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ObjectiveTo investigate the preventive and therapeutic effects of Tiaogan Huaxian pills combined with entecavir on hepatic fibrosis in chronic hepatitis B with liver Qi stagnation， spleen deficiency， and blood stasis syndrome and its effect on diffusion-weighted imaging （DWI）. MethodClinical data of 117 patients with liver disease who visited the Department of Hepatology at the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2021 to April 2022 were retrospectively analyzed. According to different treatment plans， they were divided into a control group （59 cases） and a treatment group （58 cases）. Both groups of patients received entecavir-based etiology treatment， and the treatment group added Tiaogan Huaxian pills on the basis of basic treatment. Both groups were treated for 24 weeks. Before and after treatment， the two groups were compared in terms of alanine aminotransferase （ALT）， advanced surgical technologies （AST）， total bilirubin （TBil）， hepatitis B virus （HBV）-DNA conversion rate， liver stiffness measurement （LSM）， four items of liver fibrosis （hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， and laminin）， the fibrosis index based on four factors （FIB-4）， the aspartate aminotransferase to platelet ratio index （APRI）， the apparent diffusion coefficient （ADC） value in magnetic resonance imaging （MRI）， and traditional Chinese medicine symptom scores， so as to analyze the efficacy of the two groups. ResultBefore treatment， there was no significant difference in ALT， AST， TBil， LSM， four items of liver fibrosis， FIB-4， APRI， HBV-DNA conversion rate， ADC value， and traditional Chinese medicine symptom scores between the two groups. After treatment， both groups of patients showed significant reductions in ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， and APRI （P<0.05） and a significant increase in ADC value （P<0.05） and HBV-DNA conversion rate （P<0.01）. The traditional Chinese medicine symptom score of the treatment group decreased significantly （P<0.05）. Compared with the control group after treatment， the effective rate of clinical traditional Chinese medicine in the treatment group was 91.38% （53/58）， which was significantly higher than that of the control group （54.23%， 32/59） （Z=-4.325， P<0.01）. In the treatment group， ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， APRI， and traditional Chinese medicine symptom scores all decreased significantly （P<0.05）， and the increase in ADC values was more significant （P<0.05）， while the difference in HBV-DNA conversion rate was not statistically significant. There were no serious adverse reactions or events in either group. ConclusionTiaogan Huaxian pills combined with entecavir have significant clinical efficacy in the treatment of hepatic fibrosis in chronic hepatitis B， which can reduce liver inflammation activity， delay hepatic fibrosis progression， and reduce traditional Chinese medicine symptom scores. It is worthy of clinical promotion and application.
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ObjectiveTo investigate the value of two-dimensional shear wave elastography （2D-SWE） or serological models used alone or in combination in determining the stage of liver fibrosis in patients with chronic hepatitis B. MethodsA retrospective analysis was performed for the clinical data of 327 patients with chronic hepatitis B who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from August 2020 to August 2022 and underwent 2D-SWE and liver histopathological examination， including sex， age， serological markers， and 2D-SWE results. According to the degree of liver fibrosis， they were divided into S0-S1， S≥2， S≥3， and S=4 groups， and the serological models were calculated based on serological markers. A Spearman correlation analysis was used to investigate the correlation of 2D-SWE and serological models with liver fibrosis stage； the receiver operating characteristic curve was plotted with the results of liver histopathology as the standard to compare the efficiency of each parameter used alone or in combination in determining the stage of liver fibrosis； the Delong test was used to investigate the difference between different methods. ResultsLiver stiffness measurement measured by 2D-SWE was strongly correlated with the stage of liver fibrosis （r=0.741， P<0.001）， and as for the serological model， six markers （APRI， FIB-4， GPR， GP， RPR， and S index）， other than AAR， were positively correlated with the stage of liver fibrosis （all P<0.001）. 2D-SWE had an area under the ROC curve （AUC） of 0.878， 0.932， and 0.942， respectively， in the diagnosis of S≥2， S≥3， and S=4 liver fibrosis （all P<0.001）， with an optimal cut-off value of 6.9 kPa， 7.9 kPa， and 9.4 kPa， respectively. Among the serological models， APRI had the largest AUC of 0.788 and 0.875， respectively， in the diagnosis of S≥2 and S=4 liver fibrosis， and S index had the largest AUC of 0.846 in the diagnosis of S≥3 liver fibrosis. In the diagnosis of S≥2， S≥3， and S=4 liver fibrosis， 2D-SWE combined with APRI increased the AUC values to 0.887， 0.938， and 0.950， respectively， and 2D-SWE combined with S index increased the AUC values to 0.879， 0.935， and 0.941， respectively， while there were no significant differences between 2D-SWE and the above combinations （P>0.05）. Conclusion2D-SWE has a better diagnostic efficacy than the above seven serological models in determining liver fibrosis stage. The serological models have a certain diagnostic value， among which APRI and S index have a relatively high diagnostic value. There is no significant difference between 2D-SWE and 2D-SWE combined with serological models， and such combinations cannot significantly improve diagnostic efficiency. Therefore， further studies are needed to explore new combinations of diagnostic methods.
