PLIN2 and RAB14: Promising Biomarkers for Assessing Post-Bariatric Surgery Treatment Response

Advancing Non-Invasive Monitoring for MASH Progression and Treatment Response

The demand for scalable and safe alternatives to liver biopsy in monitoring metabolic dysfunction-associated steatohepatitis (MASH) progression has led to the development of HeparDx™, a monocyte-based diagnostic test using PLIN2 and RAB14 markers.

This study evaluates PLIN2 and RAB14's effectiveness in detecting MASH resolution and fibrosis improvement post-bariatric surgery, comparing their performance to cytokeratin-18 assays like Ella™ and M65 ELISA.

Study Methods

Participants:

Total enrolled: 50 patients from the BRAVES randomized controlled trial (RCT).

Procedures: Ultrasound-guided needle liver biopsies conducted at baseline and one-year post- surgery.

Definitions:

MASH Resolution: NAS < 3 without worsening fibrosis.

Fibrosis Improvement: F values at 1-year follow-up lower than baseline values.

Evaluation Metrics:

Performance of PLIN2 and RAB14 compared to liver biopsy.

Metrics used:

Area Under the Receiver Operating Curve (AUROC).

Accuracy, sensitivity and specificity calculated based on the Youden threshold.

Outcomes of Bariatric Surgery on MASH and Fibrosis

Pre-Surgery Patient Characteristics

NAS Scores:

35 patients had a Non-alcoholic Steatohepatitis (NASH) Activity Score (NAS) ≥4.

15 patients had NAS <4.

Post-Surgery MASH Outcomes

Improvement in MASH Severity:

Observed in 45 patients.

No change occurred in 5 patients.

MASH Resolution:

Complete resolution without fibrosis progression was achieved in 37 patients.

Fibrosis Outcomes

Baseline Fibrosis Severity:

Stage 1 fibrosis: 23 patients.

Significant fibrosis: 23 patients.

Advanced fibrosis: 4 patients.

Post-Surgical Fibrosis Resolution:

Significant fibrosis resolution (fibrosis stage 0 or 1) occurred in 17 patients.

No improvement in fibrosis severity in 30 patients.

Worsening of fibrosis observed in only 3 patients.

Molecular Biomarkers for MASH and Fibrosis

MASH Resolution and PLIN2:

Patients with MASH resolution showed a significant reduction in PLIN2 expression.

Predictive model using PLIN2 as a marker:

Accuracy: 84%.

AUROC: 83 (95% CI: 67–96).

Sensitivity: 91%.

Specificity: 76%.

Fibrosis Improvement and RAB14:

Patients with fibrosis improvement demonstrated increased RAB14 expression.

Predictive model incorporating RAB14:

Accuracy: 85%.

AUROC: 87 (95% CI: 74–97).

Sensitivity: 88%.

Specificity: 83%.

Comparison of Diagnostic Tools

PLIN2 and RAB14, evaluated using the HeparDx™ platform, demonstrated superior diagnostic accuracy for MASH resolution and fibrosis improvement compared to CK18.

Key Insight:

PLIN2 and RAB14 show promise as non-invasive markers for assessing liver response to bariatric surgery and new medical treatments. With further validation, they could greatly reduce or eliminate the reliance on frequent liver biopsies.

By - Eeshan Aggarwal

Reference: Hepatology. Volume 80, Issue S1. Abstract Supplement for The Liver Meeting by the American Association for the Study of Liver Diseases (AASLD), November 15-19, 2024, San Diego, CA.