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Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV‐specific T cells, which is regulated by various co‐suppressor molecules. Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) is among these co‐suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV‐specific T cells. CTLA‐4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA‐4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA‐4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA‐4 may contribute to HBV infection, as well as the development of HBV‐induced cirrhosis and hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

ABSTRACT Hepatitis E virus (HEV) is a foodborne zoonotic pathogen that is supposed to be one of the most common causes of acute viral hepatitis. However, HEV infection has been recently associated with a wide spectrum of extrahepatic manifestations, particularly neurological disorders. Previous studies have shown that HEV is able to cross the blood–brain barrier (BBB) and induce inflammatory response of the central nervous system. However, the pathogenesis of HEV‐induced neuroinflammation and tissue injury of the central nervous system have yet to be fully elucidated. In this study, activation of NLRP3 inflammasome following HEV infection were investigated. In a gerbil model infected by HEV, brain histopathological changes including gliosis, neuronophagia and neuron injury were observed and expression of NLRP3, caspase‐1, IL‐1β and IL‐18 were elevated. Brain microvascular endothelial cells (BMECs) are key components of the BBB that protects the brain from various challenges. Following HEV infection, virus‐like particles range from 30 to 40 nm in diameter were observed in human BMECs (hBMECs). Enhanced expression levels of NLRP3 and subsequent ASC, caspase‐1, IL‐1β and IL‐18 were detected in infected cells. Treatment with MCC950 alleviated HEV infection induced activation of NLRP3 inflammasome, mitochondrial damage and VE‐cadherin degradation. The findings provide new insights into HEV‐associated neuroinflammation. Moreover, targeting NLRP3 inflammasome signalling is a promising therapeutic in HEV‐induced neurological disorder. [ABSTRACT FROM AUTHOR]

ABSTRACT HCV RNA test determines current active infection and is a requirement prior to initiating HCV treatment. We investigated trends and factors associated with post‐diagnosis HCV RNA testing rates prior to HCV treatment, and risk factors for first positive HCV RNA among people living with HIV (PLHIV) with HCV in the Asia‐Pacific region. PLHIV with positive HCV antibody and in follow‐up after 2010 were included. Patients were considered HCV‐antibody positive if they ever tested positive for HCV antibody (HCVAb). Repeated measures Poisson regression model was used to analyse factors associated with post‐diagnosis HCV RNA testing rates from positive HCVAb test. Factors associated with time to first positive HCV RNA from positive HCVAb test were analysed using Cox regression model. There were 767 HCVAb positive participants included (87% from LMICs) of whom 11% had HCV RNA tests. With 163 HCV RNA tests post positive HCVAb test, the overall testing rate was 5.05 per 100 person‐years. Factors associated with increased testing rates included later calendar years of follow‐up, HIV viral load ≥1000 copies/mL and higher income countries. Later calendar years of follow‐up, ALT >5 times its upper limit of normal, and higher income countries were associated with shorter time to first positive HCV RNA test. Testing patterns indicated that uptake was predominantly in high income countries possibly due to different strategies used to determine testing in LMICs. Expanding access to HCV RNA, such as through lower‐cost point of care assays, will be required to achieve elimination of HCV as a public health issue. [ABSTRACT FROM AUTHOR]

One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012–2020. Two community‐based interventions were implemented in 2012–2013 and 2018–2020 with repeated sero‐behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti‐HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012–2013 and 2018–2020. Αnti‐HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012–2013 to 40.0% [31.3, 49.1%] in 2018–2020 (25.4% reduction, p =.007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person‐years (PYs) [29.6, 51.5] (30.5% reduction, p =.020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012–2013 and 9/55 in 2018–2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p <.001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high‐coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012–2020. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a foodborne virus transmitted through the faecal–oral route that causes viral hepatitis in humans worldwide. Ever since its discovery as a zoonotic agent, HEV was isolated from several species with an expanding range of hosts. HEV possesses several features of other RNA viruses but also has certain HEV‐specific traits that make its viral–host interactions inimitable. HEV leads to severe morbidity and mortality in immunocompromised people and pregnant women across the world. The situation in underdeveloped countries is even more alarming. Even after creating a menace across the world, we still lack an effective vaccine against HEV. Till date, there is only one licensed vaccine for HEV available only in China. The development of an anti‐HEV vaccine that can reduce HEV‐induced morbidity and mortality is required. Live attenuated and killed vaccines against HEV are not accessible due to the lack of a tolerant cell culture system, slow viral replication kinetics and varying growth conditions. Thus, the main focus for anti‐HEV vaccine development is now on the molecular approaches. In the current study, we have designed a multi‐epitope vaccine against HEV through a reverse vaccinology approach. For the first time, we have used viral ORF3, capsid protein and polyprotein altogether for epitope prediction. These are crucial for viral replication and persistence and are major vaccine targets against HEV. The proposed in silico vaccine construct comprises of highly immunogenic and antigenic T‐cell and B‐cell epitopes of HEV proteins. The construct is capable of inducing an effective and long‐lasting host immune response as evident from the simulation results. In addition, the construct is stable, non‐allergic and antigenic for the host. Altogether, our findings suggest that the in silico vaccine construct may be useful as a vaccine candidate for preventing HEV infections. [ABSTRACT FROM AUTHOR]

On March 31, 2022, severe acute hepatitis of unknown origin was first reported from the Royal Glasgow Children's Hospital in Scotland. According to the criteria by WHO‐ECDC, a probable case of unknown acute hepatitis in children is defined as a subject under 16 years of age, who tested negative for viral hepatitis and transaminases >500 U/L, starting from the 1st of October 2021. WHO invites Member States to participate in the global effort to collect anonymized clinical data on probable cases of severe acute hepatitis of unknown aetiology. As of May 26, 2021, 650 cases were already registered on the platform worldwide, of whom at least 38 cases have required liver transplants. Several hypotheses such as previous SARS‐CoV‐2 infection or coinfection or infection with another virus were examined and a strong association was found between adenovirus (41F) and acute hepatitis of unknown aetiology cases. This review article summarizes the global epidemiological evidences on acute hepatitis of unknown origin in children, analysing their incidence and characteristics. [ABSTRACT FROM AUTHOR]

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero‐surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)‐positive) prevalence and HCV exposure (HCV antibody (HCV‐Ab)‐positive) prevalence between two sero‐surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population‐attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2–2.9) in 2007 to 1.1% (95% CI: 0.8–1.3) in 2019, while HCV‐Ab prevalence increased from 5.1% (95% CI: 4.6%–5.5%) to 6.2% (95% CI: 5.6%–6.8%). The age and gender‐adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1–0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3–0.6) among adults over 2007–2019, while HCV‐Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2–0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2–1.7) in adults. HCV‐Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5–0.8) and higher (aOR = 0.5, 95%CI:0.3–0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2–2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9–3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6–2.7), being tattooed (aOR = 1.4, 95% CI: 1.0–1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0–1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7–48.4%). Overall HCV has increased over 2007–2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities. [ABSTRACT FROM AUTHOR]

