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Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.

Most patients who develop hepatocellular carcinoma reside in resource-poor countries, a category that includes most countries in sub-Saharan Africa. Age-standardised incidence rates of hepatocellular carcinoma in western, central, eastern, and southern Africa is 6·53 per 100 000 inhabitants to 11·1 per 100 000 inhabitants. In high-income countries, around 40% of patients are diagnosed at an early stage, in which interventions with curative intent or palliative interventions are possible. By contrast, 95% of patients with hepatocellular carcinoma in sub-Saharan Africa present with advanced or terminal disease. In high-income countries, targets of 30-40% that have been set for intervention with curative intent are regularly met, with expected 5-year overall survival rates in the region of 70%. These outcomes are in sharp contrast with the very small proportion of patients in sub-Saharan Africa who are treated with curative intent. Primary prevention through the eradication and reduction of risk factors is still suboptimal because of logistical challenges. The challenges facing primary prevention, in combination with difficult-to-manage historic and emerging risk factors, such as ethanol overconsumption and metabolic dysfunction-associated liver disease, mandates secondary prevention for populations at risk through screening and surveillance. Although the increased treatment needs yielded by screening and surveillance in high-income countries are manageable by the incremental expansion of existing interventional resources, the lack of resources in sub-Saharan Africa will undermine the possible benefits of secondary prevention. An estimate of the projected effect of the introduction and expansion of screening and surveillance, resulting in stage migration and possibilities for active interventions for hepatocellular carcinoma, would facilitate optimal planning and development of resources.

Given the hepatitis C virus (HCV) burden and despite curative treatments, more efforts focused on scaling-up testing and treatment in homeless populations are needed. This project aimed to implement education and flexible on-site HCV testing, treatment, and follow-up for a homeless population in south London and to evaluate engagement, therapy initiation, and cure rates.A mobile unit (van) for on-site HCV education, screening, treatment, and follow-up was placed on the street in a well-known homeless population areas from January 2018 to September 2021. Homeless was defined as living in temporary housing (hostel/hotel-based) or living on the street (street-based). Sociodemographic status, risk factors, comorbidities, concomitant medication, and data related with HCV treatment were recorded. Univariable and multivariable modeling were performed for treatment initiation and sustained virological response (SVR).Nine hundred forty homeless people were identified and 99.3% participated. 56.2% were street-based, 243 (26%) tested positive for HCV antibody, and 162 (17.4%) were viremic. Those with detectable HCV RNA had significantly more frequent psychiatric disorders, active substance use disorders, were on opioid agonist treatment, had advanced fibrosis, and had lower rates of previous treatment in comparison with undetectable HCV RNA. Overall treatment initiation was 70.4% and SVR was 72.8%. In the multivariable analysis, being screened in temporary housing (odds ratio [OR] 3.166; P = 0.002) and having opioid agonist treatment (OR 3.137; P = 0.004) were positively associated with treatment initiation. HCV treatment adherence (OR 26.552; P0.001) was the only factor associated with achieving SVR.Promoting education and having flexible and reflex mobile on-site testing and treatment for HCV in the homeless population improve engagement with the health care system, meaning higher rates of treatment initiation and SVR. However, street-based homeless population not linked with harm reduction services are less likely to initiate HCV treatment, highlighting an urgent need for a broad health inclusion system.

Chronic hepatitis B remains a global health problem with an estimated 296 million people affected worldwide. Individuals are at risk of serious complications such as cirrhosis and hepatocellular carcinoma and accurately predicting these clinical endpoints has proven difficult. However, several viral biomarkers have recently been developed, including quantitative HBV surface antigen (qHBsAg), hepatitis B RNA (HBV RNA) and core-related antigen (HBcrAg), and shown promise in a range of clinical settings.To critically appraise these novel biomarkers, exploring their potential uses, availability of assays and areas for future development.We performed a literature search of PubMed, identifying articles published in the field of hepatitis B biomarkers between 2010 and 2022.Novel biomarkers such as HBcrAg, HBV RNA and qHBsAg may be useful in predicting treatment outcomes, stratifying the risk of future complications and estimating off-treatment viral reactivation. Furthermore, HBV RNA and HBcrAg titres may accurately reflect cccDNA transcriptional activity, and this is particularly informative in the context of nucleoside analogue therapy. On a cautionary note, most studies have been performed in Caucasian or Asian populations, and methods for detecting HBV RNA lack standardisation.Novel viral biomarkers have the potential to provide additional insights into the natural history of infection and allow a more bespoke, cost-effective framework of care. However, access remains limited, and further efforts are needed to validate their use in ethnically diverse populations, confirm predictive cut-off values, and establish their role in the era of novel antiviral therapies.

