Agent Of Hepatitis Research Articles

Acute Hepatitis Related to Hepatitis E Virus Genotype 3f Infection in Brazil.

The hepatitis E virus (HEV) is an important causative agent of acute hepatitis (AH). Despite reports of human infection in Brazil, the investigation is not routinely conducted, even in cases of elevated liver enzymes. This study evaluated two groups: group 1-patients with acute hepatitis A (n = 44); group 2-patients with nonA-C AH (n = 47). They were tested by enzyme immunoassay for anti-HEV IgM/IgG and real-time PCR for HEV RNA detection. The positive sample for HEV RNA was submitted for sequencing. The seroprevalence of anti-HEV IgM and IgG in group 1 was 4% (2/44) and 14.5% (7/44), respectively. Viral RNA was not detected in any sample. In group 2, the anti-HEV IgM positivity was 4.3% (2/47), and IgG 14.9% (7/47). RNA was detectable in one case, which presented a viral load of 222.4 IU/μL and positive anti-HEV IgM/IgG. In the phylogenetic analysis, the genotype identified was HEV-3f. These results indicate that HEV infection should be considered a possible diagnosis in cases of non-A-C AH. The patient identified with acute hepatitis E had recently traveled to the Northeast region of Brazil (Garanhuns city in Pernambuco state), where there are reports of high HEV seroprevalence among pigs. The close phylogenetic relationship observed between the sequence characterized in this study and strains isolated from pigs in nearby cities where the patient went suggested a possible zoonotic transmission in this region. This study highlights the importance of expanding studies and improving surveillance to understand better and manage HEV infections nationwide.

Detection of Hepatovirus A (HAV) in wastewater indicates widespread national distribution and association with socioeconomic indicators of vulnerability.

Wastewater-based epidemiology, which seeks to assess disease occurrence in communities through measurements of infectious disease biomarkers in wastewater, may represent a valuable tool for understanding the occurrence of hepatitis A infections in communities. In this study, we measured concentrations of Hepatovirus A (HAV) RNA, in samples from 191 wastewater treatment plants spanning 40 US states and the District of Columbia from September 2023 to June 2024 and compared the measurements with traditional measures of disease occurrence. Nationally, 13.76% of the 21,079 wastewater samples were positive for HAV RNA, and both concentrations and positivity rates were associated with NNDSS hepatitis A case data nationally (Kendall rank correlation coefficient = 0.20, concentrations; and 0.33, positivity rate; both P < 0.05). We further demonstrated that higher rates of wastewater HAV detection were positively associated with socioeconomic indicators of vulnerability including homelessness and drug overdose deaths (both P < 0.0001). Areas with above average levels of homelessness were 48% more likely to have HAV wastewater detections, while areas with above average levels of drug overdose deaths were 14% more likely to have HAV wastewater detections. Using more granular case data, we present a case study in the state of Maine that reinforces these results and suggests a potential lead time for wastewater over clinical case detection and exposure events. The ability to detect HAV RNA in wastewater before clinical cases emerge could allow public health officials to implement targeted interventions like vaccination campaigns.IMPORTANCEDespite the existence of a highly effective vaccine for hepatitis A, outbreaks in vulnerable populations remain common. The disease can be asymptomatic or subclinical, and disproportionately impacts populations with inadequate access to healthcare, leading to a severe underestimation of the occurrence of this viral infection. This study investigates the potential for wastewater measurements of biomarkers of the causative agent of hepatitis A (HAV RNA) to provide insights into disease occurrence. Results highlight the potential for wastewater-based epidemiology to be a complementary tool to traditional surveillance for monitoring and controlling HAV transmission.

Human-swine interface: is the hepatitis E virus a real risk for humans?

