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

Li, Minghui; Gao, Yumei; Yang, Liu; Lin, Yanjie; Deng, Wen; Jiang, Tingting; Bi, Xiaoping; Lu, Yao; Zhang, Lu; Shen, Ge; Liu, Ruyu; Wu, Shuling; Chang, Min; Xu, Mengjiao; Hu, Leiping; Song, Rui; Jiang, Yuyong; Yi, Wei; Xie, Yao

doi:10.3389/fimmu.2022.1024333

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…At present, many drugs are available for HBV infection treatment, but completely eliminating the virus is difficult. [ 10 ] When the treatment is discontinued, the HBV may continue to replicate and rebound. PLC is currently difficult to cure clinically or has a poor prognosis after treatment, and thus causes great harm to patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer

Qiu,

Jin,

Yang

et al. 2023

Medicine

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Background: Hepatitis B virus (HBV) is closely related to the occurrence and development of primary liver cancer (PLC). The early diagnosis of PLC is difficult. The study explored the clinical application value of the HBV gene basal core promoter (BCP) region 1762/1764 combined with gamma-glutamyl transpeptidase (GGT) and its isozyme II (GGTII) in PLC. Methods: From June 2017 to June 2021, 145 hepatitis B surface antigen-positive and HBV DNA-positive patients were enrolled in the Third People Hospital of Zigong. Of them, 67 were chronic hepatitis B (CHB) patients, 30 were liver cirrhosis patients, and 48 were patients with hepatitis B-associated PLC. The HBV BCP 1762/1764 mutation was detected through the amplification refractory mutation system fluorescence PCR method, and GGTII was detected using the double-antibody sandwich method. Results: The results showed that the serum GGT activity, GGTII level, aspartate aminotransferase (AST) activity, AST/alanine aminotransferase (ALT) ratio, GGT/ALT ratio, and GGT/AST ratio were significantly different between the PLC and CHB groups. Statistically significant differences in serum GGT activity, AST activity, and GGT/ALT ratio were observed between the PLC and LC groups. The BCP 1762/1764 mutation rate between the PLC and CHB groups was statistically significant. The GGTII level in the early PLC (stage I + II) group and the advanced PLC (stage III + IV) group was higher than that in the N-PLC group. Serum GGT activity in the early PLC and advanced PLC groups was higher than that in the N-PLC group. The area under the curve of the receiver operator characteristic curve of GGT and GGTII for diagnosing PLC was 0.775 (95% confidence interval [CI] [0.697, 0.854]) and 0.608 (95% CI [0.512, 0.704]), respectively. The area under curve of GGT and GGTII for diagnosing early PLC was 0.732 (95% CI [0.620, 0.845]) and 0.579 (95% CI [0.452, 0.706]), respectively. Conclusion: HBV gene BCP 1762/1764 mutation, GGT, and GGTII may be related to PLC occurrence. The HBV gene BCP region 1762/1764 combined with GGT has certain clinical diagnostic values for PLC and early PLC. However, GGTII is not a good indicator of early PLC and is more relevant to advanced PLC.

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Section: Discussionmentioning

confidence: 99%

Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer

Qiu,

Jin,

Yang

et al. 2023

Medicine

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“…Therefore, IFN induces the expression of a variety of immune cells and indirectly induces host T-cell immunity, which may be the key to achieving HBsAg seroconversion. In addition, dynamic changes in cytokines are observed when CHB patients receive antiviral therapy ( 81 ). CHB patients receiving IFN antiviral therapy can achieve HBeAg serological conversion when the frequency of inhibitory cells (such as FoxP3(+) Tregs) is reduced ( 82 ).…”

Section: T Cells and Measures Of Hbv-mtct Preventionmentioning

confidence: 99%

Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity

Cao

Zhang

et al. 2023

Front. Immunol.

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One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 105 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants’ HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.

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“…It was also demonstrated that in the case of antiviral therapy, changes in serum cytokines were related to the response to antiviral therapy. Li M. et al reported that an early rise in IFN-a2 levels during pegylated interferon alpha (PEG-IFN-a) treatment was related to functional cure in hepatitis B e antigen (HBeAg) positive CHB patients (23,24). In addition, CXCL10 has also shown a predictive role in PEG-IFN-a treatment of chronic hepatitis C (25).…”

Section: Introductionmentioning

confidence: 99%

“…Li M. et al. reported that an early rise in IFN-α2 levels during pegylated interferon alpha (PEG-IFN-α) treatment was related to functional cure in hepatitis B e antigen (HBeAg) positive CHB patients ( 23 , 24 ). In addition, CXCL10 has also shown a predictive role in PEG-IFN-α treatment of chronic hepatitis C ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

Serum cytokine change profile associated with HBsAg loss during combination therapy with PEG-IFN-α in NAs-suppressed chronic hepatitis B patients

et al. 2023

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ObjectiveThe aim of this study was to explore the profile of cytokine changes during the combination therapy with pegylated interferon alpha (PEG-IFN-α) and its relationship with HBsAg loss in nucleos(t)ide analogs (NAs)-suppressed chronic hepatitis B patients.MethodsSeventy-six patients with chronic hepatitis B with HBsAg less than 1,500 IU/ml and HBV DNA negative after receiving ≥ 1-year NAs therapy were enrolled. Eighteen patients continued to take NAs monotherapy (the NAs group), and 58 patients received combination therapy with NAs and PEG-IFN-α (the Add-on group). The levels of IFNG, IL1B, IL1RN, IL2, IL4, IL6, IL10, IL12A, IL17A, CCL2, CCL3, CCL5, CXCL8, CXCL10, TNF, and CSF2 in peripheral blood during treatment were detected.ResultsAt week 48, 0.00% (0/18) in the NAs group and 25.86% (15/58) in the Add-on group achieved HBsAg loss. During 48 weeks of combined treatment, there was a transitory increase in the levels of ALT, IL1RN, IL2, and CCL2. Compared to the NAs group, CXCL8 and CXCL10 in the Add-on group remain higher after rising, yet CCL3 showed a continuously increasing trend. Mild and early increases in IL1B, CCL3, IL17A, IL2, IL4, IL6, and CXCL8 were associated with HBsAg loss or decrease >1 log, while sustained high levels of CCL5 and CXCL10 were associated with poor responses to Add-on therapy at week 48.ConclusionsThe serum cytokine change profile is closely related to the response to the combination therapy with PEG-IFN-α and NAs, and may help to reveal the mechanism of functional cure and discover new immunological predictors and new therapeutic targets.

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

Cited by 5 publications

References 30 publications

Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer

Clinical application value of hepatitis B virus basal core promoter 1762/1764 and GGTII and GGT in patients with HBV-DNA-positive primary liver cancer

Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity

Serum cytokine change profile associated with HBsAg loss during combination therapy with PEG-IFN-α in NAs-suppressed chronic hepatitis B patients

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