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Universal hepatitis C screening in pregnancy is not recommended by NICE due to a lack of effective interventions to prevent mother to child transmission (MTCT) and is only offered to pregnant women at increased risk of infection (intra‐venous drug use [IVDU] or with a HCV positive family member). No testing is offered to patients from high endemic areas. However, data regarding true seroprevalence in multi‐ethnic inner‐city populations in the UK are required. This study aimed to determine test positivity rates of HCV infection in an unselected South East London ethnically diverse population of pregnant women by universal screening during routine antenatal care compared with a "targeted" screening approach. "Targeted" risk‐based screening was performed in two eras (2016, n = 1002) and subsequently in 2018, after modifying the HCV risk questionnaire (n = 1122). Universal opt out screening was similarly performed in two eras in 2017 (n = 1012) and again in 2019 (n = 1057). During screening for HBV, HIV and syphilis, anti‐HCV was tested, followed by an iterative HCV RNA test in those positive for anti‐HCV. All anti‐HCV‐positive women were referred to the specialist hepatology service, and testing was offered to all family members. All HCV RNA‐positive patients were followed during pregnancy and post‐delivery period and were offered treatment. All infants of HCV RNA‐positive mothers were linked to care with paediatric team. In the 2016 "targeted" screening cohort 212/1002 had a risk of BBV (blood borne viral) infection and (0.6%) were anti‐HCV positive and HCV RNA positive. 0.3% patients were newly diagnosed. In the 2017 universal screening cohort, 1012/1038 pregnant women consented to testing. 0.96% were anti‐HCV positive and 0.86% women were HCV RNA positive with 0.67% newly diagnosed. After modification of the risk‐based questionnaire, a second risk‐based targeted cohort were tested in 2018: 342/1122 (31%) were assessed as at risk and were offered an anti‐HCV test. 0.71% were anti‐HCV positive and 0.27% were HCV RNA positive. In the 2019 cohort tested by universal screening, 1049/1057 women were tested and 0.85% tested positive for anti‐HCV, 0.28% women were HCV RNA positive. All newly diagnosed patients were born abroad. All patients had mild liver disease and had normal pregnancies. All patients were treated post‐delivery and achieved SVR. All patients were negative for other BBV infections. In conclusion, the anti‐HCV test positive rate in this ethnically diverse pregnant cohort ranged between 0.96% and 0.6% (whole cohort) but the rate depended upon the era and screening methodology used. Universal screening detected a higher numbers of anti‐HCV positive women during pregnancy, including those not previously aware of their hepatitis C. While there was not significant drop in seroprevalence in pregnant women between 2016 and 2019, we observed that the ratio of HCV RNA positive to anti‐HCV positive women has declined over time, from 0.86% in 2016 (100% HCV RNA+) to 0.28% in 2019 (33% HCV RNA+) for whole cohort probably due to increased HCV treatment rates from 2016. These data have important implications for hepatitis C testing in pregnancy and the appropriate methodology to use for maximal accuracy. [ABSTRACT FROM AUTHOR]

Coinfection with HDV causes rapid progression to liver cirrhosis and hepatic decompensation in patients with chronic hepatitis B. Factors that are associated with disease progression are poorly understood. In this study we aim to identify risk factors associated with disease progression and better characterise clinical differences and treatment response between HDV genotype 1 and 5. In this retrospective study, all patients under our care between 2005 and 2016 with HBV/HDV coinfection (HBsAg+, anti-HDV antibodies positive) were analysed. Patients were excluded if follow-up was less than 6 months, if they had HCV and/or HIV coinfection or an acute HDV infection. Demographic data, stage of liver disease, development of liver complications and treatment response were recorded. One-hundred seven patients (mean age 36.0 years, 57% male) were followed for a median period of 4.4 years (range 0.6–28.1 years); 64% were of African origin and 17% were of European origin, with 28% of patients being cirrhotic at first visit; 43% patients had actively replicating HDV virus (anti-HDV-IgG+, anti-HDV-IgM+ or HDV RNA+) and 57% of patients were HDV exposed (anti-HDV-IgG+, HDV RNA-). Patients with actively replicating HDV more often developed liver complications than HDV-exposed patients (p = 0.002), but no differences in baseline characteristics were observed. Patients with HDV genotype 5 less often developed cirrhosis or hepatic decompensation compared to patients with HDV genotype 1. Twenty-four patients were treated with peg-IFN and post-treatment response was significantly better in patients infected with genotype 5 (10% GT1 vs. 64% GT5, p = 0.013). Patients infected with HDV genotype 5 appear to have a better prognosis with fewer episodes of hepatic decompensation and better response to peg-IFN treatment than patients infected with HDV genotype 1. Hepatitis delta is a virus that affects the liver. The virus is known to have different subtypes, called genotypes. With this research we discovered that hepatitis delta virus genotype 1 behaves differently than genotype 5 and causes faster development of liver disease. This is important for education of our patients and to determine how often we need to check our patients. • Patients of African origin who contract HDV less often have cirrhosis. • Patients with HDV and detectable viral load have worse clinical outcomes. • Patients with HDV genotype 5 less often develop hepatic decompensation. • Patients with HDV genotype 5 seem to respond better to peg-IFN treatment. [ABSTRACT FROM AUTHOR]

