The synergism of hepatitis B and aflatoxicosis in hepatocellular carcinoma development: A mini-review

Hepatocellular carcinoma (HCC) is the twelfth most common cancer and the fifth leading cause of worldwide cancer related death. Chronic hepatitis B infection, caused by the hepatitis B virus (HBV) and exposure to aflatoxins is fundamental in the formation of HCC in developing countries. This review of scientific publications aims to establish the detrimental effects of aflatoxin-contaminated foods and highlights the correlation between aflatoxin and hepatitis B viral-associated hepatocellular carcinoma. Research has shown a significant increase in the occurrence of HCC in HBV-infected individuals exposed to fungal toxins. HBV demonstrates the ability to integrate and bind to p53 protein in the host DNA and propagate hepatocyte vulnerability through carcinogenic aflatoxin B1 (AFB1) damage. Although there has been clear evidence about the synergistic interaction of exposure to AFB1 and HBV infection in the induction of HCC, other literature has shown otherwise, mainly because incomplete and vague findings and hypotheses were made in regions where AFB1 and HBV pose a public health risk. Vaccination against hepatitis B and measures such as robust food safety systems to avoid hepatotoxicity and hepatocellular carcinogenesis induced by AFB1 is the most effective methods in the prevention of HCC induced by HBV and AFB1

Hepatitis B chronic infection among pregnant women attending the antenatal care in Bor State Referral Hospital, South Sudan

Introduction: Hepatitis B virus (HBV) is a major public health problem affecting 400 million people worldwide, and is a common cause of chronic liver failure (cirrhosis) and hepatocellular carcinoma. Sixty-eight percent of infected people are from the African and Pacific regions. Vertical transmission from mother to newborn baby is one of the mechanisms by which chronic hepatitis virus infection spreads, besides infections from contaminated needles and syringes and sexual contact. Hepatitis B chronic infection is endemic in many poor countries, especially in Africa. Method: A cross-sectional study was conducted between July and August 2021. Pregnant women attending the antenatal care (ANC) in Bor State referral hospital, South Sudan, were interviewed to collect information on their socio-demographic characteristics and risk factors for hepatitis B infection. The objective was to determine the seroprevalence of hepatitis B chronic infection through blood testing. Prevalence ratios for certain risk factors were calculated. Results: Two hundred pregnant women were enrolled. The Prevalence Rate for chronic infection with hepatitis B virus, diagnosed using the rapid immune-chromatographic assay for Hepatitis B surface antigen (HBsAg), was 8.5%. (95% CI; 4.7% - 12.3%). None of the suspected risk factors studied were found to be significantly associated with testing positive for HBV, except for a history of previous jaundice. Conclusion: The prevalence of HBV chronic infection among pregnant women in Bor, Jonglei State, is high hence there is a need for established public health interventions that can lead to a reduction of HBV vertical transmission. Treatment of pregnant women with HBV chronic infection using anti-viral medications during pregnancy might curb the vertical transmission rates.

Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study / 中华肝脏病杂志

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy / 中华肝脏病杂志

Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.

Regulation and influence of mitochondria on macrophages during hepatitis B virus infection / 中华肝脏病杂志

Hepatitis B virus (HBV) infection is an important public health concern, as approximately 3.5% of the world's population is currently chronically infected. Chronic HBV infection is the primary cause of cirrhosis, hepatocellular carcinoma, and deaths related to liver disease globally. Studies have found that in HBV infection, viruses can directly or indirectly regulate mitochondrial energy metabolism, oxidative stress, respiratory chain metabolites, and autophagy, thereby altering macrophage activation status, differentiation types, and related cytokine secretion type and quantity regulations. Therefore, mitochondria have become an important signal source for macrophages to participate in the body's immune system during HBV infection, providing a basis for mitochondria to be considered as a potential therapeutic target for chronic hepatitis B.

Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome / 中华肝脏病杂志

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.

Analysis of clinical characteristics and risk factors of hepatic fibrosis in children with chronic hepatitis B combined with metabolic-related fatty liver disease / 中华肝脏病杂志

