate admission required for:

• INR ≥1.5 with any degree of encephalopathy 6
• Severe nausea/vomiting preventing oral intake 6
• AST/ALT >20× ULN or bilirubin >10× ULN 5, 6
• Hepatic decompensation (ascites, encephalopathy) 5, 6
• Maddrey discriminant function >32 or MELD >20 in alcoholic hepatitis 6

Special Considerations for Hepatitis E

• Severe acute hepatitis E or acute-on-chronic liver failure: Consider ribavirin therapy, which rapidly normalizes liver enzymes and clears HEV RNA 7
• Reduce immunosuppression if possible, particularly T-cell targeting drugs 7
• If immunosuppression cannot be reduced, consider 3-month ribavirin monotherapy 7