Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study

Background Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA. Methods In this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks. Results At week 48, 3/74 participants (4%) achieved 0.25 log10 reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was −0.14 log10 IU/mL and 12% (9/74) achieved 0.25 log10 reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]). Conclusions In conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF. ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1

Quantitative HBsAg versus HBV DNA in Predicting Significant Hepatitis Activity of HBeAg-Positive Chronic HBV Infection

(1) Background: As specialparameters in predicting significant hepatitis activity of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection, the quantitative standard of HBV DNA has not been agreed and that of hepatitis B surface antigen(HBsAg) has not been formed. Our objective is to evaluate the validity of HBsAg and HBV DNA in predicting the significant hepatitis activity of HBeAg-positive patients. (2) Methods: A population of 516 patients with HBeAg-positive chronic HBV infection was enrolled. Serum ALT was measured using an Abbott Architect c16000 autoanalyzer; diagnoses of liver pathological grade and stage referred to the Scheuer standard. Three levels of significant hepatitis activity were preset, which were successively “ALT ≥ 20 IU/L or Grade > G1 or Stage > S1”, “ALT ≥ 30 IU/L or Grade > G1 or Stage > S1” and “ALT ≥ 40 IU/L or Grade > G1 or Stage > S1”. (3) Results: A subpopulation of 288 patients with possible high HBV replication was selected based on locally weighted scatterplot smoothing regression curves between ALT and HBsAg, HBeAg and HBV DNA. In the subpopulation with possible high HBV replication, areas under receiver operating characteristic curves of HBsAg for predicting the three levels of significant hepatitis activity were successively 0.868, 0.839 and 0.789, which were all significantly greater than those of HBV DNA, as those were successively 0.553, 0.550 and 0.574 (p = 0.0002, p < 0.0001 and p < 0.0001). With the standard of HBsAg ≤ 4.699 log10 IU/mL, the sensitivity and specificity of HBsAg for predicting the three levels of significant hepatitis activity were successively 75.81% and 81.82%, 79.23% and 78.57% and 80.82% and 67.44%. (4) Conclusion: Quantitative HBsAg instead of HBV DNA is valuable in predicting significant hepatitis activity of HBeAg-positive chronic HBV infection.

A baseline model including quantitative anti-HBc to predict response of peginterferon in HBeAg-positive chronic hepatitis B patients

Background Few models to predict antiviral response of peginterferon were used in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and the prediction efficacy was unsatisfied. Quantitative antibody to hepatitis B core antigen (anti-HBc) is a new predictor of treatment response. We aimed to develop a new model to identify HBeAg-positive Chinese patients who were more likely to respond to peginterferon. Methods Data from 140 peginterferon recipients with HBeAg-positive were applied with generalized additive models and multiple logistic regression analysis to develop a baseline scoring system to predict serological response (SR: HBeAg loss and HBeAg seroconversion 24 weeks post-treatment) and combined response (CR: SR plus serum HBV DNA levels <2000 IU/mL 24 weeks post-treatment). Results Anti-HBc levels, alanine aminotransferase ratio, and HBeAg were retained in the final model. The new model scored from 0 to 3. Among patients with scores of 0, 1, or ≥2, SR was achieved in 6.45% (2/31), 13.21% (7/51), and 55.36% (31/56), respectively, and CR in 3.23% (1/31), 9.43% (5/53), and 25.00% (14/56), respectively. Our model has a higher AUROC for SR comparing to Chan’s (Z = 2.77 > 1.96, p < 0.05) and Lampertico’s (Z = 2.06 > 1.96, p < 0.05) model. The negative predictive value for SR and CR were both 100% in patients with score 0 and hepatitis B surface antigen ≥20,000 IU/mL at week 12. Conclusions Patients with higher scores at baseline were more likely to respond to peginterferon. This new model may predict the treatment response.

