Requirement of Protocol Biopsy Before and After Complete Cessation of Immunosuppression After Liver Transplantation

Yoshitomi, Mami; Koshiba, T; Haga, Hironori; Liu, Ying; Zhao, Xiangdong; Cheng, Da‐Chuan; Miyagawa, Aya; Sakashita, Hiromi; Tsuruyama, Tatsuaki; Ohe, Hidenori; Ueda, Mikiko; Okamoto, Shinya; Egawa, Hiroto; Wood, Kathryn J.; Sakaguchi, Shimon; Manabe, Toshiaki; Tanaka, Kōichi; Üemoto, Shinji

doi:10.1097/tp.0b013e318195a7cb

Cited by 109 publications

(92 citation statements)

References 35 publications

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“…Weaning can either be fast or slow. In the first place, this means withdrawal of IS within 6 months, whereas slow tapering protocols consider a 3-year weaning time [26][27][28][29][105][106][107][108][109][110]. It has been suggested that CNI can be tapered by 25% of the initial dose every month until complete withdrawal is achieved.…”

Section: Drug Weaningmentioning

confidence: 97%

“…It included protocol biopsies of 29 COT live donor liver recipients (LDLR). Results were compared with a patient cohort under maintenance immunosuppressive treatment [110]. LDLR exhibited more fibrosis, ductular reactions and decreased luminal diameter of bile ducts as compared with patients under IS treatment, abnormalities which improved after resumption of IS.…”

Section: Drug Weaningmentioning

confidence: 98%

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Tolerance in clinical transplantation: progress, challenge or just a dream?

Fändrich¹

2011

Langenbecks Arch Surg

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In combination with donor bone marrow-derived stem cells, some encouraging results in COT development were reported lately for renal transplantation as well. However, less toxic conditioning protocols and more experience by use of cell products with regulatory properties in combination with synergizing immunosuppressive drugs is required to launch future tolerance trials for a broader spectrum of potential transplant candidates. New methods in immunomonitoring including biomarkers, microarray-based genetic tolerance signatures and functional assays may pave the way to achieve COT in upcoming clinical trials.

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Section: Drug Weaningmentioning

confidence: 97%

Section: Drug Weaningmentioning

confidence: 98%

Tolerance in clinical transplantation: progress, challenge or just a dream?

Fändrich¹

2011

Langenbecks Arch Surg

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“…IPTH occurred following a decrease in the overall immunosuppression in 24/37 patients (65%). A study of immunosuppression-free patients found more fibrosis (with mild portal activity but no signs of acute/chronic rejection) that regressed after the reinstatement of immunosuppression [17] . The hypothesis of a component of AMR may be discussed in the development of fibrosis/IPTH, as reported a paediatric series [18] .…”

Section: Discussionmentioning

confidence: 99%

Idiopathic Post Liver-Transplant Hepatitis Remains Obscure with Respect to Its Etiology and Relationship with Immunosuppressiona

Sebagh¹,

Coilly²,

Ha飉-Boukobzsa³

et al. 2015

Journal of Gastroenterology and Hepatology Research

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AIM: Idiopathic post-liver transplant hepatitis (IPTH) can lead to late graft fibrosis. The treatment for IPTH is not clearly delineated. We aimed to approach its pathophysiology and predictive factors for fibrosis progression (FP). METHODS: Patients whose IPTH was diagnosed in 2006 and had undergone at least one subsequent liver biopsy (LB) were included.The index LBs were reviewed and correlated with clinical, laboratory, C4d immunostaining retrospectively performed, and histological data on the most recent LBs. RESULTS: Among the 299 post-transplant LBs, 37 presented IPTH. The index LBs mostly displayed mild fibrosis (65%) and activity (67.5%), and non-significant C4d immunostaining (i.e., weak, focal and/or portal stroma staining, 21.6%). Liver tests were normal in 46% of patients. Virological markers including Hepatitis E were negative. Antinuclear auto-antibodies were present concurrently in four patients and appeared later in two patients, together with features of autoimmune hepatitis (AIH) in one. Isolated AIH features appeared later in one patient. One patient displayed AIH features on the index LB, with negative autoantibodies and elevated serum IgG. Fibrosis was stable, increased or decreased in 23, 11, and three patients, respectively. FP was less frequent in tacrolimus-treated patients (p = 0.022), more frequent in cyclosporine-(p = 0.035) and MMF-treated patients (p = 0.023), and not influenced by steroid-based treatment or increased overall immunosuppression or steroids. Under multivariate analysis, MMF remained an independent predictor of FP (p = 0.048). CONCLUSION: The physiopathology of IPTH remained unclear. Increasing steroid doses or overall immunosuppression did not prevent FP. The potential impact of MMF on FP will require prospective studies.

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“…However, in their more recent study, with a larger number of patients, approximately 15% (87/581) were reported immunosuppression free [31]. Furthermore, their most recent study revealed a higher incidence of fibrosis in protocol biopsies of immunosuppression-free patients, despite absence of clinical markers of rejection [152]. While studies in Kyoto included relatively older pediatric patients (up to 18 years old with the median age 12), Feng et al at UCSF attempted to withdraw immunosuppression in much younger liver transplant recipients, (5.5-9.1 months at transplant and 6-11 years at study enrollment) who received parental living-donor liver transplantation [153].…”

Section: Mixed Chimerism In Hla-mismatched Kidney Transplantationmentioning

confidence: 99%