An inter-individual variation study reveals new candidate biomarkers for hepatitis B and C

Chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is a major factor for hepatocellular carcinoma, liver cirrhosis, and viral hepatitis-related mortality. In addition, liver biopsy, although often regarded as the gold standard diagnostic method, presents important limitations related to safety, cost, and intraobserver and interobserver variability. Given the severity of HCV- and HBV-associated diseases, the identification of reliable biomarkers for early diagnosis and disease monitoring is essential. Over the last two decades, saliva has emerged as a promising diagnostic fluid because its collection is noninvasive, and advances in nanotechnology-based analyses have enable the detection of low-abundance biomarkers. To investigate potential salivary biomarkers associated with HBV and HCV infections, we applied a label-free approach coupled with mass spectrometry to analyze proteins in whole saliva samples obtained from infected individuals and healthy uninfected controls. Individual candidate protein biomarkers were identified and statistically analysed using nominal p values without correction for multiple testing across proteins. In infected patients, the IgG Fc-binding protein showed increased expression. In contrast, secreted proteins, including haptoglobin, prolactin-inducible protein, submandibular gland androgen-regulated protein 3, and complement C3, were significantly less abundant in these individuals than in healthy controls. These findings expand the current understanding of salivary protein profiles associated with HBV and HCV infections and support the use of saliva as a noninvasive source of biomarkers for viral hepatitis.