Early acute cellular rejection (<90 days) differential diagnosis

1)Recurrent HBV/HCV virus- can be difficult to distinguish from cellular rejection
2)Functional cholestasis
3)Cyclosporine toxicity
4)Massive hemorrhage necrosis
5)INFECTIONS– CMV, EBV, HSV, HIV
6)Drug induced liver injury

Clinical presentation (nonspecific!)

-Fever
-Malaise
-Abdominal Pain
-Hepatosplenomegaly

Abnormal labs

-Elevated aminotransferases, bilirubin, alkaline phosphatase (suspect acute cellular rejection especially if elevated AST/ALT with rising bilirubin)

Workup (if you are worried about acute cellular rejection)

-Ultrasound liver with doppler- look at hepatic artery and portal vein flow as well as other abnormalities
-Check CMV, EBV, HCV/HBV, HIV
-Check drug levels (eg: cyclosporine, tacrolimus) to look for under-dosing or toxicity
-MRCP/ERCP if suspicion for choledocholithasis or other biliary tract abnormalities
–Must do URGENT Liver Biopsy (trans-jugular vs. percutaneous) to make the diagnosis-                              Prefer trans-jugular if bleeding diathesis or large amount of ascites

Triad of biopsy results consistent with cellular rejection

-Mixed inflammatory infiltrate in portal triad
-Destruction/non-destructive non suppurative cholangitis involving the interlobular bile duct epithelium
–Endothelilitis (inflammation within the endothelium)

Treatment: high dose steroids, Solumedrol 500-1000 mg daily for 1-3d with steroid taper (HOWEVER increased mortality with steroids or T cell depletion if due to HCV infection so important to make right diagnosis)