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Background: Highly effective hepatitis C therapies are available in Australia. However, people living with hepatitis C face various barriers to accessing care and treatment. Aims: To identify gaps in the cascade of care for hepatitis C and generate estimates of the number living with untreated infection according to population group, using a representative longitudinal study population. Methods: We linked hepatitis C notification data from Victoria to national pathology, prescribing and death registry data. We assessed receipt of key clinical services in a large cohort who tested positive for hepatitis C from 1 January 2000 to 31 December 2016, with follow‐up to 30 June 2018. We estimated the number still living with hepatitis C, adjusting for spontaneous clearance and mortality. Results: The cohort comprised 45 391 people positive for hepatitis C. Of these, 13 346 (29%) received treatment and an estimated 28% (95% confidence interval (CI): 26–30%) were still living with chronic infection at 30 June 2018, with the remainder still living following spontaneous clearance (30%, 95% CI: 29–32%) or having died (12%, 95% CI: 12–12%). Half (50%) of those still living with hepatitis C were born from 1965 to 1980, and 74% first tested positive before 2011. Conclusions: Despite an enabling policy environment and subsidised therapy, many people in this cohort were not treated. Increased measures may be needed to engage people in care, including those who acquired hepatitis C more than 10 years ago. [ABSTRACT FROM AUTHOR]

Periodontitis is a cumulative inflammatory disease associated with multiple health conditions and various systemic diseases. As a common disease, virus infection along with its consequences has become a serious health burden. The study aims to evaluate the relationship between common viruses including hepatitis virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human papillomavirus (HPV), and periodontitis. The data from the US National Health and Nutrition Examination Survey (NHANES) 2009−2014 was adopted and screened through, including 10 714 participants. Generalized linear regression was conducted to verify the relationships between the virus infections and periodontitis. Moreover, we also performed analyses in age and gender subgroups. The results suggested that the infection of HCV, HSV‐1, and HSV‐2 was significantly associated with the prevalence of periodontitis (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.26−1.70; OR 1.09, 95% CI 1.05−1.13; OR 1.06, 95% CI 1.01 ‐ 1.11, respectively) and risk of developing moderate or severe periodontitis (OR 1.51, 95% CI 1.29−1.77; OR 1.08, 95% CI 1.04−1.12; OR 1.05, 95% CI 1.01−1.10, respectively) after adjusting all relevant co‐factors. Subgroup analyses revealed a steady association between periodontitis and hepatitis C virus (HCV) or HSV‐1 infection, while the relationship between HSV‐2 and HPV infection can also be found in some subgroups. The presence of HCV and HSV infection was found to be significantly associated with the prevalence of periodontitis, including moderate or severe cases. Moreover, the association of periodontitis and HPV infection can also be observed in people < 35 years. [ABSTRACT FROM AUTHOR]

Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood‐borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974–1992). Clotting factors were tested by commercial and in‐house quantitative PCRs for blood‐borne viruses hepatitis A, B, C and E viruses (HAV, HBV, HCV, HEV), HIV‐ types 1/2, parvoviruses B19V and PARV4, and human pegiviruses types 1 and 2 (HPgV‐1,‐2). HCV and HPgV‐1 were the most frequently detected viruses (both 14/24 tested) primarily in commercial clotting factors, with frequently extremely high viral loads in the late 1970s–1985 and a diverse range of HCV genotypes. Detection frequencies sharply declined following introduction of virus inactivation. HIV‐1, HBV, and HAV were less frequently detected (3/24, 1/24, and 1/24 respectively); none were positive for HEV. Contrastingly, B19V and PARV4 were detected throughout the study period, even after introduction of dry heat treatment, consistent with ongoing documented transmission to PWHs into the early 1990s. While hemophilia treatment is now largely based on recombinant factor VIII/IX in the UK and elsewhere, the comprehensive screen of historical plasma‐derived clotting factors reveals extensive exposure of PWHs to blood‐borne viruses throughout 1970s‐early 1990s, and the epidemiological and manufacturing parameters that influenced clotting factor contamination. [ABSTRACT FROM AUTHOR]

Aim: The diagnosis of drug‐induced liver injury (DILI) is challenging. We modified the revised electronic version of the Roussel Uclaf Causality Assessment Method (RUCAM) for the diagnosis of DILI (RECAM), the scoring system developed in US and Spanish cohorts in 2022, and developed RECAM‐J 2023 to align with the clinical practice in Japan. In the current study, we introduce RECAM‐J 2023 and verify its performance in the context of Japanese patients with DILI. Methods: After translation of RECAM into Japanese, modifications were made to develop RECAM‐J 2023 without any alteration to the scores. To examine the validity and performance of RECAM‐J 2023, clinical information on DILI and non‐DILI cases in Japan were retrospectively collected. The diagnosis of DILI was made by expert's decision. Then we scored each case using RECAM‐J 2023, and calculated area under curve (AUC) values for identification for DILI. Results: We collected data from 538 DILI and 128 non‐DILI cases. The sum of highly probable (HP) and probable (PR) cases categorized by RECAM‐J 2023 were only 206 (38%) in DILI cases. As the primary cause of low scores was the deduction with missing hepatitis virus markers, which is unlikely to be an issue in prospective applications, we rescored without these deductions. At this time, the sum of HP and PR was raised to 421 (78%). The AUCs of RECAM‐J 2023 without deductions were 0.70 and 0.88 for identifying at least HP, and at least PR, respectively. Conclusion: RECAM‐J 2023, when prospectively used without any missing hepatitis virus markers, provides acceptable performance for identifying at least PR DILI cases in Japanese daily clinical practice. [ABSTRACT FROM AUTHOR]

