ABSTRACT
Serum hepatitis B core antibody (anti-HBc) is associated with liver inflammation in chronic hepatitis B patients. This study aimed to investigate whether anti-HBc could serve as a predictor of significant liver inflammation in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infected patients with normal alanine aminotransferase (ALT) and detectable HBV DNA. Treatment-naïve HBeAg-negative chronic HBV infected patients with normal ALT and detectable HBV DNA who underwent liver biopsy were retrospectively included from two medical centers. Liver inflammation grade was evaluated using the Scheuer scoring system and significant liver inflammation was defined as ≥G2. Serum anti-HBc levels were measured by commercial immunoassays (Abbott GmbH & Co. KG). A total of 117 patients were included and 50 (42.7%) patients showed significant liver inflammation. Serum anti-HBc levels in patients with significant liver inflammation were significantly higher than patients with no or mild liver inflammation (Subject(s)
Hepatitis B Antibodies/blood
, Hepatitis B Core Antigens/immunology
, Hepatitis B, Chronic/blood
, Hepatitis B, Chronic/pathology
, Adult
, Alanine Transaminase/blood
, Female
, Hepatitis B e Antigens/blood
, Hepatitis B virus/genetics
, Hepatitis B, Chronic/virology
, Humans
, Logistic Models
, Male
, Middle Aged
, Multivariate Analysis
, Predictive Value of Tests
, ROC Curve
, Retrospective Studies
, Severity of Illness Index
ABSTRACT
A substantial proportion of patients with chronic hepatitis B (CHB) who do not fit into any of the usual immune states are considered to be in the 'grey zone (GZ)'. We aimed to investigate the distribution and characteristics of GZ in a large cohort of CHB patients. Four thousand seven hundred and fifty-nine consecutive treatment-naïve CHB patients were enrolled. The immune states were defined based on AASLD 2018 Hepatitis B Guidance. GZ CHB patients were classified into four groups: HBeAg positive, normal ALT levels and serum HBV DNA ≤106 IU/ml (GZ-A); HBeAg positive, elevated ALT levels and serum HBV DNA ≤2 × 104 IU/ml (GZ-B); HBeAg negative, normal ALT levels and serum HBV DNA ≥2 × 103 IU/ml (GZ-C); HBeAg negative, elevated ALT levels and serum HBV DNA ≤2 × 103 IU/ml (GZ-D). The distributions of different immune states were: 233 (4.90%) patients in immune-tolerant phase, 941 (19.77%) patients in HBeAg-positive immune active phase, 1,717 (36.08%) patients in inactive phase and 546 (11.47%) patients in HBeAg-negative immune active phase. Of note, 1,322 (27.78%) patients did not fit into any of above phases and were defined as the GZ. A high proportion of patients in GZ-B had advanced fibrosis (33.3%) or cirrhosis (25.8%). Older age, HBeAg-positive status and higher ALT levels were independently risk factors of advanced disease in GZ CHB patients. Therefore, our results revealed that more than a quarter of CHB patients were classified into the GZ and a high proportion of patients in GZ-B had advanced fibrosis or even cirrhosis.
Subject(s)
Hepatitis B, Chronic , Aged , Alanine Transaminase , DNA, Viral , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus/genetics , Hepatitis B, Chronic/epidemiology , HumansABSTRACT
B cell hyperactivation and functional impairment were identified from patients with chronic hepatitis B virus (CHB) infection; however, the underlying mechanism remains unknown. Here, we aim to elucidate the mechanisms responsible for B cell hyperactivation during HBV infection. Peripheral CD19+ B cells isolated from 4 CHB patients and 4 healthy volunteers were analysed by RNA sequencing. A total of 1401 differentially expressed genes were identified from B cell transcriptome of CHB patients vs healthy volunteers. We found that B cells from CHB patients were functional impaired, with increased TLR4 expression, activated NF-κB pathway and altered mitochondrial function. The expression of B cell activation-related genes, including TLR4, was further validated using additional clinical samples. To further verify the role of TLR4 in B cell activation during CHB, B cell phenotypes were determined in wild-type (WT) and TLR4-/- HBV-carrier mice. Hyperactivated B cell and TLR4 signalling pathway were observed in WT HBV-carrier mice, while TLR4 ablation failed to induce B cell hyperactivation, and downstream MyD88 and NF-κB were also not altered. Taken together, TLR4 pathway plays a pivotal role in B cell hyperactivation during CHB, which might serve as a promising target for B cell function restoration.
