# Effect of Hepatitis C Virus Eradication on Chronic Kidney Disease Progression

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $172,600

## Abstract

PROJECT SUMMARY/ABSTRACT
Hepatitis C Virus (HCV) infection is a common comorbidity in patients with chronic kidney disease (CKD) that
leads to accelerated progression to end-stage renal disease. Because of the recent approval of all-oral,
interferon (IFN)-free, direct-acting antiviral therapy (DAAs), HCV can now be cured in the majority who are
treated. This proposal seeks to identify factors that determine CKD outcomes in patients treated with DAAs,
and to investigate the effect of enhanced IFN activation that occurs after HCV eradication on kidney function.
Aim 1 employs the Scalable Collaborative Infrastructure for a Learning Healthcare System (SCILHS) Network,
an electronic health records network covering 12 healthcare systems, to examine a large, diverse cohort of
10,000 patients with HCV infection to (1) determine the effect of DAAs on eGFR decline over five years follow-
up and (2) identify factors that predict which HCV-infected patients are likely to have progressive CKD despite
treatment of HCV infection. Aim 2A proposes to recruit 40 patients with HCV and CKD undergoing DAA
treatment to prospectively study the IFN-pathway to determine if monocyte chemoattractant protein 1 (MCP-1),
a candidate marker of IFN-activation, predicts which patients will have progressive CKD and which will recover.
Aim 2B examines patients who develop de novo immune-mediated kidney diseases (lupus-like immune
complex glomerulonephritis and focal segmental glomerulosclerosis) after DAAs to determine if baseline and
post-treatment IFN-stimulated genes and chemokines are increased in patients who develop autoimmunity.
This K23 Mentored Patient-Oriented Research Career Development Award proposal seeks to explore the
effect of HCV eradication and IFN activation on CKD progression, and to prepare Dr. Sise for a career as an
independent translational researcher in academic medicine. Dr. Sise's clinical training is in internal medicine
and nephrology, with prior Masters-level training in biostatistics and patient-oriented research. During the
course of this career development award, she will be supported by her institution to devote 75% of her time to
focus on developing this research plan and completing didactic and hands-on training in longitudinal data
analysis and immunology through coursework and applied analytic experience. Dr. Sise will benefit from the
guidance of her primary mentor, Dr. Raymond Chung, an international leader in basic, translational, and
clinical studies of HCV and HIV, and her co-mentor Dr. Ravi Thadhani, an established clinical and translational
CKD investigator. Her training will also be overseen by an advisory committee of senior scientists, Drs. Jules
Dienstag, Steven Grinspoon, and Arthur Kim, with collective expertise in mechanisms of immune activation in
HCV and HIV, biomarker research, and clinical trials. She will work in collaboration with Dr. Kenneth Mandl
(SCILHS network PI), Dr. Sushrut Waikar (CKD biomarkers) and Dr. Yuchiao Cha...

## Key facts

- **NIH application ID:** 10159102
- **Project number:** 5K23DK117014-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Meghan E. Sise
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $172,600
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159102

## Citation

> US National Institutes of Health, RePORTER application 10159102, Effect of Hepatitis C Virus Eradication on Chronic Kidney Disease Progression (5K23DK117014-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159102. Licensed CC0.

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