Association of cytokines with hepatitis B virus and its antigen

Abstract

To investigate the characteristics of cytokines in patients with different HBV infection status and their correlation with HBV DNA, HBsAg, and HBeAg levels. Peripheral blood samples were collected from patients with chronic HBV infection in immune tolerance phase (IT), HBeAg‐positive chronic hepatitis B (CHB), and acute hepatitis B (AHB) groups, and levels of cytokines were detected by Luminex technique, and analyzed by FLEXMAP 3D analyzer. The correlation between cytokines and HBV DNA load, HBsAg, HBeAg, and alanine aminotransferase (ALT) level in patients with chronic HBV infection was analyzed. In total 312 subjects (184 males and 128 females) were enrolled in the study. There were significant differences among IT, CHB, and AHB groups in Flt‐3L value (P = .003; H = 12.312), IFN‐γ (P = .001; H = 11.723), IL‐10 (P = .001; H = 18.736), IL‐17A ((P = .001; H = 12.735), and TGF‐β1 (P = .001; Z = 48.571). IFN‐α2 levels in CHB group were significantly higher than those in IT and AHB groups (15.24 vs 35.78 pg/mL, P = .000; Z = 3.727; 13.88 vs 35.78 pg/mL, P = .024; Z = −2.258. In CHB group, the levels of HBsAg and ALT were positively correlated with the levels of IL‐10 (r = .173; P = .006; r = 0.176; P = .006, respectively), while HBeAg level was positively correlated with the IFN‐α2 level (r = .153; P = .016). In AHB group, the HBsAg level was positively correlated with Flt‐3L, IFN‐α2, IL‐10, and IL‐6 (r = .402; P = .023; r = .436; P = .016; r = .524, P = .002; r = .405; P = .022, respectively). HBeAg level was positively correlated with IFN‐γ and IL‐17A levels (r = .400; P = .023; r = .373; P = .036, respectively), and ALT level was positively correlated with IL‐6 levels (r = .367; P = .039). In either AHB or CHB group, HBV DNA load was only related to TGF‐β level (r = .493; P = .004; r = −.218, P = 0.009 respectively). The correlation between Flt‐3L and HBsAg (F = 7.422; P = .007); IL‐17, IL‐6, and HBeAg (F = 5.757; P = .017; F = 6.156; P = .014) were statistically significant. There was significant correlation between TGF‐β2 and HBV DNA (F = 11.795; P = .001), and between ALT and HBsAg, HBV DNA (F = 26.089; P = .000; F = 4.724; P = .031). HBsAg, HBeAg, and HBV DNA were correlated with cytokines and ALT in patients with HBV infection. The level of IFN‐α2 was significantly higher in patients with CHB. HBV DNA load was only correlated with the level of TGF‐β in acute or CHB.

Dynamic changes of cytokine profiles and virological markers during 48 weeks of entecavir treatment for HBeAg-positive chronic hepatitis B

“…The baseline HBsAg and HBeAg levels in the ALT normalization group were significantly lower than that in the non-normalization group. The baseline IL-10 and TGF-b1 in the ALT normalization group were lower than that in the ALT non-normalization group, while the baseline ALT level and IFN- (14,15,28), and the efficacy of NA treatment is related to the immune and viral factors of patients (2,6,7). At 3 and 6 months after treatment, the IFN-g level of the ALT normalization group was significantly higher than that in the non-normalization group.…”

“…At 3 and 6 months after treatment, the IFN-g level of the ALT normalization group was significantly higher than that in the non-normalization group. Given that IFN-g is an important cytokine for cellular immunity (14,25,28,29), the increase in IFN-g suggests that ETV can restore part of cellular immune function by reducing HBV DNA load (29). Logistic regression analyzed risk factors related to whether the ALT is normal after 48 weeks of ETV treatment.…”

“…Finally, a total of 100 CHB patients treated with ETV completed the 48-week follow-up (Figure 1). The median age was 32 years (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), with 61 men and 39 women. After 48 weeks of treatment, HBsAg decreased by ≥1 log10 in seven cases, but no patient achieved HBsAg disappearance.…”

Transforming growth factor β as a possible independent factor in chronic hepatitis B

“…Mononuclear macrophages are important immune cells involved in liver in ammation, and the increased activity of these mononuclear macrophages leads to an increase in IL-10 level. [9,22] All cytokines were included in the analysis of risk factors for CHB patients with chronic HBV infection in immune tolerant phase and chronic hepatitis B. In multivariate logistic regression analysis, TGF-β 1 and TGF-β 2 were statistically signi cant (P < 0.001).…”

HBV induces liver fibrosis via the TGF‑β1/miR‑21‑5p pathway

“…TGF-β1 has been demonstrated to serve important roles in HBV induces liver fibrosis via the TGF-β1/miR-21-5p pathway WENTING LI 1,2* , XIAOLAN YU 2,3* , XILIU CHEN 4* , ZHENG WANG 5 , MING YIN 2,6 , ZONGHAO ZHAO 1,2 and CHUANWU ZHU 7 hepatic stellate cell (HSC) activation, which is a key event in liver fibrosis (11,12). Accumulating evidence suggested that HBV infection may promote TGF-β1 production by hepatocytes, which in turn activates HSCs and accelerates liver fibrosis (13)(14)(15). HSCs is the predominant cell type responsible for liver fibrosis.…”