Subclasses of antibodies to hepatitis B core antigen in chronic HBV infection: Changes during treatment with interferons and predictors of response

Abstract Background GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator (class I) that can inhibit HBV replication by interfering with the assembly and disassembly of HBV nucleocapsid. Here, we evaluated its antiviral activity, pharmacokinetics (PK), and tolerability in a double-blind, randomized, parallel, entecavir-controlled study. Methods Twenty four chronic HBV patients were randomized to receive a 28-day course of GLS4 (120 or 240 mg) and ritonavir (100 mg) combination (cohorts A and B, respectively) or entecavir treatment (cohort C) at a 1:1:1 ratio. Patients were followed-up for 40 days in a phase 1b study. Results The GLS4/ritonavir combination was a tolerated combination for the treatment of chronic HBV infection. A total of two, three, and three subjects presented with alanine aminotransferase flare in cohorts A, B and C, respectively. This contributed to the withdrawal of one, two, and one patient from cohorts A, B and C, respectively. The mean Ctrough of GLS4 was 205–218 ng/mL, which was approximately 3.7–3.9 times the EC90 (55.8 ng/mL), with a lower accumulation (accumulation rate: 1.1–2.0). In cohorts A, B and C, the mean declines in HBV DNA after 28 days of treatment were -1.42, -2.13, and -3.5 log10 IU/mL; in hepatitis B surface antigen were -0.06, -0.14, and -0.33 log10 IU/mL; in pregenomic RNA were -0.75, -1.78, and -0.96 log10 copies/mL; and in hepatitis B core antigen (were -0.23, -0.5, and -0.44 log10 U/mL, respectively. Conclusions Treatment with 120 mg GLS4 was tolerated and had antiviral activity in patients with chronic HBV infection.

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Immune modulator and antiviral potential of dendritic cells pulsed with both hepatitis B surface antigen and core antigen for treating chronic HBV infection

Antiviral Therapy ◽

10.3851/imp1637 ◽

2010 ◽

Vol 15 (6) ◽

pp. 887-895 ◽

Cited By ~ 19

Author(s):

Sheikh Mohammad Fazle Akbar ◽

Osamu Yoshida ◽

Shiyi Chen ◽

Aguilar Julio Cesar ◽

Masanori Abe ◽

...

Keyword(s):

Dendritic Cells ◽

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbv Infection ◽

Core Antigen ◽

Chronic Hbv Infection ◽

Immune Modulator ◽

Chronic Hbv

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Clinical-laboratory diagnostics of HBsAg-negative form of chronic HBV infection

Practical medicine ◽

10.32000/2072-1757-2020-6-138-142 ◽

2020 ◽

Vol 18 (6) ◽

pp. 138-142

Author(s):

V. Kh. FAZYLOV ◽

◽

Zh. G. EREMEEVA ◽

E. R. MANAPOVA ◽

◽

...

Keyword(s):

Hepatitis B ◽

Clinical Laboratory ◽

Subsequent Development ◽

Hbv Infection ◽

Core Antigen ◽

Laboratory Diagnostics ◽

Chronic Hbv Infection ◽

Occult Hepatitis ◽

Chronic Hbv ◽

Negative Form

The purpose of the work is to determine the clinical and laboratory criteria for the activity of the infectious process in HBsAg-negative chronic HBV infection. Material and methods. An in-depth clinical and laboratory examination of 59 patients with the HBsAg-negative form of chronic HBV infection was carried out. According to the preliminary results of an enzyme immunoassay of blood serum, the patients had the only marker of the disease — total antibodies to the core antigen of the hepatitis B virus (anti-HBcor) in the absence of HBsAg. Traditional methods of biological statistics were used with Student’s reliability not less that 95%. Results. Comparative characteristics of the two groups based on the results of DNA detection in the polymerase chain reaction (DNA HBV+; n = 30 and DNA HBV–; n = 29) established comparability in terms of the minimum clinical picture, mainly due to concomitant pathology of the gastrointestinal tract in 40, 31% of cases, respectively; serological spectrum with the detection of total anti-HBcor in 100% of cases in the absence of HBsAg, a marker of inflammation and increased permeability of the hepatitis membrane — the activity of the enzyme alanine aminotransferase at a normal level in 65% of cases, and the absence of liver fibrosis in 89% of cases. Сonclusion. Thus, the relevance of studying HBsAg-negative (hidden, latent, occult) hepatitis B is of particular importance for the science and practice of healthcare today, as a source of infection with a risk of reactivation and subsequent development of the process with an outcome in liver cirrhosis and hepatocellular carcinoma.

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Cango Lyec (Healing the Elephant): Chronic Hepatitis B Virus among post-conflict affected populations living in mid-Northern Uganda

PLoS ONE ◽

10.1371/journal.pone.0251573 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251573

Author(s):

Samuel S. Malamba ◽

Herbert Muyinda ◽

D. Martin Ogwang ◽

Achilles Katamba ◽

David S. Zamar ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Surface Antigen ◽

Hbv Infection ◽

Core Antigen ◽

Northern Uganda ◽

Chronic Hbv Infection ◽

Post Conflict ◽

B Virus ◽

Chronic Hbv

Background The legacy of war in Northern Uganda continues to impact people’s health and wellbeing in the Acholi region. Despite increasing attention to Hepatitis B Virus (HBV) in Uganda and globally, concerns remain that unique drivers of infection, and barriers to screening, and treatment, persist among those affected by conflict. Methods Cango Lyec (Healing the Elephant) cohort survey involved conflict-affected adults aged 13–49 in three mid-Northern Uganda districts (Gulu, Amuru and Nwoya). Baseline (2011–2012) samples were tested for HBV surface antigen (HBsAg), HBV e-antigen (HBeAg), antibodies to HBV surface antigen (HBsAb), antibodies to HBV e-antigen (HBeAb), and antibodies to HBV core antigen (HBcAb). All HBsAg positive samples were tested for IgM antibodies to HBV B core antigen (HBc-IgM) and where available, >6-month follow-up samples were tested for HBeAg and HBV DNA. Data were analyzed using STATA 15 software. Logistic regression accounted for variance due to complex two-stage sampling that included stratification, unequal selection probabilities and community clustering. Odds ratios measured effect potential risk factors associated with chronic HBV infection. Results Among 2,421 participants, 45.7% were still susceptible to HBV infection. HBsAg seropositivity was 11.9% (10.9–13.0), chronic HBV was 11.6% (10.4–12.8), acquired immunity resulting from vaccination was 10.9%, and prior natural infection was 31.5%. Older age (OR:0.570; 95%CI:0.368–0.883) and higher education (OR:0.598; 95%CI:0.412–0.868) were associated with reduced odds of chronic HBV infection. Being male (OR:1.639; 95%CI:1.007–2.669) and having been abducted (OR:1.461; 95%CI:1.055–2.023) were associated with increased odds of infection. Among women, having 1 or 2 pregnancies (compared to none or >2) was associated with increased odds of infection (OR:1.764; 95%CI:1.009–3.084). Conclusion Chronic HBV is endemic in Gulu, Amuru and Nwoya districts. Recommended strategies to reduce post-conflict prevalence include establishment of Northern Uganda Liver Wellness Centres, integration of screening and treatment into antenatal care, and roll out of birth-dose vaccination.

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Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes

Journal of Clinical Medicine ◽

10.3390/jcm10132926 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2926

Author(s):

Sirinart Sirilert ◽

Theera Tongsong

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Pregnancy Outcomes ◽

Natural Course ◽

Hbv Infection ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv ◽

Adverse Pregnancy ◽

The Impact

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).

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