The significance of detecting HBV pgRNA and HBcrAg in HBV patients treated with NAs.

The value of detecting hepatitis B virus (HBV), pregenomic RNA (pgRNA), and hepatitis B core-related antigen (HBcrAg), both separately and jointly, in the management of HBV patients undergoing treatment with Nucleotide Analog was investigated. A total of 149 HBV patients who were being treated with Nucleotide Analog were enrolled in this study. The quantitative levels of HBV pgRNA and HBcrAg in the sera of these patients were determined, aiming to comprehend their replication levels and expression during the course of antiviral therapy. The patients were separated into 3 groups based on treatment duration: treatment time ≤ 12 months, treatment time ranging from 12 months to <60 months, and treatment time ≥ 60 months. Significantly different levels of HBcrAg and HBV pgRNA were observed among 3 groups (P < .05). In the group of patients with positive hepatitis B e antigen, both HBcrAg and pgRNA levels were higher compared to the group with negative hepatitis B e antigen, and this difference between the 2 groups was found to be statistically significant. Stratified analysis based on levels of hepatitis B surface antigen (HBsAg) revealed that the group with HBsAg levels < 100 IU/mL had lower levels of both HBcrAg and pgRNA compared to the group with HBsAg levels ≥ 100 IU/mL (P < .001). Following antiviral therapy, various degrees of transcription of covalently closed circular DNA continue to exist within the liver of HBV patients. The levels of serum HBcrAg and HBV pgRNA vary among patients with different treatment durations, indicating their efficacy in evaluating disease conditions during antiviral therapy.

Bushen Formula promotes the decrease of HBsAg levels in patients with CHB by regulating Tfh cells and B-cell subsets.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Formula (BSF) is the effective traditional Chinese medicine (TCM) for chronic hepatitis B (CHB) according to our previous researches. However, the special effectiveness of BSF treating CHB patients in different stages and the immunoregulatory mechanisms remain to be explored. AIM OF THE STUDY: To compare the therapeutic effects of BSF in both treatment-naive patients and Peg-IFN-α-treated patients, and explore the potential mechanism of immunomodulation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry and the TCMSP database were used to determine the main components of BSF. Two hundred and sixty-six patients were enrolled in the retrospective study, and they were divided into the treatment group (T-Group, BSF plus Peg-IFN-α) and the control group (C-Group, Peg-IFN-α monotherapy). Within each group, patients were further grouped into subgroups, namely T1/C1 groups (treatment-naive patients, T1 = 34, C1 = 94) and T2/C2 groups (Peg-IFN-α-treated patients, T2 = 56, C2 = 82). Serum HBV markers, serum HBV DNA levels, serum ALT/AST and TCM symptoms were obtained from the record. Bioinformatics analysis was employed to obtain the potential immunoregulatory mechanisms of BSF treating CHB patients. Among patients in T2 and C2 group, peripheral mononuclear cells from 36 patients were used to analyze the characteristics of peripheral follicular helper T (Tfh) cells and B-cell subtypes by flow cytometry. Preparation of BSF-containing serum in rats. In vitro, the co-culture system of CXCR5+ cells and HepG2.2.15 cells was built to investigate the immunoregulatory effects of BSF. RESULTS: A total of 14 main active compounds were detected in BSF, which were deemed critical for the treatment of CHB. Our findings indicated that the T2-Group exhibited the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the C2-Group (35.7% vs. 15.9%, P = 0.033; 33.9% vs. 11.0%, P = 0.002). Additionally, the T2-Group demonstrated the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the T1-Group (35.7% vs. 14.7%, P = 0.031; 33.9% vs. 2.9%, P = 0.000). The total effective rate based on TCM clinical syndrome in T1-Group and T2-Group were significantly greater than those in C1-Group and C2-Group (85.3% vs. 61.7%, P = 0.012; 89.1% vs. 63.4%, P = 0.000). Bioinformatics analysis indicated that the immunoregulatory mechanisms of BSF treating CHB patients were mainly linked to the growth and stimulation of B-cell, T-cell differentiation, and the signaling pathway of the B-cell receptor. Furthermore, the frequencies of Tfh cells and its IL-21 level, and the IL-21R expressed by B-cell were all increased after BSF treatment. Additionally, in the co-culture system of CXCR5+ cells and HepG2.2.15 cells, HBsAg and HBeAg levels were decreased after BSF-containing serum treatment，as well as the up-regulating of Tfh cell frequencies and down-regulating of B-cell frequencies. CONCLUSIONS: BSF have the higher percentage of HBsAg decline and HBeAg seroclearance in Peg-IFN-α-treated patients compared with treatment-naive patients. The potential immunoregulatory mechanism may correlate with promoting the interaction between Tfh cells and B-cell through IL-21/IL-21R signaling pathway.

