Acute Rejection of Transplanted Liver
Differential Diagnosis
- Chronic rejection
- Preservation / reperfusion injury
- Hepatitis C recurrence
- Infection (other than Hepatitis C)
- Recurrence of original disease
- Bile duct obstruction
- Vascular anastomotic problems
| Acute Rejection of Liver | Chronic Rejection of Liver |
|---|---|
| 1 week to 1 year post-transplant | Presents > 6-12 months post-transplant |
| Bile duct lymphocytic infiltrate | Bile duct loss in at least 50% of portal tracts |
| No cholestasis unless extensive bile duct damage | Centrilobular cholestasis |
| No hepatocyte swelling | Centrilobular hepatocyte swelling |
| No apoptotic bodies in lobules | Scattered apoptotic bodies may be present |
| Acute Rejection of Liver | Preservation / Reperfusion Injury of Transplanted Liver |
|---|---|
| Mixed portal and/or perivenular infiltrate | Lacks perivenular infiltrate |
| Bile duct lymphocytic infiltrate | Neutrophilic pericholangitis and bile ductular proliferation |
| Endotheliitis | Lacks endotheliitis |
| 1 week to 1 year post-transplant | Less than 3 weeks post-transplant |
| Cholestasis absent to mild | Centrilobular cholestasis |
| Acute Rejection | Acute Rejection and Hepatitis C |
Hepatitis C |
|---|---|---|
| Endotheliitis prominent | Endotheliitis prominent | Endotheliitis infrequent |
| Bile duct damage frequent | Bile duct damage frequent | Bile duct damage infrequent |
| Eosinophils frequent | Eosinophils frequent | Eosinophils few or rare |
| Steatosis infrequent | Steatosis occasional | Steatosis occasional |
| Acidophil bodies absent | Acidophil bodies frequent | Acidophil bodies frequent |
| Serum HCV RNA absent | Serum HCV RNA present | Serum HCV RNA present |
Infectious processes in transplanted liver may present clinically or histologically in the differential diagnosis of acute rejection
- Cytomegalovirus (CMV)
- Variable features
- Microabscesses, microgranulomas
- Lymphocytic portal and sinusoidal infiltrate
- Hepatocyte ballooning
- Viral inclusions may be small and/or rare
- We perform immunoperoxidase stain for CMV when there are microabcesses or prominent hepatocyte necrosis or possible inclusions
- Even on immunoperoxidase stain inclusions may be small and/or rare
- Variable features
- Herpes simplex virus
- Features
- Nuclear inclusions with ground glass appearance
- Nuclear chromatin margination
- We perform immunoperoxidase stain for Herpes when there is prominent hepatocyte apoptosis or possible inclusions
- Features
- Adenovirus
- Scattered individual or clustered necrotic hepatocytes with smudgy nuclei
- May be rare and nuclear features may be subtle
- More common in pediatric patients
- We perform immunoperoxidase stain for adenovirus when there is prominent hepatocyte apoptosis or possible inclusions
- Scattered individual or clustered necrotic hepatocytes with smudgy nuclei
- Epstein-Barr virus (EBV)
- Often a reactivation of latent virus
- Two presentations
- Systemic viral syndrome with EBV hepatitis
- Portal tracts and lobules infiltrated by monotonous immunoblasts
- Post-transplant lymphoproliferative disorder (PTLD)
- Systemic viral syndrome with EBV hepatitis
- In situ hybridization for EBV is useful for the diagnosis
- Fungal infections
- Most often Candida
- Ascending cholangitis
- Neutrophils in lumens of interlobular bile ducts
- Involvement of bile ductules or cholangioles is not sufficient
- Neutrophils in lumens of interlobular bile ducts
- Sepsis
- Bile ductular proliferation with neutrophilic infiltrate
- Bile plugs in portal areas
Acute rejection of liver versus recurrence of original disease
- Recurrences usually seen more than 6-12 months post-transplant
- Diseases with a significant incidence of recurrence in transplants
- Autoimmune hepatitis
- Hepatocellular carcinoma
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Viral hepatitis B
- Viral hepatitis C
| Acute Rejection of Liver | Bile Duct Obstruction |
|---|---|
| Mixed infiltrate frequently with eosinophils | Eosinophils infrequent |
| Bile duct lymphocytic infiltrate | Bile ductular proliferation with cholestasis and bile plugs, neutrophilic pericholangitis |
| Endotheliitis | Lacks endotheliitis |
| Acute Rejection of Liver | Acute Vascular Anastomotic Problems |
|---|---|
| Mixed infiltrate frequently with eosinophils | No significant inflammation even in preserved parenchyma |
| No hepatocyte necrosis or infarction | Extensive areas of infarction, with or without congestion |
| Endotheliitis | Lacks endotheliitis |