Background and Objectives: In Canada, plasma sent for fractionation is tested for both parvovirus B19 (B19V) and hepatitis A virus (HAV). This study compared positivity rates of B19 and HAV nucleic acid tests (NATs) in Canadian plasma samples for the pre‐COVID‐19 restriction era (2015 to end of February 2020 [Q1] 2020) and the post‐COVID‐19 restriction era. Materials and Methods: Pooled EDTA plasma specimens were tested within 24 months of blood draw using the Procleix Panther System (Grifols Diagnostic Solutions Inc, San Diego, CA, USA) for B19V and HAV detection. Reactive pools were resolved by individual specimen testing. Results: Between 1 January 2015, and 31 March 2022, 3,928,619 specimens from Canadian plasma donors were tested for B19V. For the same period, 3,922,954 specimens were tested for HAV. To account for a lag in specimen testing for up to 24 months, the data were divided into: (1) a pre‐pandemic period (1 January 2015–31 March 2020; B19V tested n = 2,412,701, B19V NAT‐positive n = 240 [0.01%], HAV tested n = 2,407,036, HAV NAT‐positive n = 26 [0.001%]); (2) a two‐year mixed‐impact period (1 April 2020–31 March 2022; B19V tested n = 968,250, B19V NAT‐positive n = 14 [0.001%], HAV tested n = 968,250, HAV NAT‐positive n = 2 [0.0002%]); and (3) a pandemic‐impact period (1 April 2022–31 March, 2023; B19V tested n = 597,668, B19V NAT‐positive n = 3 [0.0005%], HAV tested n = 597,668, HAV NAT‐positive n = 1 [0.0002%]). Conclusion: The percentage of B19V‐ and HAV‐positive donations was significantly reduced from the pre‐pandemic period to the pandemic‐impact period. [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic hepatitis B (CHB) in Aboriginal and Torres Strait Islander Australians in Far North Queensland (FNQ) is greater than twice that of the general Australian population. CHB is common in Torres Strait Islanders diagnosed with hepatocellular carcinoma (HCC) – and in Aboriginals with HCC living in the Northern Territory – however, Aboriginals diagnosed with HCC in FNQ very rarely have CHB. The explanation for this apparent disparity is uncertain. Aims: To determine the HBV genotypes in the FNQ Aboriginal and Torres Strait Islander population and their correlation with clinical phenotype. Methods: We determined the HBV genotype of Aboriginal and Torres Strait Islander Australians living with CHB in FNQ and correlated this with demographic and clinical findings. Results: 134/197 (68%) enrolled individuals had a sufficient viral load for genotyping. All 40 people with HBV/D genotype had Aboriginal heritage, whereas 85/93 (91%) with HBV/C had Torres Strait Islander heritage (P < 0.0001). Individuals with HBV/D were younger than those with HBV/C (median (interquartile range) age: 43 (39–48) vs 53 (42–66) years, P = 0.0002). However, they were less likely to be HBeAg positive (1/40 (3%) vs 23/93 (25%), P = 0.001). All three HCCs developed in Torres Strait Islanders; two‐thirds were infected with HBV/C14; genotyping was not possible in the other individual. All 10 diagnoses of cirrhosis occurred in Torres Strait Islanders, 6/10 were infected with HBV/C14, genotyping was not possible in the other four individuals. Conclusions: HBV genotypes in Aboriginal and Torres Strait Islander Australians in FNQ differ markedly, which could explain the significant differences in the clinical phenotype in the two populations and might be used to inform cost‐effective CHB care in the region. [ABSTRACT FROM AUTHOR]

Coronaviruses (CoVs) have continuously posed a threat to human and animal health. However, existing antiviral drugs are still insufficient in overcoming the challenges caused by multiple strains of CoVs. And methods for developing multi‐target drugs are limited in terms of exploring drug targets with similar functions or structures. In this study, four rounds of structural design and modification on salinomycin were performed for novel antiviral compounds. It was based on the strategy of similar topological structure binding properties of protein targets (STSBPT), resulting in the high‐efficient synthesis of the optimal compound M1, which could bind to aminopeptidase N and 3C‐like protease from hosts and viruses, respectively, and exhibit a broad‐spectrum antiviral effect against severe acute respiratory syndrome CoV 2 pseudovirus, porcine epidemic diarrhea virus, transmissible gastroenteritis virus, feline infectious peritonitis virus and mouse hepatitis virus. Furthermore, the drug‐binding domains of these proteins were found to be structurally similar based on the STSBPT strategy. The compounds screened and designed based on this region were expected to have broad‐spectrum and strong antiviral activities. The STSBPT strategy is expected to be a fundamental tool in accelerating the discovery of multiple targets with similar effects and drugs. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Cholestatic hepatitis is a rare complication of Epstein–Barr virus infection and is often self‐limiting. Systemic signs, including viral prodrome and lymphadenopathy, can provide crucial diagnostic cues and avoid unnecessary invasive investigations or aggressive medical therapy unless indicated. [ABSTRACT FROM AUTHOR]

In 2018, there was a hepatitis A outbreak in Japan, and hepatitis A virus (HAV) infection is considered a sexually transmitted disease. In general, patients with hepatitis A should be given attention, and this disease should be prevented more than ever. The Japan Agency for Medical Research and Development (AMED) Hepatitis A and E viruses (HAV and HEV) Study Group has worked on the project to create "Recent Advances in Hepatitis A Virus (HAV) Research and Clinical Practice Guidelines for HAV Infection in Japan". The group consists of expert hepatologists and virologists who gathered at virtual meeting on August 5, 2023. Data about the pathogenesis, infection routes, diagnosis, complications, several factors for the severities, vaccination, and current and future treatments for hepatitis A were discussed and debated for a draft version. The participants assessed the quality of cited studies. The finalized recommendations are presented in this review. The recent advances in HAV research and clinical practice for HAV infection in Japan, have been reviewed by the AMED HAV and HEV Study 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]

Norovirus (NoV) and hepatitis A virus (HAV) pose a considerable health risk worldwide. In recent years, many cases of virus infection caused by virus‐contaminated strawberries have occurred worldwide. This study applied a critical control point system to analyze the main hazards during the production and marketing of strawberries imported into China and explore the key control points in the whole process. To further evaluate the risks in the supply chain, the established quantitative microbial risk assessment (QMRA) was used to determine the probability that residents would be infected with viruses after consuming imported strawberries. It was found that the risk of virus contamination from imported strawberries was low, and the virus contamination mainly results from water resources and personnel. This research helps the regulatory authorities formulate strategies to ensure the long‐term microbial safety of imported strawberries. In addition, the methods may prove useful in evaluating the risks of other agricultural produce. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) play crucial role in mediating intercellular communication. Small RNA is an important component in EVs. However, the proportion of small RNA sequencing (smRNA‐seq) reads in EVs mapped to the human genome is much lower than that of cells, suggesting the existence of many nonhuman sequences in EVs. However, there is no systematic study on EV fragments unmapped to the human genome. Herein, using EV smRNA‐seq data, the landscape of exogenous RNA cargoes in human EVs is portrayed. The results show the distribution of nonhuman sequence fragments in 1838 EV samples; an average of 21.82% of reads are unmapped to the human genome, and 12.33% are mapped to the collected exogenous reference sequences. Furthermore, the proportion of exogenous sequences in plasma EV samples is the lowest, while in the cell line EV samples, it is much higher, mainly from animals, bacteria, or contaminants. Exogenous sequences from plants are mainly from food, and the exogenous bacteria are mainly gut microbiota. Virus‐derived sequences reflect the high prevalence of viruses in the population, such as herpesvirus and hepatitis virus. This study provides the first landscape of exogenous fragments in human EVs and implies diverse RNA sources in the human body. [ABSTRACT FROM AUTHOR]

Background and aims: Criminalization of drug use and punitive policing are key structural drivers of hepatitis C virus (HCV) risk among people who inject drugs (PWID). A police education program (Proyecto Escudo) delivering training on occupational safety together with drug law content was implemented between 2015 and 2016 in Tijuana, Mexico, to underpin drug law reform implementation. We used data from a longitudinal cohort of PWID in Tijuana to inform epidemic modeling and assess the long‐term impact of Escudo on HCV transmission and burden among PWID in Tijuana. Methods: We developed a dynamic, compartmental model of HCV transmission and incarceration among PWID and tracked liver disease progression among current and former PWID. The model was calibrated to data from Tijuana, Mexico, with 90% HCV seroprevalence. We used segmented regression analysis to estimate impact of Escudo on recent incarceration among an observational cohort of PWID. By simulating the observed incarceration trends, we estimated the potential impact of the implemented (2‐year reduction in incarceration) and an extended (10‐year reduction in incarceration) police education program over a 50‐year follow‐up (2016–2066) on HCV outcomes (incidence, cirrhosis, HCV‐related deaths and disability adjusted life‐years averted) compared with no intervention. Results: Over the 2‐year follow‐up, Proyecto Escudo reduced HCV incidence among PWID from 21.5 per 100 person years (/100py) (95% uncertainty interval [UI] = 15.3–29.7/100py) in 2016 to 21.1/100py (UI = 15.0–29.1/100py) in 2018. If continued for 10 years, Escudo could reduce HCV incidence to 20.0/100py (14.0–27.8/100py) by 2026 and avert 186 (32–389) new infections, 76 (UI = 12–160) cases of cirrhosis and 32 (5–73) deaths per 10 000 PWID compared with no intervention over a 50‐year time horizon. Conclusions: In Tijuana, Mexico, implementation of a police education program delivering training on occupational safety and drug law content appears to have reduced hepatitis C virus incidence among people who inject drugs. [ABSTRACT FROM AUTHOR]