Multiple Diagnostic Indicators in the Development of Chronic Hepatitis B, Liver Cirrhosis, and Liver Cancer.

Context: Hepatitis B can develop into cirrhosis, and most liver cancers evolve on the basis of chronic hepatitis and cirrhosis. Many patients are already at an advanced stage when diagnosed. In recent years, clinicians have advocated detection of liver cancer using multiple markers in combination to improve the sensitivity and specificity of testing. Objective: The study aimed to evaluate the clinical value of using four tumor indicators-urea, alpha L-fucosidase (AFU), carbohydrate antigen 153 (CA153), carbohydrate antigen 125 (CA125), and alpha fetoprotein (AFP) and comparing the use of combined indicators to use of a single indicator for the diagnosis of liver cancer. Design: The research team performed a prospective study. Setting: The study took place at Clinical Laboratory, Baoding People's Hospital, Baoding City, Hebei Province, China. Participants: Participants were 98 patients with chronic hepatitis B, who became the CHB group; 102 patients with liver cirrhosis, who became the cirrhosis group, and 100 patients with liver cancer, who became the liver cancer group. They all had been admitted to the hospital between March 2019 and March 2021. Outcome Measures: The research team measured the urea, AFU, CA153, CA125, and AFP levels of the three groups, constructed an ROC curve, and analyzed the diagnostic values of the indicators singly and in combination for liver cancer. Results: For the levels of urea, AFU, CA153, CA125, and AFP, the CHB group's levels were significantly lower than those of the cirrhosis and liver cancer groups (both P < .001), and the cirrhosis group's levels were significantly lower than those of the liver cancer group (P < .001). In the CHB group, the compensatory group's levels were significantly lower than those of the decompensated group (P < .05). In the cirrhosis group, no significant differences existed between the levels of the grade A and grade B groups (P < .001), between those of the grade A and grade C groups (P < .001), or between those of the grade B and grade C groups (P < .001). In the cirrhosis group, the levels of the no ascites group were significantly lower than those of the ascites group (P < .05). In the liver cancer group, the levels of the stage I-II group were significantly lower than those of the stage III and stage IV groups (both P < .05), and those of the stage IV group were significantly lower than those of the stage Ⅳ group (P < .05). The levels of the <5cm group were significantly lower than those of the ≥5cm group (P < .001). The value of using a combination of indicators for diagnosis was significantly higher than that of a single indicator (P < .001). Conclusions: Urea, AFU, CA153, CA125, and AFP all have diagnostic value in the evaluation of chronic hepatitis B-cirrhosis and liver cancer, with the highest efficacy, sensitivity and specificity from a combined test and diagnosis.

A hierarchical multilabel graph attention network method to predict the deterioration paths of chronic hepatitis B patients.

OBJECTIVE: Estimating the deterioration paths of chronic hepatitis B (CHB) patients is critical for physicians' decisions and patient management. A novel, hierarchical multilabel graph attention-based method aims to predict patient deterioration paths more effectively. Applied to a CHB patient data set, it offers strong predictive utilities and clinical value. MATERIALS AND METHODS: The proposed method incorporates patients' responses to medications, diagnosis event sequences, and outcome dependencies to estimate deterioration paths. From the electronic health records maintained by a major healthcare organization in Taiwan, we collect clinical data about 177 959 patients diagnosed with hepatitis B virus infection. We use this sample to evaluate the proposed method's predictive efficacy relative to 9 existing methods, as measured by precision, recall, F-measure, and area under the curve (AUC). RESULTS: We use 20% of the sample as holdouts to test each method's prediction performance. The results indicate that our method consistently and significantly outperforms all benchmark methods. It attains the highest AUC, with a 4.8% improvement over the best-performing benchmark, as well as 20.9% and 11.4% improvements in precision and F-measures, respectively. The comparative results demonstrate that our method is more effective for predicting CHB patients' deterioration paths than existing predictive methods. DISCUSSION AND CONCLUSION: The proposed method underscores the value of patient-medication interactions, temporal sequential patterns of distinct diagnosis, and patient outcome dependencies for capturing dynamics that underpin patient deterioration over time. Its efficacious estimates grant physicians a more holistic view of patient progressions and can enhance their clinical decision-making and patient management.

Modelling jurisdictional disparities in the cascade of care for chronic hepatitis B in Australia: impact of treatment uptake on mortality.

