← Issue №11/ week of Sep 13, 2026/Hepatology

Pharmacokinetic and Pharmacodynamic Variability Predict Late Events After Paediatric Liver Transplantation: Derivation and External Validation of a Landmark Risk Score.

From GI Signals issue №11: what this paper found, what it changes, and where it sits against the current standard of care, reviewed by Simon Mathews, MD.

Hepatology retrospective · n=93 · Sep 8, 2026 · Aliment Pharm Ther · IF 6.7

Pharmacokinetic and Pharmacodynamic Variability Predict Late Events After Paediatric Liver Transplantation: Derivation and External Validation of a Landmark Risk Score.

New evidenceliver transplantpediatricbiomarker
Clinical takeawayAt 12 months post-pediatric liver transplant in recipients without major early complications (6-12 months post-transplant), calculate tacrolimus, aspartate aminotransferase, and total bilirubin variability from prior 6 months of measurements; score of 2-3 identifies patients at 4-9x higher risk for late complications or graft loss, warranting closer surveillance. Population predominantly biliary atresia.
What it foundA variability-based risk score (tacrolimus >25%, aspartate aminotransferase >50%, total bilirubin >50%) derived and externally validated at 12 months post-transplant, where score 2-3 identified higher-risk patients with hazard ratio 4.48 (95% CI 1.79-11.17) in derivation and 8.90 (95% CI 2.66-29.81) in validation cohorts.
ContextChallenges the sufficiency of cross-sectional tacrolimus concentrations and static liver biochemistry in post-transplant monitoring. Demonstrates that longitudinal instability and variability are better predictors of adverse long-term outcomes. Derived and externally validated in pediatric recipients, predominantly with biliary atresia, without early major complications.
Refinessuggested applicable standard· AASLD/AST, 'AASLD AST Practice Guideline on adult liver transplantation: Candidate evaluation' (Dove L et al., Hepatology 2026;83(6):1609-1645). DOI 10.1097/HEP.0000000000001644, PMID 41405234.

Decision at stakeidentify which post-transplant liver recipients require intensive long-term surveillance

No single passage of this standard matched the paper closely enough to quote, so none is shown. The standard is cited above.

Our full summary of this standard

Refer patients with decompensated cirrhosis (including those with MELD-Na <15 or MELD 3.0 <15 if they have clinically significant portal hypertension, recurrent ascites, hepatic encephalopathy, or variceal bleeding), acute liver failure meeting King's College Criteria/UNOS Status 1A, or HCC within Milan/UCSF criteria for comprehensive multidisciplinary liver transplant evaluation, with MELD 3.0 driving UNOS waitlist allocation and MELD exception scoring for HCC/HPS/FAP. Optimize modifiable risk factors before listing (alcohol abstinence, HCV DAA treatment, vaccinations, DM/obesity/OSA and dental clearance) and use bridging/downstaging locoregional therapy for HCC while awaiting transplant. After transplant, maintain lifelong immunosuppression with tacrolimus plus mycophenolate ± tapered steroids alongside infection prophylaxis and recurrent-disease surveillance.

AASLD/AST, 'AASLD AST Practice Guideline on adult liver transplantation: Candidate evaluation' (Dove L et al., Hepatology 2026;83(6):1609-1645). DOI 10.1097/HEP.0000000000001644, PMID 41405234. · reviewed 2026-07-21 ↗
Tang H … Zhang M · Alimentary Pharmacology & Therapeutics · IF 6.7 · PubMed ↗Permalink
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