Abstract Background Hepatitis E virus (HEV) is the agent of hepatitis E, an emerging public-health infection with an increasing incidence in Europe. Due to the apparent lack of species barriers, HEV is considered a zoonotic agent, with swine as the main reservoir. This study investigated HEV prevalence in humans and domestic pigs in Northern Italy, a highly anthropic area with the highest pig farm density, to gain insights into the risk of HEV transmission from swine to humans. Methods A total of 508 blood samples were collected from blood donors (341 males and 167 females; from 18 to 66 years old) and from 1619 pigs in 40 different farms. Serological analyses were performed with ELISA to detect anti-HEV antibodies. In addition, 120 faecal pool samples collected from the pig farms with the highest seroprevalence and 69 salami produced in the same area were analysed to detect viral genome by Real-time PCR. Results In humans, HEV seroprevalence was 4.9% (CI95% 0.03-0.07); positive donors were mainly males, with seroprevalence increasing up to 12% (CI95% 0.09-0.15) in the 46-55 age group. Seroprevalence in swine was 53.00% (CI95% 0.50-0.55), with HEV detected in only 1% (CI95% 0.001-0.045) faeces. All food samples tested negative. Conclusions Even if the seroprevalence in pigs highlighted that HEV was actively circulating in the farms, the low seroprevalence in humans, the scarce HEV detection in swine faeces, and the absence in food products suggested that HEV transmission via faecal-oral or foodborne routes is unlikely, probably due to the implementation of severe biosecurity measures and high standards of hygiene in swine farms, and the continuous assessment of the critical points in the pig supply chain (from farm to fork). The serological surveillance of humans and the monitoring of farmed animals are needed to support the competent authorities in timely managing public health issues, improving human health and veterinary safety from a One Health perspective. Key messages • In the human-swine interface is important to monitor HEV presence. • The One Health approach is essential to control zoonotic diseases.

Exploring the tolerable region for HiBiT tag insertion in the hepatitis B virus genome.

Hepatitis B virus (HBV) is the principal causative agent of chronic hepatitis. Despite the availability of vaccines in many countries, HBV infection has spread worldwide and caused chronic infection. In chronic hepatitis B patients, liver inflammation leads to cirrhosis, and the accumulation of viral genome integration into host chromosomes leads to the development of hepatocellular carcinoma. The currently available treatment strategy cannot expect the eradication of HBV. To explore novel anti-HBV agents, a cell culture system that can detect HBV infection easily is indispensable. In this study, we examined the regions in the HBV genome where the high affinity and bright luminescence (HiBiT) tag could be inserted and established an HBV infection system to monitor infection by measuring the HiBiT signal by infecting the HiBiT-tagged HBV in sodium taurocholate cotransporting polypeptide-transduced HepG2 (HepG2/NTCP) cells. This system can contribute to screening for novel anti-HBV agents.

Hepatitis E and Potential Public Health Implications from a One-Health Perspective: Special Focus on the European Wild Boar (Sus scrofa).

The hepatitis E virus (HEV) has become increasingly important in recent years in terms of risk for public health, as the main causative agent of acute viral hepatitis. It is a foodborne disease transmitted to humans through the consumption of contaminated water or contaminated food. Human-to-human transmission is sporadic and is linked to transfusions or transplants. The main reservoirs of the hepatitis E virus are domestic pigs and wild boars, although, compared to pigs, wild boars represent a lesser source of risk since their population is smaller and the consumption of derived products is more limited. These peculiarities often make the role of the wild boar reservoir in the spread of the disease underestimated. As a public health problem that involves several animal species and humans, the management of the disease requires an interdisciplinary approach, and the concept of "One Health" must be addressed. In this direction, the present review intends to analyze viral hepatitis E, with a particular focus on wild boar. For this purpose, literature data have been collected from different scientific search engines: PubMed, MEDLINE, and Google scholar, and several keywords such as "HEV epidemiology", "Extrahepatic manifestations of Hepatitis E", and "HEV infection control measures", among others, have been used. In the first part, the manuscript provides general information on the disease, such as epidemiology, transmission methods, clinical manifestations and implications on public health. In the second part, it addresses in more detail the role of wild boar as a reservoir and the implications related to the virus epidemiology. The document will be useful to all those who intend to analyze this infectious disease from a "One-Health" perspective.

Viral Load of HBV and HCV Correlation to Torque Teno Virus (TTV) Co-Infection in Iraqi Patients