OBJECTIVE: Investigate the cascade of care for chronic hepatitis B (CHB) and estimate impacts of increasing treatment uptake on attributable burden, according to jurisdiction. METHODS: A mathematical model of CHB in Australia was utilised, combined with notifiable disease and Medicare data. We estimated the proportion with CHB who were diagnosed, engaged in care and receiving treatment in each state/territory, and projected future mortality. RESULTS: The highest uptake of all measures was in New South Wales, however, the largest increase over time occurred in Northern Territory. No jurisdiction is due to meet 2022 targets of treatment uptake or mortality reduction. Previously declining mortality is predicted to plateau or increase in all jurisdictions except Northern Territory. The largest gap in the cascade of care was most commonly diagnosed individuals not engaged in care; however, in Victoria and Tasmania it was lack of diagnosis. CONCLUSIONS: Measures of the cascade of care varied substantially between jurisdictions; while all require improvements to reduce mortality, the specific gaps vary, as do potential impacts. IMPLICATIONS FOR PUBLIC HEALTH: Improving the cascade of care for CHB will require jurisdictionally tailored approaches. If improvements are not made, more deaths will occur due to CHB in most states and territories.

Impact of Fuzheng Huayu tablet on antiviral effect of entecavir in patients with hepatitis B cirrhosis.

BACKGROUND: Fuzheng Huayu tablet is a traditional Chinese medicine (TCM) used for the treatment of liver fibrosis and cirrhosis. However, whether the combination with Fuzheng Huayu tablet could affect the antiviral efficacy of nucleos(t)ide remains a concern. The objective of this trial was to explore the impact of Fuzheng Huayu tablet on antiviral effect of entecavir in patients with hepatitis B cirrhosis. METHODS: A prospective, randomized control trial was conducted. Patients with compensated hepatitis B cirrhosis were randomly divided into the treatment group (entecavir capsule plus Fuzheng Huayu tablet) and the control group (entecavir capsule plus simulant of Fuzheng Huayu), and followed up for 48 weeks. The dynamic changes of HBV DNA load, the rate of serological conversion of HBeAg, liver function, renal function and liver stiffness measurement (LSM) were monitored. The general clinical data and adverse events were also recorded. RESULTS: There was no significant difference in the rate of virological response and cumulative virological response between the treatment group and the control group (P > 0.05). After 48 weeks of treatment, the HBeAg seroconversion rate, biochemical response rate and LSM value were 21.05% and 4.76% (P = 0.164), 86.96% and 65.96% (P = 0.017), 9.5 kpa and 10.6 kpa (P = 0.827) in the treatment group and the control group, respectively. No serious adverse events related to the study therapy occurred during the trial. CONCLUSIONS: The antiviral entecavir combined with Fuzheng Huayu tablet did not affect the antiviral efficacy of entecavir, but could improve the rate of biochemical response, and had a tendency to improve the rate of serological conversion of HBeAg and liver fibrosis in patients with hepatitis B cirrhosis. Fuzheng Huayu tablet is clinically safe for patients with hepatitis B cirrhosis.

DNA Methylation and Transcription of HLA-F and Serum Cytokines Relate to Chinese Medicine Syndrome Classification in Patients with Chronic Hepatitis B.

OBJECTIVE: To explore the molecular bases of Chinese medicine (CM) syndrome classification in chronic hepatitis B (CHB) patients in terms of DNA methylation, transcription and cytokines. METHODS: Genome-wide DNA methylation and 48 serum cytokines were detected in CHB patients (DNA methylation: 15 cases; serum cytokines: 62 cases) with different CM syndromes, including dampness and heat of Gan (Liver) and gallbladder (CHB1, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan stagnation and Pi (Spleen) deficiency (CHB2, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan and Shen (Kidney) yin deficiency (CHB3, DNA methylation: 5 cases, serum cytokines: 16 cases), CHB with hidden symptoms (HS, serum cytokines:16 cases) and healthy controls (DNA methylation: 6 cases). DNA methylation of a critical gene was further validated and its mRNA expression was detected on enlarged samples. Genome-wide DNA methylation was detected using Human Methylation 450K Assay and furthered verified using pyrosequencing. Cytokines and mRNA expression of gene were evaluated using multiplex biometric enzyme-linked immunosorbent assay (ELISA)-based immunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. RESULTS: Totally 28,667 loci, covering 18,403 genes were differently methylated among CHB1, CHB2 and CHB3 (P<0.05 and |Δß value| > 0.17). Further validation showed that compared with HS, the hg19 CHR6: 29691140 and its closely surrounded 2 CpG loci were demethylated and its mRNA expressions were significantly up-regulated in CHB1 (P<0.05). However, they remained unaltered in CHB2 (P>0.05). Levels of Interleukin (IL)-12 were higher in CHB3 and HS than that in CHB1 and CHB2 groups (P<0.05). Levels of macrophage inflammatory protein (MIP)-1α and MIP-1ß were higher in CHB3 than other groups and leukemia inhibitory factor level was higher in CHB1 and HS than CHB2 and CHB3 groups (P<0.05). IL-12, MIP-1α and MIP-1ß concentrations were positively correlated with human leukocyte antigen F (HLA-F) mRNA expression (R2=0.238, P<0.05; R2=0.224, P<0.05; R=0.447, P<0.01; respectively). Furthermore, combination of HLA-F mRNA and differential cytokines greatly improved the differentiating accuracy among CHB1, CHB2 and HS. CONCLUSIONS: Demethylation of CpG loci in 5' UTR of HLA-F may up-regulate its mRNA expression and HLA-F expression was associated with IL-12, MIP-1α and MIP-1ß levels, indicating that HLA-F and the differential cytokines might jointly involve in the classification of CM syndromes in CHB. REGISTRATION NO: ChiCTR-RCS-13004001.