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ABSTRACT Background: Persistent hepatitis B virus (HBV) infection can lead to hepatocellular carcinoma (HCC) alone, that is, without the development of previous cirrhosis, which makes it of paramount importance to predict the risk patients with chronic hepatitis B have for developing HCC in the future. Thus, the mPAGE-B score was developed in order to predict very low risks of HCC, becoming an important score, since with low risk, patient surveillance can be spread out. Objective: The main objective of this study was to predict the risk of HCC according to the mPAGE-B score for patients with chronic hepatitis B, using antiviral therapy. Methods: A cross-sectional, descriptive, quantitative, and retrospective study was conducted. Patients with chronic hepatitis B from the Hepatology Outpatient Clinic of the Federal University of the Fronteira Sul/HCPF in Passo Fundo, Rio Grande do Sul, covering a period of 12 years, were analyzed. Results: Of the 67 patients submitted to data collection, the mean age at diagnosis was 51.4 (±12.1) years, with a predominance of males (76.1%-n.51). All patients were HBeAg negative at diagnosis and 11 (16.4%) had cirrhosis. Regarding the antiviral regimen, 70.1% used tenofovir disoproxil fumarate (TDF) and 29.9% entecavir (ETV). According to m-PAGE-B stratification, 18 (25%) patients were classified as low-risk, 30 (41.7%) as intermediate-risk, and 19 (26.4%) as high-risk of developing HCC. The probability of developing HCC of these 67 patients in 3 years was 0.4% for low, 2.8% for moderate, and 9% for high risk. In 5 years, the probability was 0.5% for low, 4.4% for moderate, and 14% for high risk. Conclusion: This study demonstrates that the mPAGE-B score can be applied to decrease the number of consultations of patients with chronic hepatitis B in specialized outpatient clinics and, based on this population, patients aged ≤40 years may have one consultation per year instead of semi-annual.
