Review Article

Chemokines in Chronic Liver Allograft Dysfunction Pathogenesis and Potential Therapeutic Targets

Table 1

Causes of chronic liver allograft dysfunction.

CausesHistopathologic changes and diagnosis

ImmunologicalEarly allograft dysfunctionEarly high transaminases persistent cholestasis and prolonged coagulopathy [4] acute hepatocellular damage or death.
Acute rejectionPredominantly mononuclear portal inflammation containing neutrophils, lymphocytes, and eosinophils; inflammatory bile duct damage; and portal or central venous subendothelial inflammation or perivenular inflammation [22].
Chronic rejectionA majority of small bile ducts damage bile duct loss affecting >50% of the portal tracts and foam cell obliterative arteriopathy [22].
Chronic hepatitisThe 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 hepatitisSignificant 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].

ViralDe 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].

IschemiaLate effects of I/R injuryHepatocytes 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 lesionsThe 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].

ToxicDrugs and other toxinsChanges are usually mild and nonspecific like hepatitis, cholestasis, nodular regenerative hyperplasia, and veno-occlusive disease (sinusoidal congestion) or centrizonal necrosis [8].

Recurrent diseaseIdiopathic posttransplantation hepatitisBile 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 PBCNoninfectious granulomatous cholangitis in the proper setting presence of antimitochondrial antibodies and absence of other causes such as infections and biliary strictures [30].
Alcoholic and nonalcoholic steatohepatitisMacrovesicular steatosis Mallory’s hyaline ballooning cell degeneration perisinusoidal fibrosis and scattered neutrophilic inflammation [31, 32].

HBV: hepatitis B virus; HCV: hepatitis C virus; I/R injury: ischemia reperfusion injury; PSC: primary sclerosing cholangitis; PBC: primary biliary cirrhosis.