This article discusses the characterization of hepatitis A virus (HAV) RNA-positive blood donations during an epidemic in Poland. The study used two nucleic acid amplification technique (NAT)-based methods to screen the donations for HAV RNA. The sensitivity of the two methods was found to be very similar and extremely sensitive. The article also discusses the evaluation of the 1st World Health Organization (WHO) International Standard (IS) for HAV RNA and the use of RT-droplet digital PCR (RT-ddPCR) to determine the HAV RNA content of the IS. The study found that the IU:copy number ratio of the IS was significantly higher than previously reported, suggesting limitations in the sensitivities of the methods used to determine the potency of the IS. The article concludes by highlighting the importance of understanding the HAV RNA load in transfusion transmission and the need for further research in this area. The study was supported by funding from the German Ministry of Health and the authors declare no conflicts of interest. [Extracted from the article]

Background: Pediatric liver transplant recipients are at increased risk of post‐transplant infections. The purpose of this study was to quantify hepatitis A and B non‐immunity based on antibody titers in liver transplant recipients. Methods: We conducted a retrospective chart review of 107 pediatric liver transplant recipients at a single medical center from 2000 to 2017. We compared hepatitis immune patients to non‐immune patients and studied response to vaccination in patients immunized post‐transplantation. Results: Eighty‐one percent of patients had pre‐transplant immunity to hepatitis A whereas 68% had pre‐transplant immunity to hepatitis B. Post‐transplant hepatitis B immunity decreased to 33% whereas post‐transplant hepatitis A immunity remained high at 82%. Older age and time since transplantation were significantly associated with hepatitis B non‐immunity. Most patients responded to doses post‐transplantation with 78% seroconversion following hepatitis A re‐immunization and 83% seroconversion following hepatitis B re‐immunization. Conclusions: Pediatric liver transplant recipients are at risk of hepatitis A and B non‐immunity, particularly with respect to hepatitis B. Boosters post‐transplant may improve immunity to hepatitis viruses. [ABSTRACT FROM AUTHOR]

Background: Fulminant herpetic hepatitis due to herpes simplex virus (HSV), serotype 1 or 2, is a rare but often fatal complication after solid organ transplantation (SOT). HSV hepatitis in SOT recipients can occur either due to primary infection acquired post transplantation, viral reactivation in a seropositive patient, or as donor‐derived infection. Cases of fatal hepatitis have been reported in the liver as well as in other SOT recipients. The fatal outcome is mostly due to delayed diagnosis and treatment, which is explained by the lack of clinical specificity of HSV hepatitis. Methods: We report two cases of fatal donor‐derived HSV hepatitis in liver‐transplanted recipients. We reviewed all published cases of donor‐derived HSV infections after SOT with an evaluation of the presence of prophylaxis and outcome. Results: In both liver recipients, the retrospective determination of HSV serostatus was negative, and both cases occurred in the absence of cytomegalovirus or HSV prophylaxis. A review of the literature showed a significant series of cases of severe hepatitis, mostly fatal, as well as the absence of specific preventive therapy guidelines in cases of HSV serology mismatch. Conclusions: The occurrence of two fatal donor‐derived hepatitis made the Swiss Transplant Infectious Diseases working group modify its national recommendations regarding pretransplant serostatus determination and HSV prophylaxis after liver transplantation. Further studies are needed to assess this approach. [ABSTRACT FROM AUTHOR]

Objectives: To investigate if hepatitis A virus cell receptor 1/kidney injury molecule 1 (HAVCR1/KIM1) in urine is detectable concurrently with increases in serum creatinine concentrations in horses receiving a recommended dose of phenylbutazone (PBZ) for 7 days. Design: Preliminary study. Methods: Ten clinically healthy horses with normal physical examination and laboratory work were randomly assigned to PBZ or placebo groups (5 each). The PBZ group received PBZ at 4.4 mg/kg mixed with corn syrup orally every 12 hours. The placebo group received corn syrup orally every 12 hours. Both groups were treated for 7 days. Kidney ultrasonography was performed, and venous blood and urine samples were collected prior to commencement and at the end of treatment. Samples from 1 additional healthy horse, 3 horses with acute kidney failure, and 1 horse with chronic kidney failure were also evaluated. Results: None of the 10 horses had detectable HAVCR1/KIM1 in urine at baseline. Serum creatinine concentrations in placebo group did not increase, and HAVCR1/KIM1 was undetectable in urine. At the end of treatment, 3 of 5 horses receiving PBZ developed increases in serum creatinine of >26.5 μmol/L (>0.3 mg/dL), and HAVCR1/KIM1 was detectable in urine, despite normal findings on kidney ultrasonography in all horses. Conclusions: HAVCR1/KIM1 is detectable in urine and is associated with increases in serum creatinine concentrations of >26.5 μmol/L in horses following treatment with PBZ for 7 consecutive days. Thus, HAVCR1/KIM1 might aid in the early detection of acute kidney injury in horses. [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]

Aim: To describe epidemiological characteristics of multi‐country outbreak of severe acute hepatitis of unknown origin in children in 2022. Methods: A descriptive epidemiological study design was used. The review based on the available information concerning this multi‐country outbreak aims to summarise the current knowledge about the severe acute hepatitis of unknown origin in children, highlights the suggested working hypotheses, introduces some of the potential explanations for its occurrence and reports on public health measures undertaken to control the disease. Results: Since the first 10 cases of severe acute hepatitis of unknown origin in children in the United Kingdom on 5 April 2022, and up until the 29 August 2022, more than 1000 probable cases have been reported in 35 countries in the world. Up to today, 22 children died in this multi‐country outbreak. Despite the numerous theories that have been suggested on the possible underlying causes of the outbreak, an association with hepatitis A–E viruses has been excluded. Adenovirus serotype 41 has been detected in numerous cases, which makes it the most likely underlying cause of the disease. Conclusion: Efficient surveillance and comprehension advancements of the epidemiology of this disease are especially important for effective prevention and outbreak response. [ABSTRACT FROM AUTHOR]