Assessment of liver fibrosis in children with chronic HBV infection by non!invasive methods

Purpose — to assess liver fibrosis in children with chronic HBV infection with nonEinvasive methods: instrumental (shear wave elastography) and serological (APRI score). Materials and methods. 70 children with HCV aged 2–17 years were examined. The stage of liver fibrosis was determined by the APRI index and the method of shear wave elastography. Results. The majority (82.8%; n=58) of children were diagnosed with HBeAgEpositive HBV infection: HBeAg-positive chronic hepatitis occurred in 54.3% (n=38) of children, HBeAg-positive chronic infection in 28.6% (n=20). 15.7% (n=11) of children had HBeAg-negative chronic infection, and only one (1.4%) patient had HBeAg-negative chronic hepatitis. According to the results of shear wave elastography, in 64.3% (n=45) the stage of liver fibrosis F0-1 was diagnosed; in 35.7% (n=25) — stage of fibrosis >F2. According to APRI score, 63.0% (n=44) had liver fibrosis F0-1, and liver fibrosis stage >F2 was diagnosed in 37.2% (n=26). According to liver elastography, 42.0% of patients with HBeAg-positive chronic hepatitis were diagnosed with liver fibrosis stage >F2. According to APRI score, almost 66% (n=46) of children with HBeAg-positive chronic hepatitis had progressive liver fibrosis >F2. According to the correlation analysis results, a direct correlation was found between liver enzymes levels and APRI score — ALT (τ=0.67; p<0.05), AST (τ=0.72; p<0.05) and GGT (τ=0.26; p<0.05). Conclusions. Most children with chronic HBV infection had stage F0-1 liver fibrosis according to both elastography and APRI score (64% and 63%, respectively). Elastography fibrosis stage >F2 was diagnosed in 42% of HBeAg-positive chronic hepatitis, while APRI index fibrosis stage >F2 was diagnosed in 66% of patients with HBeAg-positive chronic hepatitis. Thus, the results of the liver fibrosis evaluation according to the liver elastography and APRI score in children with chronic HBV infection are similar and can be used in clinical practice to select patients who require antiviral therapy. The APRI score depends on the activity of hepatitis and its use in children with HBeAg-positive chronic hepatitis has certain limitations. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, chronic HBV infection, fibrosis, shear wave elastography, APRI.

Biological Profile of Chronic Hepatitis B and its Predictive Factors According to Liver Histological Activity at the Renaissance Hospital, N’Djamena, Chad

Background: No study in black Africa has investigated the profile of chronic hepatitis B according to the new European association for the study of the liver (EASL) classification. The aim of the study was to determine the biological profile of chronic HBsAg carriers according to the EASL classification of chronic hepatitis B. Method: This is a prospective cross-sectional study carried out in the gastroenterology outpatient department at the Renaissance Hospital in N’Djamena from January, 2018 to July, 2019. All patients with chronic HBsAg were included and documented for at least one year. Patients with hepatitis C, hepatitis D or HIV or alcoholic were excluded. The biological profile was determined according the EASL classification: HBeAg-positive chronic infection, HBeAg-positive chronic hepatitis, HBeAg-negative chronic infection, HBeAg-negative chronic hepatitis and HBsAg-negative phase. Factors associated with presence of significant liver fibrosis were founded by logistical regression. Results: 106 patients were included. The average age were 42.4 years old. The sex ratio was 1.43. The median of the transaminase were 24 IU/ml (AST) and 21 IU/ml (ALT). 61 patients had HBeAg-negative chronic infection (59.8%) and 37 patients had HBeAg-negative chronic hepatitis (36.2%). HBeAg-positive chronic infection and HBeAg-positive chronic hepatitis were both seen in 2% of the cases. Significant liver fibrosis was independently associated with the ALT levels (Odds ratio=1.038 [1.009-1.068]; p=0.009). Conclusion: Chronic HBeAg-negative B infection is the main form in chronic HBsAg-positive carriers. Transaminases are a predictive factor for the presence of hepatic fibrosis.