Prevalence of occult hepatitis B virus infection in adults: a systematic review and meta-analysis.

BACKGROUND: Despite growing concerns about transmissibility and clinical impact, occult hepatitis B virus (HBV) infection has received little attention in the hepatitis elimination agenda. We aimed to estimate the prevalence of occult HBV infection at a global and regional scale and in specific populations. METHODS: For this systematic review and meta-analysis, we searched the MEDLINE, Embase, Global Health, and Web of Science databases for articles published in any language between Jan 1, 2010, and Aug 14, 2019. We included original articles and conference abstracts of any study design that reported the proportion of HBsAg-negative adults (aged ≥18 years) who are positive for HBV DNA (ie, people with occult HBV infection). The prevalence of occult HBV infection was pooled, using the DerSimonian-Laird random-effects model, in the general population and specific groups defined by the type of study participants (blood donors; other low-risk populations; high-risk populations; and people with advanced chronic liver disease), and stratified by HBV endemicity in each country. We also assessed the performance of anti-HBc as an alternative biomarker to detect occult HBV infection. The study was registered with PROSPERO, CRD42019115490. FINDINGS: 305 of 3962 articles were eligible, allowing a meta-analysis of 140 521 993 individuals tested for HBV DNA. Overall, only two studies evaluated occult HBV infection in the general population, precluding unbiased global and regional estimates of occult HBV infection prevalence. In blood donors, occult HBV infection prevalence mirrored HBV endemicity: 0·06% (95% CI 0·00-0·26) in low-endemicity countries, 0·12% (0·04-0·23) in intermediate-endemicity countries, and 0·98% (0·44-1·72), in high-endemicity countries (p=0·0012). In high-risk groups, occult HBV infection prevalence was substantial, irrespective of endemicity: 5·5% (95% CI 2·9-8·7) in low-endemicity countries, 5·2% (2·5-8·6) in intermediate-endemicity countries, and 12·0% (3·4-24·7) in high-endemicity countries. The pooled sensitivity of anti-HBc to identify occult HBV infection was 77% (95% CI 62-88) and its specificity was 76% (68-83). INTERPRETATION: A substantial proportion of people carry occult HBV infection, especially among high-risk groups across the globe and people living in highly endemic countries. Occult HBV infection should be part of the global viral hepatitis elimination strategy. FUNDING: None.

Terahertz Spectral Properties of PEO-Based Anti-Adhesion Films Cross-Linked by Electron Beam Irradiation.

We investigated the spectral property changes in anti-adhesion films, which were cross-linked and surface-modified through electron beam irradiation, using terahertz time-domain spectroscopy (THz-TDS). Polyethylene oxide (PEO), which is a biocompatible and biodegradable polymer, was the main component of these anti-adhesion films being manufactured for testing. The terahertz characteristics of the films were affected by the porosity generated during the freeze-drying and compression processes of sample preparation, and this was confirmed using optical coherence tomography (OCT) imaging. An anti-adhesion polymer film made without porosity was measured by using the THz-TDS method, and it was confirmed that the refractive index and absorption coefficient were dependent on the crosslinking state. To our knowledge, this is the first experiment on the feasibility of monitoring cross-linking states using terahertz waves. The THz-TDS method has potential as a useful nondestructive technique for polymer inspection and analysis.

Improving care of migrants is key for viral hepatitis elimination in Europe.

By 2040, deaths from chronic viral hepatitis worldwide are projected to exceed those from human immunodeficiency virus infection, tuberculosis and malaria combined. The burden of this disease is predominantly carried by low-resource countries in Africa and Asia. In resource-rich countries, the epidemiological spread of viral hepatitis is partially driven by migrant movements from areas of high endemicity. In the last decade, Member States of the European Union and the European Economic Area have experienced an unprecedented influx of migrants, which has resulted in the polarization of political views about migration. In addition, the coronavirus disease 2019 pandemic has worsened the economic and health conditions of migrants and contributed to hostility to ensuring their health rights. Moreover, the implementation of hostile laws in some host nations has increased the vulnerability of marginalized migrant subgroups, such as asylum seekers and undocumented individuals. These developments have complicated the historical challenge of identifying high-risk migrant groups for screening and treatment. However, if European countries can apply the simplified assessment tools and diagnostic tests for viral hepatitis that have been used for decentralized screening and monitoring in resource-poor countries, the uptake of care by migrants could be dramatically increased. Given the global calls for the elimination of viral hepatitis, European nations should recognize the importance of treating this vulnerable migrant population. Political and health strategies need to be adapted to meet this challenge and help eliminate viral hepatitis globally.