RESUMO Contexto: A infecção persistente do vírus da hepatite B (HBV) pode levar ao carcinoma hepatocelular (CHC) de forma independente, ou seja, sem o desenvolvimento de cirrose anteriormente, o que torna de suma importância predizer o risco que os pacientes com hepatite B crônica têm para desenvolver CHC no futuro. Assim, o escore mPAGE-B surgiu com o intuito de prever riscos baixos de CHC, tornando-se um escore de extrema relevância, uma vez que diante de risco baixo, pode-se espaçar a vigilância do paciente. Objetivo: O principal objetivo deste trabalho é predizer o risco de CHC, conforme o escore mPAGE-B, para os pacientes com hepatite B crônica em uso de terapia antiviral. Métodos: Foi realizado um estudo transversal, descritivo, quantitativo e retrospectivo. Foram analisados pacientes com hepatite B crônica do ambulatório de hepatologia, da Universidade Federal da Fronteira Sul/HCPF, em Passo Fundo, no Rio Grande do Sul, abrangendo um período de 12 anos. Resultados: Dos 67 pacientes submetidos à coleta de dados, a média de idade no diagnóstico foi 51,4 (±12,1) anos, com uma predominância do sexo masculino (76,1%-n.51). Todos os pacientes eram HBeAg negativos no diagnóstico e 11 (16,4%) tinham cirrose. Conforme a estratificação do mPAGE-B, 18 pacientes (25%) foram classificados como de baixo risco, 30 (41,7%) como risco intermediário, e 19 (26,4%) como alto risco de desenvolver CHC. A probabilidade de desenvolver CHC desses 67 pacientes em 3 anos é de 0,4% para risco leve, 2,8% para moderado e 9% para alto. Em 5 anos, a probabilidade é de 0,5% para risco leve, 4,4% para moderado e 14% para alto. Conclusão: Este estudo demonstra que o mPAGE-B pode ser um escore aplicado para diminuir o número de consultas de pacientes com hepatite B crônica em ambulatórios especializados e, baseado nessa população, talvez os pacientes com idade ≤40 anos possam ter uma consulta por ano ao invés de ser semestralmente.
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Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.
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Myeloid-derived suppressor cells (MDSCs) are a group of immature and heterogeneous cells that can inhibit T cell function. In pathological conditions such as tumors, infections, and chronic inflammation, the large expansion of MDSCs is involved in processes of immune escape, immune tolerance and inflammatory reactions. MDSCs are also crucial in the pathophysiology of hepatitis B virus (HBV) infection, however, their activation, differentiation, and function during HBV infection are still unclear. This article reviews the general characteristics and roles of MDSCs in HBV infection, as well as related drug therapies, in order to provide information for further research on the related mechanism and potential targeted treatment.
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Objective:To study the value of sound touch elastography (STE) linear combined with ultrasound score (US) in the diagnosis of chronic hepatitis B (CHB) liver fibrosis, and to investigate whether their combination can improve the diagnostic efficiency of subdividing the degree of CHB liver fibrosis. Furthermore, a comparison with STE linear combined with the serological model was performed to seek the optimal linear combination model.Methods:A total of 313 subjects were enrolled from September 2018 to December 2021 in Shenzhen Third People′s Hospital Affiliated to Guangdong Medical University, including 259 patients with CHB who had completed liver biopsy and 54 healthy volunteers. CHB patients were divided into liver fibrosis group (F1-F4 group) according to METAVIR classification standard, and healthy volunteers were used as the control group. All subjects underwent liver ultrasound examination, STE and blood biochemical indexes of liver function. The US was performed according to the liver ultrasound examination, and the liver stiffness measurement (LSM) was measured by STE, aspartate aminotransferase and platelet ratio index (APRI) was calculated by blood biochemical index. Fisher discriminant analysis was used to establish the linear combination (LC) diagnostic marker of US and LSM, and the linear combination (LC2) diagnostic marker of LSM and APRI, successively. Spearman rank correlation coefficient was used to analyze the correlations between US, LSM, APRI, LC2, LC and pathological results. The ROC curves of US, LSM, APRI, LC2 and LC for diagnosing CHB liver fibrosis were plotted, and the diagnostic efficiency of above diagnostic markers was evaluated according to the accuracy, sensitivity, specificity and area under the ROC curve (AUC).Results:The formula for the linear combination of US and LSM was LC=0.986 0×US+ 0.166 7×LSM, and LC was highly positively correlated with pathological findings ( rs=0.851, P<0.001), higher than US, LSM, LC2 and APRI ( rs=0.825, 0.775, 0.802, 0.586, all P<0.001). LC showed the best diagnostic efficiency. The AUCs for diagnosing ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis were 0.945, 0.911, 0.954, 0.955, respectively, which superior to the AUCs of US (0.913, 0.879, 0.934 and 0.916, respectively), the AUCs of LSM (0.860, 0.871, 0.934 and 0.952, respectively) and the AUCs of LC2(0.899, 0.883, 0.941, 0.946, respectively). Compared with US, the AUC of LC diagnosis of ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis increased by 3.2%, 3.2%, 2.0% and 3.9%, respectively, with all significant differences ( P<0.05). Compared with LSM, the AUC of LC increased by 8.5%, 4.0%, 2.0% and 0.3%, respectively, with significant difference ( P<0.05) except for stage =F4 cirrhosis.Compared with LC2, the AUC of LC increased by 4.6%, 2.8%, 1.3% and 0.9%, respectively, and there were significant differences in the diagnosis of ≥F1 and ≥F2 liver fibrosis ( P<0.05). Moreover, the overall efficiency of LC2 was not significantly improved than LSM, the difference was not significant ( P>0.05). Conclusions:US, LSM, LC2 and LC can be used to diagnose the degree of CHB liver fibrosis, but LC is better than US or LSM and LC2 alone, especially in the subdivision of mild liver fibrosis, which is a promising new diagnostic marker to subdivide the degree of CHB liver fibrosis.