Screening for viral hepatitis is considered a high‐priority area in the Veterans Health Administration (VHA). Yet, few studies have examined viral hepatitis screening test use among low‐income veterans who are considered high‐risk with limited healthcare access. Using cross‐sectional data from 933 participants in the 2021–2022 National Veteran Homeless and Other Poverty Experiences (NV‐HOPE) study, we examined rates and correlates of lifetime screening for hepatitis B (HBV) and hepatitis C (HCV) infections. Multivariable logistic regression models evaluated characteristics associated with HBV/HCV screening. Nearly 16% and 21% reported lifetime HBV and HCV screening, respectively. These rates are considerably lower than HBV (47.3%) and HCV (92.9%) screening rates documented among contemporaneous veterans in VHA electronic health records. In the NV‐HOPE data, veterans 50–79 years were more likely than those ≥80 years of age to ever‐screen for HBV/HCV. Whereas, household income was inversely related to lifetime screening behaviours, veterans reporting ‘other’ employment types (vs. full‐time/part‐time employment) were more likely to ever‐screen for HBV/HCV. Ever‐screening for HBV was more likely among veterans reporting non‐Hispanic ‘other’ (vs. non‐Hispanic ‘white’) race, housing instability, Medicaid insurance, as well as drug use and cognitive disorder histories. Living with ≥5 members (vs. alone), histories of alcohol use, cancer, and liver disorders were also correlated with ever‐screening for HCV. HIV/AIDS history correlated with ever‐screening for HBV/HCV. In conclusion, fewer than one‐third of low‐income US veterans ever‐screened for HBV/HCV, with lower screening rates among those less likely to be exposed to viral hepatitis, thereby informing interventions aimed at promoting available screening, treatment and vaccinations for HBV/HCV. [ABSTRACT FROM AUTHOR]

In Vietnam and the Philippines, viral hepatitis is the leading cause of cirrhosis and liver cancer. This study aims to understand the barriers and enablers of people receiving care for hepatitis B and C to support both countries' efforts to eliminate viral hepatitis as a public health threat by 2030. Retrospective, semi‐structured interviews were conducted with a purposive, quota‐based sample of 63 people living with hepatitis B or C in one province of Vietnam and one region of the Philippines. A rapid deductive approach to thematic analysis produced key findings among the three phases of care: (1) pre‐awareness and testing, (2) linkage and treatment initiation and (3) ongoing treatment and recovery. The research found that participants followed five typical journeys, from a variety of entry points. Barriers during the pre‐awareness and testing phase included limited awareness about hepatitis and its management, stigma and psychological impacts. Enablers included being familiar with the health system and/or patients benefiting from social connections within the health systems. During the linkage and treatment initiation phase, barriers included difficult physical access, complex navigation and inadequate counselling. In this phase, family support emerged as a critical enabler. During the ongoing treatment and recovery phase, the cost of care and socially and culturally informed perceptions of the disease and medication use were both barriers and enablers. Exploring peoples' journeys with hepatitis B and C in Vietnam and the Philippines revealed many similarities despite the different cultural and health system contexts. Insights from this study may help generate a contextualized, people‐centred evidence base to inform the design and improvement of primary care services for hepatitis in both research sites. [ABSTRACT FROM AUTHOR]

The current World Health Organization (WHO) Hepatitis Elimination Strategy suffers from lack of a target for diagnosing or expunging occult HBV infection. A sizable segment of the global population has an undetected HBV infection, particularly the high‐risk populations and those residing in countries like India with intermediate endemicity. There is growing proof that people with hidden HBV infection can infect others, and that these infections are linked to serious chronic hepatic complications, especially hepatocellular carcinoma. Given the current diagnostic infrastructure in low‐resource settings, the WHO 2030 objective of obliterating hepatitis B appears to be undeniably challenging to accomplish. Given the molecular basis of occult HBV infection strongly linked to intrahepatic persistence, patients may inexplicably harbour HBV genomes for a prolonged duration without displaying any pronounced clinical or biochemical signs of liver disease, and present histological signs of moderate degree necro‐inflammation, diffuse fibrosis, and hence the international strategy to eradicate viral hepatitis warrants inclusion of occult HBV infection. [ABSTRACT FROM AUTHOR]

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non‐hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post‐transplant outcomes in patients with HBV or HCV positivity receiving non‐hepatic solid‐state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006–2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post‐transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p >.05). Similarly, there was no difference in post‐transplant survival between lung transplant recipients with vs. without anti‐HCV (all p >.05). Heart transplant recipients with HCV+ had higher crude post‐transplant mortality (all p <.01). Similarly, there was higher post‐transplant mortality in kidney transplant recipients with HCV+ (1‐year: 6% vs. 3%; 5‐year: 21% vs. 13%; 10‐year: 47% vs. 31%; all p <.0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post‐kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12–1.20), p <.0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p >.05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post‐transplant outcomes in non‐hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post‐transplant mortality. [ABSTRACT FROM AUTHOR]

Adolescents and young adults are the driving force of social development, and the prevalence of acute viral hepatitis (AVH) in this population cannot be ignored. At present, there are few studies on the disease burden of AVH in this age group, and most studies focus on chronic liver disease. In this study, we identified global trends in the burden of AVH among adolescents and young adults (15–29) to help policymakers implement precise disease interventions. In this observational study of disease trends, we collected data exclusively from the Global Burden of Disease (GBD) 2019 study. This study examined the trends in the prevalence, incidence and mortality of AVH among adolescents and young adults in 21 regions of the world from 2009 to 2019. Age‐specific disease trends were analysed with a joinpoint regression model. The overall global disease burden of AVH declined. The prevalence rate per 100,000 people decreased from 316.13 in 2009 to 198.79 in 2019, the incidence rate decreased from 3245.52 in 2009 to 2091.93 in 2019, and the death rate decreased from 0.87 in 2009 to 0.43 in 2019. During the study period, the prevalence of hepatitis B virtues (HBV) in the young population decreased, but the downward trend of other types of hepatitis other than HBV was not obvious, especially HAV, which even showed an upward trend. Among adolescents and young adults aged 15–29 years, Western Saharan Africa had the highest prevalence of AVH in 2019. There were significant differences in mortality rates among different age groups; 20–24 was the age group with the highest mortality rate from 2009 to 2019, followed by the 15–19 and 25–29 age groups. Although the overall global AVH disease burden declined, some causes of AVH, such as HAV, showed an upward trend during the study period. In addition, the prevalence of AVH among adolescents and young adults in Asia and Africa was higher than that in other parts of the world and warrants more attention. Finally, more research should be conducted on mortality in the 20–24 age group. [ABSTRACT FROM AUTHOR]

Infection with hepatitis D virus leads to liver disease and cancer most rapidly of all hepatitis viruses. However, knowledge about hepatitis D remains poor and the burden and impact are underestimated, even though some 12–15 million people mainly in low‐ and middle‐income countries may be affected. Its epidemiology is changing, with increasing migration leading to increased risks of infection and disease. A recent Viral Hepatitis Prevention Board meeting reviewed the current epidemiological status, improvements in diagnostic testing, advances in the development of novel antiviral agents in phase III trials and the need for a greater public health response, such as new guidelines and recommended testing of all people newly identified as infected with hepatitis B virus for hepatitis D virus infection. It identified issues and needs for attention with regard to prevention, diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Data on the acceptability and usability of hepatitis C virus self‐testing (HCVST) remain scarce. We estimated the pooled rates of acceptability/feasibility and re‐reading/re‐testing agreement of HCVST using oral fluid tests (PROSPERO‐CRD42022349874). We searched online databases for studies that evaluated acceptability, usability and inter‐reader/operator variability for HCVST using oral fluid tests. Pooled estimates of feasibility, agreement and post‐testing perspectives were analysed. Sensitivity analyses were performed in men who have sex with men (MSM) and people who inject drugs (PWID). Heterogeneity was assessed using the I2 statistics. A total of six studies comprising 870 participants were identified: USA (n = 95 with liver disease), Kenya (n = 150 PWID), Egypt (n = 116 from the general population), Vietnam (n = 104 MSM and n = 105 PWID), China (n = 100 MSM) and Georgia (n = 100 MSM and n = 100 PWID)]. All studies used OraQuick® HCV Rapid Antibody Test. The pooled overall estimates for correct sample collection and for people who performed HCVST without needing assistance in any step (95% confidence interval [CI]) were 87.2% [76.0–95.3] (n = 755; I2 = 93.7%) and 62.6% [37.2–84.8] (n = 755; I2 = 98.0%), respectively. The pooled estimate of agreement for re‐reading was 95.0% [95% CI 91.5–97.6] (n = 831; I2 = 74.0%) and for re‐testing was 94.4% [90.3–97.5] (n = 726; I2 = 77.1%). The pooled estimate of those who would recommend HCVST was 94.4% [84.7–99.6] (n = 625; I2 = 93.7%). Pooled estimates (95% CI) of correct sample collection (72.8% [63.3–81.5] vs. 90.8% [85.9–94.8]) and performance of HCVST without needing assistance (44.1% [14.1–76.7] vs. 78.1% [53.4–95.3]) was lower in PWID compared to MSM. In summary, HCV testing with oral fluid HCVST was feasible and well‐accepted. Oral fluid HCVST should be considered in key populations for uptake HCV testing. [ABSTRACT FROM AUTHOR]

