Cessation of Nucleos(t)ide Analogue Therapy in Non-Cirrhotic Hepatitis B Patients with Prior Severe Acute Exacerbation

Chronic hepatitis B (CHB) with severe acute exacerbation (SAE) is an urgent problem requiring nucleos(t)ide analogue (NA) therapy. We aim to evaluate the clinical relapse (CR) risk after discontinuing NA in patients with prior SAE. Methods: In this retrospective cohort study, CHB patients who discontinued NA therapy were screened between October, 2003 and January, 2019. A total of 78 non-cirrhotic patients who had received NA therapy for CHB with SAE, i.e., bilirubin ≥ 2 mg/dL and/or prothrombin time prolongation ≥3 s, (SAE group) were matched 1:2 with 156 controls without SAE (non-SAE group) by means of propensity scores (age, gender, NA categories, NA therapy duration, and HBeAg status). Results: The 5-year cumulative incidences of severe CR, i.e., ALT > 10X ULN, (42.78%, 95%CI: 27.84–57.73% vs. 25.42%, 95%CI: 16.26–34.58%; p = 0.045) and SAE recurrence (25.91%, 95%CI: 10.91–40.91% vs. 1.04%, 95%CI: 0–3.07%; p < 0.001) were significantly higher in the SAE group. Prior SAE history (HR 1.79, 95%CI: 1.04–3.06) was an independent factor for severe CR. The 5-year cumulative incidence of HBsAg seroclearance was significantly higher in the SAE group than that in the non-SAE group (16.82%, 95%CI: 2.34–31.30% vs. 6.02%, 95%CI: 0–13.23%; p = 0.049). Conclusions: Even though it creates a greater chance of HBsAg seroclearance, NA therapy cessation may result in a high risk of severe CR in non-cirrhotic CHB patients with prior SAE.

Correlation between APRI, FIB-4 and GPR Indices to Fibroscan and HBeAg Status in Patients with Chronic Hepatitis B

Liver fibrosis is a complication of chronic hepatitis B. Early detection of liver fibrosis is important for therapy. The aspartate aminotransferase index (AST)-to-platelet ratio index (APRI) and the fibrosis index based on 4 factors (FIB-4) in chronic hepatitis B have been widely studied despite the inconsistent results. Research on other serum markers is extensively carried out, including Gamma-Glutamyl Transpeptidase (GGT)-to-platelet ratio (GPR). Previous studies have shown that the GPR index was more accurate than APRI and FIB-4. HBeAg status is an indication for therapy. There have not been many studies on the correlation of serum markers with HBeAg status. This study aimed to determine the correlation of APRI, FIB-4, and GPR with Fibroscan and HBeAg status in chronic hepatitis B patients. A cross-sectional study was carried out from June to September 2020 and found 50 chronic hepatitis B patients. Platelet count was measured using a Sysmex XN-1000 hematology device; AST, alanine aminotransferase (ALT), and GGT levels were measured using the Dimension RXL clinical chemistry device; and the degree of fibrosis was determined using transient elastography (Fibroscan). Spearman correlation test was used in this study for the correlation analysis. The results showed a significant correlation between APRI, FIB-4 and GPR indices with Fibroscan (r=0.454, p 0.001; r=0.610, p < 0.001; r=0.540, p < 0.001, respectively). A significant correlation was found between APRI, FIB-4 and GPR indices with negative (-) HBeAg (r=0.486, p 0.004; r=0.648, p < 0.001; r=0.595, p < 0.001, respectively). In addition, a significant correlation was found between FIB-4 and positive (+) HBeAg (r=0.499, p 0.049), but no correlation was found between APRI and GPR with positive (+) HBeAg (r=0.295, p 0,267; r=0.386, p 0.140, respectively).