D'ici 2040, les décès causés par l'hépatite virale chronique dans le monde devraient dépasser ceux dus à trois grandes maladies réunies: l'infection au virus de l'immunodéficience humaine, la tuberculose et la malaria. Le fardeau que représente cette affection repose surtout sur les pays disposant de ressources limitées en Afrique et en Asie. Dans les pays riches en ressources, la propagation épidémiologique de l'hépatite virale est en partie liée aux mouvements migratoires depuis les zones à endémicité élevée. Au cours de la dernière décennie, les États membres de l'Union européenne et l'Espace économique européen ont connu un afflux de migrants sans précédent qui a polarisé les opinions politiques concernant la migration. En outre, la pandémie de maladie à coronavirus 2019 a aggravé la situation économique et sanitaire des migrants, contribuant à l'animosité ambiante à l'égard du respect de leurs droits en matière de santé. L'adoption de lois hostiles dans certains pays d'accueil a également accru la vulnérabilité des sous-groupes de migrants marginalisés, tels que les demandeurs d'asile et les sans-papiers. Des conditions qui compliquent la tâche d'identification des groupes de migrants à haut risque pour le dépistage et le traitement. Néanmoins, si les pays européens pouvaient appliquer les outils d'évaluation simplifiés et les tests de diagnostic de l'hépatite virale, qui ont été employés pour la surveillance et le dépistage décentralisé dans les pays disposant de ressources limitées, la prise en charge des migrants pourrait nettement s'améliorer. Compte tenu des nombreux appels internationaux à éliminer l'hépatite virale, les nations européennes devraient reconnaître l'importance de soigner ces populations de migrants vulnérables. Les stratégies politiques et sanitaires doivent être adaptées afin de relever ce défi et de contribuer à éradiquer l'hépatite virale dans le monde.

Para 2040, se prevé que las muertes por hepatitis vírica crónica en todo el mundo superen a las causadas por la infección del virus de la inmunodeficiencia humana, la tuberculosis y la malaria juntas. La carga de esta enfermedad recae sobre todo en los países con recursos limitados de África y Asia. En los países ricos en recursos, la propagación epidemiológica de las hepatitis víricas se debe en parte a los movimientos migratorios desde las zonas altamente endémicas. En la última década, los Estados miembros de la Unión Europea y del Espacio Económico Europeo han experimentado una afluencia de inmigrantes sin precedentes, lo que ha polarizado las opiniones políticas sobre la inmigración. Además, la pandemia de la enfermedad del coronavirus de 2019 ha empeorado las condiciones económicas y sanitarias de los inmigrantes y ha contribuido a la hostilidad para garantizar sus derechos sanitarios. Además, la aplicación de leyes hostiles en algunas naciones de acogida ha aumentado la vulnerabilidad de subgrupos de inmigrantes marginados, como los solicitantes de asilo y los indocumentados. Estos acontecimientos han complicado el reto histórico de identificar a los grupos de inmigrantes de alto riesgo para su detección y tratamiento. Sin embargo, si los países europeos pueden aplicar las herramientas de evaluación y las pruebas de diagnóstico simplificadas para la hepatitis vírica que se han utilizado para el cribado y el seguimiento descentralizados en los países con pocos recursos, la aceptación de la atención por parte de los inmigrantes podría aumentar drásticamente. Dados los llamamientos mundiales para la eliminación de la hepatitis vírica, las naciones europeas deberían reconocer la importancia de tratar a esta población inmigrante vulnerable. Es necesario adaptar las estrategias políticas y sanitarias para hacer frente a este reto y ayudar a eliminar la hepatitis vírica a nivel mundial.

Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) carries a poor prognosis, is increasing in incidence and its causes are poorly understood. Although some risk factors are known, they vary globally and collectively account for a minority of cases. The aim of this study was to perform a comprehensive meta-analysis of risk factors for intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA), from Eastern and Western world studies. METHODS: A literature search of case-control studies was performed to identify potential risk factors for iCCA and eCCA. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Funnel plots were used to assess publication bias, and meta-regression was used to select risk factors for comparison between Eastern and Western studies. RESULTS: A total of 13 risk factors were selected from 25 case-control studies in 7 geographically diverse countries. The strongest risk factors for both iCCA and eCCA were biliary cysts and stones, cirrhosis, hepatitis B and hepatitis C. Choledochal cysts conferred the greatest risk of both iCCA and eCCA with pooled ORs of 26.71 (95% CI 15.80-45.16) and 34.94 (24.36-50.12), respectively. No significant associations were found between hypertension and obesity for either iCCA or eCCA. Comparing Eastern and Western populations, there was a difference for the association of hepatitis B with iCCA (coefficient = -0.15195; 95% CI -0.278 to -0.025; p = 0.022). CONCLUSION: This is the most comprehensive meta-analysis of CCA risk factors to date. Some risk factors, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of this cancer. LAY SUMMARY: Cholangiocarcinoma (CCA) is a cancer arising in the bile ducts inside (intrahepatic CCA) and connected to the liver (extrahepatic CCA). It is a very aggressive cancer: 95% of patients die within 5 years. CCA rates are increasing globally, but the causes of CCA are poorly understood. The few risk factors that are known account for only a minority of cases. In this study, we found that the strongest risk factors for both intrahepatic and extrahepatic CCA are cysts and stones in the bile ducts, cirrhosis, and hepatitis B and C viruses. Some risk factors for CCA, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of CCA.

Assessment of the effectiveness of PMTCT program in eight service delivery points in North Central Nigeria.

BACKGROUND: Mother-to-child transmission (MTCT) of HIV is one of the commonest avenues through which infants are infected with HIV. To achieve an HIV-free generation, MTCT of HIV should be eliminated. Nigeria began prevention of mother-to-child transmission (PMTCT) services 13 years ago, but it still contributes to over one-third of global MTCT burden. We set out to explore and define the effectiveness of PMTCT in selected sites in North Central Nigeria. METHODS: We conducted a retrospective secondary data analysis at eight service delivery points in two states. One thousand four hundred and fifty-four mother-infant pair data sets from 2012 to 2016 were extracted and analyzed. Maternal/infant antiretroviral (ARV) services, early infant diagnosis (EID), and final outcomes were reviewed to examine the predictors of MTCT of HIV in these centers. RESULTS: We retrieved 1,454 mother-infant pair data sets. While 89.5% (1,302) of positive pregnant women (PPW) and 92.2% (1,340) of HIV-exposed infants (HEIs) received ARV prophylaxis/ARV treatment (ART), 88.4% (1,285) infants were breastfed with 32.5% still receiving breast milk at the time of dry blood spot (DBS) collection. EID PCR positivity rate was 3.5% (range, 0.0%-11.1%). Facility of delivery (χ2=24.99, P<0.00), mother on ARV (χ2=48.8, P<0.00), mother having received ARV prophylaxis (χ2=89.59, P<0.00), infant having received ARV prophylaxis (χ2=58.56, P<0.00), and baby having received cotrimoxazole (χ2=55.24, P<0.00) all significantly prevented positive EID results. However, mode of delivery and breastfeeding were not significantly associated with positive EID results. CONCLUSION: This study supports PMTCT services as it minimizes the transfer of HIV from infected mothers to HEIs. To eliminate HIV and achieve zero new HIV infections, every HIV-positive pregnant woman should receive ARV prophylaxis and should be supported postdelivery to prevent transfer of infection to the newborn. Also, HEIs should receive timely ARV and cotrimoxazole prophylaxis.

A time for new north-south relationships in global health.

The modern concept of globalization in health care and clinical research often carries a positive message for the "Global South" nations of Africa, South America and Southeast Asia. However, bioethical abuse of participants in clinical trials still exists in the Global South. Unethical studies directed by the "Global North", formed by the medically advanced nations in North America, Western Europe and Japan, have been hugely concerning. The issue between the Global North and South is a well-recognized socioeconomic phenomenon of globalization. Medical exploitation has its roots in the socioeconomic interactions of a postcolonial world, and solutions to reducing exploitation require a deeper understanding of these societal models of globalization. We explore the fundamental causes of imbalance and suggest solutions. Reflecting on the globalization model, there must be an effort to empower the Global South nations to direct and govern their own health care systems efficiently on the basis of equality.

A pilot evaluation of a computer-based psychometric test battery designed to detect impairment in patients with cirrhosis.

