Hepatitis B Virus (HBV) Disease

HBV disease is a significant cause of acute and chronic liver disease worldwide. Mother-to-infant transmission is the main mode of transmission to susceptible subjects, which can be prevented with HBV vaccine alone or in combination with hepatitis B immunoglobulin. This intervention markedly reduces the number of new HBsAg carriers. For subjects not responding to current HBV vaccines as reflected by an inadequate anti-HBs titer, future generation vaccines incorporating additional vaccine components such as preS1 and preS2 may improve the efficacy of protective antibody production. Apart from preventative vaccines, future therapeutic vaccines along with current anti-HBV treatment strategies might enhance the rate of functional cures as indicated by the loss of HBsAg.

Pegylated Interferon Treatment for the Effective Clearance of Hepatitis B Surface Antigen in Inactive HBsAg Carriers: A Meta-Analysis

BackgroundExpanding antiviral therapy to benefit more populations and optimizing treatment to improve prognoses are two main objectives in current guidelines on antiviral therapy. However, the guidelines do not recommend antiviral therapy for inactive hepatitis B surface antigen (HBsAg) carriers (IHCs). Recent studies have shown that antiviral therapy is effective with good treatment outcomes in IHC populations. We conducted a systematic review and meta-analysis of HBsAg clearance and conversion in IHCs.MethodsWe searched PubMed, Embase, Medline, and Web of Science to retrieve articles on HBsAg clearance in IHCs published between January 2000 and August 2021. Data were collected and analysed using the random-effects model for meta-analysis.ResultsA total of 1029 IHCs from 11 studies were included in this analysis. The overall HBsAg clearance rate was 47% (95% confidence interval (CI): 31% - 64%), with a conversion rate of 26% (95% CI: 15% - 38%) after 48 weeks of Pegylated interferon (Peg-IFN) treatment. In the control group (including nucleos(t)ide analogue (NA) treatment or no treatment), the overall HBsAg clearance rate was only 1.54% (95% CI: 0.56% - 3.00%), which was markedly lower than that in the Peg-IFN group. Further analysis showed that a low baseline HBsAg level and long treatment duration contributed to a higher HBsAg clearance rate.ConclusionThis study showed that treatment of IHCs can be considered to achieve a clinical cure for chronic hepatitis B virus (HBV) infection. After Peg-IFN treatment, the HBsAg clearance rate was 47%, and the conversion rate was 26%, which are markedly higher than those reported by previous studies on Peg-IFN treatment in patients with chronic hepatitis B (CHB). A low baseline HBsAg level and long treatment duration were associated with HBsAg clearance in IHCs. Therefore, antiviral therapy is applicable for IHCs, a population who may be clinically cured.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, CRD): CRD42021259889.

Noninvasive Evaluation of Liver Fibrosis in a Sample of Putative Inactive HBV Carriers in Rome, Italy

Background. Noninvasive methods are useful for investigating patients with chronic HBV infection. The severity of liver disease in inactive HBsAg carriers can be noninvasively assessed by transient elastography (TE) alone or in association with biochemical markers of fibrosis. Objectives. The study evaluates the effectiveness of the TE compared to common fibrosis scores (FSs), APRI, Forns Index, and FIB4, for identifying significant fibrosis in Italian and foreigner HBsAg carriers. To investigate the risk of progression of the liver disease, liver stiffness (LS) and HBV-DNA were monitored over time. Methods. Viral load, biochemical parameters, and LS have been retrospectively evaluated in 125 putative inactive HBV carriers, who visited two outpatient departments (Colleferro Hospital and INMP) from 01/03/2014 to 31/12/2019. Differences in clinical, biochemical, and demographic variables between Italians and foreigners were analyzed. 66 of 125 patients were followed up for 24 months by monitoring liver stiffness and HBV-DNA. Results. Mean overall LS was 5.55 ± 1.92 kPa; 18 (14.4%) patients had a LS ≥7.5 kPa. Mean of APRI, Forns, and FIB4 was 0.29 ± 0.11, 4.15 ± 1.63, and 1.16 ± 0.59, respectively. FS did not differ between the patients with LS <7.5 kPa and those with LS ≥7.5 kPa. Italians displayed a significant lower ALT (0.53 ± 0.18 vs. 0.67 ± 0.33, p < 0.05 ) and AST (0.59 ± 0.16 vs. 0.70 ± 0.21, p < 0.01 ) value than foreigners. No differences in LS and HBV-DNA levels were observed. In 66 patients followed up for 24 months, HBV-DNA increased by ≥2000 UI/ml after 12 months in 15 individuals and remained ≥2000 UI/ml after 24 months in 10/15 individuals. 7/10 patients showed LS ≥ 7.5 kPa after 24 months, and 4 of them underwent antiviral therapy for HBV. Patients with HBV-DNA <2000 IU/ml had a significantly lower LS than those with HBV-DNA ≥2000 IU/ml (5.30 ± 1.43 vs. 7.69 ± 1.07, p < 0.0001 ). Conclusions. Analysis shows lower effectiveness of FS vs. TE in the assessment of putative inactive HBV carriers. Furthermore, using FibroScan® and HBV-DNA can identify “false” inactive carriers.