Cirrhosis remains a major public health concern globally; the burden of cirrhosis should be further clarified worldwide and helped us to understand the current situation of cirrhosis. In the present study, we estimate DALYs and mortality rates attributable to several major cirrhosis risk factors and use joinpoint and age‐period‐cohort methods to determine the trends of cirrhosis incidence and deaths in the global population in the 1990–2019 period. Globally, from 1990 to 2019, the incidence of cirrhosis, deaths due to cirrhosis, and cirrhosis DALY cases increased from 1274 (103, 95% uncertainty interval [UI]: 1027.2–1548.5) to 2051.6 (103, 95% UI: 1661.4–2478.1), 1013 (103, 95% UI: 948.9–1073.9) to 1472 (103, 95% UI: 1374.6–1578.7), and 34727.7 (103, 95% UI: 32383.0–37132.8) to 46189.4 (103, 95% UI: 43027.1–49551.3), respectively. Hepatitis virus was the most important cirrhosis mortality risk factor. Globally, hepatitis virus infection (HBV+HCV) accounted for more than 45% of the incidence of cirrhosis cases and about 50% of cirrhosis deaths. Importantly, from 1990 to 2019, the proportion of cirrhosis incidence due to HBV decreased from 24.3% to 19.8%, whereas that due to alcohol use increased from 18.7% to 21.3%. Additionally, the proportion of NAFLD‐induced cirrhosis incidence increased from 5.5% to 6.6% over the same period. Our findings on the global disease burden of cirrhosis provide a valuable resource for developing targeted prevention strategies. [ABSTRACT FROM AUTHOR]

Background: People with serious mental illness (SMI) are underserved from a hepatitis C virus (HCV) screening and treatment perspective. Aims: To examine the HCV care cascade in people with SMI and to pilot a supported HCV treatment integration programme. Methods: HCV prevalence was retrospectively analysed from 4492 consecutive individuals admitted to a tertiary hospital mental health service between January 2017 and December 2018. Subcohort analysis of screening patterns and predictors of seropositive infection was performed. Referral pathways and community care integration were analysed for HCV‐positive individuals, and a prospective community‐based 'identify and treat' HCV programme was assessed. Results: Screening for HCV had been performed in 18.6% (835/4492) of the cohort. Seroprevalence was 4.6% (207/4492). HCV seropositivity was associated with age >40 years (odds ratio (OR) = 9.30; confidence interval (CI) 3.69–23.45; P < 0.01), injecting drug use (OR = 24.26; CI 8.99–65.43; P < 0.01) and previous incarceration (OR = 12.26; CI 4.51–33.31; P < 0.01). In a cohort of treatment‐eligible individuals, 43.3% (90/208) had neither been referred to specialist services or general practitioners for HCV management. Amongst those referred to specialist services, 64.7% (57/88) did not attend scheduled follow up, and 48.3% (15/31) of attendees were lost to follow up. Through an intensified community access programme, 10 people were successfully treated for HCV, although 22 could not be engaged. Conclusion: People with SMI are underserved by traditional models of HCV healthcare. Intensified community‐based support can partially bolster the treatment cascade, although investment in innovative screening and management strategies are required to achieve healthcare parity. [ABSTRACT FROM AUTHOR]

Hepatitis A virus (HAV) has some life‐threatening extrahepatic complications, such as acute acalculous cholecystitis (AAC). We present HAV‐induced AAC in a young female, based on clinical, laboratory, and imaging findings, and conduct a literature review. The patient became irritable, which progressed to lethargy, as well as a significant decline in liver function, indicating acute liver failure (ALF). She was immediately managed in the intensive care unit with close airway and hemodynamic monitoring after being diagnosed with ALF (ICU). The patient's condition was improving, despite only close monitoring and supportive treatment with ursodeoxycholic acid (UDCA) and N‐acetyl cysteine (NAC). [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]

Around 30 years ago, the hepatitis C virus (HCV) was identified and soon it was shown that this virus, further to the liver, could affect a variety of organ systems. This article summarizes how an association between HCV and a relatively common oral disorder, oral lichen planus (OLP), was revealed. Through key publications, many of them published in Journal of Oral Pathology and Medicine, it is shown the building of strong epidemiologic evidence supporting the association and how a plausible pathogenic link between HCV and OLP was discovered. As HCV infection is now potentially curable, modern direct antiviral agents can be used to effectively cure also OLP in HCV‐infected patients. [ABSTRACT FROM AUTHOR]

To characterize viral hepatitis co‐infections in a cohort of immigrants living in southern Italy. In a prospective multicenter study, all undocumented immigrants and low‐income refugees consecutively evaluated for a clinical consultation at one of the five first‐level clinical centers in southern Italy from January 2012 to February 2020 were enrolled. All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti‐hepatitis C virus (HCV) and anti‐HIV; the HBsAg‐positive were screened also for anti‐delta. Of the 2923 subjects enrolled, 257 (8%) were HBsAg‐positive alone (Control group B), 85 (2.9%) only anti‐HCV‐positive (Control group C), 16 (0.5%) HBsAg/anti‐HCV‐positive (Case group BC), and 8 (0.2%) HBsAg/anti‐HDV‐positive (Case group BD). Moreover, 57 (1.9%) subjects were anti‐HIV‐positive. HBV‐DNA positivity was found less frequently in the 16 subjects in Case group BC (43%) and in the 8 in Case group BD (12.5%) than in the 257 in Control group B (76%; p = 0.03 and 0.0000, respectively). Similarly, HCV‐RNA positivity was more frequent in Case group BC than in Control group C (75% vs. 44.7% p = 0.02). The subjects in Group BC had a lower prevalence of asymptomatic liver disease (12.5%) than Control group B (62.2%, p = 0.0001) and Control group C (62.3%, p = 0.0002). Conversely, liver cirrhosis was more frequently identified in Case group BC (25%) than in Control groups B and C (3.11% and 2.35%, p = 0.0000 and 0.0004, respectively). The present study contributes to the characterization of hepatitis virus co‐infections in the immigrant population. [ABSTRACT FROM AUTHOR]

Background: In Poland, hepatitis A virus (HAV) RNA screening was performed in plasma for fractionation usually immediately before shipment. Objective: Our goal was to study epidemiology, rate of transfusion transmitted HAV during epidemic (2017–2019), and viral characteristics of infected plasma donors. Study Design and Methods: HAV RNA was tested in 1,866,590 donations from 1,210,423 donors using RT‐PCR in mini pools of 96 (MP96) or TMA in MP16. Virological characteristics included RNA level (RL), antibody testing, and sequencing. Results: Twenty‐one HAV infections were identified (1.13/100,000 donations; 95% confidence interval [95% CI]: 0.74–1.72) and (1.73/100,000 donors; 95% CI: 1.35–2.65). The Blood Transfusion Centers were also informed about three donors, who were hospitalized for hepatitis A soon after their blood donation. In addition, we identified a donor, who had reactive result for HAV after receiving HAV vaccination. He tested positive twice 10 days after receiving the first and the second dose. The highest RL was 16 million IU/ml, mean 1,706,905 IU/ml, and median 220 IU/ml. The longest detectable RL lasted for 113 days. HAV‐infected donors were seronegative (36%) or IgM positive (64%). We followed up on 12 HAV contaminated blood components issued for transfusion. In two out of seven identified patients viral transmission was confirmed (28.6%). Conclusion: Based on our results, we propose a 6 month deferral after HAV infection and 14 days post HAV vaccination. The infectivity rate was below 30%. The HAV RNA testing could be considered as an additional safeguard against HAV transmission at the time of increased incidence of HAV infections in the general population. [ABSTRACT FROM AUTHOR]