Most clinic attenders with chronic hepatitis B (CHB) are serum HBeAg‐negative, and a minority will require suppressive antiviral treatment. Expert guidelines propose schedules for the monitoring of untreated patients, but the recommended frequency of patient review does not reflect recognised demographic determinants of HBeAg‐negative chronic hepatitis. Also, the impact of patient ethnicity on risk has not been defined. The aim of our study was to determine the rates and determinants of antiviral treatment initiation in a large multi‐ethnic cohort of CHB patients attending a single centre. We undertook a retrospective study using entirely electronic sources of patient information. Treatment initiation dates were identified from electronic pharmacy records. Crude and time‐dependent statistical analyses were undertaken to identify rate and risk factors for treatment initiation. Treatment was initiated for 232/1256 (18.5%) patients with rates of 23.2% and 33.2% at 5 and 10 years. An increased risk of treatment was associated with male sex (RR 1.803), older age at presentation (RR 1.027 per year increase) and with non‐Black ethnicity (RR 1.654). Patient sex, baseline age and ethnicity also determined risk for treatment in the subset of patients with normal serum ALT and low HBV DNA at baseline, though overall treatment rate in this group was low (only 2% per annum). Thus, patient demographics permit risk stratification for treatment initiation and could determine to a significant extent the frequency of review required for untreated HBeAg‐negative patients. Black ethnicity is associated with a significant reduction in risk of treatment initiation. [ABSTRACT FROM AUTHOR]

Keywords: Europe; hepatitis B infection; hepatitis C infection; migrants; refugees EN Europe hepatitis B infection hepatitis C infection migrants refugees 634 637 4 07/25/23 20230801 NES 230801 Abbreviations EEA European Economic Area EU European Union HBV hepatitis B virus HCV hepatitis C virus Migrants from some areas of the world bear a high burden of hepatitis C virus (HCV) chronic infection and may represent a major proportion of chronic HCV carriers in countries where the background infection rate is otherwise low. The rate of HBV infection among migrants to European Union (EU) countries born in highly endemic regions was reported as 6%, compared to 1% in the general population.[4] Regarding HCV infection, migrants account for a large proportion of HCV cases in the EU/EEA (on average 14% of cases and >50% of cases in some countries).[4] Data from 50 studies reporting on 38,635 migrants from all world regions show an overall seroprevalence of HCV of 1.9% (95% CI: 1.4-2.7, I I i SP 2 sp 96.1). Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: a focus on migrants from anti-HCV endemic countries. In this country, migrants account for 35% of HCV infections, despite representing only 22% of the population.[1] Passos-Castilho and colleagues aimed to investigate sub-groups of migrants, defined as persons born outside of Canada with permission to live permanently in Canada, who displayed the highest HCV infection rates and changes over time. [Extracted from the article]

Immigrants living in low hepatitis C (HCV) prevalence countries bear a disproportionate HCV burden, but there are limited HCV population‐based studies focussed on this population. We estimated rates and trends of reported HCV diagnoses over a 20‐year period in Quebec, Canada, to investigate subgroups with the highest rates and changes over time. A population‐based cohort of all reported HCV diagnoses in Quebec (1998–2018) linked to health administrative and immigration databases. HCV rates, rate ratios (RR) and trends overall and stratified by immigrant status and country of birth were estimated using Poisson regression. Among 38,348 HCV diagnoses, 14% occurred in immigrants, a median of 7.5 years after arrival. The average annual HCV rate/100,000 decreased for immigrants and nonimmigrants, but the risk (RR) among immigrants increased over the study period [35.7 vs. 34.5 (RR = 1.03) and 18.4 vs. 12.7 (1.45) between 1998–2008 and 2009–2018]. Immigrants from middle‐income Europe & Central Asia [55.8 (RR = 4.39)], sub‐Saharan Africa [51.7 (RR = 4.06)] and South Asia [32.8 (RR = 2.58)] had the highest rates between 2009 and 2018. Annual HCV rates decreased more slowly among immigrants vs. nonimmigrants (−5.9% vs. −8.9%, p < 0.001), resulting in a 2.5‐fold (9%–21%) increase in the proportion of HCV diagnoses among immigrants (1998–2018). The slower decline in HCV rates among immigrants over the study period highlights the need for targeted screening for this population, particularly those from sub‐Saharan Africa, Asia and middle‐income Europe. These data can inform micro‐elimination efforts in Canada and other low‐HCV‐prevalence countries. [ABSTRACT FROM AUTHOR]

Primary liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death. Advances in sequencing technology are opening genomics to widespread application for diagnosis and research. The poor prognosis of advanced HCC warrants a personalized approach. The objective was to assess the value of genotyping for risk stratification and prognostication of HCC. We performed a systematic review of manuscripts published on MEDLINE from 1 January 2009 to 1 January 2022, addressing the value of genotyping for HCC risk stratification and prognostication. Publication information for each has been collected using a standardized data extraction form. Twenty‐five articles were analysed. This study showed that various genomics approaches (i.e., NGS, SNP, CASP or polymorphisms in circadian genes' association) provided predictive and prognostic information, such as disease control rate, median progression‐free survival, and shorter median overall survival. Genotyping, which advances in understanding the molecular origin, could be a solution to predict prognosis or treatment response in patients with HCC. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is the main etiological agent of hepatocellular carcinoma (HCC) worldwide. It has been classified into nine genotypes and several subgenotypes, with uneven global distribution. There is growing evidence that the viral genotype influences the course and outcome of chronic hepatitis B infection. Two evolutionarily different clusters of the subgenotype F1b, called basal and cosmopolitan, have been described. The two clusters have constrained geographical distribution, with the particular feature that the basal cluster is present in regions of high HCC incidence, while the Cosmopolitan cluster is found in regions of low HCC incidence. The BCP/pC region was sequenced in 68 cases chronically infected with the F1b subgenotype to determine if there was a differential pattern of pathogenic‐associated mutations between both clusters. Twenty‐two of the 68 cases belonged to the subgenotype F1b basal cluster and 46 to the cosmopolitan cluster. Among the HBeAg‐negative patients the A1762T/G1764A and G1896A mutations were more frequently found in the basal samples (85.7 and 92.9%) compared to the cosmopolitan ones (50 and 18.2%). Interestingly, no HBeAg loss‐associated mutations were observed in 7.1 and 36.4% of the basal and cosmopolitan cases, respectively. The different rate of mutations associated with a more severe course of chronic hepatitis in the basal cluster would support the difference in the HCC incidence rate in the geographical regions where the basal cluster is restricted. [ABSTRACT FROM AUTHOR]

