Post-transplant liver biopsy and the immune response: lessons for the clinician

Shetty, Shishir; Adams, David H.; Hübscher, Stefan G.

doi:10.1586/eci.12.65

Cited by 15 publications

(14 citation statements)

References 205 publications

(114 reference statements)

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“…The correlation between a significant histological fibrosis (Table 4). Moreover, patients who showed significant fibrosis F ≥ 2 (r = .56, P < .05), but not patients staged as F0 or F1 at histology, also had a statistically significant correlation between liver stiffness assessed at TE and time interval from LT (r = .61, P < .001) 5,39,41 Liver biopsy is considered the gold standard for diagnosing graft fibrosis, [40][41][42] also due to the fact that LFT do not seem to be reliable indicators of this condition. 38,39 However, liver biopsy is considered an invasive procedure by parents and many pediatricians, with a clinical risk of 1/10 000.…”

Section: Resultsmentioning

confidence: 99%

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Transient elastography for non‐invasive evaluation of post‐transplant liver graft fibrosis in children

Vinciguerra

Brunati

David

et al. 2018

Pediatric Transplantation

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As graft survival in pediatric LT is often affected by progressive fibrosis, numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols differ from center to center, but all biopsies are progressively spaced out, as time from transplant increases. Therefore, there is a need for non-invasive techniques to evaluate graft fibrosis progression in those children who have no clinical or serological signs of liver damage. Indirect markers, such as the APRI, should be relied on with caution because their sensitivity in predicting fibrosis can be strongly influenced by the etiology of liver disease, severity of fibrosis, and patient age. A valid alternative could be TE, a non-invasive technique already validated in adults, which estimates the stiffness of the cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy sample. The aims of this study were to evaluate the reliability of TE in children after LT and to compare both the TE and the APRI index results with the histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT recipients were studied. All patients underwent both TE and biopsy within a year (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology and staged according to METAVIR. There was a statistically significant correlation between TE stiffness values and METAVIR scores (P = .005). The diagnostic accuracy of TE for the diagnosis of significant fibrosis (F ≥ 2) was measured as the area under the curve (AUROC = 0.865), and it demonstrated that the method had a good diagnostic performance. APRI was not so accurate in assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for a significant graft fibrosis (METAVIR F ≥ 2) on liver biopsy, with a 75% sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5% negative predictive value. These data suggest that TE may represent a non-invasive, reliable tool for the assessment of graft fibrosis in the follow-up of LT children, alerting the clinicians to the indication for a liver biopsy, with the aim of reducing the number of protocol liver biopsies.

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Section: Resultsmentioning

confidence: 99%

“…Liver biopsy is considered the gold standard for diagnosing graft fibrosis, also due to the fact that LFT do not seem to be reliable indicators of this condition . However, liver biopsy is considered an invasive procedure by parents and many pediatricians, with a clinical risk of 1/10 000 .…”

Section: Discussionmentioning

confidence: 99%

Transient elastography for non‐invasive evaluation of post‐transplant liver graft fibrosis in children

Vinciguerra

Brunati

David

et al. 2018

Pediatric Transplantation

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“…It typically presents with non-specific clinical symptoms and predominantly cholestatic liver biochemistry. Liver biopsy is required for diagnostic confirmation and shows a dense portal-based mixed inflammatory cell infiltrate with evidence of damage to biliary epithelium, portal and hepatic vein endothelium and hepatocytes ( 18 ) ( Figure 1 ). Early episodes of TCMR do not impact on long-term outcomes ( 19 ) although persistent rejection episodes refractory to standard therapies remain problematic.…”

Section: The Immunological Basis Of T-cell Mediated Rejectionmentioning

confidence: 99%

The Immunological Basis of Liver Allograft Rejection

et al. 2020

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Liver allograft rejection remains a significant cause of morbidity and graft failure in liver transplant recipients. Rejection is caused by the recognition of non-self donor alloantigens by recipient T-cells. Antigen recognition results in proliferation and activation of T-cells in lymphoid tissue before migration to the allograft. Activated T-cells have a variety of effector mechanisms including direct T-cell mediated damage to bile ducts, endothelium and hepatocytes and indirect effects through cytokine production and recruitment of tissue-destructive inflammatory cells. These effects explain the histological appearances of typical acute T-cell mediated rejection. In addition, donor specific antibodies, most typically against HLA antigens, may give rise to antibody-mediated rejection causing damage to the allograft primarily through endothelial injury. However, as an immune-privileged site there are several mechanisms in the liver capable of overcoming rejection and promoting tolerance to the graft, particularly in the context of recruitment of regulatory T-cells and promotors of an immunosuppressive environment. Indeed, around 20% of transplant recipients can be successfully weaned from immunosuppression. Hence, the host immunological response to the liver allograft is best regarded as a balance between rejection-promoting and tolerance-promoting factors. Understanding this balance provides insight into potential mechanisms for novel anti-rejection therapies.

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“…In our previous work, fibrosis correlated with portal inflammation, being less frequent among those with low‐dose steroids, whereas steatosis only associated with high body mass index . Inflammatory changes in patients with stable graft function have been attributed to chronic immunological challenge, representing a form of chronic rejection .…”

Section: Introductionmentioning

confidence: 92%

Liver and serum expression of matrix metalloproteinases in asymptomatic pediatric liver transplant recipients

et al. 2016

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We related hepatic gene and serum expression of matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) to liver histology in pediatric LT recipients. Liver biopsies and serum samples were obtained from 52 patients 10.6 years post-LT and age-matched controls for analyses of MMPs and TIMPs. Patients with fibrosis had significantly higher hepatic gene expression of MMP-2, MMP-9, MMP-14, TIMP-1, and TIMP-2 than patients without. Expression of these genes correlated with graft Metavir fibrosis stage (r = 0.494-0.684, P ≤ 0.006 for all). Gene expression of MMP-1, MMP-3, MMP-8, TIMP-3, and TIMP-4 was undetectable in both patients and controls. Portal inflammation and cytokeratin 7 correlated positively with gene expression of TIMP-1. Gene expression of MMP-2, MMP-9, and TIMP-2 correlated negatively with the time of low-dose cortisone usage (r = -0.448 to -0.422, P < 0.05 for all). Serum concentrations of MMP-8 and TIMP-1 were significantly increased and MMP-9 decreased among patients compared with controls, but no correlations to graft histology or gene expression were observed. Hepatic gene expression of certain MMPs and TIMPs is increased in stable pediatric LT recipients displaying graft fibrosis, but this did not reflect to their serum concentrations. Increased hepatic gene expression of TIMP-1 correlated with graft fibrosis stage, inflammation, and chronic cholestasis.

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Post-transplant liver biopsy and the immune response: lessons for the clinician

Cited by 15 publications

References 205 publications

Transient elastography for non‐invasive evaluation of post‐transplant liver graft fibrosis in children

Transient elastography for non‐invasive evaluation of post‐transplant liver graft fibrosis in children

The Immunological Basis of Liver Allograft Rejection

Liver and serum expression of matrix metalloproteinases in asymptomatic pediatric liver transplant recipients

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