Objective: To compare the clinical and pathological features of children with chronic viral hepatitis B combined with metabolic-associated fatty liver disease (CHB-MAFLD) and chronic viral hepatitis B alone (CHB alone), and to further explore the effect of MAFLD on the progression of hepatic fibrosis in CHB. Methods: 701 initially treated CHB children confirmed by liver biopsy admitted to the Fifth Medical Center of the PLA General Hospital from January 2010 to December 2021 were collected continuously. They were divided into CHB-MAFLD and CHB-alone groups according to whether they were combined with MAFLD. A retrospective case-control study was conducted. CHB-MAFLD was used as the case group, and 1:2 propensity score matching was performed with the CHB alone group according to age and gender, including 56 cases in the CHB-MAFLD group and 112 cases in the CHB alone group. The body mass index (BMI), metabolic complications, laboratory indicators, and pathological characteristics of liver tissue were compared between the two groups. The related factors affecting liver disease progression in CHB were analyzed by a binary logistic regression model. The measurement data between groups were compared using the t-test and rank sum test. The χ (2) test was used for the comparison of categorical data between groups. Results: Alanine aminotransferase (ALT, P = 0.032) and aspartate aminotransferase (AST, P = 0.003) levels were lower in the CHB-MAFLD group than those in the CHB alone group, while BMI (P < 0.001), triglyceride (TG, P < 0.001), total cholesterol (P = 0.016) and the incidence of metabolic syndrome (P < 0.001) were higher in the CHB alone group. There were no statistically significant differences in HBsAg quantification or HBV DNA load between the two groups (P > 0.05). Histologically, the proportion of significant liver fibrosis (S2-S4) was higher in the CHB-MAFLD group than that in the CHB alone group (67.9% vs. 49.1%, χ (2) = 5.311, P = 0.021). Multivariate regression results showed that BMI (OR = 1.258, 95% CI: 1.145 ~ 1.381, P = 0.001) and TG (OR = 12.334, 95% CI: 3.973 ~ 38.286, P < 0.001) were the risk factors for hepatic steatosis occurrence in children with CHB. MAFLD (OR = 4.104, 95% CI: 1.703 ~ 9.889, P = 0.002), liver inflammation (OR = 3.557, 95% CI: 1.553 ~ 8.144, P = 0.003), and γ-glutamyl transferase (OR = 1.019, 95% CI: 1.001 to 1.038, P = 0.038) were independent risk factors for significant hepatic fibrosis in children with CH. Conclusion: MAFLD occurrence is related to metabolic factors in children with CHB. Additionally, the combination of MAFLD may promote liver fibrosis progression in CHB patients.

A conceptual framework for dynamics of cccDNA in hepatitis B virus / 中华肝脏病杂志

The resolution of the hepatitis C issue has raised expectations for a chronic hepatitis B cure, driving the industry to expand investment in research and development efforts to strengthen functional cure strategies. These strategies have a wide variety of types, and the published research findings are heterogeneous. The theoretical analysis of these strategies is of great significance for determining prioritized research orientations as well as sensibly allocating research and development resources. However, due to a paucity of necessary conceptual models, current theoretical analysis has not been able to unify various therapeutic strategies into a proper theoretical framework. In view of the fact that the decrease in the quantity of cccDNA is an inevitable core event accompanied by the process of functional cure, this paper intends to analyze several chronic hepatitis B cure strategies using cccDNA dynamics as a framework. Furthermore, there are currently few studies on the dynamics of the cccDNA field, hoping that this article can promote recognition and research in this field.

Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection / 中华肝脏病杂志

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

Hepatic pathological characteristics and factors influencing alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B / 中华肝脏病杂志

Objective: To analyze the hepatic pathological characteristics and factors influencing an alanine transaminase value below twice the upper limit of normal in patients with chronic hepatitis B (CHB) and further explore the optimal ALT threshold strategy for initiating antiviral therapy. Methods: Clinical data of treatment-naïve CHB patients who underwent liver biopsies from January 2010 to December 2019 were retrospectively collected. Multiple regression models were used to explore the ALT levels and significant risk of hepatic histological changes (≥G2/S2). Receiver operating characteristic curve was used to evaluate the value of different models in diagnosing liver tissue inflammation≥G2 or fibrosis ≥ S2. Results: A total of 447 eligible CHB patients, with a median age of 38.0 years and 72.9% males, were included. During ALT normalization, there was significant liver inflammation (≥G2) and fibrosis (≥S2) in 66.9% and 53.0% of patients, respectively. With an ALT rise of 1-2×ULN, the proportions of liver inflammation≥G2 and fibrosis≥S2 were 81.2% and 60.0%, respectively. After adjusting for confounding factors, higher ALT levels (> 29 U/L) were found to be associated with significant liver inflammation (OR: 2.30, 95% CI: 1.11 ~ 4.77) and fibrosis (OR: 1.84, 95% CI: 1.10 ~ 3.09). After the measurement of glutamyltransferase-platelet ratio (GPR), the proportion of CHB patients with≥G2/S2 was significantly reduced under different treatment thresholds of ALT standards, and in particular, the erroneous evaluation of liver fibrosis≥S2 was significantly improved (33.5% to 57.5%). Conclusion: More than half of CHB patients have a normal ALT or one within 2 × ULN, regardless of whether or not there is apparent inflammation and fibrosis. GPR can significantly improve the precise assessment of different conditions of treatment thresholds for the ALT value in CHB patients.