Abstract Background: While hepatitis viruses A–E are established, emerging evidence points to additional, novel viral hepatitis agents. The torqueteno virus (TTV) has garnered interest due to its prevalence among patients with hepatitis, suggesting potential hepatotropism. Aim: This study was conducted to detect TTV antigens in individuals infected with chronic hepatitis B (HBV) and/or C (HCV) using molecular diagnostics and to explore any associations between TTV presence and demographic characteristics of the cohort. Materials and Methods: The current study was conducted from the period of September 2022 to April 2023, the investigation involved Iraqi patients aged between 32 and 83 years and diagnosed with HBV and HCV in National Iraqi Central Laboratories, Virology Section. We employed real-time PCR to quantify HBV and HCV viral loads and conventional PCR for TTV DNA detection. Results: TTV DNA was detected in 17 of the 60 patients (28.3%) with chronic HBV and HCV infections. Viral load distribution was found to be similar for both HBV and HCV. An age-related increase in viral load was noted, suggesting a trend where older individuals exhibited higher concentrations. However, no significant variation was observed that could link alterations in HBV and HCV viral loads to TTV status directly. Statistical analysis indicated a positive correlation between age and the likelihood of presenting with the virus, aligning with observed trends in other age-associated chronic conditions, such as Type 2 diabetes mellitus and chronic kidney disease. Conclusion: The presence of TTV in patients with enduring HBV or HCV infection could implicate the virus as a contributing factor to hepatitis pathology. Studies such as this are pivotal for elucidating the age-associated risk profiles for various pathologies and shaping corresponding public health policies and preventative approaches.

High incidence of hepatocarcinoma in patients with advanced fibrosis treated with direct-acting antiviral agents for hepatitis C: A real-world retrospective study

BackgroundPatients treated with direct-acting antivirals for hepatitis C exhibit high cure rates and improved survival. However, there is limited knowledge on their long-term clinical evolution. AimsIn this study, we aimed to analyse the risk of hepatocarcinoma and hepatic decompensation in patients treated with direct-acting antivirals. MethodsWe conducted a retrospective single-centre study of Portuguese patients with advanced fibrosis treated with direct-acting antiviral agents between 2015 and 2022 at a tertiary hospital. ResultsOut of 460 patients, 50 (10.9 %) developed hepatocarcinoma and 36 (7.8 %) experienced hepatic decompensation. The risk for hepatocarcinoma was higher in patients aged over 55 (HR 4.87, 95 % CI 2.34–10.13, p < 0.001), with signs of portal hypertension (HR 3.83, 95 % CI 2.05–7.13, p < 0.001) and arterial hypertension (HR 1.98, 95 % CI 1.09–3.58, p = 0.024). Alcohol consumption (HR 3.30, 95 % CI 1.22–8.94, p = 0.019), signs of portal hypertension (HR 4.56, 95 % CI 2.19–9.48, p < 0.001) and hepatocarcinoma (HR 3.47, 95 % CI 1.69–7.10, p < 0.001) increased the risk of hepatic decompensation. ConclusionOur study found a high incidence of hepatocarcinoma and hepatic decompensation, along with high mortality, in patients with advanced fibrosis treated with direct-acting antivirals. We identified risk factors such as arterial hypertension, alcohol consumption, and signs of portal hypertension, highlighting their role in clinical management and patient monitoring.

Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication

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.

Mechanisms of Hepatitis B Virus cccDNA and Minichromosome Formation and HBV Gene Transcription.

Hepatitis B virus (HBV) is the etiologic agent of chronic hepatitis B, which puts at least 300 million patients at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. HBV is a partially double-stranded DNA virus of the Hepadnaviridae family. While HBV was discovered more than 50 years ago, many aspects of its replicative cycle remain incompletely understood. Central to HBV persistence is the formation of covalently closed circular DNA (cccDNA) from the incoming relaxed circular DNA (rcDNA) genome. cccDNA persists as a chromatinized minichromosome and is the major template for HBV gene transcription. Here, we review how cccDNA and the viral minichromosome are formed and how viral gene transcription is regulated and highlight open questions in this area of research.

Second- and third-line treatment agents in autoimmune hepatitis (AIH): Where do we stand?

Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology that can lead to end stage liver disease if left without treatment. Corticosteroids with or without azathioprine (AZA) are considered the recommended standard first-line treatment option for the induction and maintenance of remission. The aim of treatment is to achieve complete biochemical response (CBR), defined by normal transaminases and immunoglobulin G (IgG) within 6–12 months after treatment initiation. However, response rates to standard treatment vary widely as approximately 10–25% of cases develop intolerance, insufficient response, or rarely non-response to AZA. Mycophenolate mofetil (MMF) is an effective and safe alternative first-line treatment in AIH, based on its high rates of CBR among treatment-naive patients, but can also be considered as second-line drug in patients with poor response or intolerance to AZA. However, even after the administration of second line treatment there is a small proportion of patients with refractory disease that bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma. For this difficult to treat subgroup of patients third-line treatments are warranted. Therefore, the aim of this review is to summarize the current evidence on second- and third-line therapies for AIH, as well as, to set the background for future perspectives on safer and more efficient treatment strategies.

