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).

Loss of HBsAg in Patients with High Levels of HBV-DNA During Treatment with Nucleoside or Nucleotide Analogs

Background: HBsAg is synthesized in the endoplasmic reticulum and is necessary for the formation of complete HBV particles. A decreased synthesis of this antigen leads to an intracellular inhibition of virus production. Methods: The study aimed to assess the incidence of HBsAg elimination among 1,290 patients who suffered from chronic HBV infection undergoing an antiviral treatment with nucleoside or nucleotide analogs (NAs). Furthermore, possible predictive factors for this elimination were analyzed. Results: A permanent HBsAg loss was confirmed in 3% of the patients, which was more frequent in men than in women (4.4% vs. 1.9%; P = 0.009). The HBsAg elimination occurred in 5% of HBeAg (+) patients and 2.8% of HBeAg (-) patients. The age of patients whose HBsAg was eliminated was higher than the age of the remaining patients (60 vs. 51 y/o). The effect of initially used pegylated interferon alfa (PEG-IFN) therapy on the HBsAg elimination was not observed. It occurred with the use of entecavir (ETV) and tenofovir (TDF); however, among patients treated with ETV, HBsAg was significantly more often eliminated in HBeAg (+) patients. Conclusions: The HBsAg elimination in patients undergoing antiviral treatment occurs more often in men, patients with positive HBeAg before treatment, individuals above 60 years, and patients treated with ETV.

Peginterferon and Entecavir combination therapy improves outcome of non-early response Hepatitis B e antigen-positive patients

Background It is still controversial that the efficacy of nucleot(s)ide analogs (NAs) and pegylated interferon (PegIFN) combination therapy for hepatitis B e antigen positive (HBeAg +) patients. It was assessed whether PegIFN and entecavir (ETV) combination therapy could bring more benefit for HBeAg + patients. Methods The treatment naïve HBeAg + patients initiated with PegIFN alfa-2a (PegIFNα-2a) for 24 weeks without early response (early response: HBsAg &lt; 1500 IU/mL and HBV DNA &lt; 10 5 copies/mL) were recruited in the current study. Among total of 94 patients, 51 were continued with PegIFNα-2a monotherapy, 43 were offered PegIFNα-2a and ETV combined therapy. Results It was demonstrated that better outcomes in response to the combined therapy compared to that of the monotherapy, including more HBsAg decline and loss, HBV DNA decline and HBeAg clearance. Importantly, the patients with HBsAg levels between 1500 - 20,000 IU/mL initially or between 5000 - 20000 IU/mL after 24 weeks of PegIFNα-2a were more benefit from the combined therapy, compared to that of monotherapy. Conclusions The combined therapy of PegIFNα-2a and ETV is more efficacy for HBeAg + patients without early response to PegIFN monotherapy, and the HBsAg levels are a good predictor of the treatment outcomes.

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.

Circulating MicroRNAs in Plasma of Hepatitis B e Antigen Positive Children Reveal Liver-Specific Target Genes

Background and Aim. Hepatitis B e antigen positive (HBeAg-positive) children are at high risk of severe complications such as hepatocellular carcinoma and cirrhosis. Liver damage is caused by the host immune response to infected hepatocytes, and we hypothesise that specific microRNAs play a role in this complex interaction between virus and host. The study aimed to identify microRNAs with aberrant plasma expressions in HBeAg-positive children and with liver-specific target genes.Methods. By revisiting our previous screen of microRNA plasma levels in HBeAg-positive and HBeAg-negative children with chronic hepatitis B (CHB) and in healthy controls, candidate microRNAs with aberrant plasma expressions in HBeAg-positive children were identified. MicroRNAs targeting liver-specific genes were selected based on bioinformatics analysis and validated by qRT-PCR using plasma samples from 34 HBeAg-positive, 26 HBeAg-negative, and 60 healthy control children.Results. Thirteen microRNAs showed aberrant plasma expressions in HBeAg-positive children and targeted liver-specific genes. In particular, three microRNAs were upregulated and one was downregulated in HBeAg-positive children compared to HBeAg-negative and healthy control children, which showed equal levels.Conclusion. The identified microRNAs might impact the progression of CHB in children. Functional studies are warranted, however, to elucidate the microRNAs’ role in the immunopathogenesis of childhood CHB.