Liver cancer is the sixth most commonly diagnosed cancer globally, primarily occurring as hepatocellular carcinoma (HCC). In sub-Saharan Africa and other developing regions, chronic hepatitis B virus (HBV) infection persists as a critical public health challenge and a primary driver of HCC cases.
To improve HBV drug targets and predict disease severity, researchers at the University of Pittsburgh School of Public Health’s Department of Infectious Diseases and Microbiology (IDM) collaborated with an international team, including partners in Burkina Faso, to examine region-specific genetic factors influencing HBV progression.
Published in January 2026 in Clinical Proteomics, the study is part of an ongoing series that used mass spectrometry to identify plasma proteins across the disease spectrum—from healthy controls and chronic HBV carriers to patients with cirrhosis and HBV-associated HCC.
Jeremy Martinson, PhD, IDM assistant professor and a senior author on the study, said he started the collaboration when co-lead author and Fulbright scholar Florencia Wendkunni Djigma brought DNA samples collected in Burkina Faso to Pitt. What started as a study of genetic variation related to HBV has since grown into a broader, multi-year research effort.
The findings help explain why, in some people, the immune system clears the virus—similar to recovering from a cold—while in others, the virus persists and becomes chronic, significantly increasing the risk of liver cancer. Martinson said the study builds knowledge in populations that have historically been underrepresented in research.
“The genetic background of populations in sub-Saharan Africa is different from populations in Europe or the U.S., so we wanted to understand whether there are region-specific genetic factors that influence how the disease progresses,” said Martinson.
While a highly effective vaccine exists, Martinson warned that if someone isn’t vaccinated or doesn’t mount a strong immune response, they remain at risk.
The researchers identified several proteins linked to disease progression. Levels of tissue inhibitor of metalloproteinases 1 (TIMP1) and insulin-like growth factor-binding protein 7 (IGFBP7)—both involved in inflammation and immune signaling—were consistently higher in people with liver cancer. In contrast, platelet factor 4 variant 1 (PF4V1) and glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1) were decreased. Other proteins, including profilin 1 (PFN1), tubulin alpha-1B chain (TUBA1B) and malate dehydrogenase 1 (MDH1), showed more dynamic changes across disease stages, pointing to complex shifts in metabolism and tissue remodeling.
“We’re continuing to expand the study. This proteomics work is just one piece of a larger effort that also includes genetics and other approaches,” said Martinson.
“This has been one of the most globally relevant projects I’ve worked on, and it’s been very rewarding to be part of.”
Other authors of the study include researchers from Université Joseph KI-ZERBO and affiliated research centers in Burkina Faso; the University of Arkansas for Medical Sciences; Mayo Clinic in Arizona and Minnesota; Louisiana State University and Southern University and A&M College; the Clinical Research Unit of Nanoro; the MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine; the University of the Witwatersrand in South Africa; and Tengandogo University Hospital in Ouagadougou.
-Ava Dzurenda