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Viruses May 2023Patients with chronic hepatitis B (CHB) gradually develop T cell exhaustion, and the inhibitory receptor molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4), may play a... (Review)
Review
Patients with chronic hepatitis B (CHB) gradually develop T cell exhaustion, and the inhibitory receptor molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4), may play a role in this phenomenon. This systematic review investigates the role of CTLA-4 in the development of T cell exhaustion in CHB. A systematic literature search was conducted on PubMed and Embase on 31 March 2023 to identify relevant studies. Fifteen studies were included in this review. A majority of the studies investigating CD8 T cells demonstrated increased expression of CTLA-4 in CHB patients, though one study found this only in HBeAg-positive patients. Three out of four studies investigating the expression of CTLA-4 on CD4 T cells found upregulation of CTLA-4. Several studies showed constitutive expression of CLTA-4 on CD4 regulatory T cells. CTLA-4 blockade resulted in heterogeneous responses for all T cell types, as it resulted in increased T cell proliferation and/or cytokine production in some studies, while other studies found this only when combining blockade of CTLA-4 with other inhibitory receptors. Although mounting evidence supports a role of CTLA-4 in T cell exhaustion, there is still insufficient documentation to describe the expression and exact role of CTLA-4 in T cell exhaustion in CHB.
Topics: Humans; CTLA-4 Antigen; Hepatitis B, Chronic; CD8-Positive T-Lymphocytes; T-Cell Exhaustion; T-Lymphocytes, Regulatory; Hepatitis B virus
PubMed: 37243227
DOI: 10.3390/v15051141 -
Asian Journal of Surgery Oct 2023
Meta-Analysis
Topics: Humans; Hepatitis B virus; Hepatitis B; Osteoporosis
PubMed: 37230817
DOI: 10.1016/j.asjsur.2023.05.035 -
BMC Cancer May 2023Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, worldwide. The predominant causative factor for HCC is hepatitis B virus (HBV)... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the unresectable hepatocellular carcinoma and the benefit for hepatitis B virus etiology subgroup: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, worldwide. The predominant causative factor for HCC is hepatitis B virus (HBV) infection. We conducted a meta-analysis to estimate the efficacy and safety of PD-1/PD-L1 inhibitors combined with anti-angiogenic therapy for the first-line treatment of the unresectable HCC and to evaluate the benefits of different geographic regions and etiology stratifications.
METHODS
Randomized clinical trials published up to 12th November 2022 were searched by online databases. Moreover, effects of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were extracted from included studies. Pooled odds ratio (OR) and 95% CI for objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) were calculated.
RESULTS
A total of 3057 patients from five phase III randomized clinical trials were collected and reviewed for this meta-analysis. The pooled HR of OS (HR = 0.71; 95% CI: 0.60-0.85) and PFS (HR = 0.64; 95% CI: 0.53-0.77) demonstrated significantly better benefit in PD-1/PD-L1 inhibitors combination group than targeted monotherapy to treat unresectable HCC. In addition, combination therapy showed better ORR and DCR, with ORs of 3.29 (95% CI: 1.92-5.62) and 1.88 (95% CI: 1.35-2.61), respectively. The subgroup analysis indicated that PD-1/PD-L1 inhibitors combination therapy was significantly superior to anti-angiogenic monotherapy for HBV-related HCC in terms of OS (HR = 0.64; 95% CI: 0.55-0.74) and PFS (HR = 0.53; 95% CI:0.47-0.59), while there was no significant difference in patients with HCV (OS, HR = 0.81, p = 0.1) or non-viral (OS, HR = 0.91, p = 0.37; PFS, HR = 0.77, p = 0.05).