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OBJECTIVE@#To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis.@*METHODS@#This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed.@*RESULTS@#Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment.@*CONCLUSION@#BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).
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Humans , Gastrointestinal Microbiome , Prospective Studies , Liver Cirrhosis/drug therapy , Hepatitis B/drug therapyABSTRACT
Objective To analyze the correlation of hepatic steatosis with blood lipids and uric acid metabolism in elderly patients with chronic hepatitis B (CHB). Methods The clinical data of 120 patients with CHB admitted to the hospital from January to December 2021 were retrospectively analyzed. According to the presence or absence of hepatic steatosis, the patients were divided into steatosis group (n=35) and non-steatosis group (n=85). The general clinical data, serological indicators of hepatitis B virus, blood lipid and uric acid levels were compared between the two groups. The correlation of hepatic steatosis grading with blood lipids and uric acid metabolism was analyzed. Results The inflammation and fibrosis degree of liver tissues were significantly different in the two groups (P0.05). Pearson correlation analysis found that the grade of hepatic steatosis in patients with CHB was negatively correlated with liver tissue inflammation, fibrosis degree and HDL-C level (P<0.05), and positively correlated with TG and TC levels (P<0.05). Conclusion Elderly patients with CHB and hepatic steatosis have abnormal blood lipid metabolism. Hepatic steatosis will exacerbate abnormal blood lipid metabolism but not liver tissue inflammation or fibrosis degree. Clinically, attention should be paid to blood lipid monitoring of elderly patients with CHB.
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Hepatitis B virus biomarkers are mainly used in clinical practice to diagnose infection, monitor disease progression, evaluate response to chronic hepatitis B treatment, and evaluate the efficacy of novel antiviral drugs in clinical trials. In combination with the recent research progress of antiviral therapy for chronic hepatitis B and the actual needs of clinical diagnosis and treatment, the expert consensus was formulated by the Cooperative Group of Basic Research and Experimental Diagnosis of Liver Diseases, Chinese Society of Hepatology, Chinese Medical Association. It summarized the evidence and recommended the key points for the clinical application of classic and novel hepatitis B virus related biomarkers in order to guide the standardized and reasonable clinical application for these biomarkers.
