# Interaction of Schistosomiasis mansoni and hepatitis B virus infections on hepatocellular carcinoma

> **NIH NIH U54** · JOHNS HOPKINS UNIVERSITY · 2024 · $446,205

## Abstract

Hepatocellular carcinoma (HCC) is a very common and lethal cancer in Africa, and as patients with HIV live
longer, the HCC burden may increase. In prior studies, our team identified chronic infection with hepatitis B
and C viruses (HBV, HCV), HIV and Schistosomiasis mansoni (Sm) as independent risk factors for HCC.
Compared to the US, HCC in sub-Saharan Africa occurs at younger age and more advanced stage with
survival of only months. Proposed is an East and West African partnership between colleagues at Makerere
University in Uganda, Fann University in Senegal and Johns Hopkins University focused on HIV and
hepatocellular carcinoma (HCC) in Africa: The H2A Consortium. Building on long-standing collaborative
research, mentoring and clinical activities in both countries, our overarching goal is to reduce the heavy burden
of HCC in sub-Saharan Africa. We advocate investigating cancer interception strategies using appropriate
medical treatments to interrupt or reverse the impact of HCC-causing infections. To understand our data
demonstrating synergistic interaction between chronic HBV and Sm infections, we will examine HBV clinical
and immunological responses in the periphery and the liver in response to Sm treatment with praziquantel.
Over time, liver Sm-related inflammation transitions from a Th1 to Th2 bias, and we hypothesize this transition
may promote HBV replication. We will evaluate the dynamics of plasma HBV DNA during Sm treatment and
correlate these with contemporaneous changes in plasma cytokines to characterize Th1 shifted inflammation.
We also concurrently examine HBV specific CD4+ and CD8+ T cell responses, and measures of Sm treatment
efficacy. Through investigation of liver biopsies on patients before and after SM treatment as well as with HCC,
we anticipate confirming in humans that Sm is pro-carcinogenic and that Sm treatment only partially diminishes
expression of pro-carcinogenic genes. HIV will be evaluated as a modifier of each relationship. Given our
strong record, the proposed research has a high likelihood for successful contribution to reducing the burden
and improving understanding of chronic infections and HCC in Africa.

## Key facts

- **NIH application ID:** 10903776
- **Project number:** 5U54CA254565-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** David L Thomas
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $446,205
- **Award type:** 5
- **Project period:** 2020-09-09 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903776

## Citation

> US National Institutes of Health, RePORTER application 10903776, Interaction of Schistosomiasis mansoni and hepatitis B virus infections on hepatocellular carcinoma (5U54CA254565-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10903776. Licensed CC0.

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