Subclinical Liver Transplant Rejection

A recent study (S Feng, JC Bucuvalas, et al. Gastroenterol 2018; 155: 1838-51) found a high prevalence of chronic histologic injury even among highly selected long term liver transplant recipients with consistently normal liver biochemical tests. The authors were able to enroll 157 patients. In addition to histology, the authors examined gene expression/microarray transcriptional analysis, and immunohistochemical staining.

Key findings:

  • Three clusters of patients were identified: interface activity (group 1, n=34), periportal/perivenular fibrosis without interface activity (group 2, n=45), and a group with neither (group 3, n=78).
  • In this cohort, 96 (61%) had Ishak Fibrosis of Stage 0-1, 27  (17%) had Stage 2, 33 (21%) had Stage 3, and 1 (1%) had Stage 4-5.
  • The authors identified a module of genes that regulate T-cell-mediated rejection that were associated with interface activity. Thus, interface activity in these patients connotes subclinical rejection, even in patients with consistently normal liver biochemistries.

What to do with this information:

“For patients whose biopsy samples harbor neither inflammation nor fibrosis, immunosuppression dose reduction may be reasonable…For patients, whose biopsy samples show fibrosis in the absence of inflammation, our data do not support any recommendations…for patients whose biopsy samples show interface hepatitis, our data indicate that dose reduction may be unwise.  Although the intuitive response may be to escalate immunosuppression, data evidencing the benefit of this approach are lacking.”

My take: This study shows why a liver biopsy has been important prior to reducing immunosuppression (in liver transplantation and autoimmune hepatitis). My question is whether the authors could identify a gene signature/biomarker (like their gene module) that could be used as an alternative to a liver biopsy.

Related blog post:

View from Golden Gulch Trail, Death Valley

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