Serum cholestasis markers as predictors of early outcome after liver transplantation

Ben‐Ari, Ziv; Weiss-Schmilovitz, Hemda; Sulkes, Jaqueline; Brown, Marius; Bar-Nathan, N; Shaharabani, E; Yussim, A; Shapira, Z; Tur–Kaspa, Ran; Mor, Eytan

doi:10.1046/j.1399-0012.2003.00135.x

Cited by 48 publications

(34 citation statements)

References 33 publications

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“…The goal of this study was not to derive new cutoffs for variables, but rather to assess the validity of prior definitions that used objective posttransplant criteria. The variables were chosen to be easily obtainable, objective, and used by prior investigators with strong clinical correlation to graft outcome, and applicable in the MELD era 11, 12. On the basis of these guidelines, we determined the incidence of EAD when one or more of the following variables were present: (1) bilirubin ≥10 mg/dL on postoperative day 7; (2) INR ≥1.6 on postoperative day 7; (3) aminotransferase level (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) >2000 IU/mL within the first 7 postoperative days.…”

Section: Methodsmentioning

confidence: 99%

“…This definition of EAD was associated with worse patient and graft survival and has stood the test of time over the last decade. More recent definitions of EAD have been reported from single centers and have been a variation on this earlier definition, incorporating aminotransferases, bilirubin, international normalized ratio (INR), and other variables 12‐14. None have been validated in a large multicenter population in the MELD era.…”

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confidence: 99%

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Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors

et al. 2010

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Translational studies in liver transplantation often require an endpoint of graft function or dysfunction beyond graft loss. Prior definitions of early allograft dysfunction (EAD) vary, and none have been validated in a large multicenter population in the Model for End-Stage Liver Disease (MELD) era. We examined an updated definition of EAD to validate previously used criteria, and correlated this definition with graft and patient outcome. We performed a cohort study of 300 deceased donor liver transplants at 3 U.S. programs. EAD was defined as the presence of one or more of the following previously defined postoperative laboratory analyses reflective of liver injury and function: bilirubin !10mg/dL on day 7, international normalized ratio !1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L within the first 7 days. To assess predictive validity, the EAD definition was tested for association with graft and patient survival. Risk factors for EAD were assessed using multivariable logistic regression. Overall incidence of EAD was 23.2%. Most grafts met the definition with increased bilirubin at day 7 or high levels of aminotransferases. Of recipients meeting the EAD definition, 18.8% died, as opposed to 1.8% of recipients without EAD (relative risk ¼ 10.7 [95% confidence interval: 3.6, 31.9] P < 0.0001). More recipients with EAD lost their grafts (26.1%) than recipients with no EAD (3.5%) (relative risk ¼ 7.4 [95% confidence interval: 3.4, 16.3] P < 0.0001). Donor age and MELD score were significant EAD risk factors in a multivariate model. In summary a simple definition of EAD using objective posttransplant criteria identified a 23% incidence, and was highly associated with graft loss and patient mortality, validating previously published criteria. This definition can be used as an endpoint in translational studies aiming to identify mechanistic pathways leading to a subgroup of liver grafts with clinical expression of suboptimal function. Liver Transpl 16:943-949,

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors

et al. 2010

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“…(7) Rather than deriving novel variable cut-offs, the study was aimed at validation of previous definitions; objective variables that could be easily obtained over the course of patient follow-up were selected. (2,17) In that study, EAD diagnosis was established when one or more of the following variables were present: serum bilirubin levels ≥10mg/dL; INR ≥1.6 on postoperative day 7; and serum AST or ALT levels >2,000IU/L within the first 7 days of surgery. (7) Friedman et al hypothesized that serum inflammatory protein expression in response to surgery might reflect EAD; (18) hence, inflammatory cytokine profiles could be used to diagnose the condition.…”

Section: Early Allograft Dysfunctionmentioning

confidence: 99%

Primary graft dysfunction of the liver: definitions, diagnostic criteria and risk factors

Neves

Rusi

Díaz

et al. 2016

Einstein (São Paulo)

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Primary graft dysfunction is a multifactorial syndrome with great impact on liver transplantation outcomes. This review article was based on studies published between January 1980 and June 2015 and retrieved from PubMed database using the following search terms: "primary graft dysfunction", "early allograft dysfunction", "primary non-function" and "liver transplantation". Graft dysfunction describes different grades of graft ischemia-reperfusion injury and can manifest as early allograft dysfunction or primary graft non-function, its most severe form. Donor-, surgery-and recipient-related factors have been associated with this syndrome. Primary graft dysfunction definition, diagnostic criteria and risk factors differ between studies.

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“…Termed early allograft dysfunction (EAD), this condition affects approximately one quarter of liver recipients and is associated with decreased graft and patient survival (1,2). EAD is usually manifested by high transaminases, persistent cholestasis, or prolonged coagulopathy (2)(3)(4)(5)(6). The clinical parameters defining EAD are commonly indices of hepatocellular damage and synthetic impairment, leaving its underlying molecular/cellular mechanisms still unclear.…”

Section: Introductionmentioning

confidence: 99%

Genomic Profiles and Predictors of Early Allograft Dysfunction After Human Liver Transplantation

Kurian

Fouraschen

Langfelder

et al. 2015

American Journal of Transplantation

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y These authors contributed equally to this manuscript.Early hepatic allograft dysfunction (EAD) manifests posttransplantation with high serum transaminases, persistent cholestasis, and coagulopathy. The biological mechanisms are poorly understood. This study investigates the molecular mechanisms involved in EAD and defines a gene expression signature revealing different biological pathways in subjects with EAD from those without EAD, a potential first step in developing a molecular classifier as a potential clinical diagnostic. Global gene expression profiles of 30 liver transplant recipients of deceased donor grafts with EAD and 26 recipients without graft dysfunction were investigated using microarrays of liver biopsies performed at the end of cold storage and after graft reperfusion prior to closure. Results reveal a shift in inflammatory and metabolic responses between the two time points and differences between EAD and non-EAD. We identified relevant pathways (PPARa and NF-kB) and targets (such as CXCL1, IL1, TRAF6, TIPARP, and TNFRSF1B) associated with the phenotype of EAD. Preliminary proof of concept gene expression classifiers that distinguish EAD from non-EAD patients, with Area Under the Curve (AUC) >0.80 were also identified. This data may have mechanistic and diagnostic implications for EAD.

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Serum cholestasis markers as predictors of early outcome after liver transplantation

Cited by 48 publications

References 33 publications

Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors

Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors

Primary graft dysfunction of the liver: definitions, diagnostic criteria and risk factors

Genomic Profiles and Predictors of Early Allograft Dysfunction After Human Liver Transplantation

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