The incidence of hepatitis A virus (HAV) infection has declined significantly worldwide, including in Japan. A nationwide seroepidemiological study on hepatitis A in Japan has taken place almost every 10 years since 1973, and the last study was performed in 2003. In the present study, we describe the latest seroepidemiological pattern of hepatitis A in Japan using 7867 serum specimens obtained from healthy individuals collected between 2013 and 2017, approximately 10 years after the last study. Among them, 223 were anti‐HAV positive. About 68% of individuals aged 60 years and older had anti‐HAV antibodies, whereas only 1.1% of those aged below 60 years old had immunity; thus, almost all individuals younger than 60 years of age were HAV susceptible. In comparison with previous investigations, the susceptible population has increased and aged. According to data from the National Epidemiological Surveillance of Infectious Diseases (NESID) program, between 1989 and 2016, the proportion of patients with hepatitis A aged 60 years and older continuously increased with each year. The NESID data also suggested that recently, typical large foodborne outbreaks of hepatitis A have become rare, and cases tend to be reported among at‐risk groups; overseas travelers contributed to 25% of hepatitis A cases, and in 2018, the first nationwide hepatitis A outbreak that affected mostly men who have sex with men was reported. The purpose of this study was to determine the current status of HAV infection in Japan, based on both seroepidemiology and the national surveillance data from the NESID. [ABSTRACT FROM AUTHOR]

The article discusses the recommendations made by the Infected Blood Inquiry (IBI) to improve hospital transfusion practice. While the IBI primarily focused on the failings that led to transfusion-transmitted HIV and hepatitis viruses, it also highlighted the need for better transfusion practices. The report identified issues such as poor documentation of risks and benefits discussed with patients, low compliance with quality standards, paper-based traceability of blood, and inadequate documentation of clinical outcomes. Key recommendations include embedding transfusion consent as part of Getting it right first time (GIRFT), improving staffing and training in transfusion laboratories, considering tranexamic acid in surgical checklists, standardizing and benchmarking transfusion performance between hospitals, and prioritizing funding for enhanced electronic clinical systems. The report urges the government to consider implementing these recommendations within 12 months. [Extracted from the article]

Background: Sustained viral response (SVR) improves survival for patients with hepatitis C (HCV) and hepatocellular carcinoma (HCC) after curative treatment; however, the benefit of SVR in those with active HCC with a significant competing risk of mortality is unknown. This study aimed to evaluate the association between SVR and outcomes in patients with active HCC.Methods: The authors performed a multicenter, retrospective cohort study including consecutive adults with HCV cirrhosis and treatment-naive HCC diagnosed between 2014 and 2018. Patients were stratified into two groups: active viremia (n = 431) and SVR before HCC diagnosis (n = 135). All patients underwent nonsurgical therapy as their initial treatment and were followed until liver transplantation, last follow-up, or death. The primary outcome was incident or worsening hepatic decompensation within 6 months and the secondary outcome was overall survival. All analyses used inverse probability of treatment weights (IPTW) to account for differences between the nonrandomized cohorts.Results: Post-SVR patients had significantly lower odds of hepatic decompensation compared to viremic patients (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.06-0.59). Results were consistent among subgroups of patients with Child Pugh A cirrhosis (OR, 0.22; 95% CI, 0.04-0.77), Barcelona Clinic Liver Cancer stage B/C HCC (OR, 0.20; 95% CI, 0.04-0.65), and those receiving nonablative HCC therapies (OR, 0.21; 95% CI, 0.07-0.67). However, in IPTW multivariable Cox regression, SVR was not associated with improved survival (hazard ratio, 0.79; 95% CI, 0.56-1.12).Conclusions: Patients with HCV-related HCC and SVR are less likely to experience hepatic decompensation than viremic patients, suggesting patients with HCC who are undergoing nonsurgical therapies may benefit from DAA treatment. [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]

To achieve the World Health Organization’s goal of eliminating hepatitis C (HCV) by 2030 requires enhanced HCV testing and treatment among people who use drugs (PWUD). Micro-elimination of HCV is a strategy to target HCV testing and treatment efforts to specific segments of the population. From February to December 2018 nurses initiated a “seek & treat” micro-elimination approach, increasing outreach and removing barriers to accessing HCV treatment in a clinic setting by testing and treating individuals, including PWUD, where they live. The aim of this study was to evaluate the proportion of clients with HCV antibodies and HCV RNA and the response to direct acting agent (DAA therapy) among people who live at or have social connections to local supportive housing sites through this nurse-led micro-elimination project in Victoria, Canada. A chart review of electronic medical records and case management documentation was used to collect relevant data of participants treated with DAA therapy, identified through specific housing site testing and outreach interventions. In total, 180 people were tested for HCV antibodies, 72 (40%) were antibody positive: 51 (28%) were RNA positive, 13 (7%) had spontaneously cleared and 8 (4%) had been previously treated. Of the 51 that were currently living with HCV, 43 people were started on treatment, 39 have achieved sustained virologic response (SVR). By providing treatment to clients in their homes and with their friends, clinicians have been able to treat clients, including those with limited contact with the health care system. [ABSTRACT FROM AUTHOR]

Transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) is similar regarding the mode of transmission and related risk factors. Therefore, it is not rare to encounter dual HBV/HCV infection in populations at risk of parenteral exposure to hepatitis viruses. Besides, in HBV endemic countries before the era of global HBV vaccination, dual HBV/HCV infection was clinically significant likely because of HCV superinfection over pre-existing HBsAg carriage. Universal childhood HBV vaccination was implemented worldwide since 1992. Public education programs for prevention of new hepatitis viral infections have been actively promoted recently by World Health Organization. Apart from preventive measures, potent anti-HBV agents effective in the control of viral replication have been introduced gradually in the past three decades. Direct acting antiviral agents capable of curing HCV infection in more than 97% of patients with chronic hepatitis C have also been widely implemented in the past decade. These interventions will change the epidemiology of new HBV or HCV mono-infection and dual HBV/HCV infection. Understanding the evolution in the epidemiology of dual HBV/HCV infection is important for evaluation of current public health policy towards infectious disease control in different countries. The changing prevalence of dual HBV/HCV infection in certain Asia-Pacific countries will be re-visited based on endemicity of HBV or HCV, as well as in populations at risk of parenteral viral infection. [ABSTRACT FROM AUTHOR]

Transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) is similar regarding the mode of transmission and related risk factors. Therefore, it is not rare to encounter dual HBV/HCV infection in populations at risk of parenteral exposure to hepatitis viruses. Besides, in HBV endemic countries before the era of global HBV vaccination, dual HBV/HCV infection was clinically significant likely because of HCV superinfection over pre‐existing HBsAg carriage. Universal childhood HBV vaccination was implemented worldwide since 1992. Public education programs for prevention of new hepatitis viral infections have been actively promoted recently by World Health Organization. Apart from preventive measures, potent anti‐HBV agents effective in the control of viral replication have been introduced gradually in the past three decades. Direct acting antiviral agents capable of curing HCV infection in more than 97% of patients with chronic hepatitis C have also been widely implemented in the past decade. These interventions will change the epidemiology of new HBV or HCV mono‐infection and dual HBV/HCV infection. Understanding the evolution in the epidemiology of dual HBV/HCV infection is important for evaluation of current public health policy towards infectious disease control in different countries. The changing prevalence of dual HBV/HCV infection in certain Asia‐Pacific countries will be re‐visited based on endemicity of HBV or HCV, as well as in populations at risk of parenteral viral infection. [ABSTRACT FROM AUTHOR]