Effects of HBeAg Status on cellular immune function of patients with Hepatitis B virus/Treponema Pallidum Co-infection

Objectives: This study was aimed at exploring the effects of hepatitis B envelope antigen (HBeAg) status on the cellular immune function of patients with hepatitis B virus/treponema pallidum (HBV/TP) co-infection. Methods: The clinical data of 79 patients with HBV/TP co-infection admitted to our hospital from January 2019 to January 2020 were retrospectively analyzed. These patients were divided into two groups according to the different HBeAg statuses before the treatment: 41 HBeAg+ patients were included in the HBeAg+ group, while 38 HBeAg- patients were included in the HBeAg- group. The levels of HBV-DNA, T lymphocyte subsets represented by NK cells and cytokines associated with T cells in the peripheral blood (PB) of the patients were compared between both groups. Results: The HBV-DNA levels in the HBeAg+ group were significantly higher than those in the HBeAg- group (P < 0.05). The levels of CD3+, CD4+, CD4+/CD8+ and natural killer (NK) cells in the HBeAg+ group were higher than those in the HBeAg- group (P < 0.05), while the levels of CD8+ cells were lower than those in the HBeAg- group (P < 0.05). Moreover, the levels of interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-β (TGF-β) in the HBeAg+ group were all significantly higher than those in the HBeAg- group (P < 0.05), but there was no significant difference in the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) between the HBeAg+ group and the HBeAg- group (P > 0.05). Conclusion: HBeAg+ can increase the HBV-DNA levels in the PB of patients with HBV/TP co-infection, in turn triggering the body to initiate cellular immunity, increasing the levels of T lymphocyte subsets, and promote the secretion of cytokines. doi: https://doi.org/10.12669/pjms.37.7.4253 How to cite this:Luo W, Xin H, Zhao P, Jiang S. Effects of HBeAg Status on cellular immune function of patients with Hepatitis B virus/Treponema Pallidum Co-infection. Pak J Med Sci. 2021;37(7):---------. doi: https://doi.org/10.12669/pjms.37.7.4253 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Relationships between HBeAg status of patients with chronic hepatitis B and changes in serum TNF-α, viral load and severity of morphological changes in the liver according to non-invasive tests

Aim – to investigate the relationship between HBeAg status of patients with chronic hepatitis B and the content of TNF-α in the serum, the level of viral load and the severity of morphological changes in the liver according to non-invasive tests. Material and methods. 70 patients with CHB were examined. Noninvasive methods were used to determine the severity of morphological changes in the liver. The content of HBV-DNA in the blood was determined by PCR, HBeAg, anti-HBe, TNF-α by ELISA. Statistical processing was performed in Statistica 13 for Windows (StatSoft Inc., No. JPZ804I382130ARCN10-J). Results. HBeAg-negative patients (78.6 %) with anti-HBe (89.1 %) predominate among patients with CHB. Lower frequency of seroconversion in patients with stages F 2–4, compared with patients with stages F 0-1 (85.7 % vs. 100 %, P < 0.05). The highest level of HBV-DNA in the blood was in HBeAg-positive patients, compared with HBeAg-negative with stages F 0–1 (P < 0.05), of whom 83.3 % of patients had HBV-DNA >20000 IU/ml (83.3 % vs. 17.7 %). Viral load in HBeAg-positive patients with activity A 0–1 was the highest (P < 0.05), namely 4 times more often HBV-DNA was >20000 IU/ml, compared with HBeAg-negative (P < 0.05) A 0–1. The content of TNF-α in the serum of patients with CHB was higher than in healthy individuals (P < 0.05). The highest content of TNF-α in the blood in HBeAg-positive patients with F 2–4, compared with HBeAg-negative with F 2–4 (P < 0.05). The severity of liver fibrosis correlated with the level of TNF-α (r = 0.31, P < 0.05). Conclusions. HBeAg-negative (78.6 %) predominate among patients with CHB. In the presence of HBeAg-positive patients F 0–1 viral load is highest (P < 0.05). HBeAg-negative patients are 2.7 times more likely (P < 0.05) to have a viral load of HBV-DNA >20000 IU/ml in the presence of A 2–3 than in A 0–1. The highest content of TNF-α is in the serum of HBeAg-positive patients with F 2–4, compared with HBeAg-negative patients and the corresponding liver fibrosis (P < 0.05).

