HBeAg Levels Vary across the Different Stages of HBV Infection According to the Extent of Immunological Pressure and Are Associated with Therapeutic Outcome in the Setting of Immunosuppression-Driven HBV Reactivation

HBeAg is a marker of HBV-activity, and HBeAg-loss predicts a favorable clinical outcome. Here, we characterize HBeAg-levels across different phases of HBV infection, their correlation with virological/biochemical markers and the virological response to anti-HBV therapy. Quantitative HBeAg (qHBeAg, DiaSorin) is assessed in 101 HBeAg+ patients: 20 with acute-infection, 20 with chronic infection, 32 with chronic hepatitis and 29 with immunosuppression-driven HBV-reactivation (HBV-R). A total of 15/29 patients with HBV-R are monitored for >12 months after starting TDF/ETV. qHBeAg is higher in immunosuppression-driven HBV-R (median[IQR]:930[206–1945]PEIU/mL) and declines in chronic hepatitis (481[28–1393]PEIU/mL, p = 0.03), suggesting HBeAg production, modulated by the extent of immunological pressure. This is reinforced by the negative correlation between qHBeAg and ALT in acute infection (Rho = −0.66, p = 0.006) and chronic hepatitis (Rho = −0.35; p = 0.05). Interestingly, qHBeAg strongly and positively correlates with qHBsAg across the study groups, suggesting cccDNA as a major source of both proteins in the setting of HBeAg positivity (with limited contribution of integrated HBV-DNA to HBsAg production). Focusing on 15 patients with HBV-R starting TDF/ETV, virological suppression and HBeAg-loss are achieved in 60% and 53.3%. Notably, the combination of qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL at HBV-R is the only factor predicting no HBeAg loss (HBeAg loss: 0% with vs. 72.7% without qHBeAg > 2000 PEIU/mL + qHBsAg > 52,000 IU/mL, p = 0.03). In conclusion, qHBeAg varies over the natural course of HBV infection, according to the extent of immunological pressure. In the setting of HBV-R, qHBeAg could be useful in predicting the treatment response under immunosuppression.

Pradefovir Treatment in Patients with Chronic Hepatitis B: Week 24 Results from a Multicenter, Double-blind, Randomized, Noninferiority, Phase 2 Trial

Objectives Pradefovir is a liver-targeted prodrug of adefovir, a nucleotide analog with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30mg, 45mg, 60mg, and 75mg) versus tenofovir disoproxil fumarate (TDF; 300mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. Methods Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. Results A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were HBeAg positive and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/ml with pradefovir doses of 30mg, 45mg, 60mg, and 75mg, respectively, compared to 5.12 log10 IU/ml with TDF. However, HBeAg loss was attained by more participants who received 45mg, 60mg or 75mg pradefovir than those receiving TDF (12%, 6%, 9% vs. 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30mg or 45mg groups, and serum phosphate levels were comparable among all groups. Most adverse events were mild (grade 1). No treatment-related severe adverse events were reported. Overall, adverse events and laboratory abnormalities were comparable to the TDF group. Conclusions Pradefovir exhibited comparable reductions in HBV DNA levels to TDF. All treatments were safe and well tolerated.

Efficacy of 24-week Administration of Tenofovir Disoproxil Fumarate in the Management of Naïve Chronic Hepatitis B

BACKGROUND: Chronic hepatitis B (CHB) is becoming a common liver abnormality worldwide. Thus, a series of good management is needed to prevent the progression and complications of hepatitis B infection. Tenofovir disoproxil fumarate (TDF) is one of the drugs of choice that’s used for CHB management. AIM: Limited studies were found regarding the efficacy of tenofovir in dealing with CHB. Hence, the aim of this study is to determine the efficacy of TDF administration for 24 weeks in subjects with naïve CHB in Medan, Indonesia. METHODS: Retrospective study was conducted in Haji Adam Malik Hospital Medan, Indonesia, between January and December 2019. Subjects were CHB patients aged 18 years or older and were treated TDF for 24 weeks. Demographic, clinical, and CHB disease progression parameters (serum alanine aminotransferase [ALT], hepatitis B envelope antigen [HBeAg], and hepatitis B virus deoxyribonucleic acid [HBV DNA]) data were obtained. RESULTS: One hundred and twenty subjects were obtained and divided into 2 groups: HBeAg positive and HBeAg negative. Mean age of subjects was 46.5 ± 10.36 years in HBeAg positive group and 48.6 ± 10.67 years HBeAg negative group, with predominant males’ subjects in both groups (58.3% vs. 61.7%, respectively). Serum ALT normalization and undetectable serum HBV DNA were observed in more than 70% and 65% of subjects in both groups, respectively (both p < 0.001). Serum HBeAg loss was achieved in 10.8% subjects (p < 0.001). No subject showed serum HbsAg loss. CONCLUSION: Our results are consonant with current clinical guidelines and other evidence literature. For both HBeAg-positive and HBeAg-negative populations, TDF administration for 24 weeks has good efficacy in naïve CHB patients.

Long-term nucleoside analogue therapy can lead effective HBV DNA inhibition in patients with chronic HBV infection in immune tolerate phase

Background and Aims The efficacy and safety of long-term antiviral therapy with nucleoside analogues (NAs) for chronic hepatitis B (CHB) patients in immune tolerate (IT) phase is uncertain.We retrospectively evaluated the efficacy and safety of 61 CHB patients in IT phase receiving NAs therapy from 2013 through 2018. Methods We performed a retrospective study of CHB patients who had high HBV DNA, normal or minimum alanine aminotransferase (ALT), liver biopsy confirmed light necro-inflammation and received NAs therapy from 2012 through 2018.All patients received NAs at least 12 months. Patients on-treatment monitoring were in accordance with the roadmap concept and were followed after their treatment start date to the treatment end date (if any) or 6 years at least once every 6 months. The median follow-up time was 36(16; 52) months. We assessed the virological response (the proportions of patients with plasma HBV DNA loads less than the limit of quantification,100IU/ml) and serological endpoints (HBeAg loss and seroconcersion to anti-HBe, and HBsAg loss and seroconversion to anti-HBs). Safety and tolerability, including serious events, were regularly assessed. Results At 48 weeks on treatment, 55.6%(95%confidence interval(CI):37.0-70.0%) patients with CHB in IT phase achieved HBV DNA less than quantitative limit(<100IU/ml), and the accumulate proportion of patients who achieved HBV DNA less than quantitative limit was 76.7%(95%CI: 58-90.0%) and 95.8%(95%CI: 79-100%) at 96 weeks and ≥144weeks on treatment, respectively. The HBeAg loss or seroconversion rate in patients with CHB in IT phase on NAs treatment at 48, 96 and ≥144weeks was 2.7%(95%CI: 0-14.0%), 13.3% (95%CI: 4-31.0%) and 29.2%(95%CI: 13-51%), respectively. During the study only one patient achieved HBsAg seroconversion after 3years NAs therapy and only one patient experienced drug-related breakthrough during the study. Conclusion Patients with CHB in IT phase have relatively preferable safety and HBV DNA inhibition efficacy on long-term NAs treatment.