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Background Chronic HBV infection presents weak or no virus-specific T-cell responses, implying to an exhausted phenotype, characterized by overexpression of several inhibitory receptors. In the present study, it was aimed to characterize the panel of inhibitory molecules on the CD8+ T cells in patients with active chronic HBV infection. Methods In this study, 31 active and 32 inactive individuals with chronic HBV infection were recruited. Peripheral blood mononuclear cells were isolated and a multicolor flow cytometry was applied to evaluate the surface inhibitory molecules of TIM3, PD-1, and CD39. Results CD8+ T cells expressing TIM3 were significantly higher in cases with active chronic HBV infection compared to inactive chronic HBV group (8.43 ± 1.4 vs. 5.15 ± 1.43; P Conclusion It appears that CD8+ TIM3+ T cells are the major exhausted phenotype of T cells during the active state of HBV infection.

The progression of chronic hepatitis B (CHB) is associated with single-nucleotide polymorphisms (SNPs). In this study, we demonstrated the association between immune-related SNPs and delayed spontaneous HBeAg seroconversion in immune-active CHB patients. In addition, we investigated the impact of delayed spontaneous HBeAg seroconversion-related SNPs on HBeAg seroconversion within 3 years during antiviral treatment. We enrolled 332 CHB patients and genotyped 124 SNPs associated with HBV-infected clinical outcomes, including 32 interleukin-related genes, 62 HLA genes, 9 CD marker genes, 7 NK cell receptor genes, and 14 other genes, using ABI OpenArray as a platform. Comparing the immune-active CHB patients with delayed spontaneous HBeAg seroconversion (persistent HBeAg seropositivity, older than 40 years) to those with early inefficient HBeAg seroconversion (HBeAg seroconversion with high viremia, younger than 40 years), logistic analysis revealed that rs3820998 (TANK), rs2621377 (HLA-DOB), rs3130215 (HLA-DPB2), rs2255336 (KLRK1), and rs11614913 (MIR-196A2) were significantly associated with delayed spontaneous HBeAg seroconversion. Using multivariate analysis, we determined that high serum HBV DNA levels (OR = 1.66, 95% CI = 1.33–2.08), rs3820998 (CA, OR = 3.37, 95% CI = 1.24–9.12), rs2621377 (TC, OR = 4.96, 95% CI = 1.85–13.3), rs2255336 (TT, OR = 0.09, 95% CI = 0.01–0.86), and rs11614913 (TT, OR = 2.53, 95% CI = 1.05–6.11) were five independent risk factors for delayed spontaneous HBeAg seroconversion. After patients received nucleos(t)ide analogue treatment, rs3820998 heterozygous CA variant conversely became the only independent favorable factor for treatment-induced HBeAg seroconversion within 3 years (OR = 0.21, 95% CI = 0.06–0.78). These results indicate that distinct immune-related SNPs play a vital role in regulating HBeAg status in immune-active CHB patients with or without antiviral treatment.

Summary Changes characteristic of focal postneerotic cirrhosis and of active chronic hepatitis were found in high incidence among 17 cases of advanced hepatic schistosomiasis. Focal cirrhotic changes may have been induced by repeated ischemic insults tolerated f or a long time, and by "piecemeal necrosis", possibly an expression of a chronic immunologic response, either to schistosomal antigens or to liver cell breakdown products, or to both.

Another member of a previously described kindred is reported in whom active chronic hepatitis with cirrhosis led to hepatocellular carcinoma with pulmonary metastases. The patient and his relatives did not show serological evidence of Australia antigen.

A double-blind prospective trial of prednisone versus azathioprine in the treatment of forty-seven patients with active chronic hepatitis over a 2-year period showed that prednisone was superior at improving liver function, preventing the development of œsophageal varices, and prolonging survival. However, side-effects with prednisone (15 mg. per day) were troublesome and sometimes serious.

The frequency of HL-A1 and HL-A8 (60% and 68%, respectively) in 37 patients with active chronic hepatitis (A.C.H.) was significantly increased in comparison to that found in patients with other liver diseases (29% and 25%) and in normal Caucasians (31% and 18%). This was especially evident in the prototype group of young women with lupoid hepatitis. A hypothetical influence of genes expressing HL-A1,8 on the proliferative or tolerance response of immunocytes could account for the linkage disequilibrium between these antigens, and also help in the interpretation of the inherited component in autoimmune disease.

An organ-specific lipoprotein has been isolated from normal human liver and cell-mediated immune responses to it have been assayed in patients with chronic liver diseases using the leucocyte-migration test. Significant inhibition of migration was almost completely restricted to those patients with postulated autoimmune diseases of the liver, being found in 69% of patients with active chronic hepatitis and in 50% of those with primary biliary cirrhosis. The patients with active chronic hepatitis and normal migration indices had shown a satisfactory response to immunosuppressive therapy, with normal liver-function tests at the time of assay.