Lusutrombopag is an oral thrombopoietin receptor agonist (TPO-RA). Clinical trials have shown lusutrombopag's efficacy in reducing need for preoperative platelet transfusion in patients with chronic liver disease (CLD) and severe thrombocytopenia. This analysis assessed efficacy and safety of lusutrombopag in patients with severe thrombocytopenia and CLD undergoing planned invasive procedures.An electronic database search (through 1 December 2020) identified three randomised, placebo-controlled, double-blind clinical trials comparing lusutrombopag with placebo in patients with CLD and platelet count below 50 × 10The meta-analysis included 343 (lusutrombopag 3 mg, n = 173; placebo, n = 170) patients. More patients met the criteria for treatment response (platelet count at least 50 × 10This meta-analysis showed that treatment of severe thrombocytopenia with lusutrombopag in patients with CLD prior to a planned invasive procedure was efficacious and safe in increasing platelet counts, avoiding the need for platelet transfusions, and reducing risk of bleeding, thereby enhancing the certainty of evidence supporting the efficacy and safety of lusutrombopag.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. Clinical care for patients with HCV-related liver disease has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease, as well as developments in diagnostic procedures and improvements in therapy and prevention. These therapies make it possible to eliminate hepatitis C as a major public health threat, as per the World Health Organization target, although the timeline and feasibility vary from region to region. These European Association for the Study of the Liver recommendations on treatment of hepatitis C describe the optimal management of patients with recently acquired and chronic HCV infections in 2020 and onwards.

Background and aims A dichotomous separation of hepatitis B viral DNA and hepatitis B surface antigen (HBsAg) concentrations occurs during the natural history and treatment of chronic hepatitis B. We have evaluated the ability of hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg) as surrogates of silencing of covalently closed circular DNA (cccDNA), to characterize this dissociation, and virological outcomes. Approach and results Three cohorts of hepatitis B e antigen (HBeAg)-negative patients were studied: cohort A: 66 HBeAg-negative patients on long-term nucleos(t)ide analogue (NA) therapy; cohort B: 23 antibodies against hepatitis B e antigen (anti-HBe)-positive patients who stopped treatment; and Cohort C: 19 anti-HBe-positive patients on long-term NA treatment who achieved HBsAg loss and in whom treatment was withdrawn. Concentrations of HBV serological/virological biomarkers (HBV DNA, HBsAg, HBcrAg, and HBV RNA) were measured in sequential samples at different time points on/off therapy. Cohort A: After 3 years of antiviral therapy, 33% and 30% had detectable HBcrAg and HBV RNA, respectively, despite all being HBV-DNA negative. After 5 years' therapy with NA, 27% and 14% had detectable HBcrAg and HBV RNA. Detectable HBcrAg and HBV RNA at the time of treatment withdrawal was only observed in those patients who developed a severe aminotransferase flare. Only those patients with HBV reactivation in cohort C had detectable HBV RNA at treatment withdrawal, but HBcrAg and HBV DNA were not detected. Conclusions HBcrAg and HBV RNA are sensitive biomarkers of continued transcription of cccDNA in HBeAg-negative patients despite marked HBV-DNA suppression by NA. These markers were predictors of severe alanine transaminase flares, after treatment withdrawal, and HBV-DNA reactivation. Their measurement during the natural history of hepatitis B, and on treatment with current and new agents, could characterize residual HBV-RNA transcription from cccDNA and assist drug development and disease management.

Background & Aims 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. Methods 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. Results 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). Conclusion 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. Lay summary 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.

