Acute Cellular Rejection Symptoms: RUQ pain, fever, back pain, general malaise, jaundice, elevated liver enzymes, pruritis Diagnostic Testing: Complete metabolic panel, direct bili, GGT, Prograf or antirejection level (r/o non-compliance) Consider ultrasound with doppler to r/o bile strictures, vascular abnormalities, technical complications Set up for liver biopsy Consider infectious etiologies for type of presentation and: EBV PCR Quantitative not qualitative (refer to protocol for more information), and CMV PCR Quantitative not qualitative, Hep A, B, C, and HIV depending on the patient. Consider stool studies if there is diarrhea: bacterial/viral cx, Rotavirus, D-diff toxin, Crytosporidium antigen, CMV stool Setting up Biopsy: Make sure there is an INR and plts within the last few days Biopsy is best done by interventional radiology, Dr. Mark Bittles 615-835-0546 The scheduler is Amanda Perales who may be reached by e-mail to schedule tagged urgent during week days. She will call the family with procedure time and give NPO instructions. Rejection Treatment Children >=50 kg: It is preferred that rejection must be documented by biopsy. No additional immunosuppression medications are to be added without a liver biopsy. Solumedrol IV 6 day taper o o o o o o o Day #1 #2 #3 #4 #5 #6 Dose 500mg IV daily 500mg IV daily 250mg IV daily 125mg IV daily 60mg (IV or PO) daily 40mg (IV or PO) daily o Watch for hyperglycemia and hypertension Give appropriate anti-ulcer prophylaxis (PPI or H2 Blocker) Adjust Prograf if needed Prednisone 40 mg po QD – then standard taper with weekly labs over a period of 6 weeks Start Valganciclovir 15 mg/kg/day X 2 weeks (this includes late rejection) o >13 yrs old gets Valganciclovir 900 mg po daily x 7 days, THEN Valganciclovir 450 mg po daily x 7 days (this includes late rejection) Re-biopsy if LFTs have not normalized within 3-5 days Nystatin X 1 week PCP Bactrim DS q day prophylaxis X 3 mo Daily LFT’s including D-bili and GGT Should improve in 3-4 days, if not confer w/ transplant attending to consider rebiopsy and augmentation of steroid taper Consider running higher FK506 levels with transplant attending Rejection Treatment Children <50 kg: It is preferred that rejection must be documented by biopsy. No additional immunosuppression medications are to be added without a liver biopsy. Give Solumedrol IV Day #1 #2 #3 #4 #5 #6 Dose 10mg/kg IV daily 8mg/kg IV daily 6mg/kg IV daily 4mg/kg IV daily 2mg/kg IV daily 1mg/kg IV daily Max Total per day 500mg 400mg 300mg 200mg 100mg 50mg o Watch for hyperglycemia and hypertension Give appropriate anti-ulcer prophylaxis (PPI or H2 Blocker) Adjust Prograf if needed Prednisone (or Orapred) oral taper start at 0.5mg/kg/day– then standard taper with weekly labs over a period of 6 weeks Start Valganciclovir 15 mg/kg/day X2 weeks (this includes late rejection) o >13 yrs old gets Valganciclovir 900 mg po daily x 7 days, THEN Valganciclovir 450 mg po daily x 7 days (this includes late rejection) Re-biopsy if LFTs have not normalized within 3-5 days Nystatin X 1 week PCP Bactrim prophylaxis X 3 mo Daily LFT’s including D-bili and GGT Should improve in 3-4 days, if not confer w/ transplant attending to consider rebiopsy and augmentation of steroid taper Consider running higher FK506 levels with transplant attending Steroid-resistant rejection: Defined as rejection on liver BIOPSY that persists despite 2 consecutive cycles of Solumedrol (for rejection treatment) Thymoglobulin 1.5 mg/kg (round to the nearest 25 mg) IV via Central Line with 0.22 micron in-line filter every 24 hours x 14 days Anaphylaxis emergency kit at bedside Methylprednisolone injection: 2mg/kg IV (max 125mg) given 30 minutes before the first 3 doses of Thymoglobulin. While receiving Thymoglobulin, hold the steroid taper. Tylenol 10-15 mg/kg/po/pr daily; give 30 minutes before Thymoglobulin for first two doses Benadryl for children Give 30 minutes before Thymoglobulin for first two doses o ages 2 - <6 yr: 6.25mg o ages 6 - <12 yrs: 12.5mg o ages > 12 yrs: 25mg IV daily Valgancyclovir 15mg/kg/day (max 900mg/day) X 30 days o >13 yrs 900mg po BID X 30 days When Thymoglobulin is complete, restart the steroid taper at 0.5mg/kg/day Consider fungal and PCP prophylaxis Consider adding mycophenolate mofetil Consider running higher FK506 levels with transplant attending