Use of an immune functional assay to differentiate recurrent hepatitis C from acute cellular rejection in liver transplant patients

Rubinas, Tara C.; Dellon, Evan S.; Henel, Gabriella

doi:10.1002/lt.21774

Cited by 2 publications

(1 citation statement)

References 3 publications

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“…The potential utility of the ImmunKnow assay for the post-LT immune function status of HCV recipients using biopsy samples was suggested by Cabrera et al (41). Moreover, the findings from this report were further supported by Rubinas et al (42) and others (43). However, the reliable availability and accuracy of biomarkers to support or replace histopathology is scarce.…”

Section: Discussionsupporting

confidence: 61%

Molecular Pathways Differentiate Hepatitis C Virus (HCV) Recurrence from Acute Cellular Rejection in HCV Liver Recipients

Gehrau

Maluf

Archer

et al. 2011

Mol Med

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Acute cellular rejection (ACR) and hepatitis C virus (HCV) recurrence (HCVrec) are common complications after liver transplantation (LT) in HCV patients, who share common clinical and histological features, making a differential diagnosis difficult. Fiftythree liver allograft samples from unique HCV LT recipients were studied using microarrays, including a training set (n = 32) and a validation set (n = 19). Two no-HCV-ACR samples from LT recipients were also included. Probe set intensity values were obtained using the robust multiarray average method (RMA) method. Analysis of variance identified statistically differentially expressed genes (P ≤ 0.005). The limma package was used to fit the mixed-effects models using a restricted maximum likelihood procedure. The last absolute shrinkage and selection operator (LASSO) model was fit with HCVrec versus ACR as the dependent variable predicted. N-fold cross-validation was performed to provide an unbiased estimate of generalization error. A total of 179 probe sets were differentially expressed among groups, with 71 exclusive genes between HCVrec and HCV-ACR. No differences were found within ACR group (HCV-ACR vs. no-HCV-ACR). Supervised clustering analysis displayed two clearly independent groups, and no-HCV-ACR clustered within HCV-ACR. HCVrec-related genes were associated with a cytotoxic T-cell profile, and HCV-ACR-related genes were associated with the inflammatory response. The best-fitting LASSO model classifier accuracy, including 15 genes, has an accuracy of 100% in the training set. N-fold cross-validation accuracy was 78.1%, and sensitivity, specificity and positive and negative predictive values were 50.0%, 90.9%, 71.4% and 80.0%, respectively. Arginase type II (ARG2), ethylmalonic encephalopathy 1 (ETHE1), transmembrane protein 176A (TMEM176A) and TMEM176B genes were significantly confirmed in the validation set. A molecular signature capable of distinguishing HCVrec and ACR in HCV LT recipients was identified and validated.

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Section: Discussionsupporting

confidence: 61%

Molecular Pathways Differentiate Hepatitis C Virus (HCV) Recurrence from Acute Cellular Rejection in HCV Liver Recipients

Gehrau

Maluf

Archer

et al. 2011

Mol Med

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Hepatitis C virus recurrence after liver transplantation: biomarkers of disease and fibrosis progression

Maluf

Archer

Villamil

et al. 2010

Expert Review of Gastroenterology & Hepatology

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End-stage liver disease due to hepatitis C virus infection (HCV) is the principal indication for liver transplantation. In the USA, over a third of available liver allografts are transplanted into recipients with chronic HCV infection. Reinfection of the graft is universal, but the impact of reinfection on short- and long-term liver function is highly variable. HCV infection in liver transplantation recipients is characterized by an accelerated fibrogenesis, with approximately a third of patients developing cirrhosis within 5 years of follow-up. HCV is associated with decreased patient and graft survival when compared with other indications of orthotopic liver transplantation. The mechanisms responsible for the accelerated liver damage in HCV-infected orthotopic liver transplantation recipients remain largely unknown.

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Use of an immune functional assay to differentiate recurrent hepatitis C from acute cellular rejection in liver transplant patients

Cited by 2 publications

References 3 publications

Molecular Pathways Differentiate Hepatitis C Virus (HCV) Recurrence from Acute Cellular Rejection in HCV Liver Recipients

Molecular Pathways Differentiate Hepatitis C Virus (HCV) Recurrence from Acute Cellular Rejection in HCV Liver Recipients

Hepatitis C virus recurrence after liver transplantation: biomarkers of disease and fibrosis progression

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