Routinely collected and linked healthcare administrative datasets could be used to monitor mortality among people with hepatitis B (HBV) and C (HCV). This study aimed to evaluate the concordance in records of liver‐related mortality among people with an HBV or HCV notification, between data on hospitalization for end‐stage liver disease (ESLD) and death certificates. In New South Wales, Australia, HBV and HCV notifications (1993–2017) were linked to hospital admissions (2001–2018), all‐cause mortality (1993–2018) and cause‐specific mortality (1993–2016) datasets. Hospitalization for ESLD was defined as a first‐time hospital admission due to decompensated cirrhosis (DC) or hepatocellular carcinoma (HCC). Consistency of liver death definition of mortality following hospitalization for ESLD was compared with two death certificate‐based definitions of liver deaths coded among primary and secondary cause‐specific mortality data, including ESLD‐related (deaths due to DC and HCC) and all‐liver deaths (ESLD‐related and other liver‐related causes). Of 63,292 and 107,430 individuals with an HBV and HCV notification, there were 4478 (2.6%) post‐ESLD hospitalization deaths, 5572 (3.3%) death certificate liver disease deaths and 2910 (1.7%) death certificate ESLD deaths. Between 2001 and 2016, among HBV post‐ESLD hospitalization deaths (n = 891), 63% (562) had death certificate ESLD recorded, and 83% (741) had death certificate liver disease recorded. Between 2001 and 2016, among HCV post‐ESLD hospitalization deaths (n = 3587), 58% (2082) had death certificate ESLD recorded, and 87% (3135) had death certificate liver disease recorded. At least one‐third of death certificates with DC and HCC as cause of death had no mention of HBV, HCV or viral hepatitis. Our study identified limitations in estimating and tracking HBV and HCV liver disease mortality using death certificate‐based data only. The optimum data for this purpose is either ESLD hospitalisations with vital status information or a combination of these with cause‐specific death certificate data. [ABSTRACT FROM AUTHOR]

In 2020, China conducted a nationwide, sero‐epidemiological, cross‐sectional survey of viral hepatitis. The stratified multi‐stage cluster random sampling method was used to select the permanent population aged 1–69 years, followed by questionnaire survey and sample collection and detection of the serological markers of hepatitis B (HBV) and hepatitis C viruses (HCV). A total of 4747 individuals aged 1–69 years were investigated in Zhejiang Province. The positive rates of hepatitis B surface antigen and anti‐HCV were 4.3% and 0%, respectively. Compared to a similar sero‐epidemiological survey in 1992, the 2020 survey showed that the HBV infection rate in Zhejiang Province decreased by 56.5%. In both surveys, HBV infection rate increased with age (in 1992, χ2 = 185.866, p =.000; in 2020, χ2 = 1383.836, p =.000). Compared with 1992, the positive anti‐HCV rate in those aged 1–69 years in 2020 decreased by 100.0%. This result showed that the HBV vaccine and blood screening to prevent HBV and HCV infection significantly decreased the infection rate of HBV and HCV in the younger generation of Zhejiang province. However, the rate of HBV carriers aged 30–69 years was still high, which underscores the need to strengthen the management and treatment of chronic HBV infection. Hence, Zhejiang province can eliminate the public health threat of viral hepatitis. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) is a small RNA virus which needs Hepatitis B Surface Antigen for its envelope, for entry into hepatocytes and secretion. HDV chronic infection affects around 12 million people worldwide. HDV infection is believed to be the most severe form of viral hepatitis, with a high risk of developing cirrhosis and hepatocellular carcinoma. Pegylated interferons has been used and recommended by guidelines, although not approved, with low efficacy and poor tolerability. Bulevirtide (entry inhibitor) has been recently conditionally approved by the European Medicines Agency. These treatments have many advantages, but they have also limitations since there are non‐responders to these previous therapies. There is an urgent need to develop new drugs. In this article, we review antiviral treatments under development for HDV chronic infection (except bulevirtide reviewed in a specific article), including those in the HBV cure programme, outlining their respective mechanisms‐of‐action. [ABSTRACT FROM AUTHOR]

Chronic hepatitis Delta (CHD) is a rare and severe form of chronic viral hepatitis. Until recently, the only therapeutic approach has been the off‐label use of a 48 weeks course of PegInterferon alpha (PegIFNα), that was characterized by suboptimal efficacy and burdened by significant side effects that limited treatment applicability in patients with advanced liver disease. In July 2020, European Medicines Agency (EMA) conditionally approved the entry inhibitor Bulevirtde (BLV) at the dose of 2 mg/day for the treatment of adult patients with compensated CHD. Efficacy and safety of BLV in CHD have been evaluated in clinical trials either as monotherapy or in combination with PegIFNα. These results were confirmed by real‐life studies, which also evaluated long‐term BLV monotherapy in patients with advanced compensated cirrhosis. Notwithstanding these promising results there are still several issues to be addressed, such as the optimal duration of the treatment, the rates of off‐therapy responses, as well as the long‐term clinical benefits. This review summarizes updated and current literature data about clinical trials and real‐life studies with BLV monotherapy and/or in combination with PegIFNα. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) is known to cause the most aggressive and severe form of viral hepatitis, yet it remained under‐diagnosed but does require early diagnosis for accurate disease staging. Antibody to HDV (anti‐HDV) is the primary screening tool and should be assessed in patients with hepatitis B surface antigen (HBsAg) positivity, as HDV is a satellite RNA virus of hepatitis B. Additionally, the viral load (HDV RNA) should be assessed in those with positive anti‐HDV, to differentiate between active infection and resolved hepatitis delta. Data regarding immune responses in HDV are limited but show dysfunctional adaptive and innate immunity. Many studies however fail to distinguish between active and resolved infection. Limited treatments are available for HDV, but promise has been shown with the newly approved Bulevirtide, a first‐in‐class HBV entry inhibitor. Thus immune response during therapy requires further investigation, along with additional targets for HDV cure. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient‐reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real‐world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT‐F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super‐regions. The rates of advanced fibrosis varied (3–24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest – Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p < 0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non‐hepatic comorbidities (p < 0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p < 0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real‐life Global Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico‐demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non‐hepatic comorbidities are independently associated with PRO impairment in CHB patients. [ABSTRACT FROM AUTHOR]

Hepatitis D virus (HDV) infection is highly prevalent in patients with chronic hepatitis B (CHB). AASLD guidelines recommend a risk‐based screening approach. Our aim was to ascertain if the risk‐based approach leads to appropriate HDV screening, identify targets to improve screening rates, and study HDV clinical burden. CHB patients screened for HDV from 01/2016 to 12/2021 were identified. Level of training and specialty of providers ordering HDV screening tests were determined. HDV seropositive (HDV+) patient charts were reviewed for the presence of individual risk factors per the AASLD guidelines to determine if they met screening criteria. The severity of liver disease at the time of HDV screening was compared between the HDV+ group and a matched (based on age, hepatitis B e antigen status, BMI and sex) HDV seronegative (HDV−) group. During the study period, 1444/11,190 CHB patients were screened for HDV. Most screening tests were ordered by gastroenterology (90.2%) specialists and attending physicians (80.5%). HDV+ rate was 88/1444 (6%), and 72 HDV+ patients had complete information for analysis. 18% of HDV+ patients would be missed by a risk‐based screening approach due to unreported or negative risk factors (see Table). A significantly higher number of HDV+ patients had developed significant fibrosis (p = 0.001) and cirrhosis (p < 0.01) by the time of screening than HDV− (n = 67) patients. In conclusion, targeted interventions are needed towards trainees and primary care clinics to improve screening rates. Current risk‐based criteria do not appropriately screen for HDV. It is time for universal screening of HDV in CHB patients. [ABSTRACT FROM AUTHOR]