A noninvasive diagnostic model for significant liver fibrosis in patients with chronic hepatitis B based on CHI3L1 and routine clinical indicators.

BACKGROUND: In consideration of the limitations of liver biopsy, the past years have seen a great advance in the application of noninvasive indices in assessing liver fibrosis. However, the accuracies of the existing indices to determine liver fibrosis in patients with chronic hepatitis B (CHB) are still unsatisfactory. Here, we established a noninvasive diagnostic model for assessing significant liver fibrosis (SLF) in CHB patients based on serum chitinase 3-like 1 (CH3L1) and routine clinical indicators. METHODS: The clinical data of 337 CHB patients treated at Xiamen Hospital of Traditional Chinese Medicine from December 1, 2019, to September 30, 2020, were collected in this cross-sectional study. All the enrolled cases were randomly divided into a training cohort (n=270) and a validation cohort (n=67). The training cohort was further divided into a non-significant liver fibrosis (NSLF) group (stages S0-S1; n=189; used as the control group) and an SLF group (stage S2-S4; n=81) based on the Scheuer scoring system. Univariate and multivariate logistic regression analyses were performed to screen for independent predictors of SLF in CHB patients and to establish a diagnostic model. RESULTS: The results of univariate and multivariate logistic regression analysis showed that CHI3L1, AFP and PLT were independent predictors of SLF in CHB patients, and the diagnostic model was established as follows: CHI3L1/AFP/PLT (CAP) = 0.600 × CHI3L1/upper limit of normal (ULN) + 0.252 × AFP/ULN - 1.424 × PLT/lower limit of normal (LLN) - 1.223. The area under the receiver operating characteristic (AUROC) of this model for the diagnosis of SLF in the training cohort and the validation cohort was 0.805 and 0.819, respectively, showing no statistically significant difference (P>0.05), and the AUROC for the diagnosis of SLF in the whole cohort was significantly higher than those of other noninvasive markers including aspartate transaminase to platelet ratio index (APRI), fibrosis 4 score (FIB-4) and CHI3L1 (all P<0.05). CONCLUSIONS: The newly established model has a good diagnostic efficacy for SLF in CHB patients and is superior to other noninvasive markers including APRI, FIB-4, and CHI3L1. Thus, it can be used as a noninvasive diagnostic index for liver fibrosis in CHB patients.

Severe Guillain-Barré syndrome associated with chronic hepatitis B: A case report and literature review.

RATIONALE: Guillain-Barré syndrome (GBS) is a postinfectious autoimmune peripheral neuropathy characterized by acute paralysis of the limbs. Clinically, extrahepatic manifestations of neurologic involvement in chronic hepatitis B (CHB) are uncommon. Little attention has been paid to the relationship between GBS and CHB viral infection. PATIENT CONCERNS: We presented a severe case of a 34-year-old man with general fatigue, anorexia, jaundice, numbness, and even muscle atrophy in the limbs, and respiratory failure during an acute exacerbation of CHB. DIAGNOSES: Serological liver enzymes test confirmed an acute exacerbation of CHB. Nerve conduction studies revealed the features of acute motor and sensory axonal neuropathy combined with acute inflammatory demyelinating polyneuropathy, and cerebrospinal fluid analysis showed albuminocytologic dissociation. Clinical manifestations and the test results were consistent with a diagnosis of severe CHB-related GBS. INTERVENTIONS: He was treated with mechanical ventilation, 2 courses of intravenous immunoglobulin, antichronic hepatitis B drugs therapy supplemented by hepatoprotection, acupuncture and rehabilitation. OUTCOMES: After 29 days of hospitalization, his neurological condition improved. At a 6-month follow-up visit, he was able to walk with the support of another person. LESSONS: The acute exacerbation of CHB may be a potential predisposing factor for the onset of GBS. This case is a reminder to clinicians that during the acute exacerbation of CHB, patients with neurological symptoms in the limbs should be considered for potential CHB-related GBS.

