Chemokines in Chronic Liver Allograft Dysfunction Pathogenesis and Potential Therapeutic Targets
Table 1
Causes of chronic liver allograft dysfunction.
Causes
Histopathologic changes and diagnosis
Immunological
Early allograft dysfunction
Early high transaminases persistent cholestasis and prolonged coagulopathy [4] acute hepatocellular damage or death.
Acute rejection
Predominantly mononuclear portal inflammation containing neutrophils, lymphocytes, and eosinophils; inflammatory bile duct damage; and portal or central venous subendothelial inflammation or perivenular inflammation [22].
Chronic rejection
A majority of small bile ducts damage bile duct loss affecting >50% of the portal tracts and foam cell obliterative arteriopathy [22].
Chronic hepatitis
The presence of a portal and lobular mononuclear infiltrates in the absence of rejection or the graft damage caused by viral infection [3].
De novo or recurrent autoimmune hepatitis
Significant titers (1 : 160) of smooth muscle antibodies and antinuclear antibodies interface hepatitis with portal lymphocytic infiltrates hypergammaglobulinemia and exclusion of viral infection or drug-induced hepatitis [23, 24].
Viral
De novo or recurrent viral hepatitis (HBV, HCV)
The portal inflammation tends to be more diffusely distributed throughout the portal tracts; lymphocytic cholangitis is limited to a minority of bile ducts [25].
Ischemia
Late effects of I/R injury
Hepatocytes and sinusoidal endothelial cells damage adhesion and aggregation of neutrophils and platelets in the sinusoids sinusoidal narrowing and elevated liver aminotransferase enzymes [26].
Ischemic-type biliary lesions
The complete biliary system is affected or only the major extrahepatic bile ducts are involved. Epithelial and muscular necrosis of the biliary system and periductal connective tissue well preserved [27].
Toxic
Drugs and other toxins
Changes are usually mild and nonspecific like hepatitis, cholestasis, nodular regenerative hyperplasia, and veno-occlusive disease (sinusoidal congestion) or centrizonal necrosis [8].
Recurrent disease
Idiopathic posttransplantation hepatitis
Bile duct damage and venous endothelial inflammation chronic hepatitis that cannot be ascribed to a particular cause or presence of bridging fibrosis or cirrhosis [28].
Recurrent PSC
Biliary strictures presence of mild portal edema mild nonspecific pericholangitis lamellar periductal edema concentric periductal fibrosis or biliary gestalt [29].
Recurrent PBC
Noninfectious granulomatous cholangitis in the proper setting presence of antimitochondrial antibodies and absence of other causes such as infections and biliary strictures [30].