Most recent FibroScan value was 5.3 kPa (median), though 108 patients had values greater than 6, and 8 patients had values greater than 12. 135 (16.5%) patients were taking or had taken antiviral treatment before loss to follow-up. Keywords: compliance/adherence; hepatitis B; liver; viral hepatitis EN compliance/adherence hepatitis B liver viral hepatitis 223 227 5 02/17/23 20230301 NES 230301 INTRODUCTION There is emerging evidence about rates and determinants of linkage to care for HBV-diagnosed patients.[1] However, to date, little attention has been paid to the important issue of CHB (chronic hepatitis B) patient retention in the outpatient setting.[2] In western centres, most CHB patients are first-generation migrants from countries of high HBV prevalence. The patient NHS records include the patient's current registered address (i.e., on date of data capture 13/7/2022), and we calculated the distance of patient's residence from the QEH Liver Clinic. [Extracted from the article]

Hepatitis Delta virus is the smallest known human virus, exploiting the HBV surface proteins (HBsAg) for the release of its progeny and de novo entry into hepatocytes. Ever growing evidence have highlighted the existence of multiple mechanisms underlying HDV persistence including integrated HBV‐DNA as a source of HBsAg production and the capability of the HDV genome to propagate through cell proliferation, thus supporting a potential HDV persistence even in the absence of HBV. Chronic HDV‐infection causes the most severe form of viral hepatitis, leading to the development of cirrhosis in 15% of cases within 1–2 years and in 50%–60% of cases within 5–10 years. The rates of hepatocellular carcinoma and hepatic decompensation are also 2–3‐fold higher than for HBV mono‐infection. There is the evidence that persistent viral replication plays a key role in triggering liver injury, suggesting the existence of direct viral cytopathic properties that can modulate, synergistically with immune‐responses, the progression towards end‐stage liver diseases. All these aspects can be further exacerbated by the extraordinary degree of viral genetic variability that can promote HDV evasion from immune responses and has enabled viral differentiation into genotypes and subgenotypes with potential different pathobiological properties. In this light, this review aims at providing comprehensive insights of mechanisms (with a focus on virological factors) underlying HDV persistence and pathogenesis, critical in shaping the clinical outcome of the infection. Dissecting these mechanisms is pivotal to optimize therapeutic strategies aimed at fully counteracting this fascinating and fearsome virus. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. An increased risk for HEV infection has been reported in organ‐transplant recipients, mainly from Europe. Prospective data on HEV prevalence in the United States (U.S.) organ transplant population are limited. To determine the prevalence and factors associated with HEV infection among solid organ transplant‐recipients, we conducted a prospective, cross‐sectional, multicentre study among transplant‐recipients and age‐ and organ‐matched waitlist patients. Participants answered a risk‐exposure questionnaire and were tested for HEV‐RNA (in‐house PCR), HEV‐IgG, and IgM (ELISA, Wantai). Among 456 participants, 224 were transplant‐recipients, and 232 were waitlist patients. The mean age was 58 years, 35% female, and 74% White. HEV seroprevalence of the entire cohort was 20.2% and associated with older age (p < 0.0001) and organ transplantation (p = 0.02). The HEV seropositivity was significantly higher among transplant‐recipients compared with waitlist patients (24% vs. 16.4%, p = 0.042). Among transplant recipients, relative‐risk of being HEV seropositive increased with older age (RR = 3.4 [1.07–10.74] in patients >70 years compared with ≤50 years, p = 0.037); history of graft hepatitis (2.2 [1.27–3.72], p = 0.005); calcineurin inhibitor use (RR = 1.9 [1.03–3.34], p = 0.02); and kidney transplantation (2.4 [1.15–5.16], p = 0.02). HEV‐RNA, genotype 3 was detected in only two patients (0.4%), both transplant‐recipients. HEV seroprevalence was higher among transplant‐recipients than waitlist patients. HEV should be considered in transplant‐recipients presenting with graft hepatitis. Detection of HEV‐RNA was rare, suggesting that progression to chronic HEV infection is uncommon in transplant‐recipients in the U.S. [ABSTRACT FROM AUTHOR]

Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N = 12,171 CHC patients were included (GLR n = 3146, clinical trial subjects n = 9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p< 0.001). Out of 15 PRO domain and summary scores, 12 were lower in GLR patients than in subjects enrolled in clinical trials (p< 0.001). In multiple regression models, anxiety, depression, and fatigue were associated with significant PRO impairment in CHC patients (p< 0.05). After adjustment for the clinico-demographic confounders, the association of PRO scores of CHC patients with enrolment settings was no longer significant (all p > 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities. [ABSTRACT FROM AUTHOR]

When patients with chronic hepatitis B (CHB) stop nucleos(t)ide analogue (NA) therapy before achieving HBsAg loss, flares often ensue which are challenging to predict early. We determined the incidence, severity, outcome and predictors of flares after NA withdrawal. Forty-five patients enrolled in an RCT were included; 107 patients from an external, prospective cohort were used for validation. Retreatment criteria were pre-defined. Pre- and post-treatment predictors of alanine aminotransferase (ALT) flare (>5× ULN) were evaluated by Cox proportional-hazards regression. Seventy-two weeks after NA withdrawal, 23/45 (51%) patients had developed >5× ULN and 14 (31%) >20× ULN. Median time to develop ALT >5× ULN was 12 weeks after NA withdrawal. Independent predictors of ALT >5× ULN were male sex (HR [95% CI] 3.2 [1.2–8.9]; p = 0.03) and serum HBV DNA (1.2 [1.0–1.8]; p = 0.03) at Week 6 off-therapy. Specifically, week 6 HBV DNA >10,000 IU/ml predicted ALT >5× ULN (3.4 [1.4–8.4]; p = 0.01), which was externally validated. In conclusion, this study on post-treatment flares revealed a high cumulative incidence in CHB. Week 6 HBV DNA >10,000 IU/ml independently predicted flares. The proposed threshold enables prediction of imminent flares in patients who may benefit from closer monitoring and earlier retreatment. [ABSTRACT FROM AUTHOR]

Viral hepatitis is caused by a heterogenous group of viral agents representing a wide range of phylogenetic groups. Many viruses can involve the liver and cause liver injury but only a subset are delineated as 'hepatitis viruses' based upon their primary site of replication and tropism for hepatocytes which make up the bulk of the liver cell population. Since their discovery, beginning with the agent that caused serum hepatitis in the 1960s, the alphabetic designations have been utilized. To date, we have five hepatitis viruses, A through E, though it is postulated that others may exist. This chapter will focus on those viruses. Note that hepatitis D is included as a subset of hepatitis B, as it cannot exist without concurrent hepatitis B infection. Pregnancy has the potential to affect all aspects of these viral agents due to the unique immunologic and physiologic changes that occur during and after the gestational period. In this review, we will discuss the most common viral hepatitis and their effects during pregnancy. [ABSTRACT FROM AUTHOR]