BACKGROUND: Psychometric testing is used to identify patients with cirrhosis who have developed hepatic encephalopathy (HE). Most batteries consist of a series of paper-and-pencil tests, which are cumbersome for most clinicians. A modern, easy-to-use, computer-based battery would be a helpful clinical tool, given that in its minimal form, HE has an impact on both patients' quality of life and the ability to drive and operate machinery (with societal consequences). AIM: We compared the Cogstate™ computer battery testing with the Psychometric Hepatic Encephalopathy Score (PHES) tests, with a view to simplify the diagnosis. METHODS: This was a prospective study of 27 patients with histologically proven cirrhosis. An analysis of psychometric testing was performed using accuracy of task performance and speed of completion as primary variables to create a correlation matrix. A stepwise linear regression analysis was performed with backward elimination, using analysis of variance. RESULTS: Strong correlations were found between the international shopping list, international shopping list delayed recall of Cogstate and the PHES digit symbol test. The Shopping List Tasks were the only tasks that consistently had P values of <0.05 in the linear regression analysis. CONCLUSION: Subtests of the Cogstate battery correlated very strongly with the digit symbol component of PHES in discriminating severity of HE. These findings would indicate that components of the current PHES battery with the international shopping list tasks of Cogstate would be discriminant and have the potential to be used easily in clinical practice.

The Plasma and Serum Metabotyping of Hepatocellular Carcinoma in a Nigerian and Egyptian Cohort using Proton Nuclear Magnetic Resonance Spectroscopy.

BACKGROUND/AIMS: Previous studies have observed disturbances in the 1H nuclear magnetic resonance (NMR) blood spectral profiles in malignancy. No study has metabotyped serum or plasma of hepatocellular carcinoma (HCC) patients from two diverse populations. We aimed to delineate the HCC patient metabotype from Nigeria (mostly hepatitis B virus infected) and Egypt (mostly hepatitis C virus infected) to explore lipid and energy metabolite alterations that may be independent of disease aetiology, diet and environment. METHODS: Patients with HCC (53) and cirrhosis (26) and healthy volunteers (19) were recruited from Nigeria and Egypt. Participants provided serum or plasma samples, which were analysed using 600 MHz 1H NMR spectroscopy with nuclear Overhauser enhancement spectroscopy pulse sequences. Median group spectra comparison and multivariate analysis were performed to identify regions of difference. RESULTS: Significant differences between HCC patients and healthy volunteers were detected in levels of low density lipoprotein (P = 0.002), very low density lipoprotein (P < 0.001) and lactate (P = 0.03). N-acetylglycoproteins levels in HCC patients were significantly different from both healthy controls and cirrhosis patients (P < 0.001 and 0.001). CONCLUSION: Metabotype differences were present, pointing to disturbed lipid metabolism and a switch from glycolysis to alternative energy metabolites with malignancy, which supports the Warburg hypothesis of tumour metabolism.

Changes in Liver Volume in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy.

AIM: Liver volumetric analysis has not been used to detect hepatic remodelling during antiviral therapy before. We measured liver volume (LV) changes on volumetric magnetic resonance imaging during hepatitis C antiviral therapy. METHODS: 22 biopsy-staged patients (median [range] age 45(19-65) years; 9F, 13M) with chronic hepatitis C virus infection were studied. LV was measured at the beginning, end of treatment and 6 months post-treatment using 3D T1-weighted acquisition, normalised to patient weight. Liver outlines were drawn manually on 4 mm thick image slices and LV calculated. Inter-observer agreement was analysed. Patients were also assessed longitudinally using biochemical parameters and liver stiffness using Fibroscan™. RESULTS: Sustained viral response (SVR) was achieved in 13 patients with a mean baseline LV/kg of 0.022 (SD 0.004) L/kg. At the end of treatment, the mean LV/kg was 0.025 (SD 0.004, P = 0.024 cf baseline LV/kg) and 0.026 (SD 0.004, P = 0.008 cf baseline LV/kg) 6 months post-treatment (P = 0.030 cf baseline, P = 0.004). Body weight-corrected end of treatment LV change was significantly higher in patients with SVR compared to patients not attaining SVR (P = 0.050). End of treatment LV change was correlated to initial ALT (R (2) = 0.479, P = 0.037), but not APRI, AST, viral load or liver stiffness measurements. There was a correlation of 0.89 between observers for measured slice thickness. CONCLUSIONS: LV increased during anti-viral treatment, while the body weight-corrected LV increase persisted post-antiviral therapy and was larger in patients with SVR.

Hepatocellular carcinoma: Review of disease and tumor biomarkers.

Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburg's phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest.