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©The Author(s) 2021.
World J Gastroenterol. Dec 7, 2021; 27(45): 7771-7783
Published online Dec 7, 2021. doi: 10.3748/wjg.v27.i45.7771
Published online Dec 7, 2021. doi: 10.3748/wjg.v27.i45.7771
T cell-mediated chronic rejection | Antibody-mediated chronic rejection | |
Histological definition (according to the 2016 Banff Group[1]) | Presence of bile duct atrophy/pyknosis affecting the majority of bile ducts; OR Bile duct loss in more than 50% of the portal tracts; OR Foam cell obliterative arteriopathy | At least mild mononuclear portal and/or perivenular inflammation with interface and/or perivenular necroinflammatory activity; AND At least moderate portal/periportal, sinusoidal or perivenular fibrosis; AND Positive C4d staining in at least 10% of the portal tracts; AND Circulating DSAs in serum samples collected within 3 months of biopsy; AND Other causes have reasonably been excluded |
Incidence | 2%-5% | Unknown |
Risk factors | (1) History of T cell-mediated acute rejection episodes; (2) Autoimmune aetiology of the primary liver disease; (3) Non-compliance with IS therapy; (4) Cyclosporine-based IS regimens as opposed to tacrolimus-based regimens; (5) Previous re-transplantation for rejection; (6) Donor/recipient gender mismatch; and (7) Donor age greater than 40 | (1) Donor-specific antibodies (especially de novo anti-HLA class II antigens); (2) Inadequate IS (cyclosporine regimens or low CNI concentrations); (3) MELD score > 15; (4) Young age at transplantation; and (5) Re-transplantation |
Clinical implications | 15%-20% graft loss | Increased fibrosis and graft failure in an unknown percentage of patients |
Structure | Early CR | Late CR |
Small bile ducts (< 60 μm) | (1) Degenerative changes involving the majority of ducts: Eosinophilic transformation of the cytoplasm; Increased nucleus: Cytoplasm ratio; nuclear hyperchromasia; uneven nuclear spacing; ducts only partially lined by biliary epithelial cells; and (2) Bile duct loss in < 50% of the portal tracts | (1) Degenerative changes in remaining bile ducts; and (2) Loss in > 50% of the portal tracts |
Terminal hepatic venules and zone 3 hepatocytes | (1) Intimal/luminal inflammation; (2) Lytic zone 3 necrosis and inflammation; and (3) Mild perivenular fibrosis | (1) Focal obliteration; (2) Variable inflammation; and (3) Severe (bridging) fibrosis |
Portal tract hepatic arterioles | Occasional loss involving < 25% of the portal tracts | Loss involving > 25% of the portal tracts |
Other | So-called "transition" hepatitis with spotty necrosis of hepatocytes | Sinusoidal foam cell accumulation and marked cholestasis |
Large perihilar hepatic artery branches | Intimal inflammation and focal foam cell deposition without luminal compromise | (1) Luminal narrowing by subintimal foam cells; and (2) Fibrointimal proliferation |
Large perihilar bile ducts | Inflammation damage and focal foam cell deposition | Mural fibrosis |
- Citation: Angelico R, Sensi B, Manzia TM, Tisone G, Grassi G, Signorello A, Milana M, Lenci I, Baiocchi L. Chronic rejection after liver transplantation: Opening the Pandora’s box. World J Gastroenterol 2021; 27(45): 7771-7783
- URL: https://www.wjgnet.com/1007-9327/full/v27/i45/7771.htm
- DOI: https://dx.doi.org/10.3748/wjg.v27.i45.7771