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Humans , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Consensus , Antiviral Agents/therapeutic use , Biomarkers , Hepatitis B/drug therapyABSTRACT
【Objective】 To study the expression levels of suppressor of cytokine signaling 1 (SOCS1) and its clinical significance in hepatitis B virus (HBV)-related liver diseases. 【Methods】 For this study we enrolled 25 patients with chronic hepatitis B (CHB), hepatitis B cirrhosis, or HBV-associated chronic acute liver failure (HBV-ACLF), and 25 healthy controls. The expression levels of SOCS1 mRNA in peripheral blood mononuclear cells (PBMCs) were determined using the RT-PCR method. The levels of SOCS1 and interleukin-6 (IL-6) in the plasma of patients with chronic liver diseases and healthy controls were measured using the ELISA method. The relative expression levels of SOCS1, SOCS1 mRNA, and other laboratory test indicators such as HBV-DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin activity (PTA) and total bilirubin (TBil) were compared among the groups. Additionally, the correlation between the expression levels of SOCS1 mRNA and the aforementioned laboratory indicators was assessed. 【Results】 The expression levels of SOCS1 mRNA and serum SOCS1 were highest in the HBV-ACLF group, followed by the cirrhosis group, and lowest in the healthy control group, with statistically significant differences (F=109.65, P<0.001). The relative expression of SOCS1 mRNA was positively correlated with TBil (r=0.89, P<0.001), ALT (r=0.89, P<0.001), AST (r=0.84, P<0.001) and IL-6 (r=0.93, P<0.001), but negatively correlated with PTA (r=-0.89, P<0.001) and was not significantly correlated with HBV-DNA (P=0.28). 【Conclusion】 The expression levels of SOCS1 in patients with HBV-related chronic liver diseases can reflect the severity of the disease and show a significant correlation with indicators used to assess the severity of liver diseases.
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ObjectiveTo clarify the evolutionary laws of syndromes and syndrome elements at different stages during the malignant transformation of chronic hepatitis B （CHB）. MethodsA total of 671 patients with hepatitis B virus infection， who were admitted to the outpatient and inpatient departments of Dongzhimen Hospital of Beijing University of Chinese Medicine and The Fifth Medical Center of Chinese PLA General Hospital from July 1st， 2020 to June 30th， 2021， were included， involving 120 cases of CHB， 340 cases of hepatitis B liver cirrhosis （HBLC）， 64 cases of precancerous lesions with hepatitis B liver cirrhosis （PLHC）， and 147 cases of hepatitis B liver cirrhosis with hepatocellular carcinoma （HCC）. A Survey form of traditional Chinese medicine syndrome during malignant transformation of chronic hepatitis B was designed， and the general information， auxiliary examination and the four examinations results were collected. Factor analysis and K-means clustering were used to determine and statistically analyze the syndrome and syndrome elements. ResultsFive traditional Chinese medicine （TCM） syndrome types were identified in CHB patients， while there were six TCM syndrome types in HBLC， PLHC and HCC stages. Among CHB patients， the main syndromes were liver constraint and spleen deficiency （53.33%） and liver-gallbladder damp-heat （21.67%）， and the dominant syndrome elements were qi stagnation （27.60%）， heat （17.71%） and qi deficiency （17.71%）. In the HBLC stage， the syndromes were mainly blood stasis obstructing the collaterals （23.83%） and liver constraint and spleen deficiency （22.35%）， with dominant syndrome elements being blood stasis （19.25%）， dampness （17.46%）， and qi deficiency （15.01%）. For the PLHC stage， the primary syndrome types were blood stasis obstructing the collaterals （29.68%） and liver-kidney yin deficiency （20.31%）， and the leading syndrome elements were blood stasis （22.12%）， yin deficiency （15.93%）， and qi deficiency （15.04%）. In the HCC stage， the syndrome was dominated by blood stasis obstructing the collaterals （33.34%） and liver-kidney yin deficiency （19.73%）， with the main syndrome elements being blood stasis （24.52%）， yin deficiency （16.09%）， and qi deficiency （15.33%）. During the progression of CHB to malignancy， there was a gradual decrease in excess syndromes including liver-gallbladder damp-heat and water-dampness internal obstruction from 21.67% to 19.04%. In contrast， deficiency syndromes including liver-kidney yin deficiency and spleen-kidney yang deficiency increased from 15.83% to 31.97%. Additionally， excess syndrome elements including qi stagnation， heat and dampness decreased from 59.89% to 34.48%， while deficiency syndrome elements including qi deficiency， yin deficiency and yang deficiency increased from 32.30% to 41.00%. ConclusionDuring the malignant transformation of CHB， there exists a progression of syndrome and syndrome elements， shifting from qi stagnation， heat and qi deficiency to blood stasis （predominantly excess）， dampness and qi deficiency， and then to blood stasis （predominantly deficiency）， yin deficiency and qi deficiency， characterized by “deficiency-excess complex， and shift from excess to deficiency”.
