Age at Establishment of Chronic Hepatitis B Infection as a Risk Factor for Persistent Viral Replication, Liver Fibrosis and Hepatocellular Carcinoma in The Gambia, West Africa

Early age at hepatitis B virus (HBV) infection is known to increase the risk of chronic HBV (CHB) infection. This thesis investigated whether, in addition to increasing the risk of chronicity, early age at HBV infection further increases the risk of hepatocellular carcinoma (HCC) by maintaining high viral replication. A systematic review of observational studies suggested that early age at HBV infection might increase the risk of sequelae of CHB infection. However, there was no data from Africa. A project was therefore designed to explore the effect of age at HBV infection on HCC and its predictors in The Gambia, West Africa, using two proxy variables for the age at infection: birth order and maternal HBV sero-status. A historical cross-sectional study of children born to HBeAg-positive mothers and HBeAg-negative mothers found that having an HBeAg-positive mother is associated with higher risk of positive HBeAg in children. The distribution of birth order was compared between HBV-related HCC cases and HBsAg-positive controls using a historical case-control study and data from the PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) project. The former study did not find statistically significant association whilst the latter found an inverse association between birth order and HCC, suggesting that chronic carriers with low birth order might have an increased risk of HCC. Finally, an open community cohort study of HBsAg-positive people in three Gambian villages found that having an HBsAg-positive mother is associated with a number of factors predictive of disease (delayed HBeAg seroclearance, high HBV DNA and alanine transaminase levels over time, active CHB disease, significant liver fibrosis and condition requiring antiviral treatment). These findings suggest that interrupting 6 perinatal mother-to-infant transmission might significantly reduce the burden of liver disease associated with CHB infection in The Gambia

Carrier-Induced Magnetic Circular Dichloism in the Magnetoresistive Pyrochlore Tl2Mn2O7

Infrared magnetic circular dichloism (MCD), or equivalently magneto-optical Kerr effect, has been measured on the Tl2Mn2O7 pyrochlore, which is well known for exhibiting a large magnetoresistance around the Curie temperature T_C ~ 120 K. A circularly polarized, infrared synchrotron radiation is used as the light source. A pronounced MCD signal is observed exactly at the plasma edge of the reflectivity near and below T_c. However, contrary to the conventional behavior of MCD for ferromagnets, the observed MCD of Tl2Mn2O7 grows with the applied magnetic field, and not scaled with the internal magnetization. It is shown that these results can be basically understood in terms of a classical magnetoplasma resonance. The absence of a magnetization-scaled MCD indicates a weak spin-orbit coupling of the carriers in Tl2Mn2O7. We discuss the present results in terms of the microscopic electronic structures of Tl2Mn2O7.Comment: 5 pages, 5 figures, submitted to J. Phys. Soc. Jp

Unusual T_c variation with hole concentration in Bi_2Sr_{2-x}La_xCuO_{6+\delta}

We have investigated the $T_c$ variation with the hole concentration $p$ in the La-doped Bi 2201 system, Bi$_2$Sr$_{2-x}$La$_x$CuO$_{6+\delta}$. It is found that the Bi 2201 system does not follow the systematics in $T_c$ and $p$ observed in other high-$T_c$ cuprate superconductors (HTSC's). The $T_c$ vs $p$ characteristics are quite similar to what observed in Zn-doped HTSC's. An exceptionally large residual resistivity component in the inplane resistivity indicates that strong potential scatterers of charge carriers reside in CuO$_2$ planes and are responsible for the unusual $T_c$ variation with $p$, as in the Zn-doped systems. However, contrary to the Zn-doped HTSC's, the strong scatter in the Bi 2201 system is possibly a vacancy in the Cu site.Comment: RevTeX, 3 figures, to be published in the Physical Review

Risk of early horizontal transmission of hepatitis B virus in children of uninfected mothers in sub-Saharan Africa: a systematic review and 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

Quasiparticle Excitation in the Superconducting Pyrochlore Cd2Re2O7 Probed by Muon Spin Rotation

The quasiparticle excitations in the mixed state of Cd2Re2O7 have been studied by means of muon spin rotation/relaxation. The temperature dependence of the magnetic penetration depth (lambda) is consistent with a nearly isotropic superconducting order parameter, although a slight discrepancy which is dependent on the details in the analysis may be present. This is also supported by the relatively weak field dependence of lambda.Comment: 12 pages, 2 figures, to appear in J. Phys. Soc. Jp

Mott-Hubbard quantum criticality in paramagnetic CMR pyrochlores

We present a correlated {\it ab initio} description of the paramagnetic phase of Tl$_2$Mn$_2$O$_7$, employing a combined local density approximation (LDA) with multiorbital dynamical mean field theory (DMFT) treatment. We show that the insulating state observed in this colossal magnetoresistance (CMR) pyrochlore is determined by strong Mn intra- and inter-orbital local electron-electron interactions. Hybridization effects are reinforced by the correlation-induced spectral weight transfer. Our result coincides with optical conductivity measurements, whose low energy features are remarkably accounted for by our theory. Based on this agreement, we study the disorder-driven insulator-metal transition of doped compounds, showing the proximity of Tl$_2$Mn$_2$O$_7$ to quantum phase transitions, in agreement with recent measurements.Comment: 4 pages, 4 figure

