Preservation / Reperfusion Injury in Transplanted Liver

Definition

• Damage to the transplanted liver caused by cold or warm ischemia

Diagnostic Criteria

• Centrilobular changes (zone 3)
  • Hepatocyte swelling
  • Cholestasis
  • Hepatocyte dropout, centrilobular > portal
• Portal changes
  • Bile ductular proliferation
  • Pericholangitis (neutrophils)
  • Occasionally bile plugs
• May be seen up to three weeks post transplantation
  • Changes diminish in severity with time post-transplant
• Similar changes can be seen in sepsis, bile duct obstruction and TPN administration
• Cold ischemia damages sinusoidal endothelium
• Hepatocytes are more sensitive to warm ischemia

Neeraja Kambham MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : May 9, 2007

Differential Diagnosis

• Acute rejection
• Bile duct obstruction
• Viral infection
• Sepsis
• Vascular anastomotic problems

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

Bile Duct Obstruction	Preservation / Reperfusion Injury of Transplanted Liver
May occur any time post transplant	May be seen up to 3 weeks post transplant
Hepatocyte dropout not usual	Hepatocyte dropout frequently seen
Pericentral hepatocyte swelling may be present in severe cases	Pericentral hepatocyte swelling and cholestasis

Many features overlap and ERCP may be necessary to distinguish

Viral Infection	Preservation / Reperfusion Injury of Transplanted Liver
May have lobular inflammation	Lobular inflammation infrequent
May have inclusions or acidophil bodies, depending on type of infection	Lacks inclusions; scattered acidophil bodies
Bile ductular proliferation not a feature	Frequent bile ductular proliferation
May be seen at any time	May be seen up to 3 weeks post-transplant

Sepsis	Preservation / Reperfusion Injury of Transplanted Liver
May have positive cultures	Cultures negative
Systemic symptoms of sepsis	Lacks systemic symptoms of sepsis
May be seen at any time	May be seen up to 3 weeks post-transplant
Bile plugs frequent	Bile plugs infrequent

Sepsis and preservation injury may show simlar features

Vascular Anastomotic Problems	Preservation / Reperfusion Injury of Transplanted Liver
Large areas of necrosis	No areas of necrosis
Prominent congestion	Congestion not prominent

Clinical

• Rise in AST, ALT, Alk Phos in the immediate post-transplant period (<3 weeks)
  • Elevation may be prolonged
  • Rise may follow an improvement in levels post-transplant
• Biopsy may be done to rule out early acute rejection

Bibliography

• Portmann B, Koukoulis G. Pathology of the liver allograft. Curr Top Pathol. 1999;92:61-105.
• Jones KD, Ferrell LD. Interpretation of biopsy findings in the transplant liver. Semin Diagn Pathol. 1998 Nov;15(4):306-17.