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Mother-to-child transmission of hepatitis B virus (HBV) is one of the main ways of transmission and the main cause of chronic hepatitis B after infection. Therefore, preventing mother-to-child transmission of HBV is particularly important in reducing the incidence of chronic hepatitis B. Currently, nucleoside ( acid) analoids ( Nas ) used for mother-to-child blocking of HBV include lamivudine (LAM) , tibivudine (LdT) and tenofovir fumarate ( TDF). Propofol tenofovir fumarate (TAF) has also been used in pregnant chronic hepatitis B pa- tients. This paper summarizes the efficacy, safety and antiviral treatment indications and termination time of the above-mentioned drugs in mother-to-child preventing to provide suggestions for the selection and rational application of mother-to-child preventing Nas.
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Objective @#To identify the factors affecting the adherence to administration of nucleoside/nucleotide analogues among patients with chronic hepatitis B (CHB), so as to provide insights into improving medication adherence among CHB patients. @*Methods@#CHB patients at ages of 18 to 44 years that underwent treatment in Hangzhou First People's Hospital Affiliated to Zhejiang University School of Medicine from June 2021 to December 2022 were enrolled, and subjects' demographic and clinical characteristics were collected. The medication adherence was evaluated with the Morisky Medication Adherence Scale, and the negative illness perception was evaluated using the simplified Illness Perception Questionnaire, while the social support level was evaluated with the Social Support Scale. In addition, factors affecting the medical adherence were identified using a multivariable logistic regression model among CHB patients.@*Results@#A total of 225 questionnaires were allocated and 210 valid questionnaires were recovered, with an effective recovery rate of 93.33%. The respondents had a mean age of (35.94±8.72) years, and included 119 men (56.67%) and 91 women (43.33%), with a mean total illness perception score of (44.09±12.06) points. Morisky Medication Adherence Scale classified good in 149 cases (70.95%) and poor in 61 cases (29.05%). Multivariable logistic regression analysis identified an educational level of college degree and above (OR=1.676, 95%CI: 1.105-2.910), family monthly per capita income of >5 000 Yuan (OR=2.518, 95%CI: 1.360-5.033), receiving health education pertaining to CHB (OR=3.590, 95%CI: 1.611- 7.932), high or medium level of social support (high: OR=3.202, 95%CI: 1.613-5.870; medium: OR=1.267, 95%CI: 1.085-2.409) as factors improving the medication adherence, and administration of more than 3 types of drugs (OR=0.388, 95%CI: 0.204-0.526) and high illness perception score (OR=0.601, 95%CI: 0.395-0.808) as factors constraining medication adherence among CHB patients.@*Conclusions@#The medication adherence are affected by educational level, family monthly per capita income, types of drugs, illness perception score, health education pertaining to CHB and social support level among CHB patients. Individualized intervention strategy is required targeting these influencing factors to improve the medication adherence among CHB patients.
