Increase in Serum Soluble Tim-3 Level Is Related to the Progression of Diseases After Hepatitis Virus Infection

Abstract

BackgroundViral hepatitis is a widespread and serious infectious disease, and most patients with liver cirrhosis and hepatocellular carcinoma are prone to viral infections. T cell immunoglobulin-and mucin-domain-containing molecule-3 (Tim-3) is an immune checkpoint molecule that negatively regulates T cell responses, playing an extremely important role in controlling infectious diseases. However, reports about the role of serum soluble Tim-3 (sTim-3) in hepatitis virus infection are limited. Therefore, this study explored changes in sTim-3 levels in patients infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV).MethodsThis study applied high-sensitivity time-resolved fluorescence immunoassay for the detection of sTim-3 levels. A total of 205 cases of viral hepatitis infection (68 cases of HBV infection, 60 cases of HCV infection, and 77 cases of HEV virus infection) and 88 healthy controls were quantitatively determined. The changes in serum sTim-3 level and its clinical value in hepatitis virus infection were analyzed.ResultsPatients with HBV infection (14.00, 10.78–20.45 ng/mL), HCV infection (15.99, 11.83–27.00 ng/mL), or HEV infection (19.09, 10.85–33.93 ng/mL) had significantly higher sTim-3 levels than that in the healthy control group (7.69, 6.14–10.22 ng/mL, P < 0.0001). Patients with hepatitis and fibrosis infected with HBV (22.76, 12.82–37.53 ng/mL), HCV (33.06, 16.36–39.30 ng/mL), and HEV (28.90, 17.95–35.94 ng/mL) had significantly higher sTim-3 levels than patients with hepatitis without fibrosis (13.29, 7.75–17.28; 13.86, 11.48–18.64; 14.77, 9.79–29.79 ng/mL; P < 0.05).ConclusionsTim-3 level was elevated in patients infected with HBV, HCV, or HEV and gradually increased in patients with either hepatitis or hepatitis with hepatic fibrosis. It has a certain role in the evaluation of the course of a disease after hepatitis virus infection.

Serum Concentrations of TIM-3, LAG-3, and PD-1 in Patients with Hemorrhagic Fever with Renal Syndrome

“…This finding is consistent with a study by Chen et al (2022), which reported significantly higher concentrations of TIM-3 protein in the serum of patients with viral hepatitis compared to healthy controls. The study also emphasized the association of TIM-3 protein with the extent of liver damage and its potential influence on the pathogenesis of the disease [35]. Similarly, in chronic viral infections such as HIV and HBV, increased TIM-3 expression correlated with disease progression and viral load, while decreased frequencies of TIM-3 positive T-cells correlated with antiviral treatment and resolution of viral infection [36,37], suggesting that TIM-3 expression levels may be a prognostic indicator of disease progression in chronic viral infections [38].…”

Expression changes of Tim-3 as one of supplementary indicators for monitoring prognosis of liver pathological changes in chronic HBV infection

“…According to the previous description, sTim-3 may serve as a biomarker for patients with osteosarcoma [ 45 ] and graft-versus-host disease [ 46 ]. Increased serum sTim-3 was related to the progression of hepatitis virus infection diseases [ 47 ], which indicated that Tim-3 can act as a biomarker beside as a clinical target. On this basis, Tim-3 was considered to be closely associated with the clinical prognosis of chronic HBV infection [ 48 ], which could be used as a new index to evaluate the prognosis in CHB patients.…”

Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation

“…As Gal-9 circulates in the serum in a soluble form, soluble TIM-3 (sTIM-3) can also be found in the circulation, but its role in the disease is not yet clarified. In CHB patients, sTIM-3 levels are increased in the serum compared to healthy controls, and are associated with a higher viral burden and liver inflammation ( 170 , 172 , 173 ). Moreover, when looking at different stages of the disease from inactive hepatitis to liver cirrhosis and cancer, sTIM-3 levels rise gradually suggesting a close association with the disease progression ( 172 , 173 ).…”

“…In CHB patients, sTIM-3 levels are increased in the serum compared to healthy controls, and are associated with a higher viral burden and liver inflammation ( 170 , 172 , 173 ). Moreover, when looking at different stages of the disease from inactive hepatitis to liver cirrhosis and cancer, sTIM-3 levels rise gradually suggesting a close association with the disease progression ( 172 , 173 ). However, antiviral treatment did not modulate sTIM-3 levels in treated patients which were rather more elevated in the NUC-treated group compared to the non-treated one ( 170 ).…”