Chronic hepatitis B is a numerically important cause of cirrhosis and hepatocellular carcinoma. Nucleoside analogue therapy may modify the risk. However, maintenance suppressive therapy is required, as a functional cure (generally defined as loss of HBsAg off treatment) is an uncommon outcome of antiviral treatment. Chronic hepatitis B is a numerically important cause of cirrhosis and hepatocellular carcinoma. Nucleoside analogue therapy may modify the risk. However, maintenance suppressive therapy is required, as a functional cure (generally defined as loss of HBsAg off treatment) is an uncommon outcome of antiviral treatment. Currently numerous investigational agents being developed to either interfere with specific steps in HBV replication or as host cellular targeting agents, that inhibit viral replication, and deplete or inactivate cccDNA, or as immune modulators. Synergistic mechanisms will be needed to incorporate a decrease in HBV transcription, impairment of transcription from HBV genomes, loss of cccDNA or altered epigenetic regulation of cccDNA transcription, and immune modulation or immunologically stimulated hepatocyte cell turnover. Nucleoside analogue suppressed patients are being included in many current trials. Trials are progressing to combination therapy as additive or synergistic effects are sought. These trials will provide important insights into the biology of HBV and perturbations of the immune response, required to effect HBsAg loss at different stages of the disease. The prospect of cures of hepatitis B would ensure that a wide range of patients could be deemed candidates for treatment with new compounds if these were highly effective, finite and safe. Withdrawal of therapy in short-term trials is challenging because short-term therapies may risk severe hepatitis flares, and hepatic decompensation. The limited clinical trial data to date suggest that combination therapy is inevitable.

© 2021 Elsevier Ltd. All rights reserved., Liver diseases have become a major health threat across Europe, and the face of European hepatology is changing due to the cure of viral hepatitis C and the control of chronic viral hepatitis B, the increasingly widespread unhealthy use of alcohol, the epidemic of obesity, and undiagnosed or untreated liver disease in migrant populations. Consequently, Europe is facing a looming syndemic, in which socioeconomic and health inequities combine to adversely affect liver disease prevalence, outcomes, and opportunities to receive care. In addition, the COVID-19 pandemic has magnified pre-existing challenges to uniform implementation of policies and equity of access to care in Europe, arising from national borders and the cultural and historical heterogeneity of European societies. In following up on work from the Lancet Commission on liver disease in the UK and epidemiological studies led by the European Association for the Study of the Liver (EASL), our multidisciplinary Commission, comprising a wide range of public health, medical, and nursing specialty groups, along with patient representatives, set out to provide a snapshot of the European landscape on liver diseases and to propose a framework for the principal actions required to improve liver health in Europe. We believe that a joint European process of thinking, and construction of uniform policies and action, implementation, and evaluation can serve as a powerful mechanism to improve liver care in Europe and set the way for similar changes globally., The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193; COMPARE: CIT5-CT-2005-028857; SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N°211909; SHARE-LEAP: GA N°227822; SHARE M4: GA N°261982; DASISH: GA N°283646), and Horizon 2020 (SHARE-DEV3: GA N°676536; SHARE-COHESION: GA N°870628; SERISS: GA N°654221; SSHOC: GA N°823782) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2; P01_AG005842; P01_AG08291; P30_AG12815; R21_AG025169; Y1-AG-4553-01; IAG_BSR06-11; OGHA_04-064; HHSN271201300071C), and from various national funding sources is gratefully acknowledged. PC acknowledges support by the French National Agency for HIV, hepatitis and emerging infectious diseases research (ANRS / EMERGING INFECTIOUS DISEASES).

International audience; In patients with chronic hepatitis B (CHB), loss of hepatitis B surface antigen (HBsAg) is considered a functional cure. However, HBsAg loss is uncommon with existing therapies, and predictive factors associated with HBsAg seroreversion are unknown. Using pooled data from three phase 3 clinical trials of patients with CHB treated with nucleos(t)ide analogue (NUC) monotherapy or peginterferon (Peg-IFN) ± NUC combination therapy, we conducted a retrospective analysis to characterize patients who achieved sustained HBsAg loss, the predictors of HBsAg seroreversion, and the impact of hepatitis B surface antibody (anti-HBs) seroconversion on durability of HBsAg loss. In these three international trials, 1,381 adults with CHB received either NUC monotherapy for up to 10 years or Peg-IFN-containing regimens for up to 1 year. A total of 55 patients had confirmed HBsAg loss, defined as two or more consecutive negative-qualitative HBsAg results, with a minimum of one repeat result after the end of treatment. Throughout a median of 96 (quartile [Q]1, Q3, 46, 135) weeks follow-up after HBsAg loss, HBsAg loss was durable in 82% (n = 45) of patients, with 10 patients experiencing HBsAg seroreversion. Anti-HBs seroconversion was observed during follow-up in 78% of patients who lost HBsAg and in 60% of those who subsequently seroreverted. In analyzing predictors of HBsAg seroreversion, study treatment was significant, yet anti-HBs seroconversion and treatment duration after initial HBsAg loss were not. Risk of HBsAg seroreversion was observed to be lower if HBsAg loss was sustained through the off-treatment week 24 visit (8/10 seroreversions occurred by posttreatment week 24). Conclusion: HBsAg loss after NUC or Peg-IFN-containing regimens was durable in 82% of patients with CHB. Anti-HBs seroconversion and treatment duration after initial HBsAg loss were not significantly associated with durability of HBsAg loss.