Hepatitis A virus (HAV) is a major causative agent of acute hepatitis worldwide. Although discovered in 1973, due to limitations of applicable serological and/or molecular methods, HAV remained under limited diagnosis until the late 1980s. This study aimed to retrospectively evaluate the serological and molecular prevalence of the HAV infection among 421 (n = 421) patients with a clinical and laboratory suspicion of acute hepatitis who were admitted in a reference laboratory in the Brazilian Eastern Amazon during 1982 and 1983. The 421 serum samples were screened for anti‐HAV IgM antibodies by enzymatic immunoassays. Positive samples were submitted to total RNA purification and tested by Nested reverse‐transcription polymerase chain reaction to amplify the HAV‐RNA VP1‐2A (522 bp) region. Anti‐HAV IgM antibodies were detected in 66% (278/421) of the patients. The highest prevalence was observed among males (57.9%, 161/278), and most often among children under 10 years old (63.3%, 176/278). HAV‐RNA was detected in 74.4% (207/278) of anti‐HAV IgM positive samples. HAV genotyping was performed in 71 samples, and 69 were classified into subgenotype IA. Two samples belonged to the HAV subgenotype IIIA. In this sense, retrospective studies can help in understanding the evolution and determination of wild genotypes and subtypes of HAV. Highlights: Serological and molecular evaluation of 421 suspected cases of hepatitis A from the Brazilian Amazon in 1982 and 1983.Anti‐HAV IgM antibodies were detected in 66% (278/421) of the patients.Higher serological prevalence among children younger than 10 years old.The HAV‐RNA was detected in 74.4% (207/278) of anti‐HAV IgM positive samples.HAV genotyping was performed in 71 samples, and 69 were classified into subgenotype IA and two belonged to subgenotype IIIA. [ABSTRACT FROM AUTHOR]

A quantitative risk assessment of hepatitis A virus (HAV) and hepatitis E virus (HEV) from raw oyster consumption from farm and retail was evaluated over three seasons. This risk assessment comprises four steps: hazard identification, dose–response assessment, exposure assessment, and risk characterization. We used probabilistic models for prevalence, concentration, and oyster consumption. HEV dose–response (DR) model based on HEV dosing in chimpanzees and used to perform a dose–response assessment of HEV was proposed. Both HAV and HEV were simultaneously enumerated by real‐time PCR to determine viral doses. The probabilistic prevalences of HAV and HEV were in the ranges of 8–20% and 8–40%, respectively. The best‐fit DR model was the beta‐Poisson with alpha and N50 equal to 216.9 and 3.03 × 107, respectively. After running the Monte Carlo simulation, the annual cases of foodborne hepatitis A and hepatitis E from raw oyster consumption from farms were 9,264–17,526 and 1–604, respectively, while those at retail were 7,694–14,591 and 1–204, respectively. This study suggested that consuming farm oysters poses a significantly higher risk of hepatitis A than hepatitis E. The best‐fit DR model for HEV developed in this study could determine risks of hepatitis E from raw oyster consumption in Thailand. [ABSTRACT FROM AUTHOR]

Mouse hepatitis virus (MHV) is a murine coronavirus and one of the most important pathogens in laboratory mice. Although various strains of MHV have been isolated, they are generally excreted in the feces and transmitted oronasally via aerosols and contaminated bedding. In this study, we attempted to determine the basic reproduction numbers (R0) of three strains of MHV to improve our understanding of MHV infections in mice. Five‐week‐old female C57BL/6J mice were inoculated intranasally with either the Y, NuU, or JHM variant strain of MHV and housed with two naïve mice. After 4 weeks, the presence or absence of anti‐MHV antibody in the mice was determined by ELISA. We also examined the distribution of MHV in the organs of Y, NuU, or JHM variant‐infected mice. Our data suggest that the transmissibility of MHV is correlated with viral growth in the gastrointestinal tract of infected mice. To the best of our knowledge, this is the first report to address the basic reproduction numbers among pathogens in laboratory animals. [ABSTRACT FROM AUTHOR]

Food‐ and waterborne viruses, such as human norovirus, hepatitis A virus, hepatitis E virus, rotaviruses, astroviruses, adenoviruses, and enteroviruses, are major contributors to all foodborne illnesses. Their small size, structure, and ability to clump and attach to inanimate surfaces make viruses challenging to reduce or eliminate, especially in the presence of inorganic or organic soils. Besides traditional wet and dry methods of disinfection using chemicals and heat, emerging physical nonthermal decontamination techniques (irradiation, ultraviolet, pulsed light, high hydrostatic pressure, cold atmospheric plasma, and pulsed electric field), novel virucidal surfaces, and bioactive compounds are examined for their potential to inactivate viruses on the surfaces of foods or food contact surfaces (tools, equipment, hands, etc.). Every disinfection technique is discussed based on its efficiency against viruses, specific advantages and disadvantages, and limitations. Structure, genomic organization, and molecular biology of different virus strains are reviewed, as they are key in determining these techniques effectiveness in controlling all or specific foodborne viruses. Selecting suitable viral decontamination techniques requires that their antiviral mechanism of action and ability to reduce virus infectivity must be taken into consideration. Furthermore, details about critical treatments parameters essential to control foodborne viruses in a food production environment are discussed, as they are also determinative in defining best disinfection and hygiene practices preventing viral infection after consuming a food product. [ABSTRACT FROM AUTHOR]

Hepatitis, a significant cause of mortality worldwide, results in around 1.34 million deaths each year globally. Africa is not exempt from the plague of Hepatitis. Around 100 million estimated individuals are infected with Hepatitis B or C. Egypt has the highest prevalence of cases of Hepatitis followed by Cameroon and Burundi. The continent is severely affected by the onset of the COVID-19 pandemic, as the virus has added an additional burden on the already fragile continent. With the pandemic, it is presumable that Hepatitis like other viral diseases will pose a threat to collapsing healthcare system. Therefore, for Africa to become more resilient in the face of such menaces, including Hepatitis, further prevention policies are required to be implemented. [ABSTRACT FROM AUTHOR]

Background: Hepatitis E viruses (HEV) are an underestimated global cause of enterically transmitted viral hepatitis, which may persist in immunocompromised hosts, posing a risk for progressive liver fibrosis with limited treatment options. We previously established liver‐humanized mice as a model for chronic HEV infections, which can be cleared by a 2‐week pegylated (peg)‐Interferon(IFN)α treatment course. However, severe side effects may hamper the use of IFNα in immunocompromised transplant recipient patients. IFNλ may be a valuable alternative, as its receptor is less ubiquitously expressed. Aims: In this study, we assess the in vitro and in vivo potency of pegIFNλ to induce innate immune signalling in liver cells and to clear a persistent HEV infection in liver‐humanized mice. Methods & Results: We found that human liver cells expressed the IFNλ receptor (IFNLR1) and are responsive to pegIFNλ. Treatment with pegIFNλ of liver‐humanized mice persistently infected with HEV genotype 3 showed that pegIFNλ was well tolerated. Dose escalation studies showed that although HEV was not cleared at pegIFNλ doses up to 0.12 mg/kg for a maximum of 8 weeks, a dose of 0.3 mg/kg pegIFNλ treatment resulted in complete clearance of HEV antigen and HEV RNA from the liver in 8 out of 9 liver‐humanized mice. Conclusions: PegIFNλ is well tolerated in mice and leads to clearance of a persistent HEV infection in liver‐humanized mice. [ABSTRACT FROM AUTHOR]