The PRIORITIZE trial (clinicaltrials.gov: NCT02786537) was the first comparative effectiveness study to directly compare ledipasvir/sofosbuvir (LDV/SOF) and elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic hepatitis C virus (HCV). A secondary aim of this study was to compare LDV/SOF and EBR/GZR on sustainable changes in several HCV‐associated symptoms and functional well‐being in patients who achieved sustained virological response (SVR). PRIORITIZE, a randomized controlled trial conducted between 2016 and 2020, evaluated change in six PROMIS® symptom scores (fatigue, sleep disturbance, cognitive disturbance, nausea, diarrhoea, abdominal pain) and functional well‐being using the disease‐specific HCV‐PRO instrument. Survey assessments were administered at baseline, early post‐treatment (median = 6 months) and late post‐treatment (median = 21 months). Constrained longitudinal linear mixed‐effects models were used to evaluate within‐treatment change and between‐treatment differences. Data from 793 participants (average 55 years old, 57% male, 44% black, 17% with cirrhosis) were analysed. From baseline to early post‐treatment, 5 out of 6 symptoms and functional well‐being significantly improved (all p's <.05). In the LDV/SOF arm, mean changes ranged from −3.73 for nausea to −6.41 for fatigue and in the EBR/GZR, mean changes ranged from −2.19 for cognitive impairment to −4.67 for fatigue. Change of >3 points was consider clinically meaningful. Improvements in most symptoms slightly favoured LDV/SOF, although the magnitude of differences between the regimens were small. Both regimens demonstrated significant improvements in symptoms and functional well‐being that were sustained during the late post‐treatment phase. EBR/GZR and LDV/SOF regimens had clinically equivalent and durable improvements in HCV symptoms and functional well‐being up to two years after SVR. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is a common cause of acute hepatitis in developing countries, but it can also take a chronic course especially in immunocompromised patients. Its epidemiology after liver transplantation (LT) is hard to assess and treatment options are still explored. Between 2009 and 2020, literature reporting HEV prevalence and treatment in LT recipients was searched and a synthesis was attempted. Sixteen studies reported HEV prevalence in consecutive LT patients: HEV RNA positivity ranged between 0%–1.4% and 0%–7.7% for Western and Eastern cohorts, respectively. In studies published between 2009–2014 and 2015–2020, HEV RNA positivity ranged between 0.35%–1.3% (all European) and 0%–7.7% (European: 0%–1.4%), respectively. Five studies evaluated HEV prevalence in LT recipients with abnormal liver enzymes: HEV RNA positivity was 2.9% in studies published between 2009 and 2014 and from 3.5% to 20% in studies published between 2015 and 2020. Twenty‐seven studies reported HEV treatment in LT recipients: sustained virologic response was achieved in 15% by immunosuppression reduction alone and in 83% of cases by ribavirin regiments. Chronic HEV infection is affecting LT recipients, mostly those with abnormal liver enzymes and in Eastern countries. HEV diagnoses should be based on PCR techniques. Successful treatment can be achieved with ribavirin in most cases. [ABSTRACT FROM AUTHOR]

Approximately 80% of primary healthcare facilities in China were ready to deliver hepatitis care services by 2021. This study aimed to assess hepatitis B and C test uptake, identify the factors associated with testing and determine the predictors of hepatitis stigma among primary care patients. We conducted a cross‐sectional survey among patients seeking care in the family medicine and primary care unit of the University of Hong Kong‐Shenzhen Hospital, China. Participants were 30 years or older and had not tested for HBV and HCV in the preceding 12 months. Test uptake was defined as self‐reported previous HBV and HCV testing. Descriptive statistics, Chi‐square test, forward multivariable logistic regression and stepwise multiple linear regression were conducted, and a p‐value <.05 was deemed statistically significant. A total of 750 eligible patients completed the survey, and 54.5% (404 ± 0.9) were between 30 and 40 years old. Most participants were heterosexuals 98.0% (n = 735), female 57.5% (n = 431), married 78.3% (587) and earned ≤1500 USD per month 54.4% (n = 408). A 66.1% (n = 496) and 13.7% (n = 103) self‐reported previous HBV and HCV testing, respectively, and 62% (n = 468) were vaccinated. HCV testing was associated with HBV testing (aOR = 13.7, 95% CI:2.1–91.5); and HBV testing was associated with family history of HBV (aOR = 2.4, 95%CI:1.1–5.5). Overall hepatitis stigma was about average and decreased with family history of HBV (p =.017). In conclusion, HCV testing uptake among primary care patients was low and needs to be further promoted. Integrating HBV and HCV testing interventions and fostering family‐based support for disclosure could effectively improve testing uptake. [ABSTRACT FROM AUTHOR]

Co‐infection with Hepatitis C virus (HCV) among HIV‐positive patients leads to accelerated progression of liver disease and AIDS. Due to increased HCV prevalence and incidence, co‐infection requires monitoring trends among HIV‐positive individuals. This will help target prevention strategies and support to reach the global goals of eliminating viral hepatitis as a public health threat. In this analysis HCV prevalence and incidence were determined for the years 1996–2019 from yearly blood samples and questionnaire details among HIV‐1‐positive patients, with a majority of men who have sex with men, belonging to a nationwide, multicentre observational, prospective cohort study. The results show that HCV prevalence for acute/chronic and resolved infection increased until 2014 to 12%. Since then, prevalence of acute/chronic HCV infection rapidly decreased and prevalence of resolved infections showed a steady increase. HCV incidence was highest in 2010 and lowest in 2017; however, no significant change in HCV incidence could be seen over the years. Therefore, the introduction of directly‐acting antiviral agents for HCV treatment notably decreased prevalence and potentially incidence of acute/chronic HCV infection. Nevertheless, prevalence and incidence of HCV among these HIV‐1‐positive study participants remain high compared with the general population and justify the need for continuous HCV prevention and treatment efforts among HIV‐positive individuals. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection is associated with neuropsychiatric changes. Also, patients with cirrhosis may develop overt or minimal hepatic encephalopathy. Sustained virological response (SVR) with direct‐acting antiviral agents (DAAs) may improve the neuropsychiatric manifestations and quality of life (QoL). Consecutive patients (with and without cirrhosis, all genders and aged 18–65 years) with hepatitis C were assessed at enrolment and at 12 weeks after therapy completion for mood (Beck's Depression Inventory [BDI]), anxiety (generalized anxiety disorder [GAD‐7]), QoL (SF‐36 ver.2) and computer‐based tests for number connection (NCT), visual memory, Stroop test and reaction times. We recruited 385 viraemic chronic HCV patients (76.1% male, 21.0% cirrhotic, mean age 39.4 ± 14.2 years, 59.3% genotype 3, mean HCV RNA load 5.8 log). Overall SVR‐12 rates were 90.6%, with cure rates 87.6% and 91.4% in patients with and without cirrhosis, respectively. Patients who achieved SVR‐12 had mean percentage reduction in BDI (11.3%, p =.000), GAD (8.6%, p =.001) and Stroop test (58.4%, p =.001), with improved NCT (1.7%, p =.001), visual memory (13.7%, p =.001) and digit span (23.8%, p =.002). On multivariate logistic regression, adherence (OR, 17.5 [95% CI 2.80–110.50], p =.000), high ALT (OR 1.02 [95% CI 1.00–1.05]), and BDI score (OR 1.73 [95% CI 1.42–3.26] p =.039) predicted cure. SVR‐12 was associated with improved visual memory ≥5.5 (AUC‐0.708; sensitivity 62.5%, specificity 63%, p =.000) and % correct Stroop test responses >26.6% (AUC‐0.918, sensitivity 94.4% specificity 80.4%, p =.000). In conclusion, given the cumulative evidence of the safety of DAAs and efficacy of improving cognitive and neuropsychological and quality‐of‐life outcomes irrespective of age and gender, as shown in our study, future recommendations should focus on integrated universal HCV care to enable HCV elimination. [ABSTRACT FROM AUTHOR]