Chronic hepatitis B (CHB) comorbidity data are limited. Using insurance claims databases, our aims were to determine the prevalence and incidence of nonliver comorbidities in CHB patients over time and the predictors of select comorbidities in CHB patients. Patients were adults with continuous coverage (commercial/Medicare or Medicaid) 6 months prior to and after the first CHB diagnosis and matched non‐CHB patients. Deyo‐Charlson Comorbidity Index (DCCI) and comorbidities were analyzed (cardiovascular disease [CVD], carcinoma, diabetes mellitus [DM], obesity, hypertension [HTN], hyperlipidemia, alcohol use, renal impairment, chronic kidney disease [CKD], and osteoporosis/fracture [OF]). The study population included 44,026 CHB cases and 121,568 matched controls. CHB patient mean age increased from 48.1 ± 11.9 years in 2006 to 51.8 ± 12.4 years in 2015 for commercial/Medicare and from 44.1 ± 11.1 years to 50.2 ± 10.2 years for Medicaid (P < 0.001 for both). The Medicaid CHB cohort was the sickest (DCCI, 2.6, P < 0.001). The commercial/Medicare 2006 CKD prevalence rate was 36.1/1,000 in CHB patients and 10.2/1,000 in controls, increasing to 97.6 and 38.8 in 2015, respectively. The 2006 CKD incidence (per 1,000 person‐years) was 10.3 and 4.8 and 15.2 and 11.3 by 2015, respectively (P < 0.05 for all). The strongest predictors for CKD were DM (hazard ratio [HR], 2.48), HTN (HR, 3.29), and CVD (HR, 2.61) (all P < 0.0001). Similar prevalence and incidence changes were observed for OF. The strongest predictors for OF were female gender (HR, 2.22), alcohol use (HR, 2.02), and viral coinfection (HR, 1.37) (all P < 0.0001). Conclusion: Insured CHB patients were older, had more comorbidities, and experienced higher incidence and prevalence of CKD and OF than controls.

Background First- and second- generation new treatments are being evaluated to provide a cure for hepatitis B. The life cycle of HBV includes several well- categorized steps that are targets for new treatments. A cure remains a major challenge even if it is measured by HBsAg seroclearance alone. The notion of a functional cure of hepatitis B has been accepted, while a partial functional cure has been more tentatively defined as a decline in HBsAg concentrations to lower levels after finite treatment. Methods More profound suppression of hepatitis B replication through the addition of capsid inhibitors with nucleoside analogues could improve patient prognosis and a sustained treatment response. Several strategies are being evaluated to achieve a cure: (a) deepening inhibition of HBV replication or (b) a reduction in HBsAg presentation for HBsAg seroclearance. Results Fortunately, there are signs of important progress in the treatment of hepatitis B including improved on- treatment reductions or seroclearance of HBsAg in phase 2 studies that was not achieved with chain terminators and inhibitors of initiation of DNA synthesis. Progress in immunomodulatory therapy has lagged behind that of antiviral therapy. Conclusions Increasing the multilayered impaired and dysfunctional immune response in hepatitis B is perhaps more likely and feasible after a reduction in host antigen burden. Other potential experimental strategies include CRISPR- Cas9 genome- editing nucleases to specifically target and cleave cccDNA or novel monoclonal antibodies.

There are important geographical differences in prevalence and in the distribution of HCV genotypes. Genotype 5 was thought to be confined to South Africa, but isolates of genotype infection have been identified in France, Spain, Syria and Belgium. HCV genotype 5 is relatively highly conserved; one subtype, 5a, has been identified. HCV genotype 5 accounts for approximately 1·4 million cases of HCV infection worldwide; genotype 6 is genetically diverse, and 23 subtypes have been described to date. HCV genotype 6 represents about 1% of the total burden of HCV infection globally. Genotype 6 is found predominantly in Southeast Asia and Southern China. Combination direct-acting antivirals with pan-genotypic activity are now available for genotype 5 and 6. Primary treatments include sofosbuvir and velpatasvir or glecaprevir and pibrentasvir or sofosbuvir and ledipasvir. The combination of sofosbuvir, velpatasvir and voxilaprevir could be reserved for salvage treatment. In low-income countries, generic sofosbuvir and daclatasvir could also be considered to scale up treatment rates. Genotype 5 and 6 HCV will need to be included in elimination target sets for 2030.

