What is the guideline for treatment of acute Graft-Versus-Host Disease (GVHD) post liver transplantation?

Treatment Guidelines for Acute Graft-Versus-Host Disease Post Liver Transplantation

Systemic corticosteroids remain the first-line therapy for acute graft-versus-host disease (aGVHD) following liver transplantation, with methylprednisolone at 1-2 mg/kg/day recommended as the initial treatment. 1

Initial Assessment and Diagnosis

• Diagnosis of aGVHD post liver transplantation should be based on clinical symptoms (fever, rash, diarrhea, pancytopenia), histopathological features, and donor T-lymphocyte chimerism 2
• Median time from liver transplantation to clinical presentation of aGVHD is approximately 22 days 2
• Biopsy of affected organs (skin, GI tract) is recommended to confirm the diagnosis and rule out other causes 1
• Liver function tests should be routinely monitored for early detection of hepatic aGVHD, which is often asymptomatic 1

First-Line Treatment

Grade I aGVHD (skin only, ≤50% body surface area)

• Continue or restart the original immunosuppressive agent 1
• Add topical skin-directed steroids (triamcinolone, clobetasol) and/or topical tacrolimus 1
• Medium to high-potency topical steroid formulations are recommended for body, with low-potency hydrocortisone for facial application 1, 3
• Antihistamines may be used for symptomatic relief of itching 1

Grade II-IV aGVHD

• Systemic corticosteroids are the standard first-line treatment 1
  • Grade II: Methylprednisolone 0.5-1 mg/kg/day 1
  • Grade III-IV: Methylprednisolone 1-2 mg/kg/day 1
• Original immunosuppressive agent should be restarted, continued, or escalated 1
• For upper GI symptoms, consider adding GI topical steroids (beclomethasone dipropionate or budesonide) 1
• Response to first-line therapy should be assessed after 5 days, as this timepoint identifies patients with different risk of transplant-related mortality 4

Steroid-Refractory aGVHD Management

For patients who fail to respond to first-line therapy after 5 days (no improvement in at least one organ or progression in any organ):

Second-Line Options

• Anti-thymocyte globulin (ATG) 1, 5
  • Thymoglobulin (rabbit ATG): 2.5 mg/kg/day for 4-6 consecutive days 1
  • ATGAM (horse ATG): 15 mg/kg twice daily for 5 days 1
• Calcineurin inhibitors (tacrolimus, cyclosporine) 1
• Basiliximab (IL-2 receptor antagonist): 20 mg on days 1 and 4 1
• Etanercept: 25 mg twice weekly for 4 weeks, then 25 mg weekly for 4 weeks 1
• Ruxolitinib: recently approved for steroid-refractory aGVHD 6

Important Considerations

• Avoid adding daclizumab to corticosteroids as initial therapy, as this combination has been associated with significantly worse survival (77% vs 94% at 100 days) 7
• Skin aGVHD tends to be more responsive to treatment than GI or liver aGVHD 1
• Infections are the most common complications of treatment for aGVHD, requiring close monitoring 5, 2
• For patients with progressive or worsening aGVHD despite multiple lines of therapy, enrollment in clinical trials should be considered 1

Treatment Algorithm

1. Confirm diagnosis through clinical presentation, histopathology, and chimerism studies
2. Grade aGVHD severity using modified Glucksberg criteria 1
3. Initiate first-line therapy based on grade:
   • Grade I: Topical therapy ± continuing immunosuppression
   • Grade II-IV: Systemic corticosteroids (methylprednisolone 0.5-2 mg/kg/day)
4. Assess response after 5 days of treatment 4
5. For non-responders, add second-line therapy:
   • ATG, calcineurin inhibitors, or ruxolitinib 1, 6
6. Monitor closely for infections and other complications 5

Prognosis and Monitoring

• Despite intensive treatment strategies, mortality remains high (approximately 67%) with most deaths due to sepsis and multiple organ failure 2
• Early diagnosis and prompt initiation of treatment are critical for improving outcomes 2
• Close monitoring for infectious complications is essential during immunosuppressive therapy 5, 2