An estimated 8–10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in Egypt as 50% or more of the Egyptian population are already exposed to HAV infection by the age of 15. In addition, over 60% of the Egyptian population test seropositive for anti‐HEV in the first decade of life. HEV mainly causes self‐limiting hepatitis; however, cases of fulminant hepatitis and liver failure were reported in Egypt. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are the main causes of chronic hepatitis, liver cirrhosis, and liver cancer (hepatocellular carcinoma [HCC]) in Egypt. Globally, Egypt had the highest age‐standardized death rate due to cirrhosis from 1990 to 2017. The prevalence rate of HBV (1.3%–1.5%) has declined after national infantile immunization. Coinfection of HBV patients with HDV is common in Egypt because HDV antibodies (IgG) vary in range from 8.3% to 43% among total HBV patients. After the conduction of multiple national programs to control HCV infection, a lower rate of HCV prevalence (4.6%) was recently reported. Data about the incidence of HCV after treatment with direct antiviral agents (DAAs) are lacking. An HCC incidence of 29/1000/year in cirrhotic patients after DAA treatment is reported. A higher rate of infiltrative pattern among HCC patients after DAA treatment is also recognized. Viral hepatitis is one of the major public health concerns in Egypt that needs more attention and funding from health policymakers. [ABSTRACT FROM AUTHOR]

Aim: We reviewed the data of a nationwide follow‐up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass‐forming (MF) type, and combined mass‐forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC). Methods: In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV‐related ICC (n = 138, 14.4%), hepatitis B virus (HBV)‐related ICC (n = 43, 4.5%) and non‐virus‐related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score‐matching to compare outcomes after surgery between HCV‐related (n = 102) and non‐virus‐related ICC cases (n = 102). Results: We successfully matched HCV‐related and non‐virus‐related ICC cases with similar liver function and tumor characteristics. Patients with HCV‐related ICC had significantly shorter recurrence‐free survival (hazard ratio 0.62, 95% confidence interval 0.42–0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37–0.88, p = 0.011) than patients with non‐virus‐related ICC. Cox proportional hazard analysis showed that HCV‐related ICC offered a worse prognosis than non‐virus‐related ICC. Conclusions: HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to explore the benefits of different antiviral regimens in pregnant women with hepatitis B virus (HBV) infection in an attempt to provide scientific reference for clinically relevant interventions. Methods: The study cohort comprised 64 pregnant women with HBV infection who presented to our hospital from May 2018 to July 2020. The women were grouped according to the treatment administered: a control group consisting of 32 pregnant women who received routine intervention and an observation group consisting of 32 pregnant women who received routine intervention plus tenofovir disoproxil fumarate (TDF) tablets. The two groups were compared in terms of liver function; HBV load (HBV DNA); neonatal characteristics (hepatitis B surface antigen and HBV DNA positivity); levels of interleukin (IL)‐2, IL‐4, and IL‐6; neonatal growth and development; Apgar scores; incidence of adverse events; and incidence of maternal adverse effects during treatment. Results: The observation group had lower levels of alanine aminotransferase, glutamic acid aminotransferase, IL‐4, IL‐6, and HBV DNA and higher levels of IL‐2 than the control group after 1 month of treatment (p < 0.05). There was no significant difference in the incidence of adverse events between the two groups (p > 0.05). Conclusion: The administration of TDF tablets significantly reduced the HBV DNA levels and did not increase the physiological burden or adverse effects in pregnant women with HBV infection. [ABSTRACT FROM AUTHOR]

Donor‐derived (DD) herpes simplex virus (HSV) hepatitis in solid organ transplant (SOT) recipients is extremely uncommon but carries a high mortality rate. The diagnosis is challenging due to the non‐specific presentation and lack of clinical suspicion. We report a case of DDHSV hepatitis in a HSV2 pre‐transplant seronegative kidney recipient who received the organ from a HSV2 seropositive donor. The case is highlighted by a few unusual features, namely severe thrombocytopenia and the development of cutaneous, oral and esophageal HSV lesions several weeks after symptom onset while recovering on appropriate treatment. A review of nine proven and probable DDHSV hepatitis cases (including eight previously published ones) showed that fever is a common presenting feature while gastrointestinal symptoms and cutaneous manifestations are uncommon. The symptoms almost always occurred within 2 weeks of transplant. Six out of the nine DDHSV hepatitis patients, including five patients who were on appropriate treatment, died within a month after transplant. [ABSTRACT FROM AUTHOR]

The nephrotoxicity of sofosbuvir (SOF) on human immunodeficiency virus and hepatitis C virus (HIV/HCV)‐coinfected patients receiving antiretroviral therapy (ART) remains controversial. We prospectively compared the estimated glomerular filtration rate (eGFR) changes in 167 patients receiving SOF‐based direct‐acting antivirals (DAAs) who also received tenofovir disoproxil fumarate (TFV)‐based (n = 116) and TFV‐free ART (n = 51). The eGFR was assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation, and the eGFR changes between ART regimens were compared by the generalized estimated equation. During DAA treatment, participants on TFV‐based ART had a higher eGFR decline than those on TFV‐free ART (slope coefficient difference: −0.82 ml/min/1.73 m2/month [95% CI: −1.21 to −0.43]; p < 0.001), whereas the eGFR changes did not differ between groups (slope coefficient difference: 0.13 ml/min/1.73 m2/month [95% CI: −0.32 to 0.58]; p = 0.42) after discontinuing DAAs. Participants on TFV TDF‐based ART had a higher eGFR decline than those on TFV alafenamide fumarate (TAF)‐based ART (slope coefficient difference: −0.31 ml/min/1.73 m2/month [95% CI: −0.50 to −0.12]; p = 0.01). After discontinuing DAAs, the eGFR changes did not differ between groups (slope coefficient difference: 0.06 ml/min/1.73 m2/month [95% CI: −0.98 to 1.10]; p = 0.91). In conclusion, HIV/HCV‐coinfected patients on TFV‐based ART had a slight eGFR decline compared to those on TFV‐free ART during SOF‐based DAA therapy. A similar trend between TDF‐based and TAF‐based ART was also observed. Because the differences of eGFR changes are limited, the physicians should not discourage the use of SOF‐based DAAs in HIV‐positive patients on TFV‐based ART. [ABSTRACT FROM AUTHOR]

Hepatitis A infections still represent a major global health concern. During the past years, a transition pattern of the hepatitis A epidemiology was noted in many parts of the world. In Tunisia, there is not a recent survey on age‐specific hepatitis A virus seroprevalence. This study aimed to investigate the seroprevalence of hepatitis A virus infection in Central‐West Tunisia, representative of regions with lowest socioeconomic level in the country, before vaccine implementation. Sera obtained from the blood samples of subjects were screened for the detection of hepatitis A virus. The seroprevalence was evaluated by detection of total antibodies to hepatitis A virus using commercially available immunoassay kits. A total of 1379 subjects, aged 5–75 years (mean age: 29.0 ± 17.3 years) were studied. The global anti‐hepatitis A virus seroplevalence was 84.7% (95% confidence interval: [82.6–86.5]). A higher hepatitis A virus seroprevalence was showed in subjects aged 10–14 years compared to those aged less than 10 years (50.0% vs. 31.0%). In subjects aged 20–29 years, a rapid increase in the hepatitis A virus prevalence was noted; it reached 97.0%. The seroprevalence of anti‐hepatitis A virus differed by zone of residence (81.1% in rural area vs. 72.4% in urban area, p =.005) and increased significantly with lower level of education (p =.019). There was no statistical significant seroprevalence difference between male and female: 84.2% versus 85.2%, respectively. Our study confirm the transition pattern of the hepatitis A virus endemicity in Tunisia from high to intermediate and provide an evaluation of the hepatitis A virus epidemiological situation before vaccine implementation. [ABSTRACT FROM AUTHOR]