Several unmet clinical needs are required to improve access to diagnosis and current therapies. Although a test for HBsAg has long been available, only 30 million individuals (10%) are believed to have been diagnosed. A relatively small proportion of persons worldwide receive treatment. Deaths will increase in infected adults unless large increases in screening and a nexus to care are implemented. The age-specific disease burden is incompletely understood in many geographical regions. Clinical research to dissect the effect of prolonged suppression on cccDNA copy number will consolidate treatment and management. Accurate data, to establish appropriate treatment criteria for chronic HBV in different regions is required. It would be invaluable to improve signature phenotyping of the disease to stratify risk, prognosis and treatment indications. New, standalone, easy-to-use point of care and affordable HBV DNA tests will overcome the inability to test more widely and facilitate treatment decisions. More precise molecular and immunological data would further identify risk and treatment indications. Timing of therapy in patients with chronic hepatitis B requires re-evaluation. Further studies are required to predict outcomes after cessation of nucleoside analogue to ensure immunological control without severe aftermath. Newer compounds interfering with translation or HBsAg assembly offer the possibility of a direct reduction of HBsAg in serum. The clinical effect of deepening inhibition or a shutdown of HBV replication could be achieved with a combination of nucleoside analogues and capsid inhibitors. Data suggest that detectable pgRNA and HBcrAg together reflect residual cccDNA and transcription.

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.

Post-partum ALT increases are observed in 30% of HBsAg+ mothers and are also noticed in mothers administered nucleoside analogues (NA) to prevent mother-to-child transmission (MTCT). As such flares may be injurious we have studied the utility of novel and sensitive markers of cccDNA transcriptional activity [hepatitis B core-related antigen (HBcrAg) and pre-genomic (pg)RNA] to predict post-partum ALT flares in both NA treated and untreated HBsAg+ mothers. We aimed to evaluate the role of serum levels of HBcrAg and pgRNA in pregnancy to predict post-delivery ALT flares, their severity and by inference, a preference to continue on NA. Methods Plasma samples from 642 HBsAg-positive pregnant women were collected during 3rd trimester and at 6, 12, 24, 36 and 48 weeks post-partum. 103(16%) were HBeAg+; median age 31 years. Samples were tested for HBeAg, HBV DNA (Roche; IU/ml); quantitative HBsAg (Abbott Architect; log10IU/ml), HBcrAg levels (CLEIA Fujirebio; log10U/ml) and pgRNA concentrations (PCR assay Abbott Diagnostic; log10U/ml). 95/642(15%) mothers with HBV DNA concentrations >200,000 IU/ml started tenofovir prophylaxis from 28 weeks of gestation to prevent HBV MTCT. The ALT flares incidence and severe flares (defined as >10xULN) was correlated with HBcrAg and pgRNA in treated and untreated mothers. Results Untreated cohort: 106/547(19%) of untreated mothers developed a post-delivery flare, but none was severe. Higher pre-delivery HBV DNA, HBcrAg and pgRNA concentrations were observed in untreated mothers with post-partum ALT flares vs. mothers without a flare. Pregnancy ALT and HBsAg concentrations were similar in flare vs. no flare patients. NA treated cohort: Higher pre-delivery HBcrAg and pgRNA concentrations were observed in NA treated mothers with a post-partum flare. 80/95(84%) treated mothers stopped NA therapy post-partum (median 4 weeks). However no difference in flares incidence was observed in mothers discontinuing treatment vs. mothers who continued NA. [56/80(70%) vs 13/15(87%)]. Seven HBeAg-negative treated patients who stopped NA developed a severe ALT flare within 12 weeks post-delivery. High pre-delivery levels of HBcrAg (>7 log10U/ml) and pgRNA (>4 log10U/ml) were exclusive in mothers with severe flare, but no flares were associated with hepatic synthetic dysfunction and resolved after re-starting NA. 13/103(13%) mothers lost HBeAg and 6(1%) lost HBsAg spontaneously within 1 year post-delivery (all mild flares). Conclusion Post-partum ALT flares are more common in pregnant women with higher pregnancy HBcrAg and pgRNA levels, in both NA treated and untreated mothers. High pre-delivery levels could suggest that NA therapy should be continued post-partum to avoid severe and injurious ALT flares.