Research Note: Rapid generation of a novel fowl adenovirus serotype 11 reverse genetic platform

Fowl adenovirus serotype 11 (FAdV-11) is one of the main causative agents of inclusion body hepatitis (IBH) in broilers. Outbreaks of FAdV-11-related IBH have been increasingly reported in China and many other geographical areas worldwide. However, the critical virulence factors of FAdV-11 remain uncertain due to the lack of technical platforms for efficient manipulation of FAdV-11 genome. Here, we reported the establishment of a FAdV-11 reverse genetic system based on a novel FAdV-11 Chinese isolate FJSW/2021 using the exonuclease combined with RecET (ExoCET), Redαβ recombineering and ccdB counter-selection techniques for the first time. A recombinant FAdV-11 was rescued efficiently by using the established reverse genetic platform through swapping the ORF11 gene of the FAdV-11 FJSW/2021 with the ZsGreen fluorescent protein expression cassette. This study provides an effective technical platform for identifying virulence factors of FAdV-11 and developing recombinant FAdV-11-vectored vaccine candidates.

Loxapine inhibits replication of hepatitis A virus in vitro and in vivo by targeting viral protein 2C.

No antiviral drugs currently are available for treatment of infection by hepatitis A virus (HAV), a causative agent of acute hepatitis, a potentially life-threatening disease. Chemical screening of a small-compound library using nanoluciferase-expressing HAV identified loxapine succinate, a selective dopamine receptor D2 antagonist, as a potent inhibitor of HAV propagation in vitro. Loxapine succinate did not inhibit viral entry nor internal ribosome entry site (IRES)-dependent translation, but exhibited strong inhibition of viral RNA replication. Blind passage of HAV in the presence of loxapine succinate resulted in the accumulation of viruses containing mutations in the 2C-encoding region, which contributed to resistance to loxapine succinate. Analysis of molecular dynamics simulations of the interaction between 2C and loxapine suggested that loxapine binds to the N-terminal region of 2C, and that resistant mutations impede these interactions. We further demonstrated that administration of loxapine succinate to HAV-infected Ifnar1-/- mice (which lack the type I interferon receptor) results in decreases in the levels of fecal HAV RNA and of intrahepatic HAV RNA at an early stage of infection. These findings suggest that HAV protein 2C is a potential target for antivirals, and provide novel insights into the development of drugs for the treatment of hepatitis A.

Genomic characterization and pathogenicity of a novel fowl adenovirus serotype 11 isolated from chickens with inclusion body hepatitis in China

Fowl adenovirus serotype 11 (FAdV-11) is one of the primary causative agents of inclusion body hepatitis (IBH), which causes substantial economic losses in the world poultry industry. In this study, we characterized the genome of the fowl adenovirus serotype 11 (FAdV-11) isolate FJSW/2021. The full genome of FJSW/2021 was 44, 154 base pairs (bp) in length and had a similar organization to that of previously reported FAdV-11 isolates. Notably, compared with those of other reported FAdV-11 strains, the preterminal protein (pTP) of FAdV-11 FJSW/2021 has six amino acid (aa) insertions (S-L-R-I-I-C) between 470 and 475 and one aa mutation of L476F; moreover, the tandem repeat (TR) regions of TR1 and TR2 were 33 bp (1 repeat) and 1,080 bp (8 repeats) shorter than those of the Canadian nonpathogenic isolate ON NP2, respectively. The pathogenicity of FJSW/2021 was studied in 10-day-old specific pathogen-free chicken embryos following allantoic cavity inoculation and in 1-day-old, 1-wk-old and 2-wk-old SPF chickens following intramuscular inoculation with 107 TCID50 of the virus. The results showed that FJSW/2021 can induce typical severe IBH in chicks less than 2 wk old. These findings highlighted the genetic differences between the pathogenic and non-pathogenic FAdV-11 isolates. The data will provide guidance for identifying the virulence factors of FAdV-11 strains. The animal challenge model developed in our study will allow precise evaluation of the efficacy of potential FAdV-11 vaccine candidates.