The association of plasma high-density lipoprotein cholesterol levels and cirrhosis development in obese patients with chronic hepatitis B: a cohort study.

OBJECTIVE: Metabolic disorder is a common risk factor for cirrhosis in Asia, and it will increase the risk of cirrhosis in patients with Chronic hepatitis B (CHB). However, studies on the efficacy of plasma lipid markers which predict the happening and development of cirrhosis in obese CHB patients are limited. METHODS: In total, 3327 patients who were followed for more than 4 years' follow-up in the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine joined the program. Finally, 287 obese CHB patients were included in this study according to the results of metabolic tests. The data of baseline and follow-up were collected, and the association between them was analyzed. RESULTS: Based on the follow-up results, enrolled patients were divided into a group of cirrhosis (n = 146) and a group of noncirrhosis (n = 141). Plasma glucose and high-density lipoprotein cholesterol (HDL-C) levels in the noncirrhosis group (5.2 and 1.2 mmol/L, respectively) were significantly higher than that in the cirrhosis group (5.0 and 1.0 mmol/L, respectively), while the amount of total bile acid (TBA) in the cirrhosis group was lower than that in the cirrhosis group. Levels of HDL-C and total cholesterol were associated with liver function. Plasma HDL-C was an independent indicator of cirrhosis in patients with CHB. Patients with HDL-C levels less than 1.03 mmol/L had a 2.21-fold higher incidence rate of cirrhosis, and patients over 40 years old or the levels of HDL-C less than 1.03 mmol/L were more likely to generate cirrhosis. CONCLUSIONS: Plasma HDL-C was an appropriate marker in predicting cirrhosis for patients with CHB.

Evaluation of Hepatitis B Reactivation Among Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors.

Hepatitis B reactivation (HBVr) in cancer patients is a well-established complication due to chemotherapy-induced immunosuppression. Studies have reported HBVr associated with immunosuppressive medications, such as rituximab, methotrexate, and high dose steroids. There are different risks for different types of chemotherapy with rituximab carrying one of the highest risks for hepatitis B reactivation. Tyrosine kinase inhibitors (TKIs) are the standard of care in patients with chronic myeloid leukemia (CML). The risk of HBVr in chronic myeloid leukemia has been reported in many studies, but to this date, there are no clear guidelines or recommendations regarding screening and monitoring of HBV in CML patients receiving TKIs. We conducted this review to identify the risk of HBVr in patients with CML who are treated with tyrosine kinase inhibitors. We recommend testing for HBV status in patients who are to be treated with TKIs and to consider giving prophylaxis in those who are positive for HBsAg at baseline. More studies are needed to assess the risk of reactivation in patients with Hepatitis B core antibody positive receiving TKIs. Currently, monitoring such patients for reactivation may be the best strategy.

Efficacy of a Chinese herbal formula on hepatitis B e antigen-positive chronic hepatitis B patients.

BACKGROUND: No guideline recommends antiviral therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus (HBV) DNA viral load. AIM: To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection. METHODS: In total, 395 patients (30-65 years old) with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk. Endpoints to evaluate therapeutic efficacy included: (1) HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96; and (2) HBeAg clearance and seroconversion rates at weeks 48 and 96. RESULTS: HBV DNA levels ≤ 4 log10 IU/mL were 10.05% at week 48 and 18.59% at week 96 in the treatment group. The HBeAg clearance and conversion rates were 8.54% and 8.04% at week 48 and 16.08% and 14.57% at week 96, respectively. However, HBV DNA levels ≤ 4 log10 IU/mL were 2.55% and 2.55% at weeks 48 and 96, respectively, and the HBeAg clearance rates were 3.06% and 5.61% at weeks 48 and 96, respectively, in the control group. The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance. CONCLUSION: High rates of HBV DNA reduction, HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments, and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase. The ability of the compound to modulate host immune function probably contributed to this effect.

Characterization and assessment of HBV chronically infected patients: Identification of those eligible for treatment in the South West region of Cameroon.

BACKGROUND: The management of patients with chronic hepatitis B infection is quite complex because it requires an in-depth knowledge of the natural history of the disease. This study was aimed at characterizing HBV infected patients in order to determine the phase of the infection and identify the proportion eligible for treatment using 3 different guidelines. METHODS: HBV chronically infected patients (negative for HIV and HCV) were enrolled and the following tests were done for them: ALT, AST, HBV viral load, HBV serologic panel and Full blood count. APRI score was calculated for all patients. These patients were classified into immunotolerant, immune clearance, immune control and immune escape phases of the infection. The WHO and the 2018 AASLD criteria was also used to identify those who need treatment. Patients were clinically examined for signs and symptoms. Questionnaire was administered to all participants to ascertain their treatment status. Statistical analysis was done using SPSS version 21. RESULTS: A total of 283 participants (101 females and 182 males) with a mean age of 31.3±8.5 were enrolled. Fifty-two (18.4%) were eligible for treatment (Immune clearance and immune escape phases) and they recorded a significantly higher mean APRI score (0.71±0.51) as compared to those in the immune control and immune tolerant phase (0.43±0.20). Based on WHO and AASLD criteria, 12(4.2%) and 15 (5.3%) were eligible for treatment respectively and these were all subsets of the 52 cases mentioned above. Six (2.1%) and 29 (10.2%) of those identified under the immune control phase were on tenofovir and traditional medication respectively. CONCLUSION: Considering treatment for patients in the immune clearance and immune escape phases of the infection can be a reliable strategy to implement in our setting as this may probably tie with considerations from other treatment guidelines. Fifty-two (18.4%) patients were eligible for treatment and none of them were among the 2.1% of patients put on Tenofovir based treatment. This calls for the need for more trained health experts to periodically assess patients, implement an adequate treatment guideline and place the right patients on treatment in Cameroon.

Altered oral microbiota in chronic hepatitis B patients with different tongue coatings.

AIM: To elucidate tongue coating microbiota and metabolic differences in chronic hepatitis B (CHB) patients with yellow or white tongue coatings. METHODS: Tongue coating samples were collected from 53 CHB patients (28 CHB yellow tongue coating patients and 25 CHB white tongue coating patients) and 22 healthy controls. Microbial DNA was extracted from the tongue samples, and the bacterial 16S ribosomal RNA gene V3 region was amplified from all samples and sequenced with the Ion Torrent PGM™ sequencing platform according to the standard protocols. The metabolites in the tongue coatings were evaluated using a liquid chromatography-mass spectrometry (LC-MS) platform. Statistical analyses were then performed. RESULTS: The relative compositions of the tongue coating microbiotas and metabolites in the CHB patients were significantly different from those of the healthy controls, but the tongue coating microbiota abundances and diversity levels were not significantly different. Compared with the CHB white tongue coating patients, the CHB yellow tongue coating patients had higher hepatitis B viral DNA (HBV-DNA) titers (median 21210 vs 500, respectively, P = 0.03) and a significantly lower level of Bacteroidetes (20.14% vs 27.93%, respectively, P = 0.013) and higher level of Proteobacteria (25.99% vs 18.17%, respectively, P = 0.045) in the microbial compositions at the phylum level. The inferred metagenomic pathways enriched in the CHB yellow tongue coating patients were mainly those involved in amino acid metabolism, which was consistent with the metabolic disorder. The abundances of bacteria from Bacteroidales at the order level were higher in the CHB white tongue coating patients (19.2% vs 27.22%, respectively, P = 0.011), whereas Neisseriales were enriched in the yellow tongue coating patients (21.85% vs 13.83%, respectively, P = 0.029). At the family level, the abundance of Neisseriaceae in the yellow tongue patients was positively correlated with the HBV-DNA level but negatively correlated with the S-adenosyl-L-methionine level. CONCLUSION: This research illustrates specific clinical features and bacterial structures in CHB patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.

Beneficial Effects of Bushen Formula Combined with Enticavir on Chronic Hepatitis B Patients with Suboptimal Response to Enticavir by Regulating B-Cell Differentiation.

