Prospective comparison of liver stiffness measurement methods in surveillance biopsies after liver transplantation

Bosselmann, Emily A.; Engel, Bastian; Hartleben, Björn; Wedemeyer, Heiner; Jaeckel, Elmar; Maasoumy, Benjamin; Potthoff, Andrej; Zender, Steffen; Taubert, Richard

doi:10.3389/frtra.2023.1148195

Cited by 2 publications

(1 citation statement)

References 35 publications

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“…These programs select long-term survivors, without contraindications for a LBx and with a high adherence and motivation to perform an invasive measurement to potentially decrease their long-term maintenance immunosuppression. The broader application of DSA measurement and elastography for the assessment of graft fibrosis can help to enrich for LTR with relevant graft injury 2,49,50 . In case of relevant fibrosis or positivity for DSA, a biopsy is often warranted.…”

Section: Discussionmentioning

confidence: 99%

Molecular signatures of chronic antibody-mediated rejection in human liver transplants

Engel,

Alaswad,

Campos-Murguia

et al. 2024

Preprint

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Background&Aims: The role of antibody-mediated rejection (ABMR) after liver transplantation (LT) remains controversial. Chronic ABMR (cABMR) is often subclinical and potentially missed without surveillance biopsies (svLbx) which are not established in most LT centers. Transcriptome analysis previously characterized molecular changes in T cell-mediated rejection (TCMR) after solid organ transplantation. We aimed to identify molecular cABMR signatures after LT for a more comprehensive understanding of cABMR. Methods: We retrospectively identified indication and svLbx from our prospective institutional biorepository (n=1207 over 12 years). We performed RNA-sequencing on liver biopsies (discovery cohort: n=71; validation cohort: n=58). Downstream analyses explored the unique and common molecular features of cABMR, clinical (clinTCMR) and subclinical TCMR (subTCMR) compared to no histological rejection (NHR). Results: Nineteen percent of LT recipients with donor-specific antibodies had cABMR. Eighty-one percent of patients with cABMR had ALT and AST ≤2x the upper limit of normal, only being recognized by svLbx. The cABMR group displayed differentially expressed genes (DEGs) uniquely enriched in fibrogenesis-, complement activation- and TNFα-signaling-related pathways. ClinTCMR showed DEGs uniquely enriched in antigen presentation-, interferon-signaling-, and T cell receptor-signaling-related pathways. Common cABMR and clinTCMR DEGs were enriched in chemokine-signaling- and cytokine response-related pathways. Gene set enrichment scores of interferon-signaling and extracellular matrix remodeling pathways discriminated cABMR and clinTCMR. Molecular signatures of clinTCMR correlated with histological TCMR-patterns. Molecular cABMR-signatures correlated with lobular graft injury and liver fibrosis scores. The validation cohort consistently showed patterns of DEGs associating cABMR with fibrogenesis- and NF-κB-signaling-related pathways and clinTCMR with interferon-signaling- and adaptive immunity-related pathways. SubTCMR was molecularly almost indistinguishable from NHR. Conclusions: We report transcriptome-unique features of cABMR that is a unique molecular identity associated with inflammation and fibrogenesis.

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Section: Discussionmentioning

confidence: 99%

Molecular signatures of chronic antibody-mediated rejection in human liver transplants

Engel,

Alaswad,

Campos-Murguia

et al. 2024

Preprint

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Overweight Impacts Histological Disease Activity of De Novo Metabolic Dysfunction‐Associated Steatotic Liver Disease After Liver Transplantation

Campos‐Murguia,

Guetzlaff,

Bosselmann

et al. 2024

Clinical Transplantation

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Background and AimsMetabolic dysfunction‐associated steatotic liver disease (MASLD) is a leading indication for liver transplantation (LT), but also occurs after LT. The prevalence of de novo MASLD (dnMASLD) after LT, based on both surveillance (svLbx) and indication biopsies (indLbx), is unknown. Furthermore, the impact of the distinct cardiometabolic risk factors on histological disease activity has not been assessed. We aimed to evaluate the prevalence of dnMASLD and the association between the cardiometabolic risk factors and histological disease activity.MethodsWe performed a retrospective single‐center study in a LT cohort with indLbx and svLbx. Patients with NAFLD before LT were excluded.ResultsWe analyzed 249 patients who underwent either svLbx or indLbx. Forty‐eight (19.2%) had either dnMASLD (n = 26/249, 10.4%) or metabolic dysfunction associated steatohepatitis (dnMASH) (n = 22/249, 8.8%). Although dnMASLD/dnMASH was more frequent in indLbx (35.1%, p < 0.01), still 16.5% of patients with svLbx had dnMASLD/dnMASH. While overweight (p < 0.01) and diabetes (p = 0.01) were more frequent in patients with dnMASH, only overweight was associated with histological disease activity in the multivariate analysis. No impact of dnMASLD on the overall survival was observed.ConclusionWhile dnMASLD is more frequent in patients with indLBX, it also occurs in 16.5% of patients without signs of graft dysfunction. Overweight has the strongest impact on histological disease activity and should be monitored carefully after LT.

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Prospective comparison of liver stiffness measurement methods in surveillance biopsies after liver transplantation

Cited by 2 publications

References 35 publications

Molecular signatures of chronic antibody-mediated rejection in human liver transplants

Molecular signatures of chronic antibody-mediated rejection in human liver transplants

Overweight Impacts Histological Disease Activity of De Novo Metabolic Dysfunction‐Associated Steatotic Liver Disease After Liver Transplantation

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