Background and Aims Thrombocytopenia complicates management of chronic liver disease (CLD), and may interfere with the performance of invasive procedures. Lusutrombopag (LUSU), an oral, small molecule thrombopoietin receptor agonist, has been studied for the treatment of thrombocytopenia in patients with CLD who are scheduled for invasive procedures. Aiming to further assess its efficacy and safety, a meta-analysis of LUSU randomised controlled trial (RCT) data is presented. Method A direct random-effects meta-analysis was conducted in Stata 14.2MP, using the method of DerSimonian and Laird, with data from three RCTs enrolling pre-procedure CLD patients with a platelet count (PC) Results LUSU is statistically significantly better than PBO in reducing the need for platelet transfusions (PT) prior to and after an invasive procedure (No PT during study: Odds ratio 11.24 (95% CI: 2.83, 44.64); p = 0.001). During the procedure window, patients who received LUSU and no PT had a statistically significant higher increase in PC than patients who received PBO and a PT (mean difference between LUSU and no PT versus PBO with PT at day 12: 34.18 × 109/L (95% CI: 30.31, 38.06; p Conclusion Lusutrombopag is well tolerated and can increase platelet count in thrombocytopenic CLD patients prior to an invasive procedure, reducing the need for platelet transfusions and lowering the risk of bleeding.

SUMMARY Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV’s epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.

In the 1980s and 1990s, thousands of people with bleeding disorders (PWBD) across the world were infected with HIV and hepatitis C virus (HCV) through contaminated treatment products. The extent of the infection, as well as the needs of those still living with HCV, were never properly assessed. The purpose of our survey was to identify how many PWBD were infected with HCV in Europe, as well as their health status and needs. HCV infection was defined as any person with a bleeding disorder who was exposed to the virus and seroconverted to become anti-HCV antibody positive. The survey also looked at testing and treatment availability. Between December 2016 and March 2017, the survey was distributed to 45 national patient organisations in the European Haemophilia Consortium (EHC), who were encouraged to respond with the support of a local hepatologist. The data gathered led us to estimate that some 15,000 people with bleeding disorders were infected with HCV in the 30 countries that responded. Although some countries have detailed records of patients with HCV, most - including some with national haemophilia registries - were unable to provide exact numbers of initial infections, HIV coinfection, survival and SVR rates. Responding countries reported varying degrees of monitoring for disease progression, as well as extremely divergent access to new direct-acting antivirals, with only eight countries prioritising PWBD for treatment. With liver disease and hepatocellular carcinoma being among the main causes of death in an aging bleeding disorders population, this survey identifies a clear gap in care. It is a frustrating paradox that today, in many European countries PWBD, such as haemophilia, may live long and productive lives due to much-improved access to factor replacement therapy, yet die prematurely of a curable disease such as hepatitis C. It has been demonstrated that HCV eradication in PWBD can be achieved through national commitment, especially when the patient population is limited and HCV eradication could be achieved in the short-term. The eradication of HCV in PWBD in Europe is an idea whose time has come.

Objectives To evaluate the efficacy and tolerability of direct‐acting antiviral (DAA) therapy in individuals aged 65 and older. Design Retrospective review between June 2014 and January 2017. Setting Viral hepatitis outpatient clinic. Participants Individuals aged 65 and older treated with DAA therapy for hepatitis C virus (HCV) during the study period (N=113) divided into 2 cohorts: aged 65 to 74 (n=88) and aged 75 and older (n=25). Measurements Drug‐drug interactions (DDIs), adverse events (AEs), and rates of sustained virologic response with DAA therapy were assessed. Results Sustained virologic response rate was 97.7% in individuals aged 65 to 74 and 95.8% in those aged 75 and older. Individuals aged 75 and older were more likely to be taking more than 2 medications per day for chronic conditions (84% vs 62%, p=.02) and more likely to have clinically significant DDIs necessitating cessation or adjustment of medications before commencement of DAA therapy (80% vs 36%, p=.001). Moreover, individuals aged 75 and older were more likely to experience an AE during therapy (50% vs 26%, p=.03) and were more susceptible to developing anemia secondary to ribavirin (60% vs 20%, p=.02). Conclusion DAA therapy is highly efficacious for the treatment of HCV in older adults, but those aged 75 and older are more likely to have clinically significant pretreatment DDIs and experience AEs, including ribavirin‐induced anemia, during therapy.