CONCLUSIONS
Meta-analysis revealed for the first-time that PD-1/PD-L1 inhibitors combination therapy for unresectable HCC was associated with better clinical outcomes than anti-angiogenic monotherapy, especially for HBV infection and Asian population.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B; Hepatitis B virus; Immune Checkpoint Inhibitors; Liver Neoplasms; Programmed Cell Death 1 Receptor; Randomized Controlled Trials as Topic
PubMed: 37226111
DOI: 10.1186/s12885-023-10960-w -
The American Journal of Tropical... Jul 2023Hepatitis B virus (HBV) infection is a major public health problem in Sierra Leone, yet reliable estimates of cases are lacking. This study aimed to provide an estimate... (Meta-Analysis)
Meta-Analysis
Hepatitis B virus (HBV) infection is a major public health problem in Sierra Leone, yet reliable estimates of cases are lacking. This study aimed to provide an estimate of the national prevalence of chronic HBV infection in the general population and select groups in Sierra Leone. We used the electronic databases PubMed/MEDLINE, Embase, Scopus, ScienceDirect, Web of Science, Google Scholar, and African Journals Online to systematically review articles reporting hepatitis B infection surface antigen seroprevalence estimates in Sierra Leone during 1997-2022. We estimated pooled HBV seroprevalence rates and assessed potential sources of heterogeneity. Of 546 publications screened, 22 studies with a total sample size of 107,186 people were included in the systematic review and meta-analysis. The pooled prevalence of chronic HBV infection was 13.0% (95% CI, 10.0-16.0) (I2 = 99%; Pheterogeneity < 0.01). During the study period, the HBV prevalence rates were as follows: 17.9% (95% CI, 6.7-39.8) before 2015, 13.3% (95% CI, 10.4-16.9) during 2015-2019, and 10.7% (95% CI, 7.5-14.9) during 2020-2022. The use of the 2020-2022 HBV prevalence estimates corresponded to 870,000 cases of chronic HBV infection (uncertainty interval, 610,000-1,213,000), or approximately one in nine people. The highest HBV seroprevalence estimates were among adolescents aged 10-17 years (17.0%; 95% CI, 8.8-30.5), Ebola survivors (36.8%; 95% CI, 26.2-48.8), people living with HIV (15.9%; 95% CI, 10.6-23.0), and those in the Northern Province (19.0%; 95% CI, 6.4-44.7) and Southern Province (19.7%; 95% CI, 10.9-32.8) regions. These findings may help inform national HBV program implementation in Sierra Leone.
Topics: Adolescent; Humans; Hepatitis B, Chronic; Seroepidemiologic Studies; Prevalence; Sierra Leone; Hepatitis B; Hepatitis B virus; Hepatitis B Surface Antigens
PubMed: 37217165
DOI: 10.4269/ajtmh.22-0711 -
Clinical and Molecular Hepatology Jul 2023Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
METHODS
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
RESULTS
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88-95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27-0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
CONCLUSION
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
Topics: Humans; Carcinoma, Hepatocellular; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Liver Neoplasms; Hepatitis B virus; Antiviral Agents; Liver Cirrhosis; Fatty Liver; DNA, Viral
PubMed: 37157776
DOI: 10.3350/cmh.2023.0004 -
Frontiers in Immunology 2023Inflammation serves as an essential driver of liver cirrhosis (LC) incidence. Accordingly, a meta-analysis was carried out to explore the association between specific... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inflammation serves as an essential driver of liver cirrhosis (LC) incidence. Accordingly, a meta-analysis was carried out to explore the association between specific polymorphisms in the interferon-γ () and tumor necrosis factor-α () genes and the incidence of LC based on comparisons of genotype and allele frequencies.
OBJECTIVES
To study the relationship between rs361525 and rs2430561 polymorphisms and the risk of LC.
METHODS
A database search was performed for all studies published as of September 10, 2022. The strength of risk relationships was assessed based on odds ratios (ORs) with 95% confidence intervals (CIs).
