Clinical characteristics and association analysis of persistent low‑level HBsAg expression in a physical examination population with HBV infection

Dai, Yuzhu; Che, Feihu; Jiang, Xiaoxiao; Cui, Dawei; Zhou, Huajun; Xu, Xujian; Sun, Changgui; Cheng, Jun

doi:10.3892/etm.2019.8217

Cited by 6 publications

(6 citation statements)

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“…As expected, TGF-β1 has a strong association with HBV replication and HBV related liver diseases (10,11). 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).…”

Section: Introductionmentioning

confidence: 61%

“…A recent study from China also showed that Persistent Low Level of Hepatitis B Virus (LLV) widely existed in HBV infected patients despite antiviral therapy ( 4 ). Moreover, despite the widespread use of strong antiviral treatments, patients with HBV infection still inevitably progress to liver fibrosis, or even liver cirrhosis ( 5 ). However, the mechanism underlying HBV-induced liver fibrosis remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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

Chen

et al. 2020

Exp Ther Med

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MicroRNA (miR)-21-5p is a newly discovered factor that mediates TGF-β1 signaling. The present study was designed to investigate the role of TGF-β1/miR-21-5p in hepatitis B virus (HBV)-induced liver fibrosis. HBV-infected sodium taurocholate co -t ra nspor ting polypeptide (NTCP)-transfected Huh7.5.1 cells were co-cultured with LX2 cells to simulate HBV infection in the present study. A total of 29 patients with chronic HBV infection were enrolled. Cells were transfected with miR-21-5p mimic or inhibitor with or without TGF-β1 stimulation. The demographic, biochemical and virological data from the 29 patients were analyzed and liver tissues were collected. miR-21-5p levels and the mRNA and protein expression of α-smooth muscle actin (SMA), collagen type 1 α 1 (CoL1A1), tissue inhibitor of metalloproteinase (TIMP)-1 and Smad from liver cells or tissues were detected by quantitative PCR analysis and western blotting, respectively. Cell viability was observed, and the liver fibrosis score was evaluated. The association between miR-21-5p and liver fibrosis was evaluated by correlation analysis. HBV infection upregulated TGF-β1/miR-21-5p mRNA expression in NTCP-Huh7.5.1 cells compared with mock infection (P<0.05). TGF-β1 incubation significantly increased miR-21-5p levels, as well as the mRNA and protein expression of α-SMA, CoL1A1 and TIMP-1, and reduced Smad7 expression in LX2 cells compared with the normal group, and these effects were counteracted by miR-21-5p inhibitor (P<0.05). miR-21-5p overexpression also contributed to TGF-β1-induced α-SMA, CoL1A1 and TIMP-1 expression in LX2 cells (P<0.05). Co-culture with HBV-infected NTCP-Huh7.5.1 cells upregulated TGF-β1/miR-21-5p activity and CoL1A1 expression in LX2 cells compared with normal control, which were significantly reduced by miR-21-5p inhibitor (P<0.05). miR-21-5p levels were significantly correlated with the liver fibrosis score (r=0.888; P<0.05). These data demonstrated that HBV induced liver fibrosis via the TGF-β1/miR-21-5p pathway and suggested that miR-21-5p may be an effective anti-fibrosis target.

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Section: Introductionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

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

Chen

et al. 2020

Exp Ther Med

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“…In China, the prevalence of smear-positive tuberculosis, which approximates 59/100,000, is one of the highest in the world ( Li et al, 2017a ). And also infection with HBV is most prevalent in China ( Dai et al, 2019 ). Therefore, the patient’s concern is truly a major clinical problem.…”

Section: Discussionmentioning

confidence: 99%

The impact of medication belief on adherence to infliximab in patients with Crohn’s disease

Li,

Ma,

Sun

et al. 2023

Front. Pharmacol.