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OBJECTIVE To compare the clinical comprehensive value of 15 Chinese patent medicines for the treatment of chronic hepatitis B， in order to provide reference for clinical rational drug use. METHODS According to the Management Guidelines for Clinical Comprehensive Evaluation of Pharmaceuticals （2021 Version for Trial Implementation）， systematic literature review， meta-analysis and other related data analysis methods were used to perform qualitative and quantitative analysis for the safety， efficacy， economy， suitability， accessibility and innovation of 15 Chinese patent medicines. RESULTS In terms of safety， most of the adverse drug reactions of chronic hepatitis B Chinese patent medicines before the market were unobserved or unclear； post-marketing safety took nucleoside analogs as the intermediate bridge for meta-analysis， there was no significant difference in the incidence of adverse drug reactions among the combined regimens of Chinese patent medicines （P＞0.05）， except that the combination regimen of Fuzheng huayu capsule， Compound yiganling capsules versus combination regimen of Jiuwei gantai capsules showed statistically significant differences （P＜0.05）. In terms of effectiveness， the results of network meta-analysis showed that most Chinese patent medicines， such as Fuzheng huayu capsules combined regimens， had no significant differences in effective rate， HBeAg negative conversion rate and HBV-DNA negative conversion rate （P＞0.05）； however， in reducing the liver elastic hardness value， the combined regimen of Dangfei liganning tablet （capsule） was better than the other combined regimens （P＜0.05）. In terms of economy， the highest cost was the Shuganning injection， and the lowest was Hepatitis B qingre jiedu granules. In terms of suitability， most of the medicines were capsules， tablets and granules， which only needed to be sealed to store and taken orally or taken with boiling water. Compared with injections and some similar products that required strict control of storage temperature， its suitability was better. In terms of accessibility， from the perspective of drug price and affordability， Shuganning injection had the highest average daily cost， the number of days that needed to be borne by the average daily wage was the highest； the average daily cost of Compound yiganling tablets was the lowest， and the number of days required to be borne by the average daily wage was the lowest. From the perspective of availability， Compound biejia ruangan tablets， Dangfei liganning capsules and Wuzhi granules were easier to obtain. In terms of innovation， the 15 Chinese patent medicines included in the study were all domestically produced medicines with a relatively long-term theoretical basis of traditional Chinese medicine and experience in human medicine， and had good industrial innovation. Among them， Compound huayu tablets （capsules） and Anluo huaxian pills were protected varieties of traditional Chinese medicine； Fuzheng huayu tablets （capsules） with more patents had 6 valid patents， all of which were patents for invention. CONCLUSIONS Wuzhi capsule， Sedum sarmentosum granules， Compound yiganling tablets， Rhubarb buchong pills and Dangfei liganning capsules have high clinical comprehensive value.
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@#Abstract: Objective To investigate the expression level and clinical significance of serum liver fibrosis-associated lncRNA1 (lnc-LFAR1) in patients with chronic hepatitis B cirrhosis, aiming to analyze its correlation with interleukin-6 (IL-6), interleukin-1β (IL-1β), and liver function. Methods Patients with chronic hepatitis B (CHB) cirrhosis and CHB diagnosed and treated in Dongguan City People's Hospital from March 2016 to December 2019 were selected and divided into the liver cirrhosis group (n=80) and the CHB group (n=80), and 80 healthy people with physical examination during the same period were selected as healthy group. The serum levels of lnc-LFAR1, interleukin-6 (IL-6), albumin (ALB), interleukin-1β (IL-1β) and liver function indicators, including albumin (ALB) and alanine aminotransferase (ALT) were measured and analyzed. The correlation between serum lnc-LFAR1 expression level and IL-6, IL-1β was assessed, and the levels of lnc-LFAR1, IL-6, IL-1β, ALB and ALT were compared among patients with CHB cirrhosis of different Child-Pugh grades. Results The serum levels of lnc-LFAR1, IL-6, IL-1β and ALT in the patients with liver cirrhosis [(1.85± 0.62), (41.76±13.92) ng/mL, (7.78±1.95) pg/mL, (148.37±29.67) U/L] were higher than those in the CHB group [(1.42±0.47), (23.56± 7.85) ng/mL, (5.42±1.41) pg/mL, (87.59±17.52) U/L] and the healthy group [(1.01±0.34), (6.70±2.23) ng/mL, (3.13± 0.78) pg/mL, (15.44±3.10) U/L] (P<0.05), while the ALB levels (30.54±3.82) g/L were lower than those in the CHB group (37.27±4.34) g/L and the healthy group (45.26±5.66) g/L (P<0.05). Serum lnc-LFAR1, IL-6, IL-1β and ALT levels in the CHB group were higher than those in the healthy group (P<0.05), and ALB levels were lower than those in the healthy group (P<0.05); the serum levels of lnc-LFAR1, IL-6, IL-1β in patients with CHB cirrhosis were negatively correlated with ALB (P<0.05), and positively correlated with ALT (P<0.05); the serum expression level of lnc-LFAR1 in patients with CHB cirrhosis was positively correlated with IL-6 and IL-1β (r=0.598, 0.571, P<0.05); with the increase of Child-Pugh grade, the serum levels of lnc-LFAR1, IL-6, IL-1β, and ALT in patients with CHB cirrhosis gradually increased (P<0.05), and the level of ALB gradually decreased (P<0.05). Conclusions Serum lnc-LFAR1 expression level is higher in patients with CHB cirrhosis, which is obviously related to IL-6, IL-1β, ALB and ALT. Therefore, the evaluation of serum lnc-LFAR1 expression level is helpful in the clinical assessment of the condition of CHB cirrhosis patients.