Long-term efficacy of a recombinant hepatitis E vaccine in adults: 10-year results from a randomised, double-blind, placebo-controlled, phase 3 trial

Hepatitis E virus (HEV) is a frequently overlooked causative agent of acute hepatitis. Evaluating the long-term durability of hepatitis E vaccine efficacy holds crucial importance. This study was an extension to a randomised, double-blind, placebo-controlled, phase-3 clinical trial of the hepatitis E vaccine conducted in Dontai County, Jiangsu, China. Participants were recruited from 11 townships in Dongtai County. In the initial trial, a total of 112 604 healthy adults aged 16-65 years were enrolled, stratified according to age and sex, and randomly assigned in a 1:1 ratio to receive three doses of hepatitis E vaccine or placebo intramuscularly at month 0, month 1, and month 6. A sensitive hepatitis E surveillance system including 205 clinical sentinels, covering the entire study region, was established and maintained for 10 years after vaccination. The primary outcome was the per-protocol efficacy of hepatitis E virus vaccine to prevent confirmed hepatitis E occurring at least 30 days after administration of the third dose. Throughout the study, the participants, site investigators, and laboratory staff remained blinded to the treatment assignments. This study is registered with ClinicalTrials.gov (NCT01014845). During the 10-year study period from Aug 22, 2007, to Oct 31, 2017, 90 people with hepatitis E were identified; 13 in the vaccine group (0·2 per 10 000 person-years) and 77 in the placebo group (1·4 per 10 000 person-years), corresponding to a vaccine efficacy of 83·1% (95% CI 69·4-91·4) in the modified intention-to-treat analysis and 86·6% (73·0 to 94·1) in the per-protocol analysis. In the subsets of participants assessed for immunogenicity persistence, of those who were seronegative at baseline and received three doses of hepatitis E vaccine, 254 (87·3%) of 291 vaccinees in Qindong at the 8·5-year mark and 1270 (73·0%) of 1740 vaccinees in Anfeng at the 7·5-year mark maintained detectable concentrations of antibodies. Immunisation with this hepatitis E vaccine offers durable protection against hepatitis E for up to 10 years, with vaccine-induced antibodies against HEV persisting for at least 8·5 years. National Natural Science Foundation of China, Fujian Provincial Natural Science Foundation, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and the Fundamental Research Funds for the Central Universities.

Mouse Type-I Interferon-Mannosylated Albumin Fusion Protein for the Treatment of Chronic Hepatitis.

Although a lot of effort has been put into creating drugs and combination therapies against chronic hepatitis, no effective treatment has been established. Type-I interferon is a promising therapeutic for chronic hepatitis due to its excellent anti-inflammatory effects through interferon receptors on hepatic macrophages. To develop a type-I IFN equipped with the ability to target hepatic macrophages through the macrophage mannose receptor, the present study designed a mouse type-I interferon-mannosylated albumin fusion protein using site-specific mutagenesis and albumin fusion technology. This fusion protein exhibited the induction of anti-inflammatory molecules, such as IL-10, IL-1Ra, and PD-1, in RAW264.7 cells, or hepatoprotective effects on carbon tetrachloride-induced chronic hepatitis mice. As expected, such biological and hepatoprotective actions were significantly superior to those of human fusion proteins. Furthermore, the repeated administration of mouse fusion protein to carbon tetrachloride-induced chronic hepatitis mice clearly suppressed the area of liver fibrosis and hepatic hydroxyproline contents, not only with a reduction in the levels of inflammatory cytokine (TNF-α) and fibrosis-related genes (TGF-β, Fibronectin, Snail, and Collagen 1α2), but also with a shift in the hepatic macrophage phenotype from inflammatory to anti-inflammatory. Therefore, type-I interferon-mannosylated albumin fusion protein has the potential as a new therapeutic agent for chronic hepatitis.

Comparative efficacy and safety of Sofosbuvir/Velpatasvir and Danoprevir for the treatment of chronic hepatitis C: the real-world data in China

BackgroundSofosbuvir/Velpatasvir (Epclusa, ECS) is the first pan-genotype direct-acting antiviral agent (DAA) for hepatitis C virus (HCV) infection, and Danoprevir (DNV) is the first DAA developed by a Chinese local enterprise, which is suitable for combined use with other drugs to treat genotype 1b chronic hepatitis C. However, previous reports have never compared the real-world data of ECS and DNV.Patients and methods178 chronic hepatitis C patients were retrospectively recruited, and 94cases were accepted with Sofosbuvir/Velpatasvir ± Ribavirin (ECS group), and others (n = 84 treated with DNV combination therapy (DNV group). The HCV genotype, virological response, adverse effects and some laboratory biochemical indexes were contrasted between above two groups in the real world study.ResultsDNV group had significantly lower level of alpha-fetoprotein (AFP), lower rates of decompensated cirrhosis ( P < 0.05). ECS group possessed more 6a (31.91% vs.13.10%) while DNV group was provided with more 1b (48.81% vs. 22.34%) patients. Significantly poor liver function was detected in ECS group at 4-week treatment (ALT and AST) and 12-week follow-up (AST) (all P < 0.05). The SVR12 undetectable rates of both groups were 100%, and no serious event was observed during the treatment and follow-up in both groups.ConclusionIn this retrospective real-world study, the efficacy of DNV combined therapy is similar to Sofosbuvir/Velpatasvir ± Ribavirin for chronic HCV infection, and the safety is comparable. DNV based therapy is a promising regimen for chronic hepatitis C.