RESULTS
Pooled analyses were conducted for one common polymorphism (rs361525) as well as one common polymorphism (rs2430561). Both of these SNPs were identified as LC-related risk factors. Specifically, rs361525 was related to LC incidence in both alcoholic liver cirrhosis (OR: 1.86, 95%CI: 1.03-3.34) and hepatitis B virus (HBV)-related cirrhosis cases (OR: 1.44, 95%CI: 1.00-2.06) when using an allelic contrast model. Moreover, rs2430561 was significantly related to LC in an Asian population (OR: 1.45, 95%CI: 1.13-1.86) and in the context of HBV-related cirrhosis (OR: 1.48, 95%CI: 1.13-1.93) when using an allelic contrast model.
CONCLUSION
These findings indicate that rs361525 and rs2430561 represent LC-related risk factors, although additional large-scale clinical and case-control studies will be vital to confirm these results.
Topics: Humans; Fibrosis; Genetic Predisposition to Disease; Hepatitis B virus; Interferon-gamma; Liver Cirrhosis; Polymorphism, Single Nucleotide; Tumor Necrosis Factor-alpha
PubMed: 37122734
DOI: 10.3389/fimmu.2023.1129767 -
The Lancet. Global Health May 2023Sub-Saharan Africa is highly endemic for hepatitis B virus (HBV); historically, most people were exposed during childhood through vertical or horizontal transmission.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sub-Saharan Africa is highly endemic for hepatitis B virus (HBV); historically, most people were exposed during childhood through vertical or horizontal transmission. Although all African countries now provide a three-dose infant hepatitis B vaccination starting at age 6-8 weeks, only a third of African countries have introduced birth dose (HepB-BD) vaccine. Adding HepB-BD is fundamental to prevent vertical transmission, but its effectiveness in preventing horizontal transmission, compared with the three-dose infant vaccination alone, is unknown. We aimed to estimate the risk of early horizontal transmission in children of hepatitis B surface antigen (HBsAg)-negative mothers in sub-Saharan Africa stratified according to the vaccination schedule.
METHODS
In this systematic review and meta-analysis we searched MEDLINE, Global Health, Embase, African Index Medicus and African Journals Online from their inception to Oct 24, 2022, for studies reporting HBsAg or HBV DNA, or both, in children (aged 0-5 years) of HBsAg-negative mothers. We excluded studies if children were only tested at birth. Two reviewers independently screened the titles and abstracts of all articles and data were extracted using a standardised pre-piloted data extraction sheet, and authors were contacted if any important information was missing. The primary outcome was the risk of HBV infection in children of HBsAg-negative mothers, stratified by vaccination schedule (no vaccination, first dose at 6-8 weeks, or first dose at birth). We pooled the child risks of HBsAg or HBV DNA-positivity from the age of 0 years to 5 years via a random-effect meta-analysis using a generalised linear mixed model. The study was registered on PROSPERO, CRD42021236203.
FINDINGS
Of 8856 articles identified, 27 studies evaluating 10 003 children of HBsAg-negative mothers were included. The pooled risks of infection were 6·16% (95% CI 3·05-12·04; 155/1407) in the no vaccination group, 0·21% (0·04-1·15; 10/3425) in children who received their first dose at 6-8 weeks, and 0·05% (0·00-1·32; 3/2902) in children who received their first dose at birth. The difference was not statistically significant in children who received their first dose at 6-8 weeks and children who received their first dose at birth after adjusting for the study period, region, and maternal HIV status (test of moderators p=0·37).
INTERPRETATION
In children of HBsAg-negative mothers, the risk of infection might be minimal even with the vaccination starting at 6-8 weeks, without clear additional benefit from HepB-BD. When births take place at home and timely administration of HepB-BD is challenging, antenatal HBsAg screening and selective HepB-BD might allow efficient allocation of resources to mother and child pairs at high risk compared with universal HepB-BD.