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Objective: Crohn’s disease (CD) is an incurable chronic disease that requires long-term treatment. As an anti-tumor necrosis factor (TNF) agent, Infliximab (IFX) is widely used in the treatment of Crohn’s disease, while the adherence is not high. The purpose of this study was to investigate the adherence to IFX among CD patients in China and evaluate the association between medication belief and IFX adherence.Methods: Demographic data, clinical information and patients’ medication beliefs were collected using an online questionnaire and reviewing electronic medical records (EMRs). The Beliefs about Medicines Questionnaire (BMQ)-specific was used to assess medication beliefs which contains the BMQ-specific concern score and the BMQ-specific necessity score. An evaluation of adherence factors was conducted using univariate and multidimensional logistic regression analyses.Results: In all, 166 CD patients responded the online questionnaire among which 77 (46.39%) patients had high adherence. The BMQ-specific concern score in patients in low adherence was 30.00 and in high adherence patients was 27.50, and patients with lower BMQ-specific concern score had higher adherence (p = 0.013). The multiple regression analysis showed that the BMQ-specific concern score (OR = 0.940, 95% CI: 0.888–0.996) significantly affected the IFX adherence in CD patients. Otherwise, gender, marital status, time spent on the way (including the waiting time in infusion center) and accommodation to the center were also the influencing factors of adherence.Conclusion: The IFX adherence to CD in China was not high. Medicine concerns may be predictive factor of adherence. Education, the duration of IFX therapy and experience of adverse effects were not significantly associated with IFX adherence. By enhancing knowledge and relieving medicine concerns, we may increase patients’ adherence to IFX.

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“…The patients were all from the physical examination center of the hospital, and were found during the normal physical examination. Definition of chronic ASC is characterized by the presence of positive serum HBsAg for more than 6 months, normal serum amino transferase levels and no evidence of liver cirrhosis (LC) or hepatocellular carcinoma (HCC) based on the clinical criteria and ultrasound examination ( 31 ). The study was carried out in accordance with the principles of the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

Analysis of S gene characteristic sequences and changes in properties of protein expression in HBV ASCs with low-level HBsAg

Zhang

Dai

et al. 2022

Front. Med.

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ObjectiveWe detected the serum HBsAg immune complex (HBsAg-CIC) and sequenced the HBV S gene in these patients to reveal the association between sustained low-level expression of HBsAg and mutated S gene sequence characteristics, protein function changes, and HBsAg immune complex formation.MethodsA total of 204 samples were collected and divided into high-level (n = 60, HBsAg level >10 IU/ml) and low-level (n = 144, HBsAg level ≤ 10 IU/ml) HBsAg groups. The clinical and epidemiological data of the two groups were statistically compared. According to different serological patterns and genotypes, the HBsAg-CIC results of the high-level and low-level HBsAg groups were divided into different subgroups, and then the HBsAg-CIC positive rates among different subgroups were compared. We sequenced the S gene of HBV from the two groups and identified the relevant mutations in the MHR of the S gene. In addition, we compared the changes in HBsAg protein properties and functions after hot spot mutation in the MHR of the S gene.ResultsComparing the positive rates of HBsAg-CIC under different serological patterns and genotypes in the two groups, the HBsAg-CIC positive rate was higher in the low-level HBsAg group. Moreover, there was weak correlation between HBsAg-CIC and HBsAg or HBV DNA in both groups (r = 0.32, 0.27, 0.41, 0.48; P < 0.05). Sequencing of S gene in the two groups, showed that the hot-spot mutations were T126A, M133L/T/S, and F134L/T/I in MHR of S gene of genotype B, and hot-spot mutations were Q101R and I126S/T in MHR of S gene of genotype C. Additionally, the positive rate of MHR mutation in the S gene from HBsAg-CIC positive patients was higher in the low-level HBsAg group.ConclusionThe host immune process of clearing HBV seems to have multiple site mutations in MHR, which changes the physicochemical properties and functions of HBsAg and intensifies the formation of HBsAg-CIC, thus avoiding the effective recognition of HBsAg by the host and resulting in immune tolerance between the host and HBV, which may be one of the formation mechanisms of sustained low-level expression of HBsAg in the serum of HBV-infected persons.

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Clinical characteristics and association analysis of persistent low‑level HBsAg expression in a physical examination population with HBV infection

Cited by 6 publications

References 38 publications

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

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

The impact of medication belief on adherence to infliximab in patients with Crohn’s disease

Analysis of S gene characteristic sequences and changes in properties of protein expression in HBV ASCs with low-level HBsAg

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