Point‐of‐care (POC) diagnostics overcome barriers to conventional hepatitis C (HCV) testing in people who inject drugs. This study assessed impact on hepatitis C treatment uptake of POC HCV testing in needle and syringe exchange programs (NSPs). Rapid EC was a single‐arm interventional pilot study of HCV POC testing conducted in three inner‐city community clinics with NSPs. Twelve months after the POC testing, a retrospective medical record and Pharmaceutical Benefits Scheme audit was performed to determine the number of HCV RNA‐positive participants who were prescribed HCV treatment. 70 HCV RNA‐positive Rapid EC study participants were included. 44 (63%) were prescribed DAAs; 26 (59%) completed treatment and 15 (34%) had SVR testing, all of whom were cured. Age ≥ 40 years (aOR 3.45, 95% CI 1.10–11.05, p =.03) and secondary school education (aOR 5.8, 95% CI 1.54–21.80, p =.009) had higher likelihood of being prescribed DAAs, whereas homelessness was inversely associated with prescription of DAAs (aOR 0.30, 95% CI 0.09–1.04, p =.057). Median time to receive a DAA script from date of diagnosis was seven days (IQR 0 to 14 days), and time to filling the DAA prescription was 2 days (IQR 0–12 days). In conclusion, provision of POC testing through NSPs was effective for linking new clients to HCV treatment and reduced the time to treatment. Further studies are needed to define the most cost‐effective use of POC testing in models of care for people who inject drugs to increase HCV treatment uptake. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) and hepatitis C virus (HCV) contribute to significant healthcare burden globally. We aim to provide an updated and comprehensive analysis of global trends in the incidence and mortality of HBV and HCV related acute infections, cirrhosis and hepatocellular carcinoma (HCC). Estimates of annual cause‐specific disease incidence and mortality for HBV and HCV were analysed using the 2010–2019 Global Burden of Diseases, Injuries and Risk Factors Study database. Three distinct disease states were evaluated: acute infections, cirrhosis and HCC. Age‐standardized disease incidence and mortality were presented per 100,000 population and stratified by age, sex, year and 21 world regions. From 2010 to 2019, overall incidence of acute HBV declined by 19.3% (95% CI 4.1–32.0, p <.05) and HBV cirrhosis declined by 15.0% (95% CI 9.8–20.7, p <.05). Incidence of HCV cirrhosis increased by 5.6% (95% CI 0.3–10.2, p <.05) and HCV HCC remained stable. Incidence of acute HCV declined until 2015, after which it began increasing. From 2010 to 2019, overall mortality for HBV cirrhosis and HCV cirrhosis declined, whereas mortality for acute infections and HCC remained stable. Major differences in HBV and HCV incidence and mortality trends were observed when stratified by world regions. In conclusion, while our analyses of global trends in HBV and HCV incidence and mortality demonstrate encouraging trends, disparities in disease epidemiology were observed across world regions. These observations will identify regions and populations where greater focus and resources are needed to continue progressing towards viral hepatitis elimination. [ABSTRACT FROM AUTHOR]

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. 'Recommended monitoring' was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the 'definite' category, and 34.1% (208/610 patients) in the 'equivocal' category, of whom 109 moved up to 'definite' status at some point during follow‐up. Sex, age and specialist care were independently associated with receipt of treatment in 'definite' patients. Routine monitoring rates were high prior to treatment in 'definite/ treated' patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in 'definite/ untreated' patients (ALT: 48%; DNA: 32%). Among 'equivocal/ treated' patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among 'treatment ineligible' patients was similar to those in the 'equivocal' and untreated 'definite' groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one‐third of patients with 'definite' indications for antiviral therapy remained untreated. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic interrupted routine healthcare services. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are often asymptomatic, and therefore, screening and on/post‐treatment monitoring are required. Our aim was to determine the effect of the first, second and third waves of the pandemic on HBV and HCV testing in Ontario, Canada. We extracted data from Public Health Ontario for HBV and HCV specimens from 1 January 2019 to 31 May 2021. Testing volumes were evaluated and stratified by age, sex and region. Changes in testing volumes were analysed by per cent and absolute change. Testing volumes decreased in April 2020 with the first wave of the pandemic and recovered to 72%–75% of prepandemic volumes by the end of the first wave. HBsAg testing decreased by 33%, 18% and 15%, and HBV DNA testing decreased by 37%, 27% and 20%, in each consecutive wave. Anti‐HCV testing decreased by 35%, 21% and 19%, and HCV RNA testing decreased by 44%, 30% and 36% in each consecutive wave. These trends were consistent by age, region and sex. Prenatal HBV testing volumes were stable. In conclusion, significant decreases in HBV and HCV testing occurred during the first three waves of the pandemic and have not recovered. In addition to direct consequences on viral hepatitis elimination efforts, these data provide insight into the impacts of the pandemic on chronic disease screening and management. Strategies to make up for missed testing will be critical to avoid additional consequences of COVID‐19 long after the pandemic has resolved. [ABSTRACT FROM AUTHOR]

There are limited data to provide better understanding of the knowledge/awareness of general population towards liver health in Asia. We sought to identify the knowledge gaps and attitudes towards liver health and liver diseases as well as evaluate associated individual‐level and macro‐level factors based on contextual analysis. An online survey assessing knowledge, awareness and attitudes towards liver health and disease was conducted among 7500 respondents across 11 countries/territories in Asia. A liver index was created to measure the respondents' knowledge level and the degree of awareness and attitudes. Multilevel logistic regression was performed to identify individual factors and contextual effects that were associated with liver index. The overall liver index (0–100‐point scale) was 62.4 with 6 countries/territories' liver indices greater than this. In the multilevel model, the inclusion of geographical information could explain for 9.6% of the variation. Residing in a country/territory with higher HBV prevalence (80% IOR: 1.20–2.79) or higher HCV death rate (80% IOR: 1.35–3.13) increased the individual probability of obtaining a high overall liver index. Individual factors like age, gender, education, household income, disease history and health screening behaviour were also associated with liver index (all p‐values<0.001). The overall liver index was positively associated with the two macro‐level factors viz. HBV prevalence and HCV death rate. There is a need to formulate policies especially in regions of lower HBV prevalence and HCV death rate to further improve the knowledge, awareness and attitudes of the general public towards liver diseases. [ABSTRACT FROM AUTHOR]

In chronic hepatitis B (CHB) and C (CHC) infections, the composition of the immune cell microenvironment at the site of infection is poorly understood. Thus, our aim was to characterize and compare liver infiltrates to identify shared and exclusive hepatic immune components. Immunohistochemistry was performed on 26 CHB and 42 CHC liver biopsies to determine Th (CD4+), Th1 (T‐bet+), Th17 (IL‐17A+), Treg (Foxp3+) and CTL (CD8+) cells frequency in portal/periportal and intralobular areas and relate them to liver damage. CHB and CHC cases shared a portal/periportal CD4+ lymphocyte predominance and a lobular CD8+ lymphocyte majority. However, CHC exhibited a concomitant lobular T‐bet+ cell dominance while in CHB FoxP3+ cells prevail. CHC disclosed higher frequencies of P/P FoxP3+, IL‐17A+ and T‐bet+ cells and intralobular CD4+, IL‐17A+ and T‐bet+ lymphocytes. HBeAg+ chronic hepatitis and CHC cell frequencies were similar except for lobular T‐bet+ that remained higher among CHC cases. Comparison among cases with less severe liver disease revealed lower lymphocyte frequencies in CHB samples, while no differences were observed between patients with more severe stages. Interestingly, in CHB portal/periportal CD4+ and lobular CD4+, CD8+ and IL‐17A+ cells were associated with severe hepatitis. Even when all studied populations were identified in both infections preferential lymphocyte frequencies and prevalence at different areas along with their association with liver damage highlighted that CHB and CHC immune responses are not the same. [ABSTRACT FROM AUTHOR]