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@#Abstract: Objective To explore the influencing factors of serum HBeAg loss in patients with chronic hepatitis B (CHB) and and provide evidence for effective treatment of CHB. Methods A follow-up cohort of HBeAg-positive CHB patients was established in the the Infectious Diseases Outpatient Clinic of hospital. Regular follow-up and laboratory test indicators were collected to analyze the changes of serum HBeAg in HBeAg-positive CHB patients during the follow-up period. The subjects were divided into the case group (serum HBeAg loss) and the control group (serum HBeAg not loss) according to whether serum HBeAg loss occurred. The baseline data characteristics of the two groups were analyzed and compared, and the influencing factors of serum HBeAg loss were analyzed by Cox univariate and multivariate regression. Results A total of 634 HBeAg-positive CHB patients were enrolled, with a total follow-up of 2 570.01 person-years. Among them, 237 cases of serum HBeAg loss occurred, with the mean follow-up time of 40.92 months, and the rate of HBeAg loss was 9.22/100 person-years. There were significant differences in HBV family history, antiviral therapy, baseline WBC, PLT, ALT, AST, T˗Bil, GGT, AFP, quantitative HBsAg and quantitative HBeAg between serum HBeAg loss group and serum HBeAg not loss group (P<0.05). Cox regression analysis showed that family history of HBV (HR 0.68, 95％CI:0.50-0.92, P=0.012), ALT (HR2.06, 95％CI:1.52-2.79, P<0.001), quantitative HBsAg (HR 0.68, 95％CI:0.48-0.95, P=0.024), quantitative HBeAg (HR 0.48, 95％CI:0.31-0.74, P=0.001) were independent influencing factors for HBeAg loss in HBeAg-positive CHB patients. Conclusions HBeAg-positive CHB patients without family history of HBV, initial ALT≥80 U/L, quantitative HBsAg<1 000 IU/ml, quantitative HBeAg<1 000 C.O.I are more likely to have serum HBeAg loss.
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@#Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with <ULN accounted for 32.38%, 35.03% and 36.07% of significant liver tissue injury, respectively. And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%, 41.85% and 50.30%, respectively. The optimal ALT critical values were 33 U/L for overall patients, 25 U/L for females, 45 U/L for males, 45 U/L for ≤30 years olds, 33 U/L for>30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.
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Objective: To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods: A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results: A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion: In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.
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Humans , Adult , Hepatitis B, Chronic/complications , Retrospective Studies , Cross-Sectional Studies , Hepatitis B e Antigens , DNA, Viral , Antiviral Agents/therapeutic use , Hepatitis B virus/genetics , DemographyABSTRACT
This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT 2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 ( t = 10.58, P < 0.001), 5.59 ( t = 3.37, P = 0.028) and 10.83 ( t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
Subject(s)
Humans , Healthy Volunteers , Hepatitis B, Chronic/genetics , Immunotherapy , Interleukin-15 , Leukocytes, Mononuclear , Nuclear Proteins , Oligonucleotide Array Sequence Analysis/methods , Interferons/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVES@#Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT).@*METHODS@#This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored.@*RESULTS@#Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910).@*CONCLUSIONS@#The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.