Cytokine profile links occult hepatitis B to six elevated growth factors

Occult hepatitis B virus infection was associated with elevated interleukin-10 and six growth factors in a human screening study that examined 6,773 healthy adults, identifying 57 cases of occult infection and comparing them with 37 controls selected from the same original cohort. Using MAGPIX multiplex analysis, the researchers found that macrophage colony-stimulating factor, FLT-3 ligand, granulocyte colony-stimulating factor, epidermal growth factor and transforming growth factor alpha had potential as diagnostic biomarkers. A decision-tree analysis indicated that combined detection of macrophage colony-stimulating factor and FLT-3 ligand was more valuable diagnostically than the individual measurements considered in that model.

Occult hepatitis B infection, abbreviated OBI, is defined by the presence of hepatic hepatitis B virus DNA despite the absence of detectable serum hepatitis B surface antigen, or HBsAg. The study initially enrolled 6,773 healthy volunteers, with individuals under 18 excluded. Screening for hepatitis B markers then identified 57 cases of OBI.

The comparison group comprised 37 donors selected from the same initial cohort who had no viral hepatitis markers, HIV or somatic diseases. The investigators measured cytokines, chemokines and growth factors in blood plasma to characterize the immune-mediator profile associated with occult infection. The group also showed elevated concentrations of six growth factors: epidermal growth factor, FLT-3 ligand, transforming growth factor alpha, granulocyte colony-stimulating factor, macrophage colony-stimulating factor and vascular endothelial growth factor.

Rather than indicating a uniformly reduced inflammatory response, the pattern combined anti-inflammatory activity with some concurrent elevation of pro-inflammatory signals. The authors characterized occult hepatitis B as having a dominant anti-inflammatory and pro-fibrotic background, a profile they said could facilitate viral persistence and promote liver fibrosis. Receiver operating characteristic analyses indicated diagnostic potential for five measured mediators: macrophage colony-stimulating factor, FLT-3 ligand, granulocyte colony-stimulating factor, epidermal growth factor and transforming growth factor alpha.

The decision-tree results further supported measuring macrophage colony-stimulating factor together with FLT-3 ligand as a combined diagnostic approach. These findings represent associations and model-based estimates within the screened cohort, not proof of clinical performance in routine use. The supplied study abstract does not provide sensitivity, specificity, confidence intervals or independent validation, so the strength of the proposed biomarkers cannot be fully evaluated from the reported information alone.

The authors interpreted the elevated growth-factor response as a feature of aberrant tissue repair. They linked transforming growth factor alpha and epidermal growth factor to incomplete regeneration and scarring, while the broader cytokine environment was described as favoring persistence of the virus. FLT-3 ligand appeared to have a potentially dual role, associated with hepatoprotection on one hand and fibrotic progression on the other.

These are mechanistic interpretations of the observed pattern rather than demonstrated causal effects. The study was an observational comparison of circulating immune mediators, not a treatment trial or longitudinal analysis, so it does not establish that the measured cytokines preceded infection or fibrosis. Its strongest supported contribution is the identification of a blood-based cytokine and growth-factor pattern associated with occult hepatitis B, including a combination with potential diagnostic value that requires further validation.

Subject of Research: Circulating cytokine and growth-factor profiles associated with occult hepatitis B virus infection in screened adults

Article Title: Cytokine signature behind occult hepatitis B virus infection

Article References: Arsentieva, N. A., Korobova, Z. R., Lyubimova, N. E., Batsunov, O. K., Ostankova, Y. V., Shcemelev, A. N., Serikova, E. N., Petrova, O. A., & Totolian, A. A. (2026). Cytokine signature behind occult hepatitis B virus infection. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14334-y

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14334-y

Keywords: occult hepatitis B, hepatitis B virus, interleukin-10, cytokine profile, growth factors, M-CSF, FLT-3 ligand, liver fibrosis, diagnostic biomarkers, MAGPIX analysis, Cytokine, signature