Evaluation of peripheral blood T-lymphocyte subpopulations features in patients with hepatitis B virus-related acute-on-chronic liver failure based on single-cell sequencing technology / 中华肝脏病杂志

Objective: T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Methods: Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Results: Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets (P = 0.007) and CD8(+)LAG3(+) (P = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. Conclusion: There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.

Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022) / 中华肝脏病杂志

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients / 中华预防医学杂志

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

Demographic characteristics and associated influencing factors in treated patients with chronic hepatitis B with hypoviremia : a single-center retrospective cross-sectional study / 中华肝脏病杂志

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.

Interferon-related gene array in predicting the efficacy of interferon therapy in chronic hepatitis B / 生物医学工程学杂志

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.

Clinicopathologic characteristics of liver inflammation and fibrosis in 310 patients with chronic hepatitis B / 中南大学学报(医学版)

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.

Expert consensus on the clinical application of the markers of hepatitis B virus / 中华肝脏病杂志

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.

Prevalence of Hepatitis B and C Virus Infection among Pregnant Women in Sharkia Governorate, Egypt

Viral infections is the cause of liver inflammation, cirrhosis and even liver hepatocellular carcinoma (HCC). Despite the availability of HBV vaccine and antiviral treatment for HBV and HCV both remain a major health problem. The aim of this study To determine the seroprevalence of HBV and HCV infection among pregnant women in Sharkia governorate, Egypt.

Prévalence de l'hépatite virale B chronique à Bangui et Bimbo en République Centrafricaine: cas des donneurs bénévoles réguliers non éligibles pour les dons de sang / Prevalence of chronic viral hepatitis B in Bangui and Bimbo in the Central African Republic: cases of regular voluntary donors not eligible for blood donations

Contexte & objectif. L'hépatite virale B (HVB) par son évolution peut déboucher vers la guérison ou vers une forme chronique qui est très peu documentée chez les donneurs bénévoles de sang (DBS). L'objectif de la présente étude était de déterminer la prévalence de l'HVB chronique. Méthodes. L'étude réalisée au Centre National de Transfusion Sanguine de Bangui était rétrospective et portait sur les données de contrôle sérologique des DBS de Bimbo et de Bangui, capitale de la République centrafricaine (RCA). L'échantillonnage exhaustif concerne la période de juillet 2013 à décembre 2019. Le DBS est porteur d'une infection chronique si l'antigène de surface de l'HVB persiste pendant plus de six mois. Le test de Chi carré de Pearson au seuil de 5 % et l'odd ratio (OR) ont été utilisés comme test d'association. Résultats. Les données de contrôle sérologique de 702 DBS âgés de 18 à 62 ans ont été analysées. Le sexe masculin était prépondérant (n=598). La prévalence de l'HVB chronique était de 70,5 %. Cette prévalence était plus élevée chez les DBS de 25 à 34 ans (30,4 %), les hommes (58,8 %) et les DBS qui résident à Bangui (61,2 %). La forme chronique était significativement associée au jeune âge (18 à 44 ans) et au sexe masculin (p< 0,05). La coïnfection par le VIH et l'hépatite C était retrouvée dans 5,5 % des cas (39/702). Conclusion. La prévalence de l'HVB chronique est très élevée chez les DBS de Bangui et Bimbo. La forme chronique était significativement associée à l'âge et au sexe. La gratuité de la charge virale et du traitement antiviral sont des perspectives à mettre en œuvre

Context and objective. Viral hepatitis B (VHB) by its evolution can lead to recovery or to a chronic form. This chronic form, a source of new contaminations, is not documented among voluntary blood donors (VBD) in Bangui and Bimbo. The present study aimed to determine the prevalence of chronic VHB among VBD in the two cities in the Central African Republic (CAR). Methods. The study carried out at the Bangui National Blood Transfusion Center was retrospective and focused on serological control data from VBD from Bangui, capital of CAR and Bimbo. The exhaustive sampling is from July 2013 to December 2019. A VBD carries a chronic infection if the VHB surface antigen persists for more than six months. Results. Serological control data from 702 VBD aged 18 to 62 years were analyzed. Male sex predominated at inclusion (n = 598). The prevalence of chronic VHB was 70.5 %. This prevalence was higher among young VBD aged 25 to 34 years (30.4 %), the male gender (58.4 %) and VBD residing in Bangui (61.2 %). The chronic form was significantly associated with young age (18 to 44 years) and male sex (p< 5%). Co-infection with HIV and hepatitis C was found in 5.5 % of cases (39/702). Conclusion. The prevalence of chronic VHB is very high in VBD from Bangui and Bimbo. The chronic form was significantly associated with age and sex. Free viral load and antiviral treatment are prospects to be implemented.

Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center retrospective cohort study / 医学前沿

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.