Changing epidemiology and viral interplay of hepatitis B, C and D among injecting drug user-dominant prisoners in Taiwan

The spreading of viral hepatitis among injecting drug users (IDU) is an emerging public health concern. This study explored the prevalence and the risks of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) among IDU-dominant prisoners in Taiwan. HBV surface antigen (HBsAg), antibodies to HCV (anti-HCV) and HDV (anti-HDV), viral load and HCV genotypes were measured in 1137(67.0%) of 1697 prisoners. 89.2% of participants were IDUs and none had HIV infection. The prevalence of HBsAg, anti-HCV, dual HBsAg/anti-HCV, HBsAg/anti-HDV, and triple HBsAg/anti-HCV/anti-HDV was 13.6%, 34.8%, 4.9%, 3.4%, and 2.8%, respectively. HBV viremia rate was significantly lower in HBV/HCV-coinfected than HBV mono-infected subjects (66.1% versus 89.9%, adjusted odds ratio/95% confidence intervals [aOR/CI] = 0.27/0.10–0.73). 47.5% anti-HCV-seropositive subjects (n = 396) were non-viremic, including 23.2% subjects were antivirals-induced. The predominant HCV genotypes were genotype 6(40.9%), 1a(24.0%) and 3(11.1%). HBsAg seropositivity was negatively correlated with HCV viremia among the treatment naïve HCV subjects (44.7% versus 72.4%, aOR/CI = 0.27/0.13–0.58). Anti-HCV seropositivity significantly increased the risk of anti-HDV-seropositivity among HBsAg carriers (57.1% versus 7.1%, aOR/CI = 15.73/6.04–40.96). In conclusion, IUDs remain as reservoirs for multiple hepatitis viruses infection among HIV-uninfected prisoners in Taiwan. HCV infection increased the risk of HDV infection but suppressed HBV replication in HBsAg carriers. An effective strategy is mandatory to control the epidemic in this high-risk group.

Hepatitis D Seroprevalence in people with chronic hepatitis B in Lubumbashi (DRC)

Hepatitis B and D viruses are responsible for about 2 million deaths annually worldwide. In co-infection with hepatitis B (HBV) and D (VHD) viruses, the prognosis for hepatitis B is exacerbated by HDV. This study aimed at estimating the seroprevalence of hepatitis D among blood donors at Cliniques Universitaires and Hôpital Jason Sendwe in Lubumbashi. Screening for HBsAg was performed using rapid diagnostic tests and then confirmed by the Liaison XL test which was also used for screening for anti-HDV antibodies. Of 200 blood donors who tested positive for HBsAg, only four (2%) tested positive for anti-HDV antibodies. This study has the merit of highlighting, for the first time, HBV-HDV co-infection in Lubumbashi. Hepatitis D should be screened for in all HBsAg carriers with severe or chronic hepatitis in order to allow early management of these patients and thus avoid aggravation of liver disease. The limitations of this study are the lack of data on the course of liver disease, the genotype of HBV and HDV, the viral load of HDV and any current treatments. Les virus des hépatites B et D sont responsables d’environ 2 millions de décès annuellement dans le monde. Lors de la coïnfection par les virus de l’hépatite B (VHB) et D (VHD), le pronostic de l’hépatite B est aggravé par le VHD. Cette étude voudrait estimer la séroprévalence de l’hépatite D chez les donneurs de sang des Cliniques Universitaires et Hôpital Jason Sendwe de Lubumbashi. Le dépistage de l’AgHBs a été réalisé au moyen des tests de diagnostic rapide puis confirmé par test de Liaison XL qui a été également utilisé pour le dépistage d’anticorps anti-VHD. Sur 200 donneurs de sang testés positifs pour l’AgHBs, seuls quatre (2%) se sont révélés positifs en anticorps anti-VHD. Cette étude a le mérite d’avoir mis en évidence, pour la première fois, la co-infection VHB-VHD à Lubumbashi. L’hépatite D devrait être recherchée chez tous porteurs d’AgHBs présentant une hépatite sévère ou chronique afin de permettre une prise en charge précoce de ces patients et éviter ainsi l’aggravation de la maladie hépatique. Le manque des données sur l’évolution de la maladie hépatique, le génotype de VHB et VHD, la charge virale de VHD et les traitements éventuels en cours constituent les limites de cette étude.