FUNDING
None.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Topics: Infant; Infant, Newborn; Child; Female; Humans; Pregnancy; Hepatitis B virus; Mothers; Hepatitis B Surface Antigens; DNA, Viral; Hepatitis B; Hepatitis B Vaccines; Infectious Disease Transmission, Vertical; Africa South of the Sahara
PubMed: 37061310
DOI: 10.1016/S2214-109X(23)00131-6 -
Scientific Reports Apr 2023Hepatitis B virus (HBV) has ten genotypes (A-J) and over 40 sub-genotypes based on the divergence of ≥ 8% and 4 to < 8% in the complete genome respectively.... (Meta-Analysis)
Meta-Analysis
Hepatitis B virus (HBV) has ten genotypes (A-J) and over 40 sub-genotypes based on the divergence of ≥ 8% and 4 to < 8% in the complete genome respectively. These genotypes and sub-genotypes influence the disease prognosis, response to therapy and route of viral transmission. Besides, infection with mixed genotypes and recombinant genotypes has also been reported. This study aimed at mapping the de novo genotypes and correlate them with the immigration trends in order to inform future research on the underlying reasons for the relative distribution of HBV genotypes from a large sample size pooled from many primary studies. Data was extracted from 59 full research articles obtained from Scopus, PubMed, EMBASE, Willy library, African Journal Online (AJOL) and Google Scholar. Studies that investigated the genotypes, sub-genotypes, mixed genotypes and recombinant were included. The Z-test and regression were used for the analysis. The study protocol is registered with PROSPERO under the registration number CRD42022300220. Overall, genotype E had the highest pooled prevalence significantly higher than all the other genotypes (P < 0.001). By region, genotype A posted the highest pooled prevalence in eastern and southern Africa, E in west Africa and D in north Africa (P < 0.0001). Regarding the emerging genotypes B and C on the African continent, genotype B was significantly higher in south Africa than C (P < 0.001). In contrast, genotype C was significantly higher in east Africa than west Africa (P < 0.0001). The A1 and D/E were the most diverse sub-genotypes and genotype mixtures respectively. Finally, we observed a general progressive decrease in the prevalence of predominant genotypes but a progressive increase in the less dominant by region. Historical and recent continental and intercontinental migrations can provide a plausible explanation for the HBV genotype distribution pattern on the African continent.
Topics: Humans; Hepatitis B virus; Africa, Northern; Genotype; Emigration and Immigration; Prognosis; Hepatitis B
PubMed: 37029173
DOI: 10.1038/s41598-023-32865-1 -
The Lancet. Global Health May 2023People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to...
Epidemiology of injecting drug use, prevalence of injecting-related harm, and exposure to behavioural and environmental risks among people who inject drugs: a systematic review.
BACKGROUND
People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to undertake a global systematic review of the prevalence of IDU, key IDU-related harms (including HIV, hepatitis C virus [HCV], and hepatitis B virus [HBV] infection and overdose), and key sociodemographic characteristics and risk exposures for people who inject drugs.
METHODS
We systematically searched for data published between Jan 1, 2017, and March 31, 2022, in databases of peer-reviewed literature (MEDLINE, Embase, and PsycINFO) and grey literature as well as various agency or organisational websites, and disseminated data requests to international experts and agencies. We searched for data on the prevalence, characteristics, and risks of people who inject drugs, including gender, age, sexuality, drug-use patterns, HIV, HCV, and HBV infections, non-fatal overdose, depression, anxiety, and injecting-related disease. Additional data were extracted from studies identified in our previous review. Meta-analyses were used to pool the data where multiple estimates were available for a country. We present country, regional, and global estimates for each variable examined.