Hepatitis C is a leading cause of liver disease and transplantation and is a significant burden on public health worldwide. This study aimed to apply the Electronic Nose (E‐Nose) and quadrupole Mass Spectrometry (MS/MS) technologies for screening blood samples from hepatitis C patients and healthy controls. We analysed volatile organic compounds (VOCs) in the headspace over blood samples to identify those VOCs characteristic for diagnosing hepatitis C patients. The study comprised 150 acute hepatitis C patients with age range: 24–59 years, and mean age ±SD: 41.5 ± 12.8 years and 150 age‐matched healthy controls (age range: 24–51 and mean age: 40.11 ± 4.89 years) from the Hospital of the Medical Research Institute, Alexandria University, Alexandria, Egypt. Collected blood samples were analysed qualitatively and quantitatively using the E‐Nose and MS/MS techniques, respectively. Principal component analysis of the E‐Nose 10‐sensor responses accurately classified blood samples from hepatitis C patients and healthy controls. The first two principal components explained over 98.35% of the variance in signals with no false‐positive (healthy controls) or false‐negative (hepatitis C patients) results. MS/MS showed two fragmentation ions at m/z of 104 and 151 Da with the positive electrospray ionization mode (ESI+) in blood samples for hepatitis C patients, but not for healthy controls or background water samples. We identified the two specific fragmentation ions at m/z 104 and m/z 151 Da as malonic acid (MF: C3H4O4; MW: 104.06 g/mol) and monosaccharide pentose (MF: C5H10O5; MW: 150.13 g/mol) in VOCs of the headspace over blood samples for hepatitis C patients. This provides a rationale for developing diagnostic tests for hepatitis C virus based on altered trace VOCs concentrations using the relatively inexpensive, easy‐to‐use, portable and non‐invasive E‐Nose technology. [ABSTRACT FROM AUTHOR]

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic‐regression analysis. The incidence of acute HDV per 1‐million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991–1999 to 44 years in the decade 2010–2019 (p <.001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p =.003) and that of HBsAg positive acute hepatitis tested for by IgM anti‐HDV linearly decreased from 50.1% to 34.1% (p <.001). People born abroad accounted for 24.6% of cases in 2004–2010 and 32.1% in 2011–2019. In the period 2010–2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4–12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15–10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM‐anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the leading cause of liver cirrhosis and cancer in West Africa. Despite current recommendations, HBV is often not tested for in clinical routine in the region. We included all people living with HIV (PLWH) in care between March and July 2019 at Fann University Hospital in Dakar (Senegal) and proposed hepatitis B surface antigen (HBsAg) test to those never tested. All HBsAg‐positive underwent HIV and HBV viral load (VL) and liver stiffness measurement. We evaluated, using logistic regression, potential associations between patient characteristics and (a) HBV testing uptake; (b) HIV/HBV co‐infection among individual HBsAg tested. We determined the proportion of co‐infected who had HBV DNA >20 IU/ml on ART and sequenced HBV polymerase in those with HBV replication.of 1076 PLWH in care, 689 (64.0%) had never had an HBsAg test prior to our HBV testing intervention. Women and individuals >40 years old were less likely to have been previously tested. After HBV testing intervention,107/884 (12.1%) PLWH were HBsAg‐positive. Seven of 58 (12.1%) individuals newly diagnosed with HIV/HBV co‐infection had a detectable HBV VL, of whom five were HIV‐suppressed. Two patients on ART including 3TC and AZT as backbone showed the presence of the triple resistance mutation 180M/204I/80V. In this Senegalese urban HIV clinic, the majority of patients on ART had never been tested for HBV infection. One in ten co‐infected individuals had a detectable HBV VL despite HIV suppression, and 8% were not receiving a TDF‐containing regimen. [ABSTRACT FROM AUTHOR]

As pegylated interferon alpha (PEG‐IFN‐α) is increasingly used in combination regimens of novel drugs, we aimed to characterize ALT flares and their relationship with serum HBsAg and HBV RNA kinetics in a large combined cohort of chronic hepatitis B (CHB) patients on PEG‐IFN‐α‐based therapy. In this post hoc analysis of four international randomized trials, 269/130/124/128 patients on PEG‐IFN‐α monotherapy, PEG‐IFN‐α plus nucleos(t)ide analogue (NA) de novo combination, PEG‐IFN‐α add‐on to NA or NA monotherapy were included, respectively. A flare was defined as an episode of ALT ≥5 × ULN. The association between flares and HBsAg and HBV RNA changes were examined. On‐treatment flares occurred in 83/651 (13%) patients (median timing/magnitude: week 8 [IQR 4–12], 7.6 × ULN [IQR 6.2–10.5]). Flare patients were more often Caucasians with genotype A/D and had higher baseline ALT, HBV DNA, HBV RNA and HBsAg levels than the no‐flare group. More flares were observed on PEG‐IFN‐α monotherapy (18%) and PEG‐IFN+NA de novo combination (24%) vs. PEG‐IFN‐α add‐on (2%) or NA monotherapy (1%) (p <.001). On‐treatment flares were significantly and independently associated with HBsAg and HBV RNA decline ≥1 log10 at the final visit declines started shortly before the flare, progressing towards 24 weeks thereafter. On‐treatment flares were seen in 16/22 (73%) patients who achieved HBsAg loss. In conclusion, ALT flares during PEG‐IFN‐α treatment are associated with subsequent HBsAg and HBV RNA decline and predict subsequent HBsAg loss. Flares rarely occurred during PEG‐IFN‐α add‐on therapy and associated with low HBsAg loss rates. Combination regimens targeting the window of heightened response could be promising. [ABSTRACT FROM AUTHOR]

Hepatitis B viral (HBV) load and hepatic enzymes play a critical role in hepatocellular carcinoma (HCC) development. However, the clinical significance of these in HBV‐related HCC patients after hepatectomy remains unclear. In this study, we analysed 1,940 HBV‐related HCC patients who underwent hepatectomy from four hospitals in west China. Risk classification was constructed based on baseline HBV‐DNA load and AST/ALT ratio. Based on the HBV‐DNA load and AST/ALT ratio classification, four types with distinguishable prognoses were established. Type 1 patients had the best prognosis with 5‐year overall survival (OS) of 69.8%, followed by type 2 and type 3 patients, whereas type 4 patients had the worst prognosis with 5‐year OS of 42.7%. Similarly, the four types had statistically different recurrence‐free survival. This classification was significantly associated with HCC recurrence (hazard ratio [HR]:1.492, p <.001) and long‐term survival (HR: 1.574, p =.001). Pathologically, type 4 correlated with more advanced tumours considering tumour size and microvascular invasion than those in type 1, 2, or 3. Moreover, type 4 patients had more severe hepatic inflammation in underlying liver. Conversely, type 1 patients had an active tumour immune microenvironment as indicated by more CD8+ T cell infiltration and less PD‐L1 expression. In conclusion, the classfication based on baseline HBV‐DNA load and AST/ALT ratio could effectively stratify HBV‐related HCC patients with distinguishable prognoses after hepatectomy. [ABSTRACT FROM AUTHOR]

Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB). Among children and adults with CHB and without HIV, HCV or HDV co‐infection enrolled in the Hepatitis B Research Network prospective cohort studies, 819 were HBeAg positive at their first assessment (treatment naïve or >24 weeks since treatment). Of these, 577 (200 children, 377 adults) were followed every 24–48 weeks. HBeAg loss was defined as first HBeAg‐negative value; sustained HBeAg loss was defined as ≥2 consecutive HBeAg‐negative values ≥24 weeks apart. During a median follow‐up of 1.8 years, 164 participants experienced HBeAg loss, a rate of 11.4 (95% CI, 9.8–13.3) per 100 person‐years. After adjustment for confounders, HBeAg loss rate was significantly higher in males than females, in older than younger individuals, in Whites or Blacks than Asians, in those with genotype A2 or B versus C, and in those with basal core promoter/pre‐core mutations versus wild type. Additionally, during follow‐up, an ALT flare and a lower quantitative HBsAg, quantitative HBeAg or HBV DNA level predicted higher rates of HBeAg loss. The majority (88%) with HBeAg loss had sustained HBeAg loss. In conclusion, a number of specific demographic, clinical and viral characteristics impacted rate of HBeAg loss and may prove useful in design and interpretation of future therapeutic studies. [ABSTRACT FROM AUTHOR]