Infection with Hepatitis B Virus May Increase the Serum Concentrations of Osteopontin

Background: Serum osteopontin (OPN) concentrations were found to be significantly increased in patients infected with hepatitis B virus (HBV) and patients with hepatocellular carcinoma (HCC). Objective: The aim of this study was to determine the association among HCC, OPN, and HBV. Methods: Two hundred and forty-one subjects were recruited and divided into 6 groups: healthy controls, asymptomatic HBsAg carriers, HBsAg (−) patients with other tumors, HBsAg (+) chronic liver disease patients, HBsAg (+) patients with HCC, and HBsAg (−) patients with HCC or liver cirrhosis (LC). Serum concentrations of OPN and HBsAg were measured and analyzed. Results: OPN concentrations in the HBsAg (+) HCC group were significantly higher than the healthy control group and the HBsAg (−) patients with other cancers (both p = 0.0001). The OPN concentrations of the HBsAg (−) patients with HCC or LC also did not differ significantly from those of the healthy control group (p = 0.075). There is a correlation between the titer of HBsAg and concentrations of OPN in all 3 HBsAg (+) groups (all p values <0.05). Conclusions: Infection with HBV may increase the serum concentrations of OPN. The association of OPN and HCC may be not attributable to tumor development per se but, rather, to HBV infection.

Correction to: Maternal HBsAg carriers and pregnancy outcomes: a retrospective cohort analysis of 85,190 pregnancies

An amendment to this paper has been published and can be accessed via the original article.

A Male-ABCD Algorithm for Hepatocellular Carcinoma Risk Prediction in HBsAg Carriers

BACKGROUND: Hepatocellular carcinoma (HCC) development among hepatitis B surface antigen (HBsAg) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBsAg-positive male adults.METHODS: HBsAg-positive, 35-69 years males (N=6 153) were recruited from a multi-center population-based liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using B-ultrasonography and α-fetoprotein (AFP). We used logistic regression models to determine potential risk factors, built and examined the operating characteristics of a point-based algorithm for HCC risk prediction.RESULTS: With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant’s Age, Blood levels of GGT (γ-glutamyl-transpeptidase), Counts of platelets, white cells, Concentration of DCP (des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91(0.89-0.93), larger than existing models. At 1.5 points of risk-score, 26.10% of the participants in training, 14.94% in validation were recognized at-low-risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training, 33.68% in validation were recognized at-low-risk with 99.06% and 97.78% of sensitivity. At 4.5 points, only 20.86% of training, 23.73% of validation were recognized at-high-risk, with positive prediction value of 22.85% and 12.35% respectively.DISCUSSION: Male-ABCD algorithm identified individual’s risk for HCC occurrence within short-term for their HCC precision surveillance.

B cells were related to HBsAg seroconversion in inactive HBsAg carriers following peginterferon therapy

Our recent study showed high rate of HBsAg seroconversion achieved in inactive HBsAg carriers (IHCs) treated with peginterferon (PEG-IFN). To better understand the immune-mediated component to the HBsAg seroconversion, we investigated the role of B cells in this study. A total of 44 IHCs were given 48 weeks of PEG-IFN. Fifteen cases achieve HBsAg seroconversion (R group), whereas 29 failed (NR group). The proportion of total B cells and plasma B cells were measured before and during treatment. We found that the proportion of total B cells and plasma B cells was no significant between R group and NR group at baseline, but significantly higher in R group than NR group during PEG-IFN treatment, even when the exact age-, sex-, and treatment period-match was made. In conclusion, we demonstrated the increase of total B cell and plasma B cells during PEG-IFN treatment favored HBsAg seroconversion for IHC, and B cells may play a role in HBV seroconversion.