FINDINGS
We screened 40 427 reports published between 2017 and 2022, and the 871 eligible reports identified were added to the 1147 documents from the previous review. Evidence of IDU was documented in 190 of 207 countries and territories, and 14·8 million people (95% uncertainty interval [UI] 10·0-21·7) aged 15-64 years globally were estimated to inject drugs. Existing evidence suggests that there might be 2·8 million (95% UI 2·4-3·2) women and 12·1 million (95% UI 11·0-13·3) men who inject drugs globally, and that 0·4% (95% CI 0·3-1·3) of people who inject drugs identify as transgender. The amount of available data on key health and social risks among people who inject drugs varied widely across countries and regions. We estimated that 24·8% (95% CI 19·5-31·6) of people who inject drugs globally had experienced recent homelessness or unstable housing, 58·4% (95% CI 52·0-64·8) had a lifetime history of incarceration, and 14·9% (95% CI 8·1-24·3) had recently engaged in sex work, with substantial geographical variation. Injecting and sexual risk behaviour varied considerably geographically, as did risks of harms. Globally, we estimated that 15·2% (95% CI 10·3-20·9) of people who inject drugs are living with HIV, 38·8% (95% CI 31·4-46·9) have current HCV infection, 18·5% (95% CI 13·9-24·1) have recently overdosed, and 31·7% (95% CI 23·6-40·5) have had a recent skin or soft tissue infection.
INTERPRETATION
IDU is being identified in a growing number of countries and territories that comprise more than 99% of the global population. IDU-related health harms are common, and people who inject drugs continue to be exposed to multiple adverse risk environments. However, quantification of many of these exposure and harms is inadequate and must be improved to allow for better targeting of harm-reduction interventions for these risks.
FUNDING
Australian National Health and Medical Research Council.
Topics: Male; Humans; Female; Substance Abuse, Intravenous; Prevalence; Drug Users; Australia; Hepatitis C; Hepatitis B; Substance-Related Disorders; Hepacivirus; Hepatitis B virus; HIV Infections
PubMed: 36996857
DOI: 10.1016/S2214-109X(23)00057-8 -
The Medical Journal of Malaysia Mar 2023Worldwide, around 296 million people have hepatitis B virus (HBV) infection, most commonly transmitted from mother-to-child. Global Health Sector Strategy on Viral...
Prevention of mother-to-child transmission of hepatitis B virus: An observation of routine practice in a tertiary liver centre before and after the introduction of the global health sector strategy on viral hepatitis.
INTRODUCTION
Worldwide, around 296 million people have hepatitis B virus (HBV) infection, most commonly transmitted from mother-to-child. Global Health Sector Strategy on Viral Hepatitis (GHSSVH) was introduced in May 2016, calling for elimination of viral hepatitis by 2030. This study aims to compare practice in a tertiary liver centre before and after GHSSVH introduction for prevention of mother-to-child transmission (MTCT).
MATERIALS AND METHODS
This retrospective cohort study was performed in a tertiary referral liver centre in Malaysia, using data from electronic medical record from January 2015 to December 2019. A total of 1457 medical records of female with HBV infection were screened. The inclusion criteria of the study were pregnant women with HBsAg positive or known to have HBV infection during the study period. We excluded patients with co-infections of other types of viral hepatitis or human immunodeficiency virus, concurrent liver diseases (e.g.: autoimmune hepatitis, Wilson’s disease), previous organ transplant and malignancy—except for hepatocellular carcinoma (HCC).
RESULTS
This study included 117 pregnancies and 21/117 (17.9%) were on antiviral therapy (AVT) for HBV. In 2017– 2019, 13/18 (72.2%) of those with HBV DNA >200,000IU/ml were on AVT, compared to 5/9 (55.6%) for 2015–2016, indicating 58% (95% CI −63% to 568%) higher odds of being on AVT in post GHSSVH group after accounting for HBV DNA.
CONCLUSION
Uptake of maternal AVT for the prevention of MTCT shows an increased trend since the introduction of GHSSVH, with room for improvement.
Topics: Female; Humans; Fixatives; Hepatitis B virus; Infectious Disease Transmission, Vertical; Global Health; Formaldehyde; Hepatitis, Viral, Human; Sugars
PubMed: 36988536
DOI: No ID Found