Physiological Roles of Flavodiiron Proteins and Photorespiration in the Liverwort <i>Marchantia polymorpha</i>

Against the potential risk in oxygenic photosynthesis, that is, the generation of reactive oxygen species, photosynthetic electron transport needs to be regulated in response to environmental fluctuations. One of the most important regulations is keeping the reaction center chlorophyll (P700) of photosystem I in its oxidized form in excess light conditions. The oxidation of P700 is supported by dissipating excess electrons safely to O2, and we previously found that the molecular mechanism of the alternative electron sink is changed from flavodiiron proteins (FLV) to photorespiration in the evolutionary history from cyanobacteria to plants. However, the overall picture of the regulation of photosynthetic electron transport is still not clear in bryophytes, the evolutionary intermediates. Here, we investigated the physiological roles of FLV and photorespiration for P700 oxidation in the liverwort Marchantia polymorpha by using the mutants deficient in FLV (flv1) at different O2 partial pressures. The effective quantum yield of photosystem II significantly decreased at 2kPa O2 in flv1, indicating that photorespiration functions as the electron sink. Nevertheless, it was clear from the phenotype of flv1 that FLV was dominant for P700 oxidation in M. polymorpha. These data suggested that photorespiration has yet not replaced FLV in functioning for P700 oxidation in the basal land plant probably because of the lower contribution to lumen acidification, compared with FLV, as reflected in the results of electrochromic shift analysis

Hepatitis B testing and treatment in HIV patients in The Gambia - compliance with international guidelines and clinical outcomes

Background Compliance with WHO guidelines on HBV screening and treatment in HIV-coinfected patients is often challenging in resource limited countries and has been poorly assessed in sub-Saharan Africa. Methods Between 2015 and 2016, we assessed physician’s compliance with WHO guidelines on HIV-HBV coinfection in the largest HIV clinic in The Gambia, and the hepatic outcomes in HIV-HBV coinfected patients as compared to randomly selected HIV-monoinfected controls. Results 870 HIV-infected patients regularly seen in this clinic agreed to participate in our study. Only 187 (21.5%, 95% CI 18.8–24.3) had previously been screened for HBsAg, 23 (12.3%, 95% CI 8.0–17.9) were positive of whom none had liver assessment and only 6 (26.1%) had received Tenofovir. Our HBV testing intervention was accepted by all participants and found 94/870 (10.8%, 95% CI 8.8–13.1) positive, 78 of whom underwent full liver assessment along with 40 HBsAg-negative controls. At the time of liver assessment, 61/78 (78.2%) HIV-HBV coinfected patients received ART with 7 (11.5%) on Tenofovir and 54 (88.5%) on Lamivudine alone. HIV-HBV coinfected patients had higher APRI score compared to controls (0.58 vs 0.42, p = 0.002). HBV DNA was detectable in 52/53 (98.1%) coinfected patients with 14/53 (26.4%) having HBV DNA >20,000 IU/L. 10/12 (83.3%) had at least one detectable 3TC-associated HBV resistance, which tended to be associated with increase in liver fibrosis after adjusting for age and sex (p = 0.05). Conclusions Compliance with HBV testing and treatment guidelines is poor in this Gambian HIV programme putting coinfected patients at risk of liver complications. However, the excellent uptake of HBV screening and linkage to care in our study suggests feasible improvements

Cost-effectiveness of different monitoring strategies in a screening and treatment programme for hepatitis B in The Gambia

Background: Clinical management of chronic hepatitis B virus (HBV) infection is complex and access to antiviral treatment remains limited in sub-Saharan Africa. International guidelines recommend monitoring at least annually for disease progression among HBV-infected people not meeting treatment criteria at initial diagnosis. This study aimed to assess the impact and cost-effectiveness of alternative strategies for monitoring. Methods: We used a mathematical model of HBV transmission and natural history, calibrated to all available West African data, to project the population-level health impact, costs and cost-effectiveness of different monitoring strategies for HBV-infected individuals not initially eligible for antiviral treatment. We assumed that these patients were found in the year 2020 in a hypothetical community-based screening programme in The Gambia. Monitoring frequencies were varied between every 5 and every 1 year and targeted different age groups. Results: The currently recommended annual monitoring frequency was likely to be not cost-effective in comparison with other strategies in this setting. 5-yearly monitoring in 15-45-year olds, at US$338 per disability-adjusted life year averted, had the highest probability of being the most effective cost-effective monitoring strategy. Conclusions: Monitoring less frequently than once a year is a cost-effective strategy in a community-based HBV screening and treatment programme in The Gambia, with the optimal strategy depending on the cost-effectiveness threshold. Efficiencies may be gained by prioritising the 15-45-year age group for more intensive monitoring