BACKGROUND/AIMS: To investigate the clinical effects of the combination therapy with Bushen Formula (BSF) plus enticavir (ETV) on chronic hepatitis B (CHB) patients with suboptimal response to ETV and explore the regulatory mechanisms of BSF on B cells-mediated humoral immunity. METHODS: Sixty-four HBeAg-positive CHB patients with suboptimal response to ETV were enrolled, and were randomly assigned into control group (C-Group, placebo combined with ETV for 12 months) or treatment group (T-Group, BSF combined with ETV for 12 months). Serum samples from 57 treatment-naïve CHB patients and 15 healthy controls were collected. Serum HBV DNA levels were evaluated by real-time PCR. Characteristics of peripheral blood B-cell subtypes were analyzed by flow cytometry. Serum HBV markers and B cell-activating factor (BAFF) levels were detected by ELISA. Chinese medicine symptom complex score was evaluated and recorded. RESULTS: After treatment, the rates of patients with a reduction of HBsAg > 0.5 log10 IU/ml or 1.0 log10 IU/ml and the rates of HBeAg clearance in T-Group were all higher than those in C-group, with no significant intergroup difference. Only in T-Group, Chinese medicine symptom complex score and the frequency of total B cells were significantly decreased, and the frequencies of Bm1, CD24+CD27-switched B cells and plasma cells were markedly increased after treatment compared with those before treatment. Compared with healthy controls, serum BAFF levels in treatment-naïve CHB patients were increased, and there was a significant positive correlation between serum BAFF and HBsAg levels. However, serum BAFF levels did not differ after treatment in T-Group and C-Group. CONCLUSIONS: The combination therapy with BSF plus ETV promotes the reduction of HBsAg level and the clearance of HBeAg in CHB patients with partial response to ETV through regulating the differentiation of B-cell subsets.

Mapping progress in chronic hepatitis B: geographic variation in prevalence, diagnosis, monitoring and treatment, 2013-15.

OBJECTIVE: To measure progress towards Australia's National Hepatitis B Strategy 2014-17 targets, and assess geographic variation in disease burden and access to care for those living with chronic hepatitis B (CHB). METHODS: Data were generated from routinely collected sources, including risk-group prevalence and population data, infectious diseases notifications, Medicare records, and immunisation registry data, and assessed nationally and according to geographic area for 2013-15. RESULTS: CHB prevalence in 2015 was 239,167 (1.0%), with 62% of those affected having been diagnosed (target 80%). Treatment uptake was 6.1% (target 15%), and only 15.3% of people with CHB received guideline-based care. CHB prevalence ranged within Australia's 31 Primary Health Networks (PHNs) from 1.77% (NT) to 0.56% (Grampians & Barwon South West VIC). No PHN reached the 15% treatment target, with uptake highest in South Western Sydney (13.7%). Immunisation coverage reached the 95% target in three PHNs. CONCLUSIONS: The CHB burden in Australia is significant and highly geographically focused, with notable disparities in access to care across Australia. Implications for public health: Efforts to improve progress toward National Strategy targets should focus on priority areas where the prevalence of CHB is substantial but access to treatment and care remains low.

Effect of modified Xiaochaihu decoction­containing serum on HepG2.2.15 cells via the JAK2/STAT3 signaling pathway.

The present study aimed to investigate the possible mechanisms underlying the effect of modified Xiaochaihu decoction (mXCHD) in the treatment of chronic hepatitis B (CHB). Patients with CHB, in addition to liver stagnation and spleen deficiency syndrome were randomly assigned to receive either Chinese (mXCHD) or western (entecavir) treatment, with 30 cases in each group. Serum was collected following treatment with mXCHD or entecavir for 7 days. A healthy group of 30 individuals was also included. HepG2.2.15 cells were cultured in vitro and randomly divided into four groups: Healthy; entecavir­treated; 10% mXCHD­treated; and 20% mXCHD­treated. The HepG2.2.15 cells in the four groups were treated with either serum from the healthy volunteers, entecavir­containing serum, or mXCHD­containing serum at different concentrations (10 or 20%, respectively). Following treatment with the corresponding serum, cell proliferation was examined using an MTT assay, and the expression of hepatitis B surface antigen (HBsAg) in the cell supernatant was detected using an enzyme­linked immunosorbent assay. The mRNA and protein expression levels of Janus kinase (JAK)2 and signal transducer and activator of transcription (STAT)3 were measured using reverse transcription­quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that the most effective treatment for the promotion of HepG2.2.15 cell proliferation was a 20% concentration of mXCHD serum. The expression of HBsAg was significantly decreased in the groups treated with 10 and 20% mXCHD 48 h following intervention (P<0.01). The mRNA and protein expression levels of STAT3 in the 20% mXCHD serum group were significantly increased, compared with those in the healthy group (P<0.01 and P<0.05, respectively), whereas no significant difference was observed in the expression of JAK2 among the four groups. These results indicated that mXCHD suppressed the hepatitis B virus, and treatment of the cells with mXCHD­containing serum promoted HepG2.2.15 cell proliferation via modulating the expression of STAT3, which may contribute to the clinical efficacy of mXCHD against CHB.

