Great article showcasing work our CEO and Founder, Dr. Yang Li, performed as a pilot study using human Liver tissues with biliary atresia (BA). The article describes how CHPs can be used as a novel measurement of tissue fibrosis associated with BA severity, and that CHP signal intensity can be leveraged as an early predictor to identify infants with BA with the greatest likelihood or requiring a liver transplant. The image below shows how CHP signal can help predict the need for liver transplant based on the amount of fibrotic tissue. Top: Patient requiring a liver transplant. Bottom: Patient who did not require a liver transplant.


Background/Rationale: Biliary atresia (BA) is a cholangiopathy characterized by bile flow obstruction due to destruction of the biliary tree. Without surgical correction with Kasai portoenterostomy (KPE), BA leads to death or liver transplant (LTx). Early-onset, progressive liver fibrosis is a defining characteristic of BA. Collagen hybridizing peptide (CHP) is a synthetic peptide which binds to denatured collagen strands allowing quantification of fibrosis. This technique has not been used on human liver tissue. The aim of this pilot study was to evaluate the utility of CHP as a measurement of quantitative fibrosis to allow earlier survival with native liver (SNL) prognostication.

Results: We identified 21 patients with wedge liver biopsies available, of which 14 required LTx. No deaths occurred. Patients requiring LTx tended to be female with a significantly different mean bilirubin (p = 0.002), albumin (p = 0.001) and ALT (p = 0.03) at 3-months post-KPE. By 1-year post-KPE, 50% of patients in the high-CHP intensity group required LTx versus 27% in the low-CHP. Overall, fibrosis as quantified by CHP at time of KPE was associated with more than three-times the risk of requiring LTx by 4-years of age (HR 3.6, 95%CI 1.15–10.93, p = 0.03). When controlling for gender and TB > 2 mg/dL and albumin at 3-months post-KPE, it predicted nearly seven times the risk of LTx (HR 6.89, 95%CI 1.38–34.32, p = 0.02).

Conclusion: Our results suggest that quantitative assessment of fibrosis at the time of KPE holds promise as an earlier predictor of LTx requirement in BA. A larger study is justified to assess quantitative fibrosis as a BA prognostic tool.


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