Significantly decreased islet β cell function and increased fasting plasma glucose in patients with chronic hepatitis B: a cross-sectional study

Background: The contributing factors of abnormal glucose metabolism and the characteristics of the homeostasis model assessment of β cell function (HOMA-β) value in chronic hepatitis B (CHB) patients are unclear and worth studying.Method: This cross-sectional study recruited 110 CHB patients (CHB group) and 110 patients without hepatitis B virus (non-HBV group); the groups were matched according to sex, age, and body mass index. The contributing factors of abnormal glucose metabolism and the characteristics and differences in glucose metabolism parameters between the two groups were analyzed. Results: The abnormal glucose metabolism rate was higher in CHB patients with liver cirrhosis (LC) and patients with hepatitis B envelope antigen (HBeAg) (-) status. In addition, under the same glucose metabolism conditions, the fasting plasma glucose (FPG) levels of the CHB group was higher than that of the non-HBV group, especially in those with LC that had higher FPG levels (all p=0.000), while the HOMA-β values was significantly lower in the CHB group than in the non-HBV group, especially under normal glucose tolerance conditions (all p=0.000). Further analyses revealed that the main contributing factors of abnormal glucose metabolism were HBeAg (-) status and hepatitis B envelope antibody levels, but HBV serological and virological indicators had no direct effect on the HOMA-β value.Conclusion: These findings provide a reference that will allow clinicians to monitor abnormal glucose metabolism in CHB patients, especially those with LC or HBeAg (-) status, focus on the protection of islet β-cell function, and avoid the application of insulin secretagogues in CHB patients with abnormal glucose metabolism.

Significantly Decreased Islet β Cell Function and Increased Fasting Plasma Glucose in Patients With Chronic Hepatitis B: a Cross-sectional Study

Background: The contributing factors of abnormal glucose metabolism and the characteristics of the homeostasis model assessment of β cell function (HOMA-β) value in chronic hepatitis B (CHB) patients are unclear and worth studying.Method: This cross-sectional study recruited 110 CHB patients (CHB group) and 110 patients without hepatitis B virus (non-HBV group); the groups were matched according to sex, age, and body mass index. The contributing factors of abnormal glucose metabolism and the characteristics and differences in glucose metabolism parameters between the two groups were analyzed.Results: The abnormal glucose metabolism rate was higher in CHB patients with liver cirrhosis (LC) and patients with hepatitis B envelope antigen (HBeAg) (-) status. In addition, under the same glucose metabolism conditions, the fasting plasma glucose (FPG) levels of the CHB group was higher than that of the non-HBV group, especially in those with LC that had higher FPG levels (all p=0.000), while the HOMA-β values was significantly lower in the CHB group than in the non-HBV group, especially under normal glucose tolerance conditions (all p=0.000). Further analyses revealed that the main contributing factors of abnormal glucose metabolism were HBeAg (-) status and hepatitis B envelope antibody levels, but HBV serological and virological indicators had no direct effect on the HOMA-β value.Conclusion: These findings provide a reference that will allow clinicians to monitor abnormal glucose metabolism in CHB patients, especially those with LC or HBeAg (-) status, focus on the protection of islet β-cell function, and avoid the application of insulin secretagogues in CHB patients with abnormal glucose metabolism.

Analysis of clinical and virologic features in Hepatitis B e Antigen (HbeAg)-negative and HbeAg-positive Egyptian chronic Hepatitis B patients

Background: HBeAg–negative chronic hepatitis B infection has a divergent clinical course from that of HBeAg-positive infection. Objectives: To analyze the frequency and to compare the different features of HBeAg-negative and HBeAg-positive chron- ic hepatitis B patients. Methods: One hundred and twenty one Egyptian patients with chronic hepatitis B (CHB), underwent laboratory investiga- tions and transient elastography (TE). Comparisons according to HBeAg status were conducted regarding their demograph- ic, liver biochemical and virologic characters. Results: 97 patients (80.2%) were HBeAg-negative while 24 patients (19.8%) were HBeAg-positive. HBeAg-negative pa- tients were significantly older in age than CHBeAg-positive patients (p=0.001). ALT levels in HBeAg-negative patients were significantly lower than those in HBeAg-positive patients (p=0.02), whereas serum albumin was lower in the HBeAg-posi- tive group (p=0.03). The percentage of HBV DNA higher than 20000 IU/mL in HBeAg-negative patients was lower than those in HBeAg-positive patients (p=0.24). Stages of fibrosis by TE showed that 30.9% of HBeAg-negative and 41.7% of HBeAg-positive had a fibrosis score >F2. Four patients (3.3%) were diagnosed with HCC; all of whom were HBeAg-neg- ative. Conclusion: HBeAg-negative patients compared with HBeAg-positive patients had older age, lower ALT and serum HBV- DNA levels, but more incidence of HCC. Keywords: Hepatitis B; HBeAg; fibrosis; Egypt.