Improving access to health care for chronic hepatitis B among migrant Chinese populations: A systematic mixed methods review of barriers and enablers.

Migrant Chinese populations in Western countries have a high prevalence of chronic hepatitis B but often experience poor access to health care and late diagnosis. This systematic review aimed to identify obstacles and supports to timely and appropriate health service use among these populations. Systematic searches resulted in 48 relevant studies published between 1996 and 2015. Data extraction and synthesis were informed by models of healthcare access that highlight the interplay of patient, provider and health system factors. There was strong consistent evidence of low levels of knowledge among patients and community members; but interventions that were primarily focused on increasing knowledge had only modest positive effects on testing and/or vaccination. There was strong consistent evidence that Chinese migrants tend to misunderstand the need for health care for hepatitis B and have low satisfaction with services. Stigma was consistently associated with hepatitis B, and there was weak but consistent evidence of stigma acting as a barrier to care. However, available evidence on the effects of providing culturally appropriate services for hepatitis B on increasing uptake is limited. There was strong consistent evidence that health professionals miss opportunities for testing and vaccination. Practitioner education interventions may be important, but evidence of effectiveness is limited. A simple prompt in patient records for primary care physicians improved the uptake of testing, and a dedicated service increased targeted vaccination coverage for newborns. Further development and more rigorous evaluation of more holistic approaches that address patient, provider and system obstacles are needed.

Key symptoms selection for two major syndromes diagnosis of Chinese medicine in chronic hepatitis B.

OBJECTIVE: To identify key symptoms of two major syndromes in chronic hepatitis B (CHB), which can be the clinical evidence for Chinese medicine (CM) doctors to make decisions. METHODS: Standardization scales on diagnosis for CHB in CM were designed including physical symptoms, tongue and pulse appearance. The total of 695 CHB cases with dampness-heat (DH) syndrome or Pi (Spleen) deficiency (SD) syndrome were collected for feature selection and modeling, another 275 CHB patients were collected in different locations for validation. Key symptoms were selected based on modified information gain (IG), and 5 classifiers were applied to assist with models training and validation. Classification accuracy and area under receiver operating characteristic curves (AUC) were evaluated. RESULTS: (1) Thirteen DH syndrome key symptoms and 13 SD syndrome key symptoms were selected from original 125 symptoms; (2) The key symptoms could achieve similar or better diagnostic accuracy than the original total symptoms; (3) In the validation phase, the key symptoms could identify syndromes effectively, especially in DH syndrome, which average prediction accuracy on 5 classifiers could achieve 0.864 with the average AUC 0.772. CONCLUSION: The selected key symptoms could be simple DH and SD syndromes diagnostic elements applied in clinical directly. (Registration N0.: ChiCTR-DCC-10000759).

iTRAQ-Based Proteomics Identification of Serum Biomarkers of Two Chronic Hepatitis B Subtypes Diagnosed by Traditional Chinese Medicine.

Background. Chronic infection with hepatitis B virus (HBV) is a leading cause of cirrhosis and hepatocellular carcinoma. By traditional Chinese medicine (TCM) pattern classification, damp heat stasis in the middle-jiao (DHSM) and liver Qi stagnation and spleen deficiency (LSSD) are two most common subtypes of CHB. Results. In this study, we employed iTRAQ proteomics technology to identify potential serum protein biomarkers in 30 LSSD-CHB and 30 DHSM-CHB patients. Of the total 842 detected proteins, 273 and 345 were differentially expressed in LSSD-CHB and DHSM-CHB patients compared to healthy controls, respectively. LSSD-CHB and DHSM-CHB shared 142 upregulated and 84 downregulated proteins, of which several proteins have been reported to be candidate biomarkers, including immunoglobulin (Ig) related proteins, complement components, apolipoproteins, heat shock proteins, insulin-like growth factor binding protein, and alpha-2-macroglobulin. In addition, we identified that proteins might be potential biomarkers to distinguish LSSD-CHB from DHSM-CHB, such as A0A0A0MS51_HUMAN (gelsolin), PON3_HUMAN, Q96K68_HUMAN, and TRPM8_HUMAN that were differentially expressed exclusively in LSSD-CHB patients and A0A087WT59_HUMAN (transthyretin), ITIH1_HUMAN, TSP1_HUMAN, CO5_HUMAN, and ALBU_HUMAN that were differentially expressed specifically in DHSM-CHB patients. Conclusion. This is the first time to report serum proteins in CHB subtype patients. Our findings provide potential biomarkers can be used for LSSD-CHB and DHSM-CHB.