Fulminant hepatic failure (FHF) is a lethal manifestation of hepatitis A virus (HAV) infection, whose underlying mechanisms are poorly understood. We aimed to evaluate the importance of the modulation of the RANTES‐chemokine receptor type 5 (CCR5) signaling axis and its immunomodulatory effects in directing hepatitis A disease pathogenesis using an in silico, in vitro and patient cohort‐based approach. In silico interaction studies were performed using computation approaches with suitable software. Differential expression of relevant cytokines and immune cell markers were studied using real‐time quantitative reverse transcription PCR (qRT‐PCR), enzyme‐linked immunosorbent assay, and flow‐cytometry‐based methods. In the HepG2 cell line, we studied inflammatory responses and susceptibility to HAV infection following RANTES stimulation and antibody blockade of CCR5. The HAV‐VP3 region exhibited high interaction in CCR5: HAV complexes. RANTES levels were significantly increased in FHF cases. Reduced monocyte and T‐cell activation were observed in FHF cases. RANTES expression inversely correlated with viremia but positively correlated with proinflammatory responses. Hyper Th1‐biased immune responses, marked by high interleukin (IL)‐12/IL‐10 ratio were observed in FHF cases, which were also characterized by upregulated tumor necrosis factor‐alpha (TNF‐α) expression and reduced interferon‐gamma expression. In vitro, RANTES was protective against HAV infection but resulted in upregulated TNF‐α expression. Although viral load increased upon the regulation of inflammatory responses by CCR5 blocking, it was still significantly lower compared to control HAV‐infected cells. Our study suggests the importance of RANTES‐CCR5 signaling and linked‐immunomodulation in HAV disease pathogenesis, as well as highlights the utility of CCR5 antagonists as a risk‐reduction strategy in FHF patients. Our findings, therefore, have important implications for the management of high‐risk HAV infections. Highlights: Hepatitis A virus infection mediated significant RANTES expression in patients.Fulminant patients exhibited altered RANTES‐linked Th1‐biased immunomodulation.Supportive correlations were observed between immunomodulation and outcome.Immune responses were studied in RANTES‐stimulated, HAV‐infected HepG2 cell line.Inflammatory outcomes of protective RANTES could be regulated by CCR5 blocking. [ABSTRACT FROM AUTHOR]

Hepatitis E, a public health concern in developing countries, frequently presents in epidemic, as well as in sporadic forms. This study investigated an outbreak of viral hepatitis at Yavatmal, Maharashtra, India in March 2019. Blood samples from 10 patients were received at Indian Council of Medical Research‐National Institute of Virology, Pune to test for the presence of enterically transmitted hepatitis viruses. Subsequently, 49 suspected cases were screened for anti‐hepatitis E virus (HEV)/hepatitis A virus (HAV) immunoglobulin M and immunoglobulin G (IgG) antibodies, alanine amino‐transferase levels and HEV RNA. Water samples were screened for HEV and HAV RNA followed by phylogenetic analysis. Overall 32 of 49 (65.3%) suspected cases had recent acute HEV infection, while dual infection with HAV was noted in one case (2.04%). Forty‐eight of 49 suspected cases were positive for anti‐HAV IgG antibodies indicative of previously acquired immunity against HAV. Water samples had evidence of HEV contamination as detected by reverse transcription‐polymerase chain reaction. Sequencing of HEV RNA from both patients (n = 2) and water samples (n = 5) indicated HEV genotype 1 to be the etiological agent of this outbreak. Serological and molecular evidence confirmed HEV as the etiology. Mixing of contaminated drain water with the domestic water supply may have triggered this outbreak. Subsequent changing of the defaulted water pipelines and its segregation from drain pipelines by the health authorities resulted in progressive decline of this outbreak. Despite the limitations, periodic surveillance of HEV exposure pattern and reporting of small outbreaks would supplement to the global disease burden data of hepatitis E. Highlights: ‐ Hepatitis E outbreak at Yavatmal, Maharashtra, India in March 2019.‐ Major cause of the outbreak was mixing of contaminated drain water with domestic water supply.‐ Serological and molecular evidences confirmed HEV genotype 1 as the etiological agent.‐ Data suggest a need to consider outbreak investigation along with periodic surveillance to avoid future outbreaks. [ABSTRACT FROM AUTHOR]

The hepatitis A vaccine is recommended for all children greater than or equal to 1 year of age, however, the duration of vaccine protection is unknown and protection through adulthood is crucial to prevent symptomatic hepatitis later in life. We report on 25 years of follow‐up of a cohort of Alaska Native individuals who were vaccinated in early childhood. We assessed the duration of vaccine protection by calculating the geometric mean concentration and proportion of participants with protective levels of IgG antibody to hepatitis A virus (anti‐HAV) (≥20 mIU/mL) every 2 to 3 years. We estimated the amount of time until the anti‐HAV dropped below protective levels using survival analyses. At 25 years, 43 of the original 144 participants were available, mean anti‐HAV levels were 91.5 mIU/mL, and 35 (81.4%) had protective levels of anti‐HAV. Using data from all persons and all time points, a survival analysis estimated 78.7% of participants had protective levels of anti‐HAV at 25 years. The high level of protective antibodies in this cohort indicate that supplemental doses of hepatitis A vaccine are not needed 25 years after completion of the vaccine series. Highlights: Our data indicate that a supplemental vaccine dose is not necessary up to 25 years after hepatitis A vaccine is administered in childhood. [ABSTRACT FROM AUTHOR]

Unfortunately, the United Network for Organ Sharing is not currently required to report HAV test results as part of the donor summary, as it does for HBV or HCV.11 The impact of HAV transmission on kidney transplant recipients is uncertain. Effective vaccination has led to a decrease in hepatitis A incidence in the United States.1 Donor-derived hepatitis A virus (HAV) transmission has rarely been reported after kidney transplantation or other solid organ transplant. Keywords: donor-derived infection; hepatitis A; kidney transplant EN donor-derived infection hepatitis A kidney transplant 1 3 3 08/12/22 20220801 NES 220801 INTRODUCTION Hepatitis A remains a significant global health problem. [Extracted from the article]

The main aim of this study is to analyze the dynamical properties of hepatitis B‐type virus (HBV) infection in terms of mathematical model. The presented mathematical model on HBV involves the various factors such as immune impairment, total carrying capacity, logistic growth term, and antiretroviral therapies. In addition, the effect of time delays is also considered into the model, which are inevitable during the activation of immune response and time taken to infect the healthy cells. Mathematically, the qualitative analyses such as stability, bifurcation, and stabilization analysis are performed to explore the dynamical characteristics of HBV over the period of time. The significance of the model parameters is revealed through Hopf‐type bifurcation analysis and the global stability analysis of the proposed model. With the help of data set values that are extracted from the literature, the efficiency of the derived theoretical results is explored. [ABSTRACT FROM AUTHOR]