Long-Term Outcome of Immunosuppression Withdrawal After Liver Transplantation

Girlanda, Raffaele; Rela, Mohamed; Williams, Roger; O’Grady, John; Heaton, Nigel

doi:10.1016/j.transproceed.2005.03.070

Cited by 83 publications

(52 citation statements)

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“…These include such diverse factors as the putative role of extrahepatic stem cells, age, etiology of the liver failure, graft-to-native liver size, reciprocal blood supply, and trophic factor delivery as well as the quality of graft function and effect of immunosuppression. 4,20 In conclusion, our study based on the sequential histology of native livers after ALT for ALF reaffirms the apparent duality of liver regeneration following confluent necrosis. On the one hand, an efficient and rapid process of liver replenishment in the presence of enough surviving parenchyma underpins the rationale to perform ALT.…”

Section: Discussionsupporting

confidence: 69%

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Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration

et al. 2008

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Auxiliary liver transplantation (ALT) permits the serial assessment of regeneration in livers of patients with acute liver failure (ALF). Forty-nine ALF patients [32 adults (median age, 23 years; range, 16-40 years) and 17 children (median age, 12 years; range, 1-15 years)] underwent ALT between 1994 and 2004 at King's College Hospital. Twenty-four patients had seronegative liver failure, 15 had acetaminophen toxicity, 4 had hepatitis B virus (HBV) infection, 3 had drug-induced liver failure, 2 had autoimmune hepatitis, and 1 had mushroom poisoning. Nine patients without post-ALT native liver histology were excluded from review. All acetaminophen-induced, HBV, and drug-related patients had diffuse injury. Twelve seronegative patients and the autoimmune hepatitis patient had a map-like injury. On follow-up, 9 acetaminophen-induced patients, 9 seronegative patients, 2 drug-induced ALF patients, 3 HBV patients, and the autoimmune patient recovered to a near-normal native liver with inconsequential scarring. The hepatocyte proliferative rate in diffuse necrosis was 27.4% (range, 3.1%-69.4%) at hepatectomy and sharply decreased after 8 days post-ALT, being minimal months and years after ALT. In conclusion, in patients undergoing ALT for ALF with a diffuse pattern of liver injury-mainly acetaminophen toxicity-hepatocyte proliferation occurs in the native liver within a few days of transplantation. If the injury is map-like (most cases of seronegative ALF), regeneration seems to involve variable hepatocellular proliferation and potential ductular hepatopoiesis, but sequential assessment is difficult because of sampling variation. The likelihood of histological recovery appears to be minimal in livers with total hepatocyte loss at the time of ALT.

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Section: Discussionsupporting

confidence: 69%

“…Following ALT, immunosuppression can be withdrawn in a significant proportion of patients. 4 Patient age Ͻ 40 and ALF may predict complete native liver regeneration, 1 but large studies investigating clinical predictors of regeneration are still needed, and data on histological predictors of regeneration are scant.…”

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confidence: 99%

Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration

et al. 2008

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“…14,15 Assessment of the completeness and durability of the tolerance may require follow-ups of 2 or more years since the effects of conditioning with a potent lymphoid depleting antibody are long-lasting. Nevertheless, the observations in the 3 cases described by Donckier et al add to the considerable historical evidence 15,34,[38][39][40][41][42] that drug-free tolerance in a significant number of HLA-mismatched liver transplant recipients is a realizable objective.…”

Section: See Article On Page 1523mentioning

confidence: 96%

Tolerance for organ recipients: A clash of paradigms

Marcos¹,

Lakkis²,

Starzl³

2006

Liver Transpl

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“…In case of human liver allografts, its susceptibility to rejection is lower than other organs (Wall and Ghent, 1995), but increasing number of reports regarding to the rejection indicate that immunosuppressive regimens are necessary and beneficial for liver transplantation (Girlanda et al, 2005). Early immunosuppressive regimens used in liver transplantation consisted of cyclosporine A (CsA), a calcinurin inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory Effects of UDCA on Splenocytes Exposed to PMA/Ionomycin

Park¹,

Woo²,

Jung³

et al. 2008

Biomolecules and Therapeutics

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− Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-γ and TNF-α. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-γ and TNF-α) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.

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Long-Term Outcome of Immunosuppression Withdrawal After Liver Transplantation

Cited by 83 publications

References 1 publication

Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration

Auxiliary transplantation for acute liver failure: Histopathological study of native liver regeneration

Tolerance for organ recipients: A clash of paradigms

Anti-inflammatory Effects of UDCA on Splenocytes Exposed to PMA/Ionomycin

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