Universal hepatitis B virus vaccination has been effective in reducing incident chronic hepatitis B but will not have the requisite effect on the prevalence of end-stage liver disease in chronically infected persons. The natural history and immunological stages of hepatitis B virus infection are still being defined. Over three decades, current therapies have reduced morbidity from chronic hepatitis B. The majority require nucleoside analog maintenance therapy. The preferential preservation of covalently closed circular DNA (cccDNA), and capsid reverse transcriptase–cccDNA interactions currently precludes cure in most. A functional cure in the host may require several synergistic antiviral and immunological intercessions. The correct sequencing and combinations of treatment with either host or viral targeting agents have yet to be determined. Proven surrogates for cccDNA for clinical trials are required. Different strategies may become apparent for patients at different stages of the disease. Curative therapies will require affordability. This review focuses on steps toward a cure.

In 2016, WHO adopted a strategy for the elimination of viral hepatitis by 2030. Africa, and more specifically, sub-Saharan Africa, carries a substantial portion of the global burden of viral hepatitis, especially chronic hepatitis B and hepatitis C virus infections. The task that lies ahead for sub-Saharan Africa to achieve elimination is substantial, but not insurmountable. Major developments in the management of hepatitis C have put elimination within reach, but several difficulties will need to be navigated on the path to elimination. Many of the challenges faced are unique to sub-Saharan Africa and the development of strategies is complicated by a scarcity of good data from countries and regions within sub-Saharan Africa. However, this hindrance should not act as a barrier to delay interventions in screening, detection, and linkage to care. Moreover, by sharing experiences from across sub-Saharan Africa, countries can create supranational synergies to develop their programmes and work together in a more cohesive manner to tackle the burden of hepatitis C in sub-Saharan Africa. In this Series paper, several issues related to hepatitis C in sub-Saharan Africa are addressed, including prevalence, risk factors, and fibrosis assessment, and recommendations are given by experts from across the region. Simplified diagnostic algorithms and treatment regimens for both HIV co-infected and hepatitis C mono-infected patients are suggested. The recommendations are consensus based and provided to guide the development of programmes in sub-Saharan Africa. Political will and appropriate funding will be required to provide impetus to implement these recommendations.

The WHO global health sector strategy on viral hepatitis, created in May, 2016, aims to achieve a 90% reduction in new cases of chronic hepatitis B and C and a 65% reduction in mortality due to hepatitis B and C by 2030. Hepatitis B virus (HBV) is endemic in sub-Saharan Africa, and despite the introduction of universal hepatitis B vaccination and effective antiviral therapy, the estimated overall seroprevalence of hepatitis B surface antigen remains high at 6·1% (95% uncertainty interval 4·6-8·5). In this Series paper, we have reviewed the literature to examine the epidemiology, burden of liver disease, and elimination strategies of hepatitis B in sub-Saharan Africa. This paper reflects a supranational perspective of sub-Saharan Africa, and recommends several priority elimination strategies that address the need both to prevent new infections and to diagnose and treat chronic infections. The key to achieving these elimination goals in sub-Saharan Africa is the effective prevention of new infections via universal implementation of the HBV birth-dose vaccine, full vaccine coverage, access to affordable diagnostics to identify HBV-infected individuals, and to enable linkage to care and antiviral therapy.

Instruments to assess the impact of hepatitis C virus infection on health and measurements of reported outcomes in patients (health-related quality of life [HRQOL]) are not frequently used to assign priority for treatment. Several systematic reviews have been performed that provide a comprehensive analysis to help understand patient reported outcomes (PROs) with direct acting antiviral treatment. Clinical trials with direct acting antivirals (DAAs) provide an important opportunity to assess PROs without interferon or ribavirin. Significant improvement in quality of life parameters have been noted with DAA therapy. The results show improvement in HRQOL indices when interferon-free and particularly interferon and ribavirin-free treatments are compared to interferon and ribavirin treatment. Improvements in HRQOL indices are an encouraging aspect of the cure of chronic hepatitis C. It is unclear whether these measurable HRQOL improvements can be translated into a net benefit improvement in work productivity and a social dimension that is significant enough to convince payers of the added value of early and more widespread treatment.