# Novel alveolar mechanisms of hypoxemia in hepatopulmonary syndrome

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2024 · $737,804

## Abstract

Project Summary & Abstract
Cirrhosis afflicts more than 4.5 million Americans and hepatopulmonary syndrome (HPS), the most common
pulmonary complication of cirrhosis, occurs in up to 30% of patients and significantly increases mortality. No
effective therapies exist due to our incomplete understanding of cellular mechanisms. Although classically
recognized as alveolar microvascular remodeling causing hypoxemia, the poor correlation between hypoxemia,
the degree of microvascular changes, and outcomes in HPS remain unexplained. To address this knowledge
gap, we have identified novel abnormalities in the alveolus itself in experimental HPS, along with restrictive
ventilatory defects and elevated circulating bile acids in human disease. Our hypothesis is that elevated
circulating bile acid levels in cirrhosis, affect alveolar epithelial type 2 cells (AT2 cells), leading to impaired
surfactant production and restrictive ventilatory defects which influence the progression and outcome of HPS.
To elucidate the role of bile acids and AT2 cells in HPS, we propose to 1) assess the correlation between bile
acid levels and the presence and severity of HPS 2) define the role of AT2 cells in HPS and 3) determine the
mechanisms and consequences of bile acid medicated AT2 cell loss. Completion of this work will define the
mechanisms and significance of AT2 cell dysfunction in HPS, identify novel therapeutic targets and form the
foundation for a broader understanding of how chronic liver disease influences lung function.

## Key facts

- **NIH application ID:** 10913598
- **Project number:** 5R01HL169509-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Zhiyu Dai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $737,804
- **Award type:** 5
- **Project period:** 2023-09-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913598

## Citation

> US National Institutes of Health, RePORTER application 10913598, Novel alveolar mechanisms of hypoxemia in hepatopulmonary syndrome (5R01HL169509-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10913598. Licensed CC0.

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