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Plasma-Signature-Model for End-Stage Liver Disease Score to Predict Survival in Severe Alcoholic Hepatitis
Naoto Fujiwara1, Eric Trépo2, Indu Raman3
1Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, Dallas, Texas; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Insights
A new plasma protein score (ps-MELD) accurately predicts short-term survival in severe alcoholic hepatitis (AH) patients. This non-invasive score offers a promising alternative to biopsy-dependent methods for assessing prognosis in AH.
Area of Science:
- Hepatology
- Biomarker Discovery
- Prognostic Modeling
Background:
- Severe alcoholic hepatitis (AH) presents a high mortality rate, posing challenges in accurate outcome prediction.
- Current prognostic tools, like the gene signature-MELD score, require liver biopsy, limiting clinical utility.
- There is a critical need for non-invasive biomarkers to assess prognosis in severe AH.
Purpose of the Study:
- To identify a plasma protein-based surrogate for a hepatic gene signature in severe AH.
- To develop and validate a novel prognostic score using plasma proteins and the MELD score.
- To evaluate the prognostic capability of the new score for predicting short-term outcomes in severe AH.
Main Methods:
- A computational pipeline (TexSEC) translated a hepatic gene signature to a plasma-based secretome signature.
- A 6-plasma-protein panel was identified as a surrogate for the 123-gene signature.
- A composite score, ps-MELD, was created by combining the plasma signature with the MELD score and validated in independent cohorts.
Main Results:
- The ps-MELD score, utilizing a 6-plasma-protein panel, effectively surrogated the hepatic gene signature.
- High-risk ps-MELD was significantly associated with 90-day death or liver transplantation (aHR, 4.57).
- The ps-MELD score demonstrated high prognostic accuracy (AUC >0.80), excellent calibration, and outperformed existing clinical scores.
Conclusions:
- The ps-MELD score is a robust, non-invasive predictor of short-term survival in severe alcoholic hepatitis.
- This plasma protein-based score offers a clinically applicable tool for risk stratification in severe AH.
- The findings support the use of ps-MELD for improved patient management and treatment decisions in severe AH.
Background & Aims:
Severe alcoholic hepatitis (AH) is a highly lethal condition and it is still a challenge to predict the outcome. We previously identified and validated a composite score of hepatic 123-gene prognostic signature and the model for end-stage liver disease (MELD) score: gene signature-MELD. However, the need for liver biopsy limits its clinical application. Therefore, we aimed to identify a plasma protein-based surrogate of the gene signature and independently validate its prognostic capability.
Methods:
All patients were diagnosed with severe AH at Cliniques universitaires de Bruxelles Hôpital Erasme (Brussels, Belgium), and the plasma samples were collected at admission before any treatment. The primary outcome was death or liver transplantation within 90 days. Using our computational pipeline, named translation of tissue expression to secretome (TexSEC), a hepatic-transcriptome-based prognostic signature was converted to a plasma-based secretome signature, which was optimized in 50 patients by comparing their hepatic molecular dysregulation status and combining it with the MELD score. The composite score was validated independently in 57 patients.
Results:
The TexSEC and optimization process identified a 6-plasma-protein panel as a surrogate for the 123-gene signature. A composite score with the MELD score, the plasma-signature (ps)-MELD score, was created by using the coefficients of the gene signature-MELD equation. In the validation cohort, the high-risk ps-MELD (n = 23; 40%) was associated significantly with death or liver transplantation within 90 days (adjusted hazard ratio, 4.57; 95% CI, 2.15-9.30; P < .001). The ps-MELD score showed a stable, high prognostic association (time-dependent area under receiver operating characteristics curve, >0.80) and was well calibrated over time; it consistently outperformed existing clinical scores as indicated by various model performance indices.
Conclusions:
The high-risk ps-MELD score was associated with short-term survival in patients with severe AH.
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