Reply to: "Is resistance to direct-acting antivirals in sub-Saharan Africa a threat to HCV elimination? Recall of patients for retreatment after unsuccessful DAA treatment will be difficult. 8 Sonderup MW, Smuts H, Gogela N, Spearman W. Hepatitis C virus genotype 4 diversity, RAS profiles and treatment outcomes in South Africale. [Extracted from the article]

Natural killer T (NKT) cells are thought to be involved in innate responses against infection. We investigated one specific type of NKT cell, Vα24/Vβ11 double positive, in hepatitis C virus (HCV) infection. Lower frequencies of this population were detected in the blood of HCV PCR-positive patients than in controls. Unlike Vα24/Vβ11 NKT cells found in blood, those in the liver appeared to be recently activated. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) has infected over 170 million people world wide, and in the majority sets up a chronic infection associated with hepatic inflammation. How it evades host immunity, particularly CD8+ T cells (CTL) is unclear, but two major factors are likely to operate, viral escape mutation and T cell exhaustion. We have investigated the role of CTL in control of infection during acute disease using Class I peptide tetramers. Although the immune response is quite diverse and numerous epitopes can be targeted, we observe that, especially during acute disease, one epitope (NS3 1073–81) is commonly recognised in HLA-A2 positive individuals. However, the levels of response to this epitope (and others) are very much lower if persistence is established. We examined in detail whether the cause of this low level of reactivity is due to mutation within the epitope. We find that, in fact this epitope is highly conserved during chronic infection, at a clonal level, between individuals, and over time. Thus, although variation within the epitope does occur, lack of reactivity in peripheral blood against this epitope in chronic disease, and loss of control of virus cannot be explained entirely by viral escape. Escape through mutation probably does play an important role in persistence of HCV, but we also discuss other mechanisms which lead to attenuation of T cell responses which may be important in determining the outcome. [Copyright &y& Elsevier]

Regional variability in the prevalence of hepatitis B (HBV) and C (HCV) is reported in sub-Saharan Africa, although data for people with HIV are sparse. We determined the prevalence of HBV/HCV in 2473 people of African ancestry with HIV in the UK. Overall, 6.2% were co-infected with HBV and 1.3% with HCV. Central [adjusted odds ratio (aOR) 2.40 (95% confidence interval (CI) 1.23--4.67) and West [2.10 (1.29-3.41)] African ancestry was associated with HBV and Central [6.98 (2.00-24.43)] African ancestry with HCV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource-constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV-related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20-30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV-infected persons in Africa who are co-infected with HBV. Progressive liver disease has been shown to occur in co-infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV-infected persons should be screened for HBV infection; HIV/HBV co-infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource-constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource-constrained settings., (© 2011 John Wiley & Sons A/S.)

Oral fluid testing is an effective alternative to serum antibody testing for surveillance of human immunodeficiency virus (HIV) and hepatitis B infections, and is being extended to hepatitis C infections. The objective of this study was to determine and compare the sensitivity and specificity of a modified commercial assay for the detection of antibody to hepatitis C virus (anti-HCV) in oral fluids collected by two different oral fluid collection devices (the Epitope OraSure trade mark and Sarstedt Salivette ) and in dried fingerprick blood spots. In this study, 253 anti-HCV seropositive patients and 394 blood donors (all anti-HCV negative) were recruited between August 2000 and January 2001. Each participant provided oral fluid specimens by OraSure and Salivette, and at least one dried blood spot. Serum specimens were collected from the patients whenever possible. For those injecting drug users who did not provide a serum specimen, HCV status was established on the basis of previous testing. All the nonserum samples were tested for the presence of anti-HCV, using a modified Ortho HCV 3.0 SAVe enzyme-linked immunosorbent assay (ELISA) protocol. The recommended preliminary cutoffs for the modified ELISA were suboptimal. Further, the sensitivity, specificity, and positive and negative predictive values could be improved by varying the cutoff and taking into account the likely prevalence of HCV in the population under investigation. For instance, given a population with a 50% prevalence of anti-HCV, the optimal sensitivities of the modified assay on OraSure, Salivette, and dried blood spots were 92%, 83%, and virtually 100%, respectively, in contrast to 83%, 59%, and 99% using the preliminary cutoffs. The respective optimal specificities were 99%, 93%, and 100%. In conclusion, oral fluids collected by the OraSure device provide an extremely useful method to conduct public health surveillance of not only HIV, but also hepatitis C, among injecting drug users. In addition, dried blood spot specimens may be useful for surveillance and could be employed as a first line diagnostic specimen., (Copyright 2003 Wiley-Liss, Inc.)

Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically "tolerant" since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens.