Search

Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection. In this study, the authors identify genetic insertions in the population of hepatitis E virus analyzed in serum samples of a patient with ribavirin treatment failure. They show that these genomic rearrangements promote viral replication without affecting ribavirin sensitivity. [ABSTRACT FROM AUTHOR]

The cellular prion protein (PrPC) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrPC has been difficult to establish. During viral infection, PrPC has been reported to play a pleiotropic role. Here, we have attempted to envision the function of PrPC in the neurotropic m-CoV-MHV-RSA59-induced model of neuroinflammation in C57BL/6 mice. A significant upregulation of PrPC at protein and mRNA levels was evident in infected mouse brains during the acute phase of neuroinflammation. Furthermore, investigation of the effect of MHV-RSA59 infection on PrPC expression in specific neuronal, microglial, and astrocytoma cell lines, revealed a differential expression of prion protein during neuroinflammation. Additionally, siRNA-mediated downregulation of prnp transcripts reduced the expression of viral antigen and viral infectivity in these cell lines. Cumulatively, our results suggest that PrPC expression significantly increases during acute MHV-RSA59 infection and that PrPC also assists in viral infectivity and viral replication. [ABSTRACT FROM AUTHOR]

Background: Acute hepatitis due to various tropical infections can mimic the clinical picture of acute viral hepatitis(AVH), leading to increased morbidity and mortality. We aimed to identify clinical and laboratory parameters that could help to distinguish acute hepatitis due to tropical infections from AVH. Methods: We retrospectively analyzed our database of 150 children (107 boys) with AVH and 50 children(34 boys)with acute hepatitis due to tropical infections between January 2013 and March 2023. Clinical features, investigations, complications and outcomes were compared. Results: Hepatitis A (75%) was the commonest etiology of AVH while enteric fever (34%), dengue (26%), scrub typhus (20%) and leptospirosis (16%) constituted the majority of tropical infections. Persistent fever and skin rashes were found in 88% and 16% of patients respectively in the tropical infection group and none in the AVH group (p < 0.001). On univariate analysis, prodromal symptoms, clinically detectable jaundice, cholestatic pattern, total and direct bilirubin and liver enzymes were significantly higher in AVH while headache, myalgia, leukopoenia, thrombocytopenia, hyponatremia were significantly higher in tropical infections group (all p < 0.05). Multivariate analysis identified thrombocytopenia (Odds ratio [OR] 4.237) as an independent positive predictive factor and markedly elevated total bilirubin (OR 0.575), direct bilirubin (OR 0.498), aspartate aminotransferase (OR 0.841) and alanine aminotransferase (OR 0.863) as independent negative predictive factors for acute hepatitis due to tropical infections. Conclusion: High index of suspicion for tropical infections is warranted in patients with persistent fever after the onset of jaundice, especially in the presence of skin rash and thrombocytopenia. [ABSTRACT FROM AUTHOR]

Objective: Non-alcoholic steatohepatitis (NASH) is one of the most common metabolic diseases of the liver. In patients with NASH, progression to cirrhosis can be observed in approximately 25% over a decade following diagnosis, and it is considered the most frequent cause of cryptogenic cirrhosis. Fibrinogen-like protein-2 (FGL-2) is a sub-member of the fibrinogen superfamily secreted by regulatory T cells. It inhibits the maturation of dendritic cells and induces apoptosis in B cells, playing a role in innate and adaptive immunity regulation. Recent studies have shown high serum FGL-2 levels are a poor prognostic indicator in patients with viral hepatitis. Methods: The study included 30 NASH patients diagnosed by biopsy and a control group of 21 healthy individuals. Serum FGL-2 levels of individuals in both groups were compared. The relationship between the clinicopathological features of individuals in both groups and FGL-2 levels was also examined. Results: Serum FGL-2 levels in NASH patients were found to be 47±12 ng/ml, while in the control group, it was 37±10 ng/ml. Statistical evaluation was performed using the Mann- Whitney U test. A significant difference was found between patients classified by biopsy as simple steatosis, borderline NASH, definite NASH, and the control group (p=0.002). A significant difference was also observed when evaluating these four groups among themselves (Kruskal-Wallis test, p=0.012). Conclusion: Our study identified higher serum FGL-2 levels in patients diagnosed with NASH, consistent with steatohepatitis observed in biopsies. Elevated FGL-2 levels may indicate hepatic damage at the microinflammation level. Estimating disease severity, non-invasive monitoring and control of disease progression, selecting patients for aggressive treatment approaches, and intensifying monitoring intervals for cirrhosis and HCC could be crucial. However, more comprehensive studies on this topic are needed. [ABSTRACT FROM AUTHOR]

Aim: Hepatocellular carcinoma (HCC) is a major cause of cancer‐related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD. Methods: Korean adults (n = 340 825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods. Results: In 93 HCC cases, 71 were identified in G4, whereas 20 cases (21.5%) in G2 and G3 combined where ultrasound and Fibrosis‐4 performed similarly to alpha‐fetoprotein and ultrasound. In G2, Fibrosis‐4 and ultrasound had the highest area under the receiver operating characteristic curve (0.93 [0.87–0.99]), whereas in G3, the combined screening methods had the highest area under the receiver operating characteristic curve (0.98 [0.95–1.00]). The positive predictive value was lower in G2 and G3 than in G4, but was >5% when restricted to a high Fibrosis‐4 score. Conclusions: More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the Fibrosis‐4 score in identifying individuals at high risk of HCC. [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]

Hepatitis A virus (HAV), a member of the genus Hepatovirus (Picornaviridae HepV), remains a significant viral pathogen, frequently causing enterically transmitted hepatitis worldwide. In this study, we conducted an epidemiological survey of HepVs carried by small terrestrial mammals in the wild in Yunnan Province, China. Utilizing HepV-specific broad-spectrum RT-PCR, next-generation sequencing (NGS), and QNome nanopore sequencing (QNS) techniques, we identified and characterized two novel HepVs provisionally named EpMa-HAV and EpLe-HAV, discovered in the long-tailed mountain shrew (Episoriculus macrurus) and long-tailed brown-toothed shrew (Episoriculus leucops), respectively. Our sequence and phylogenetic analyses of EpMa-HAV and EpLe-HAV indicated that they belong to the species Hepatovirus I (HepV-I) clade II, also known as the Chinese shrew HepV clade. Notably, the codon usage bias pattern of novel shrew HepVs is consistent with that of previously identified Chinese shrew HepV. Furthermore, our structural analysis demonstrated that shrew HepVs differ from other mammalian HepVs in RNA secondary structure and exhibit variances in key protein sites. Overall, the discovery of two novel HepVs in shrews expands the host range of HepV and underscores the existence of genetically diverse animal homologs of human HAV within the genus HepV. [ABSTRACT FROM AUTHOR]

Background: The effects of antihistamines on cancer risk and prognosis have been inconsistent across cancers. The aim of this multi-center cohort study was to investigate the association between antihistamine use and the risk of liver cancer in individuals with viral hepatitis. Methods: This multi-center cohort study included individuals diagnosed with hepatitis B or hepatitis C between January 2008 and March 2022. For antihistamine-treated patients, the index date was the date of antihistamine prescription, and for non-users, it was the date of hepatitis diagnosis. Participants were followed for five years, with the primary outcome of interest being new-onset liver cancer. The incidence rate and the adjusted hazard ratio (aHR) along with its 95% confidence interval (CI) of the outcome were calculated. Subgroup analyses were conducted, stratified by types of viral hepatitis including hepatitis C and hepatitis B. An additional validation study was performed. Results: The study included a total of 7748 patients with viral hepatitis. The incidence rate was 12.58 per 1000 person-years in patients with viral hepatitis on antihistamines, compared to 3.88 per 1000 person-years in those without antihistamine use. After adjusting for factors including age, sex, body mass index (BMI), comorbidities, laboratory data of liver function tests, comedications, and the use of antiviral therapies, the risk of new-onset liver cancer was significantly higher in patients on antihistamines (aHR = 1.83, 95% CI, 1.28–2.60). In patients with hepatitis C, the incidence rate in the antihistamine group was 15.73 per 1000 person-years, while non-users had a rate of 4.79 per 1000 person-years. Patients with hepatitis C on antihistamines had a significantly higher risk of developing liver cancer (aHR = 3.24, 95% CI, 2.16–4.86). Conclusions: This multi-center cohort study reported an increased risk of liver cancer in patients with hepatitis B or hepatitis C treated with antihistamines. Long-term follow-up studies are warranted to validate the findings. [ABSTRACT FROM AUTHOR]

Hepatitis A (HAV) presents a significant global health concern with diverse clinical manifestations primarily transmitted through fecal–oral routes, emphasizing the critical role of sanitation and water cleanliness in transmission dynamics. Age-related variations, notably asymptomatic presentation in children, add complexity. The World Health Organization's (WHO) endemicity classification aids in understanding prevalence and control strategies. This study examines 2023 South African epidemiological data on HAV cases, evaluating age distribution, incidence rates, and provincial disparities. Data from the national surveillance system and weather services were analyzed. Findings reveal distinct age-related trends, with the highest seroprevalence observed in the 5–9 age group with the most burdened areas located in the Western Cape, KwaZulu-Natal, and Gauteng provinces. Furthermore, seasonal rainfall variations correlate with increased incidence in Western Cape and KZN. The amalgamation of results suggest a potential epidemiological shift, emphasizing the need for updated immunization strategies. Noteworthy patterns, like the rise in 5–9-year-olds, may be influenced by factors such as school clustering and migration. Provincial disparities and the impact of climatic events underscore the necessity for dynamic vaccination strategies and surveillance network enhancements. This study highlights the urgency for improved understanding and response to HAV in South Africa. [ABSTRACT FROM AUTHOR]

A number of research studies, including ours, have spotlighted exosomes as critical facilitators of viral dissemination. While hepatitis B virus (HBV) transmission through exosomes has been studied, the focus on its satellite virus, the hepatitis delta virus (HDV), has been unexplored in this context. HDV, although being a defective virus, can replicate its genome autonomously within hepatocytes, independently of HBV. Investigations on Huh7 cells revealed an intriguing phenomenon: the HDV proteins, S-HDAg and L-HDAg, are transmitted between cells without a complete viral structure. Detailed analysis further revealed that the expression of these proteins not only bolstered exosome secretion but also ensured their enrichment within these vesicles. Our experimental approach utilized transfection of various plasmids to examine the role of HDV RNA and proteins in the process. One salient finding was the differential propagation of the HDV proteins S-HDAg and L-HDAg, suggesting intricate molecular mechanisms behind their transmission. Notably, the purity of our exosome preparations was monitored using markers such as TSG101 and CD81. Importantly, these exosomes were found to carry both HDV RNA and proteins, highlighting their role in HDV dissemination. This novel study underscores the role of exosomes in mediating the transmission of HDV components between hepatocytes independent of HBV. These revelations about the exosomal pathway of HDV transmission provide a foundation for the development of innovative therapeutic strategies against HDV infections. [ABSTRACT FROM AUTHOR]

Background/aims The effect modification by smoking and menopausal status in the association between high-density lipoprotein cholesterol (HDL-C) and liver cancer risk has not been reported. Methods This population-based cohort study included 4.486 million cancer-free individuals among those who underwent national cancer screening in 2010 and were followed up until December 2017. We conducted analyses in populations that excluded people with chronic hepatitis B, chronic hepatitis C and liver cirrhosis (Model I) and that included those diseases (Model III). HDL-C level was classified into eight groups at 10-mg/dL intervals. Liver cancer risk by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results During follow-up, 18 795 liver cancers in Model I and 20 610 liver cancers in Model III developed. In Model I, low HDL-C levels (aHR 1.83; 95% CI 1.65–2.04) and extremely high HDL-C levels (aHR 1.24; 95% CI 1.10–1.40) were associated with an increased liver cancer risk compared with a moderate HDL-C level of 50–59mg/dL. This association was similar in both men and women with larger effect size in men (aHR, 1.91; 95% CI, 1.70–2.15). The hazardous association between low HDL-C and liver cancer risk was remarkable in current smokers (aHR, 2.19; 95% CI, 1.84–2.60) and in pre-menopausal women (aHR, 2.91; 95% CI, 1.29–6.58) compared with post-menopausal women (aHR, 1.45; 95% CI, 1.10–1.93). This association was similarly observed in Model III. Conclusions Low and extremely high HDL-C levels were associated with an increased liver cancer risk. The unfavourable association between low HDL-C and liver cancer was remarkable in smokers and pre-menopausal women. [ABSTRACT FROM AUTHOR]

Background: The characteristics of autoimmune hepatitis (AIH) in Asia mostly remain elusive. Methods: A cohort study of liver biopsy-proven AIH patients was conducted in a tertiary care cancer of Taiwan. Results: From 1999 to 2022, of 13,766 patients who underwent liver biopsy, 150 patients with AIH were enrolled. The female-to-male ratio was 2.26. At baseline, the mean age was 51.09 years, mean alanine aminotransferase level was 494.11 U/L, and 17 (11.3%) had cirrhosis. All except one patient had AIH type 1. The females were older and had higher baseline cirrhosis rates than did the males. The 23-year cumulative incidences of cirrhosis, hepatocellular carcinoma (HCC), mortality/liver transplantation, autoimmune diseases and extrahepatic cancer were 64.2%, 13.3%, 23.4%, 30.7% and 21.2%, respectively. The 1-year, 2-year, 3-year, 5-year, 10-year and 20-year postimmunosuppressive therapy relapse rates were 60%, 78.2%, 81.8%, 89.1%, 94.5% and 100%, respectively. Baseline associations were as follows: alkaline phosphatase (Alk-p) levels with postimmunosuppressive therapy flare [hazard ratio (HR): 1.003; 95% CI HR: 1.000-1.005]; age with HCC (1.072; 1.010–1.138) and all-cause cancer (1.041;1.005–1.079); cirrhosis with mortality/liver transplantation (11.933;1.984–71.787); and antinuclear antibody (ANA) titers with mortality/liver transplantation (1.001;1.000-1.003), cirrhosis (1.001;1.000-1.002), and autoimmune diseases (1.001; 1.000-1.002). Conclusion: In an Asian country endemic for viral hepatitis, the female-to-male and baseline cirrhosis rates of AIH patients were lower than expected, while over 60% of the patients eventually developed cirrhosis. The high posttherapy relapse rate warrants cautious monitoring, particularly for patients with high baseline Alk-p levels. Baseline age, cirrhosis status and ANA titers are crucial for outcomes. [ABSTRACT FROM AUTHOR]

Chronic liver disease is one of the main causes of morbidity and mortality in people living with HIV (PLWH). The increasing life expectancy of PLWH, effective treatment for viral hepatitis, and Western dietary patterns as well as the adverse effects of antiretroviral therapy (ART) have rendered metabolic dysfunction-associated steatotic liver disease (MASLD) the most common chronic liver disease in PLWH. The risk factors for MASLD in PLWH include traditional MASLD risk factors and additional virus-specific factors, including the adverse effects of ART. The management of patients suffering from HIV and MASLD is often challenging. Apart from the conventional management of MASLD, there are also certain limitations concerning the use of ART in this patient population. In general, the appropriate combination of antiretroviral drugs should be chosen to achieve the triad of effective viral suppression, avoidance of mitochondrial dysfunction, and deterrence of worsening the patient's metabolic profile. In the current review, we discuss the epidemiology of MASLD in PLWH, the risk factors, and the disease pathogenesis, as well as the limitations in the use of ART in this patient population, while practical recommendations on how to overcome these limitations are also given. [ABSTRACT FROM AUTHOR]

Simple Summary: The epidemiology of primary liver cancer is changing according to effective primary prevention interventions, a strictly clinical follow up of chronic patients with hepatitis and successful drug treatments of virus-related liver diseases. A reduction in virus-related hepatocellular carcinomas cases was followed by an increase in the non-viral aetiology, including metabolic and cryptogenetic factors. We used cancer surveillance data to investigate determinants potentially associated with primary liver cancer survival in a southern Italian setting characterised by a high prevalence of hepatitis viral infections and overweight and obesity. Our study provided some new insights into the potential relationship between deprivation, geographic location, access to care and hepatocarcinoma survival. Comprehensive national and regional health plans should consider the evidence provided to ensure equitable access to prevention and care pathways. While entering the digital prevention era, interoperating cancer registries with other sources providing data on lifestyles and health determinants should be promoted. A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male), a flexible hazard-based regression model revealed factors influencing 5-year survival rates. High deprivation levels [HR = 1.41 (95%CI = 1.15–1.76); p < 0.001], poor access to care [HR = 1.99 (95%IC = 1.70–2.35); p < 0.0001], age between 65 and 75 [HR = 1.48 (95%IC = 1.09–2.01); p < 0.05] or >75 [HR = 2.21 (95%CI = 1.62–3.01); p < 0.0001] and residing in non-urban areas [HR = 1.35 (95%CI = 1.08–1.69); p < 0.01] were associated with poorer survival estimates. While deprivation appeared to be a risk factor for primary liver cancer patients residing within the urban area, the geographic distance from specialised treatment centres emerged as a potential determinant of lower survival estimates for residents in the non-urban areas. After balancing the groups of easy and poor access to care using a propensity score approach, poor access to care and a lower socioeconomic status resulted in potentially having a negative impact on primary liver cancer survival, particularly among urban residents. We emphasise the need to interoperate cancer registries with other data sources and to deploy innovative digital solutions to improve cancer prevention. [ABSTRACT FROM AUTHOR]

Bulevirtide (BLV) is a first-in-class entry inhibitor and the only approved treatment for patients chronically infected with HDV in Europe. We aimed to investigate the efficacy of BLV treatment in paired liver biopsies obtained at baseline and after 24 or 48 weeks of treatment. We performed a combined analysis of 126 paired liver biopsies derived from three clinical trials. In the phase II clinical trial MYR202, patients with chronic hepatitis D were randomised to receive 24 weeks of BLV at 2 mg, 5 mg or 10 mg/day. Patients in MYR203 (phase II) and MYR301 (phase III) received 48 weeks of BLV at 2 mg or 10 mg/day. Tenofovir disoproxil fumarate monotherapy or delayed treatment served as comparators. Virological parameters and infection-related host genes were assessed by qPCR and immunohistochemistry. At week 24, median intrahepatic HDV RNA decline from baseline was 0.9Log 10 with 2 mg (n = 7), 1.1Log 10 with 5 mg (n = 5) and 1.4 Log 10 with 10 mg (n = 7) of BLV. At week 48, median reductions were 2.2Log 10 with 2 mg (n = 27) and 2.7Log 10 with 10 mg (n = 37) of BLV, while HDV RNA levels did not change in the comparator arms. Notably, a drastic decline in the number of hepatitis delta antigen-positive hepatocytes and a concomitant decrease in transcriptional levels of inflammatory chemokines and interferon-stimulated genes was determined in all BLV-treatment arms. Despite the abundance of HBsAg-positive hepatocytes, replication and covalently closed circular DNA levels of the helper virus HBV were low and remained unaffected by BLV treatment. Blocking viral entry diminishes signs of liver inflammation and promotes a strong reduction of HDV infection within the liver, thus suggesting that some patients may achieve HDV cure with long-term treatment. Chronic infection with HDV causes the most severe form of viral hepatitis, affecting approximately 12 million people worldwide. The entry inhibitor bulevirtide (BLV) is the only recently approved anti-HDV drug, which has proven efficacious and safe in clinical trials and real-word data. Here, we investigated paired liver biopsies at baseline and after 24 or 48 weeks of treatment from three clinical trials to understand the effect of the drug on viral and host parameters in the liver, the site of viral replication. We found that BLV treatment strongly reduces the number of HDV-infected cells and signs of liver inflammation. This data implies that blocking viral entry ameliorates liver inflammation and that prolonged treatment regimens might lead to HDV cure in some patients. This concept will guide the further development of therapeutic strategies and combination treatments for patients with CHD. NCT03546621, NCT02888106, NCT03852719 [Display omitted] • Combined analysis of paired liver biopsies from three clinical trials investigating the entry inhibitor bulevirtide. • Bulevirtide strongly reduces intrahepatic HDV RNA levels and HDV-infected hepatocytes. • The reduction of infected cells reflects changes in viral loads in the serum. • Inflammatory gene expression is also decreased by bulevirtide treatment. • Intrahepatic levels of the helper virus HBV are not affected by the treatment. [ABSTRACT FROM AUTHOR]

Beyond cardiovascular disease protection, the health consequences of very low concentrations of low-density lipoprotein-cholesterol (LDL-C) remain a matter of debate. In primary hypobetalipoproteinemia (HBL), liver steatosis and cirrhosis have occasionally been reported. Here, we aimed to investigate the association between HBL and the risk of hepatic complications (cirrhosis complications and/or primary liver cancer) in the general population. A cohort study was conducted in the French population-based cohort CONSTANCES. Participants with primary HBL (LDL-C <5th percentile for age and sex, [HBL]) were compared with those with normal LDL-C concentrations (40th-60th percentile, [Control]). Participants on lipid-lowering therapies were excluded. For hepatic complications, follow-up events were compared by calculating the incidence density ratio (IDR). The same analyses were replicated in the UK Biobank (UKBB) cohort. In the CONSTANCES and UKBB cohorts, 34,653 and 94,666 patients were analyzed, with median ages of 45 and 56 years, mean LDL-C concentrations (HBL vs. control) of 71 vs. 128 mg/dl and 86 vs. 142 mg/dl, and mean follow-up durations of 5.0 and 11.5 years, respectively. The HBL group presented a higher incidence of hepatic complications than the control group: 0.32/ vs. 0.07/1,000 person-years (IDR = 4.50, 95% CI 1.91-10.6) in CONSTANCES, and 0.69/ vs. 0.21/1,000 person-years (IDR = 3.27, 95% CI 2.63-4.06) in the UKBB. This risk proved to be independent of classic risk factors for liver disease (obesity, alcohol consumption, diabetes, viral hepatitis), including in a 5-year landmark analysis excluding early events. Sensitivity analyses based on apoliprotein-B levels (instead of LDL-C levels) or genetically defined HBL showed similar results. HBL is associated with a markedly increased risk of hepatic complications. HBL must be considered as a substantial independent risk factor for liver diseases which justifies specific prevention and screening. Hypobetalipoproteinemia (HBL) is a lipid disorder characterized by permanent, inherited low levels (below the 5th percentile) of low-density lipoprotein-cholesterol. While HBL is associated with a lower risk of cardiovascular events, some studies suggest that it may be associated with a potential risk of hepatic steatosis and hepatic complications. Here, we studied the association between HBL and hepatic complications (defined as cirrhosis complications and/or primary liver cancer) in two populations of several hundred thousand people, both in France (CONSTANCES cohort) and the United Kingdom (UKBB). The results show that HBL is associated with a significant and independent excess risk of hepatic complications, including primary liver cancer. Thus, in people with HBL, the value of regular liver monitoring must be studied. [Display omitted] • Hypobetalipoproteinemia is defined by permanent, inherited low LDL-cholesterol levels. • In two large population cohorts, hypobetalipoproteinemia increased the risk of cirrhosis complications and/or liver cancer. • This risk was observed independently of classical risk factors for liver disease (obesity, alcohol, diabetes, viral hepatitis). • Hypobetalipoproteinemia is a risk factor for liver disease complications that requires appropriate monitoring. [ABSTRACT FROM AUTHOR]

Background and Objectives: Rotavirus and Hepatitis A virus are responsible for causing gastroenteritis and jaundice. The current vaccination approaches have proven insufficient, especially in low-income countries. In this study, we presented a novel dual-vaccine candidate that combines the rotavirus VP8 protein and the hepatitis A virus VP1. Materials and Methods: The VP8*-rotavirus+AAY+HAV-VP1 fusion protein was produced using an Escherichia coli expression system. The recombinant protein had a molecular weight of approximately 45.5 kDa and was purified through affinity chromatography. BALB/c mice were injected subcutaneously with the recombinant protein, VP1, VP8 and vaccines for rotavirus and hepatitis A virus, both with and without ALUM and M720 adjuvants. ELISA assays were used to measure total IgG, IgG1, IgG2, and short-term and long-term IL-5 and IFN-γ responses. Results: The fusion protein, when combined with adjuvants, elicited significantly higher total IgG, IgG1, and IgG2 responses compared to VP1 and VP8 alone, as well as the rotavirus and hepatitis A vaccines. Furthermore, it induced a higher short-term IL-5 and IFN-γ response while demonstrating a higher long-term IL-5 response compared to the rotavirus and hepatitis A vaccines. Conclusion: This study demonstrates that the VP8*-rotavirus+AAY+HAV-VP1 fusion protein is a promising dual vaccine candidate for immunization against hepatitis A and rotaviruses. [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]

Key Clinical Message: This case emphasizes the significance of COVID‐19 in pediatric patients presenting with unusual hepatic manifestations, urging clinicians to broaden their diagnostic lens. The unexpected elevation of SARS‐CoV‐2 antibodies and the effective use of N‐acetyl cysteine highlight the importance of adaptability in treatment strategies. This case report presents a unique manifestation of severe hepatic involvement in a 4‐year‐old girl with thalassemia minor and COVID‐19. Despite the absence of prominent respiratory symptoms, the patient exhibited jaundice, elevated liver enzymes, and coagulopathy. Initial suspicion of viral hepatitis was replaced by the discovery of significantly elevated SARS‐CoV‐2 antibodies. A multidisciplinary approach, including gastroenterology consultation and an extensive workup, was pivotal in ruling out alternative etiologies. Unconventional use of N‐acetyl cysteine contributed to clinical improvement, highlighting the need for adaptable treatment strategies. This case underscores the importance of heightened awareness in recognizing atypical presentations of COVID‐19 in pediatric patients, especially those with underlying health conditions. Further exploration into nuanced manifestations and treatment approaches is warranted for comprehensive clinical management. [ABSTRACT FROM AUTHOR]

An analysis of an existing mathematical framework that describes the epidemiology of the Hepatitis A Virus (HAV) via dual modes of transmission is done in this paper. Sanitation and vaccination are taken into account by the model as mitigating techniques. Using the Homotopy perturbation method, the relevant six compartments like susceptible, vaccinated, latent, infectious, recovered and HAV population (S-V-L-I-R-P) of the model are solved analytically. For each of the six compartments, specific analytical formulations are provided. Several types of model parameters are illustrated graphically to demonstrate their impacts. Comparing the results with the numerical simulation (MATLAB) yields a good fit. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disorder, and its association with viral hepatitis has been debated. We performed a meta-analysis to examine the association between PD risk and viral hepatitis. Medline, EMBASE, and the Cochrane library were searched from inception till July 2022. Meta-analysis was conducted using a fixed-effect model with the inverse variance method. Three groups were compared to controls: infection with either hepatitis B or C virus (HBV and HCV, respectively), or coinfection with both viruses. We found 551 records, and six studies comprising of 2,566,947 patients were included in the analysis. PD risk was increased in HCV-infected population (OR 1.10, 95% CI 1.03–1.17, p = 0.005) and (HR 1.37, 95% CI 1.26–1.49, p < 0.001). This increase was not observed for the HBV-infected and HBV–HCV-coinfected coinfection populations. For pooled OR, the risk was significantly lower in HBV-infected (OR 0.79, 95% CI 0.76–0.83, p < 0.001) but not significantly different in HBV–HCV-coinfected populations (OR 0.96, 95% CI 0.82–1.12, p = 0.57). For pooled HR, the risk was significantly higher in both HBV-infected (HR 1.22, 95% CI 1.14–1.31, p < 0.001) and HBV–HCV-coinfected populations (HR 1.29, 95% CI 1.05–1.58, p = 0.013). We found that the risk of PD was increased in the HCV-infected population, but results were inconsistent in those with HBV and HBV–HCV infections. Our findings provide impetus for further clinical and functional studies to unravel the role of the adaptive immune system in PD. [ABSTRACT FROM AUTHOR]

Aim: We conducted a systematic review and meta‐analysis to assess the hepatitis B virus (HBV) screening rate in cancer patients before systemic chemotherapy, aiming to identify those needing antiviral prophylaxis for HBV reactivation. Methods: We searched PubMed, Embase, Scopus, and Google Scholar for relevant studies. The pooled screening rate was estimated using a random effects model. Subgroup analyses were conducted based on malignancy types, chemotherapy regimens, study period, and HBV endemic regions. Results: The meta‐analysis included 29 studies from various endemic regions (19 low‐endemic, three lower intermediate‐endemic, and seven higher intermediate‐endemic). These studies encompassed hematologic malignancies (n = 10), solid‐organ tumors (n = 4), and combinations (n = 15). Seven studies used rituximab‐containing regimens, four did not, and the remaining 11 did not specify chemotherapy regimens. The pooled screening rate was 57% (95% confidence interval [95%CI]: 46%–68%, I2 = 100%). Over time, screening rates improved from 37% (95%CI: 23%–53%) in 2006–2010 to 68% (54%–80%) in 2011–2015 and 69% (48%–84%) in 2016–2020. Screening rates were highest at 89% (74%–96%) in high endemic countries, followed by 60% (45–73%) in lower‐intermediate and 49% (34–64%) in low‐endemic countries. Patients with hematological malignancies had a higher screening rate than those with solid organ tumors, 65% (55%–74%) versus 37% (21%–57%), respectively. A screening rate was higher in patients receiving rituximab‐containing chemotherapy than non‐rituximab regimens, 68% (55%–79%) versus 45% (27%–65%). Conclusion: Despite existing guidelines, pre‐chemotherapy HBV screening rate remains unsatisfactory, with substantial heterogeneous rates globally. These findings underscore the need for effective strategies to align practices with clinical guidelines. [ABSTRACT FROM AUTHOR]

Hepatitis E virus is a single-strand, positive-sense RNA virus that can lead to chronic infection in immunocompromised patients. Virus–host recombinant variants (VHRVs) have been described in such patients. These variants integrate part of human genes into the polyproline-rich region that could introduce new post-translational modifications (PTMs), such as ubiquitination. The aim of this study was to characterize the replication capacity of different VHRVs, namely, RNF19A, ZNF787, KIF1B, EEF1A1, RNA18, RPS17, and RPL6. We used a plasmid encoding the Kernow strain, in which the fragment encoding the S17 insertion was deleted (Kernow p6 delS17) or replaced by fragments encoding the different insertions. The HEV RNA concentrations in the supernatants and the HepG2/C3A cell lysates were determined via RT-qPCR. The capsid protein ORF2 was immunostained. The effect of ribavirin was also assessed. The HEV RNA concentrations in the supernatants and the cell lysates were higher for the variants harboring the RNF19A, ZNF787, KIF1B, RPS17, and EEF1A1 insertions than for the Kernow p6 del S17, while it was not with RNA18 or RPL6 fragments. The number of ORF2 foci was higher for RNF19A, ZNF787, KIF1B, and RPS17 than for Kernow p6 del S17. VHRVs with replicative advantages were less sensitive to the antiviral effect of ribavirin. No difference in PTMs was found between VHRVs with a replicative advantage and those without. In conclusion, our study showed that insertions did not systematically confer a replicative advantage in vitro. Further studies are needed to determine the mechanisms underlying the differences in replicative capacity. IMPORTANCE Hepatitis E virus (HEV) is a major cause of viral hepatitis. HEV can lead to chronic infection in immunocompromised patients. Ribavirin treatment is currently used to treat such chronic infections. Recently, seven virus–host recombinant viruses were characterized in immunocompromised patients. These viruses have incorporated a portion of a human gene fragment into their genome. We studied the consequences of these insertions on the replication capacity. We found that these inserted fragments could enhance virus replication for five of the seven recombinant variants. We also showed that the recombinant variants with replicative advantages were less sensitive to ribavirin in vitro. Finally, we found that the mechanisms leading to such a replicative advantage do not seem to rely on the post-translational modifications introduced by the human gene fragment that could have modified the function of the viral protein. The mechanisms involved in improving the replication of such recombinant viruses remain to be explored. [ABSTRACT FROM AUTHOR]

This study aims to investigate the prevalence of isolated core antibodies against hepatitis B (IAHBc) in different birth cohorts using a large medical record database. Hepatitis B viral serological test data were collected from a chart cloud database at a medical center in Taiwan between January 2006 and December 2018. The data collected included birth year, sex, hepatitis B viral markers (HBsAg, anti-HBs or anti-HBc), and hepatitis B vaccination records. Enrolled patients were grouped according to their birth year into three categories: ≤ 1986, 1987–1992, and ≥ 1993, which correspond to no neonatal hepatitis B immunization, plasma-derived HB vaccine (PDHBV), and recombinant hepatitis B vaccine (RHBV), respectively. Prevalence of hepatitis B viral seromarkers, including IAHBc, was calculated by sex, age groups, and birth cohorts. Those who underwent repeated hepatitis B serology tests were included for further analysis to follow up their serostatus. A total of 117,335 adults with complete hepatitis B serologic data were analyzed. Among them, 6641 individuals (5.7 %) were found to have IAHBc. The prevalence of IAHBc was 11.4 %, 0.8 %, and 0.3 % among those born before 1986, between 1987 and 1992, and after 1992, respectively. Among the 690 subjects with repeated blood tests and complete hepatitis B serologic data, 551 cases (79.9 %) remained IAHBc. The other cases included resolved infection status (13.9 %), seronegativity for three HB seromarkers (3 %), and carrier of hepatitis B virus (2.3 %). The management of individuals with IAHBc should be tailored to their age, vaccination status, and risk factors for occult hepatitis B viral infection. [ABSTRACT FROM AUTHOR]

Identifying hepatic fibrosis is paramount in managing patients with chronic liver disease. The etiology of liver disease can be owing to many factors, including chronic viral hepatitis, steatotic liver diseases such as alcohol-associated liver disease or metabolic dysfunction-associated steatotic liver disease, autoimmune hepatitis, and cholestatic liver diseases. Currently, invasive liver biopsy with histopathologic evaluation is the gold standard; however, noninvasive tests are becoming more prevalent, especially because they do not carry the risks of invasive procedures such as biopsy. This article reviews noninvasive tests for fibrosis, separating them into blood-based and imaging-based tests. [ABSTRACT FROM AUTHOR]

Globally, hepatitis B virus (HBV) affects over 250 million people, whereas hepatitis C virus (HCV) affects approximately 70 million people, posing major public health challenges. Despite the availability of vaccines and treatments, a lack of comprehensive diagnostic coverage has left many cases undiagnosed and untreated. To address the need for sensitive, specific, and accessible diagnostics, this study introduced a multiplex loop‐mediated isothermal amplification assay with lateral flow detection for simultaneous HBV and HCV testing. This assay achieved exceptional sensitivity and was capable of detecting HBV and HCV concurrently in a single tube and on a single strip within 25 min, achieving the required clinical sensitivity (10 and 103 genomic copies/reaction for HBV and HCV, respectively). The method was validated in clinical samples of various viral genotypes, achieving an equivalent limit of detection. Additionally, a custom portable heating device was developed for field use. The assay developed here, capable of direct viral detection on the strip, shows promise in supplanting current methods that solely identify antibodies and necessitate additional qPCR for viral activity assessment. This economical and rapid assay aligns with point‐of‐care testing needs, offering significant advancements in enhancing viral hepatitis diagnostics in settings with limited resources. [ABSTRACT FROM AUTHOR]

Background: The Viral Hepatitis National Strategic Plan emphasizes the importance of a collaborative provider workforce trained in hepatitis prevention and treatment to eliminate viral hepatitis in the United States by 2030. Although pharmacists play a key role in hepatitis management, literature lacks documentation of the amount of viral hepatitis education provided to pharmacy students. Aim: Our study goal was to describe viral hepatitis education provided at United States pharmacy schools. Method: In this cross-sectional survey study, investigators developed a 19-item Qualtrics questionnaire, sent questionnaire links to curricula content experts at 140 accredited pharmacy colleges/schools in May–June 2022, and allotted 28 days for completion. Questions assessed the viral hepatitis instruction provided to students and hepatitis instructors' training/experience. We used descriptive statistics for analysis. Results: Forty-eight pharmacy institutions across 29 states/territories responded; 44% had 50–99 students/class, and 58% used lecture and discussion to provide required hepatitis education. Students received more lecture (average = 3.4 h, range 0.8–1.6 h/hepatitis topic) than discussion (average = 1.7 h, range 0.6–0.9 h/hepatitis topic), with the most time spent on hepatitis C, followed by hepatitis B virus. Respondents reported 93% of their instructors had post-graduate training/certifications and 67% worked in clinical settings with hepatitis patients. Conclusion: Survey results demonstrate variability in hepatitis education across United States pharmacy curricula. Data offer stakeholders in hepatitis elimination efforts knowledge about the viral hepatitis education provided to Doctor of Pharmacy students. Future directions include consideration of implementation of minimum hepatitis education standards to further support work toward national hepatitis elimination. [ABSTRACT FROM AUTHOR]

One of the main objectives of the World Health Organization is the eradication of viral hepatitis by 2030 by identifying subjects before disease progression. In 2019, only 21% of the 58 million people chronically infected with hepatitis C virus (HCV) had been diagnosed, while overall 13% had been treated. The key recommendation of international screening programs is to reach the people at major risk of viral hepatitis and the general population. National plans, including that in Italy, have dedicated budget lines to support efforts to achieve the objective of elimination. The Italian program involves free screening for HCV in the general population born between 1969 and 1989 and also for all persons in the care of addiction services (Ser.D) and prisoners. The screening programs differed slightly among regions in Italy. In particular, referring to the screening for people born in the period of 1969–1989, in Tuscany, these people received an invitation by SMS to undergo a HCV antibody test. If the test results were positive, the subject was registered on a regional platform and required to undergo HCV RNA testing, prescribed by their GP. In the case of testing positive for HCV RNA, the linkage to care (i.e., patient entry into specialist care after diagnosis) is guaranteed. A strong effort is currently required to eliminate HCV effectively. This review highlights the most recent changes to the epidemiological scenario at the global, European, Italian, and regional (Tuscany) levels. [ABSTRACT FROM AUTHOR]

MHV-A59 is a beta-coronavirus that causes demyelinating encephalitis and hepatitis in mice. Recently, the mouse infection model of MHV-A59 has been used as an alternative animal infection model for SARS-CoV and SARS-CoV-2, aiding the development of new antiviral drugs. In this study, the MHV-A59 model was employed to investigate the potential of SARS-CoV-2 UTRs as new targets for antiviral drugs. Optimal targets within the MHV-A59 UTRs were identified using a shRNA and siRNA design tool, focusing on RNA secondary stem-loop (SL) structures in the UTRs. We then examined whether the designed RNAi constructs could inhibit MHV-A59 replication. In the 5′UTR, the stem-loop 1 (SL1) was identified as the most effective target, while in the 3′UTR, the minimal element for the initiation of negative-strand RNA synthesis (MIN) proved to be the most effective. Importantly, siRNAs targeting SL1 and MIN structures significantly reduced total RNA synthesis, negative-strand genomic RNA synthesis, subgenomic (sg) RNA synthesis, viral titer, and the plaque size of MHV-A59 compared to the control. Although not statistically significant, the combination of siSL1 and siMIN had a stronger effect on inhibiting MHV-A59 replication than either siRNA monotherapy. Interestingly, while the SL1 structure is present in both MHV and SARS-CoV-2, the MIN structure is unique to MHV. Thus, the SL1 of SARS-CoV-2 may represent a novel and promising target for RNAi-based antiviral drugs. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) remains a significant global health challenge. Approximately 50 million people were living with chronic hepatitis C based on the World Health Organization as of 2024, contributing extensively to global morbidity and mortality. The advent and approval of several direct-acting antiviral (DAA) regimens significantly improved HCV treatment, offering potentially high rates of cure for chronic hepatitis C. However, the promising aim of eventual HCV eradication remains challenging. Key challenges include the variability in DAA access across different regions, slightly variable response rates to DAAs across diverse patient populations and HCV genotypes/subtypes, and the emergence of resistance-associated substitutions (RASs), potentially conferring resistance to DAAs. Therefore, periodic reassessment of current HCV knowledge is needed. An up-to-date review on HCV is also necessitated based on the observed shifts in HCV epidemiological trends, continuous development and approval of therapeutic strategies, and changes in public health policies. Thus, the current comprehensive review aimed to integrate the latest knowledge on the epidemiology, pathophysiology, diagnostic approaches, treatment options and preventive strategies for HCV, with a particular focus on the current challenges associated with RASs and ongoing efforts in vaccine development. This review sought to provide healthcare professionals, researchers, and policymakers with the necessary insights to address the HCV burden more effectively. We aimed to highlight the progress made in managing and preventing HCV infection and to highlight the persistent barriers challenging the prevention of HCV infection. The overarching goal was to align with global health objectives towards reducing the burden of chronic hepatitis, aiming for its eventual elimination as a public health threat by 2030. [ABSTRACT FROM AUTHOR]

High mobility group box-1 protein (HMGB1) is a nuclear protein released by macrophages with late proinflammatory effect. In recent years, as a new type of inflammatory factor, HMGB1 has been widely studied by scholars at home and abroad. It has been found that this protein can act as an inflammatory mediator in many diseases, and then play a cytokine activity and participate in body damage. This article discussed the damage of HMGB1 in cardiovascular system, kidney, liver, pancreas and other related diseases and its possible mechanism, in order to provide a basis for clinical diagnosis and research of relevant diseases. [ABSTRACT FROM AUTHOR]

Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1β (IL-1β) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections. [ABSTRACT FROM AUTHOR]

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2–0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5–1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1–13.1%), followed by Pakistanis at 3.1% (95% CI 1.1–8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B (HBV) and C virus (HCV) coinfection are the major causes of liver-related morbidity and mortality among people living with Human Immunodeficiency Virus (HIV). The burden of hepatitis among HIV-positive individuals has not been studied in the Afar region. Therefore, this study aimed to determine the prevalence of HBV and HCV coinfection and associated factors among HIV-positive patients in Afar Regional State, northeast Ethiopia. Methods: A cross-sectional study was conducted on 477 HIV-positive patients between February 2019 and May 2019. A structured and pretested questionnaire was used to collect socio-demographic data and associated factors. Five milliliters of blood was collected, and Hepatitis B surface antigen (HBsAg) and HCV antibodies were detected using rapid test kits. Positive samples were confirmed using enzyme-linked immunosorbent assay (ELISA). Binary and multivariable logistic regression analyses were performed to identify associated factors. Statistical significance was set at P <0.05. Results: Among the 477 study participants, 320/477(67.1%) of them were females and 157(32.9%) males. The overall prevalence of HIV-HBV and HIV-HCV coinfection was 25(5.2%) and 7(1.5%), respectively. Multi-sexual practice was significantly associated with HIV-HBV coinfection (AOR = 5.3; 95% CI: 1.2–24.4, P = 0.032). Conclusion: The prevalence of both HIV-HBV and HIV-HCV coinfection was intermediate. Multi-sexual practice was significantly associated with HIV-HBV coinfection. Screening of all HIV-positive patients for HBV and HCV and health education regarding the transmission modes should be considered. [ABSTRACT FROM AUTHOR]

Background: Changes in plasma protein glycosylation are known to functionally affect proteins and to associate with liver diseases, including cirrhosis and hepatocellular carcinoma. Autoimmune hepatitis (AIH) is a liver disease characterized by liver inflammation and raised serum levels of IgG, and is difficult to distinguish from other liver diseases. The aim of this study was to examine plasma and IgG-specific N-glycosylation in AIH and compare it with healthy controls and other liver diseases. Methods: In this cross-sectional cohort study, total plasma N-glycosylation and IgG Fc glycosylation analysis was performed by mass spectrometry for 66 AIH patients, 60 age- and sex-matched healthy controls, 31 primary biliary cholangitis patients, 10 primary sclerosing cholangitis patients, 30 non-alcoholic fatty liver disease patients and 74 patients with viral or alcoholic hepatitis. A total of 121 glycans were quantified per individual. Associations between glycosylation traits and AIH were investigated as compared to healthy controls and other liver diseases. Results: Glycan traits bisection (OR: 3.78 [1.88–9.35], p-value: 5.88 × 10− 3), tetraantennary sialylation per galactose (A4GS) (OR: 2.88 [1.75–5.16], p-value: 1.63 × 10− 3), IgG1 galactosylation (OR: 0.35 [0.2–0.58], p-value: 3.47 × 10− 5) and hybrid type glycans (OR: 2.73 [1.67–4.89], p-value: 2.31 × 10− 3) were found as discriminators between AIH and healthy controls. High A4GS differentiated AIH from other liver diseases, while bisection associated with cirrhosis severity. Conclusions: Compared to other liver diseases, AIH shows distinctively high A4GS levels in plasma, with potential implications on glycoprotein function and clearance. Plasma-derived glycosylation has potential to be used as a diagnostic marker for AIH in the future. This may alleviate the need for a liver biopsy at diagnosis. Glycosidic changes should be investigated further in longitudinal studies and may be used for diagnostic and monitoring purposes in the future. [ABSTRACT FROM AUTHOR]

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic, or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity to exploit innovative solutions against these hazards. Recently, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs was evaluated against the non-enveloped RNA viruses, hepatitis A virus (HAV) and murine norovirus (MNV), a surrogate for human norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. The results showed that almost all peptides displayed virucidal effects, with about 90% of infectivity reduction in HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles causing their damage or hindering the recognition of cellular receptors. Hence, RiLK1 could represent a versatile antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi. [ABSTRACT FROM AUTHOR]

O-linked-β-D-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), which is dynamically regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is a post-translational modification involved in multiple cellular processes. O-GlcNAcylation of proteins can regulate their biological functions via crosstalk with other post-translational modifications, such as phosphorylation, ubiquitination, acetylation, and methylation. Liver diseases are a major cause of death worldwide; yet, key pathological features of the disease, such as inflammation, fibrosis, steatosis, and tumorigenesis, are not fully understood. The dysregulation of O-GlcNAcylation has been shown to be involved in some severe hepatic cellular stress, viral hepatitis, liver fibrosis, nonalcoholic fatty acid liver disease (NAFLD), malignant progression, and drug resistance of hepatocellular carcinoma (HCC) through multiple molecular signaling pathways. Here, we summarize the emerging link between O-GlcNAcylation and hepatic pathological processes and provide information about the development of therapeutic strategies for liver diseases. [ABSTRACT FROM AUTHOR]

In 2016, the World Health Organization introduced global targets for the care and management of hepatitis C virus (HCV) infection to eliminate hepatitis C as a public health threat by 2030. Despite significant improvements in testing and treatment, in 2020 only 23% of all persons infected with HCV globally were diagnosed. We explore examples from global hepatitis C programs in Georgia, Rwanda, and Nigeria that have used decentralized and integrated models to increase access to HCV testing. Georgia established the world's first national hepatitis C elimination program in 2015. In 2022, 2.6 million people (80% of the adults) have been screened for antibodies for HCV infection, and 80 000 persons with HCV RNA detected were treated. To achieve these results, Georgia implemented HCV core antigen testing, utilization of point-of-care (POC) HCV RNA testing, and simplification of HCV viremia detection by qualitative HCV RNA testing. Rwanda was the first country in sub-Saharan Africa to commit to HCV elimination in 2018, and as of 2022 it has achieved its screening target of 7 million people and initiated approximately 60 000 patients on hepatitis C treatment by rapid decentralization and integration of HCV services. In Nigeria, the integrated near-POC testing approach in Nasarawa State has been effective in expanding access to HCV viremia testing and enabling the possibility of same-day testing and treatment initiation. Examples of decentralization and integration of HCV testing and linkage to care in Georgia, Rwanda, and Nigeria could help inform effective strategies to reach 2030 hepatitis C elimination goals in other countries. [ABSTRACT FROM AUTHOR]

The maintenance of viral protein homeostasis depends on the interaction between host cell proteins and viral proteins. As a molecular chaperone, heat shock protein 70 (HSP70) has been shown to play an important role in viral infection. Our results showed that HSP70 can affect translation, replication, assembly, and release during the life cycle of duck hepatitis A virus type 1 (DHAV-1). We demonstrated that HSP70 can regulate viral translation by interacting with the DHAV-1 internal ribosome entry site (IRES). In addition, HSP70 interacts with the viral capsid proteins VP1 and VP3 and promotes their stability by inhibiting proteasomal degradation, thereby facilitating the assembly of DHAV-1 virions. This study demonstrates the specific role of HSP70 in regulating DHAV-1 replication, which are helpful for understanding the pathogenesis of DHAV-1 infection and provide additional information about the role of HSP70 in infection by different kinds of picornaviruses, as well as the interaction between picornaviruses and host cells. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) infection represents the most severe form of human viral hepatitis; however, the mechanisms underlying its pathology remain incompletely understood. We recently developed an HDV mouse model by injecting adeno-associated viral vectors (AAV) containing replication-competent HBV and HDV genomes. This model replicates many features of human infection, including liver injury. Notably, the extent of liver damage can be diminished with anti-TNF-α treatment. Here, we found that TNF-α is mainly produced by macrophages. Downstream of the TNF-α receptor (TNFR), the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) serves as a cell fate regulator, playing roles in both cell survival and death pathways. In this study, we explored the function of RIPK1 and other host factors in HDV-induced cell death. We determined that the scaffolding function of RIPK1, and not its kinase activity, offers partial protection against HDV-induced apoptosis. A reduction in RIPK1 expression in hepatocytes through CRISPR-Cas9-mediated gene editing significantly intensifies HDV-induced damage. Contrary to our expectations, the protective effect of RIPK1 was not linked to TNF-α or macrophage activation, as their absence did not alter the extent of damage. Intriguingly, in the absence of RIPK1, macrophages confer a protective role. However, in animals unresponsive to type-I IFNs, RIPK1 downregulation did not exacerbate the damage, suggesting RIPK1's role in shielding hepatocytes from type-I IFN-induced cell death. Interestingly, while the damage extent is similar between IFNAR KO and WT mice in terms of transaminase elevation, their cell death mechanisms differ. In conclusion, our findings reveal that HDV-induced type-I IFN production is central to inducing hepatocyte death, and RIPK1's scaffolding function offers protective benefits. Thus, type-I IFN together with TNF-α, contribute to HDV-induced liver damage. These insights may guide the development of novel therapeutic strategies to mitigate HDV-induced liver damage and halt disease progression. Author summary: Hepatitis D is the most aggressive form of viral hepatitis. Our manuscript underscores the complexity of HDV-induced liver damage, where both viral and host factors play significant roles. Previously, we demonstrated that pharmacological inhibition of TNF-α reduced HDV-induced liver damage. This result was corroborated in the present study using TNF-α-deficient mice. Moreover, we reported that the expression of the HDV antigen might have a cytotoxic effect, and HDV replication induces a strong activation of the innate immune system, accompanied by a substantial production of IFN-β. In this study, we discovered that RIPK1, a molecule described as a cell fate modulator acting downstream of TNF-α, plays a protective role during HDV replication. Contrary to our expectations, neither TNF-α nor macrophages (the primary producers of TNF-α), contributed to this protective effect. Instead, it seems type I IFN was involved. Interestingly, the role of type I IFN in HBV-induced liver damage has recently been proposed. Furthermore, our data reveals that several mechanisms of hepatocyte death are at play simultaneously during HDV replication, with apoptosis being one of them. Additional studies are needed to identify other mechanisms involved. Finally, these findings suggest that therapies targeting TNF-α and type-I IFN, or those increasing RIPK1 levels, might be effective in preventing or treating HDV-induced liver damage. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B virus infection poses a global health challenge, particularly in low- and middle-income African countries. Illicit drug use exacerbates the problem, with drug users having a higher HBV infection risk and maintaining a quiet transmission pool. This study aimed to determine HBV infection prevalence, immune status, and risk factors among illegal drug users in Enugu State, Nigeria. Materials and methods: A cross-sectional study was conducted in Enugu State, using privileged access interviewer methods to enroll drug users. Pre-tested structured questionnaires were administered after informed consent was obtained. Blood samples were tested for HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb using immunochromatographic rapid test kits. Statistical analysis was performed using SPSS version 25. Results: One hundred drug users were recruited into the study. Overall, 7% of the drug users had HBV infection. 61% were found to be susceptible to HBV infection, 15% showed serological evidence of immunity from HBV vaccination and 1% developed natural immunity from HBV exposure. Significant risk factors for HBV infection were age less than 20 years, young age (≤ 20 years) at drug initiation, being single, injecting drugs more than or equal to 20 times per month and injecting with used syringes. Conclusion: This study shows high intermediate endemicity of HBV infection among drug users, low vaccination uptake, and high susceptibility to HBV infection. This calls for the urgent inclusion of drug users in national HBV vaccination campaigns and the adoption of the World Health Organization's recommendations on the prevention of viral hepatitis among people who inject drugs. [ABSTRACT FROM AUTHOR]

Background: The Central African Republic (CAR) is one of the countries with the highest prevalence of viral hepatitis infection in the world. Coinfection with HIV increases the morbidity and mortality beyond that of mono-infection with either hepatitis or HIV. The present study describes the geographic distribution of viral hepatitis infections and molecular characterization of these viruses in the CAR. Methodology: Out of 12,599 persons enrolled during the fourth Multiple Indicator Cluster Survey of 2010 in the CAR, 10,621 Dried Blood Spot (DBS) samples were obtained and stored at -20°C. Of these DBS, 4,317 samples were randomly selected to represent all regions of the CAR. Serological tests for hepatitis B, D, and C viruses were performed using the ELISA technique. Molecular characterization was performed to identify strains. Results: Of the 4,317 samples included, 53.2% were from men and 46.8% from women. The HBsAg prevalence among participants was 12.9% and that HBc-Ab was 19.7%. The overall prevalence of HCV was 0.6%. Co-infection of HIV/HBV was 1.1% and that of HBV/HDV was 16.6%. A total of 77 HBV, 6 HIV, and 6 HDV strains were successfully sequenced, with 72 HBV (93.5%) strains belonging to genotype E and 5 (6.5%) strains belonging to genotype D. The 6 HDV strains all belonged to clade 1, while 4 recombinants subtype were identified among the 6 strains of HIV. Conclusion: Our study found a high prevalence of HBV, HBV/HDV and HBV/HIV co-infection, but a low prevalence of HCV. CAR remains an area of high HBV endemicity. This study's data and analyses would be useful for establishing an integrated viral hepatitis and HIV surveillance program in the CAR. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis E virus (HEV) genotype 3 is the major cause of acute viral hepatitis in several European countries. It is acquired mainly by ingesting contaminated pork, but has also been reported to be transmitted through blood transfusion. Although most HEV infections, including those via blood products, are usually self-limiting, they may become chronic in immunocompromised persons. It is thus essential to identify HEV-infected blood donations to prevent transmission to vulnerable recipients. Aims: Prior to the decision whether to introduce HEV RNA screening for all Swiss blood donations, a 2-year nationwide prevalence study was conducted. Methods: All blood donations were screened in pools of 12–24 samples at five regional blood donation services, and HEV RNA-positive pools were subsequently resolved to the individual donation index donation (X). The viral load, HEV IgG and IgM serology, and HEV genotype were determined. Follow-up investigations were conducted on future control donations (X + 1) and previous archived donations of the donor (X − 1) where available. Results: Between October 2018 and September 2020, 541,349 blood donations were screened and 125 confirmed positive donations were identified (prevalence 1:4331 donations). At the time of blood donation, the HEV RNA-positive individuals were symptom-free. The median viral load was 554 IU/mL (range: 2.01–2,500,000 IU/mL). Men (88; 70%) were more frequently infected than women (37; 30%), as compared with the sex distribution in the Swiss donor population (57% male/43% female, p < 0.01). Of the 106 genotyped cases (85%), all belonged to genotype 3. Two HEV sub-genotypes predominated; 3h3 (formerly 3s) and 3c. The remaining sub-genotypes are all known to circulate in Europe. Five 3ra genotypes were identified, this being a variant associated with rabbits. In total, 85 (68%) X donations were negative for HEV IgM and IgG. The remaining 40 (32%) were positive for HEV IgG and/or IgM, and consistent with an active infection. We found no markers of previous HEV in 87 of the 89 available and analyzed archive samples (X − 1). Two donors were HEV IgG-positive in the X − 1 donation suggesting insufficient immunity to prevent HEV reinfection. Time of collection of the 90 (72%) analyzed X + 1 donations varied between 2.9 and 101.9 weeks (median of 35 weeks) after X donation. As expected, none of those tested were positive for HEV RNA. Most donors (89; 99%) were positive for anti-HEV lgG/lgM (i.e., seroconversion). HEV lgM-positivity (23; 26%) indicates an often-long persistence of lgM antibodies post-HEV infection. Conclusion: The data collected during the first year of the study provided the basis for the decision to establish mandatory HEV RNA universal screening of all Swiss blood donations in minipools, a vital step in providing safer blood for all recipients, especially those who are immunosuppressed. [ABSTRACT FROM AUTHOR]

Hepatitis B and C viruses (HBV and HCV) are the leading causes of end-stage liver disease worldwide. Although there is a potent vaccine against HBV, many new infections are recorded annually, especially in poorly resourced places which have lax vaccination policies. Again, as HBV has no cure and chronic infection is lifelong, vaccines cannot help those already infected. Studies to thoroughly understand the HBV biology and pathogenesis are limited, leaving much yet to be understood about the genomic features and their role in establishing and maintaining infection. The current knowledge of the impact on disease progression and response to treatment, especially in hyperendemic regions, is inadequate. This calls for in-depth studies on viral biology, mainly for the purposes of coming up with better management strategies for infected people and more effective preventative measures for others. This information could also point us in the direction of a cure. Here, we discuss the progress made in understanding the genomic basis of viral activities leading to the complex interplay of the virus and the host, which determines the outcome of HBV infection as well as the impact of coinfections. [ABSTRACT FROM AUTHOR]

Chronic Hepatitis B and D Virus (HBV and HDV) co-infection is responsible for the most severe form of viral Hepatitis, the Hepatitis Delta. Despite an efficient vaccine against HBV, the HBV/HDV infection remains a global health burden. Notably, no efficient curative treatment exists against any of these viruses. While physiologically distinct, HBV and HDV life cycles are closely linked. HDV is a deficient virus that relies on HBV to fulfil is viral cycle. As a result, the cellular response to HDV also influences HBV replication. In vitro studying of HBV and HDV infection and co-infection rely on various cell culture models that differ greatly in terms of biological relevance and amenability to classical virology experiments. Here, we review the various cell culture models available to scientists to decipher HBV and HDV virology and host–pathogen interactions. We discuss their relevance and how they may help address the remaining questions, with one objective in mind: the development of new therapeutic approaches allowing viral clearance in patients. [ABSTRACT FROM AUTHOR]

(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999–2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999–2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999–2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39–4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999–2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality. [ABSTRACT FROM AUTHOR]

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan–Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23–0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16–0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02–2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk. [ABSTRACT FROM AUTHOR]

Background: Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)‐related hepatocellular carcinoma (HCC) and viral infection‐related HCC, the short‐ and long‐term outcomes of surgical resection of NAFLD‐related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD‐related HCC, other studies suggest higher postoperative complications in these patients. Methods: Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. Results: Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD‐related HCC (NAFLD group), and 727 had virus‐related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence‐free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. Conclusion: Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD‐HCC may improve prognosis. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization (WHO) has set targets to eliminate viral hepatitis, including hepatitis C virus (HCV) infection, by 2030. We present the results of the in‐hospital Reflex tEsting ALarm‐C (REAL‐C) model, which incorporates reflex HCV RNA testing and sending alerts to physicians. Methods: We conducted a retrospective study analysing the data of 1730 patients who newly tested positive for anti‐HCV between March 2020 and June 2023. Three distinct periods were defined: pre‐REAL‐C (n = 696), incomplete REAL‐C (n = 515) and complete REAL‐C model periods (n = 519). The primary outcome measure was the HCV RNA testing rate throughout the study period. Additionally, we assessed the referral rate to the gastroenterology department, linkage time for diagnosis and treatment and the treatment rate. Results: The rate of HCV RNA testing increased significantly from 51.0% (pre‐REAL‐C) to 95.6% (complete REAL‐C). This improvement was consistent across clinical departments, regardless of patients' comorbidities. Among patients with confirmed HCV infection, the gastroenterology referral rate increased from 57.1% to 81.1% after the REAL‐C model. The treatment rate among treatment‐eligible patients was 92.4% during the study period. The mean interval from anti‐HCV positivity to HCV RNA testing decreased from 45.1 to 1.9 days. The mean interval from the detection of anti‐HCV positivity to direct‐acting antiviral treatment also decreased from 89.5 to 49.5 days with the REAL‐C model. Conclusion: The REAL‐C model, featuring reflex testing and physician alerts, effectively increased HCV RNA testing rates and streamlined care cascades. Our model facilitated progress towards achieving WHO's elimination goals for HCV infection. [ABSTRACT FROM AUTHOR]

With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease. [ABSTRACT FROM AUTHOR]