Subject(s)
B-Lymphocytes/immunology , B-Lymphocytes/virology , Hepatitis B virus/physiology , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/virology , Lymphocyte Activation/immunology , Toll-Like Receptor 4/metabolism , Animals , Case-Control Studies , Cell Proliferation , Disease Models, Animal , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , Genome, Human , Hepatitis B Vaccines/immunology , Hepatitis B, Chronic/genetics , Heterozygote , Humans , Mice, Inbred C57BL , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Reproducibility of Results , VaccinationABSTRACT
BACKGROUND: Serum hepatitis B e antigen (HBeAg) status is associated with the progression of chronic hepatitis B (CHB). The authors aimed to investigate the relationship between HBeAg status and liver pathology in CHB patients. METHODS: A total of 683 treatment-naive CHB patients who had undergone liver biopsy were retrospectively enrolled from 2 medical centers. Propensity score-matching (PSM) method was performed to adjust the imbalance of baseline confounders between HBeAg-positive and HBeAg-negative CHB patients. RESULTS: HBeAg-negative CHB patients (n=338) exhibited more advanced liver fibrosis than HBeAg-positive CHB patients (n=345) before PSM (P<0.001). However, there were no significant differences in the distribution of inflammation grades between HBeAg-positive and HBeAg-negative CHB patients (P=0.051). Of these 683 CHB patients, 123 patients were included in each group after PSM. HBeAg-negative CHB patients still showed significantly advanced liver fibrosis as compared with HBeAg-positive CHB patients (P=0.03) after PSM. Furthermore, the distribution of liver inflammation grades in the HBeAg-negative CHB patients was also more severe than patients with HBeAg-positive (P=0.037). HBeAg-negative status was identified as an independent risk factor of significant liver fibrosis (P=0.011) by multivariate analysis. CONCLUSIONS: HBeAg negativity is associated with more advanced liver fibrosis in CHB patients.
Subject(s)
Hepatitis B e Antigens , Hepatitis B, Chronic , DNA, Viral , Hepatitis B virus/genetics , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/pathology , Humans , Liver/pathology , Liver Cirrhosis/pathology , Propensity Score , Retrospective StudiesABSTRACT
BACKGROUND: Bloodstream infection (BSI) caused by Klebsiella pneumoniae (KP), especially carbapenem-resistant KP (CRKP), results in high morbidity and mortality. AIMS: We aim to identify risk factors that associated with the mortality of patients with KP BSI, as well as predictors of developing CRKP BSI. RESULTS: In this retrospective cohort study, we examined 285 inpatients with BSI caused by KP in a tertiary hospital in China between 2014 and 2018, and 46 patients were infected with CRKP. We identified that hematological tumor (odds ratio (OR): 8.359, [95% CI: 2.162-33.721], P=0.002), CRKP isolation (OR: 7.766, [95% CI: 2.796-21.576], P=0.001), chronic lung disease (OR: 5.020, [95% CI: 1.275-19.768], P=0.020), and septic shock (OR: 4.591, [95% CI: 1.686-12.496], P=0.003) were independent risk factors for the death of KP BSI. A 28-day mortality of KP BSI score ranging from 0 to 22 was developed based on the above 4 independent variables. Our scoring system revealed that the 28-day mortality were 9.14%, 35.29%, 38.10 %, 75% and 100% for carriers with a score of 0, 5, 6-10, 11-13 and ≥14, respectively. Additionally, CRKP infection were independently associated with intensive care unit stay (OR: 5.506, [95% CI: 2.258-13.424], P=0.001), exposure to antifungals (OR: 4.679, [95% CI: 2.065-10.063], P=0.001), exposure to fluoroquinolones (OR: 2.892, [95% CI: 1.151-7.267], P=0.020), and the number of isolated bacterial species from the patient ≥ 3 (OR: 2.414, [95% CI: 1.306-4.463], P=0.005). CONCLUSION: Our study may be useful for the reduction of the mortality of patients with KP BSI and the prevention of developing CRKP BSI in hospitals.