How a common liver gene change may drive liver cancer in fatty liver disease

Bile Acid-Mediated Signaling In HCC

NIH-funded research Virginia Commonwealth University · NIH-11159519

Testing whether a common genetic change (PNPLA3 I148M) in people with fatty liver disease increases inflammation and raises the chance of developing liver cancer.

Quick facts

Grant typeP01 program project
Study typeNIH-funded research
Funding institutionVirginia Commonwealth University NIH-funded
Lab location1 site (Richmond, United States)
Project IDNIH-11159519 on NIH RePORTER

What this research studies

You'll hear researchers looking at how the PNPLA3 I148M gene change alters signaling in liver cells and immune cells to promote NASH and hepatocellular carcinoma (HCC). They will use laboratory models that carry the human gene change, study bile-acid and S1PR2 signaling pathways, and analyze tissue and blood markers tied to liver injury. The team will connect lab findings to patient-derived samples and clinical data to pinpoint steps that push fatty liver toward cancer. The work aims to find measurable signals and potential treatment targets for people with fatty liver disease who carry this gene change.

Who could benefit from this research

Good fit: People with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), especially those known to carry or at high risk for the PNPLA3 I148M genetic variant, would be the most relevant candidates.

Not a fit: People whose liver disease is unrelated to NAFLD/NASH or who do not carry the PNPLA3 I148M variant are less likely to see direct benefit from this project.

Why it matters

Potential benefit: Could lead to tests or treatments that prevent or slow liver cancer in people with NAFLD/NASH who have the PNPLA3 I148M variant.

How similar studies have performed: Previous human genetic studies consistently link PNPLA3 I148M to higher liver-fat and cancer risk, but mechanistic lab work tying this variant to bile-acid signaling and cancer development is newer and less established.

Where this research is happening

Richmond, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Cancer CauseCancer EtiologyCancer GenesCancer-Promoting GeneCancers
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.