Noninferiority Outcomes of Besifovir Compared to Tenofovir Alafenamide in Treatment-Naïve Patients with Chronic Hepatitis B.

: Besifovir dipivoxil maleate (BSV) and tenofovir alafenamide fumarate (TAF) have been recently approved in Korea as the initial antiviral agents for chronic hepatitis B (CHB). However, the real-world outcome data for these drugs remain limited. Therefore, we conducted a noninferiority analysis using real-world data to compare the clinical outcomes of the two nucleotide analogs in treatment-naïve patients with CHB. : We retrospectively investigated a cohort of patients with CHB who received BSV or TAF as first-line antiviral agents. The endpoints were virological response (VR) and liver-related clinical outcomes. : A total of 537 patients, consisting of 202 and 335 patients administered BSV and TAF, respectively, were followed up for 42 months. No significant difference was observed between the VRs of the patients from the two groups. The rates of biochemical response, virologic breakthrough, and incidence rates of hepatocellular carcinoma did not differ between the groups. However, the hepatitis B e antigen seroclearance rate was higher and the renal function declined less in the BSV group. Multivariable analysis indicated older age, alcohol abuse, cirrhosis and ascites, and lower serum HBV DNA level to be independently associated with increased hepatocellular carcinoma risk. The 1:1 propensity score-matched analysis with 400 patients showed VR rates of 85.0% and 88.7% in the BSV and TAF group patients, respectively, at 2 years. The absolute value of the 95% confidence interval for the difference (-0.04 to 0.12) satisfied the a priori limit of a noninferiority of 0.15. : BSV is noninferior to TAF in terms of VR, and their clinical outcomes are comparable to CHB.

Prevalence of positive serology for sexually transmitted infections among older adults

Objective: To determine the seroreactivity profile for sexually transmitted infections (STIs) in a sample of community-dwelling older adults. Methods: Epidemiological survey using serological screening tests for reactivity to Treponema pallidum, HIV 1/2, and hepatitis B and C viruses in 495 older individuals (59.9% women) investigated regardless of signs or symptoms of STIs. Results: Reactivity rates for the etiological agents of AIDS and viral hepatitis B and C were compatible with the usual prevalence of these STIs in the Brazilian population. However, there was a very high prevalence of reactivity to syphilis (symptomatic or asymptomatic) in the group, equivalent to approximately 1290 cases per 10 000 older population, which suggests a proportionally greater exposure of older adults to infection with T. pallidum and to the risk of morbidity and mortality associated with STIs. Conclusions: This scenario indicates that adjustments are needed in geriatric centers to consider screening for STIs as an integral part of the routine clinical care of older people.

Viral Hepatitis Necessitating Liver Transplantation in Children.

Viral hepatitis accounts for a significant global disease burden and mortality, both in children and adults. There are significant differences in the viral etiology, epidemiology, and complications in children worldwide. Children of all ages may have devastating complications with a significant risk of mortality and long-term morbidity because of viral hepatitis. Liver transplantation is the only curative option for pediatric patients with end-stage liver disease, hepatocellular carcinoma, or acute liver failure because of viral hepatitis. The introduction of universal vaccination for hepatitis B across the world and hepatitis A in some countries had led to significant changes in the incidence of disease and the need for liver transplantation for the complications of viral hepatitis in children. The development of effective treatment with directly acting antiviral agents for hepatitis C has already transformed outcomes in adults and children and reduced the need for liver transplantation. Although newer therapy for hepatitis B is being evaluated in adults, current therapy for children is not curative, indicating the need for lifelong therapy and potential necessity for liver transplantation. The recent epidemic of acute hepatitis in children across the world has highlighted the importance of understanding the etiology of unusual causes for acute liver failure and the urgent need for liver transplantation.

Ser235 phosphorylation of hepatitis C virus NS5A is required for NS5A dimerization and drug resistance

Hepatitis C virus (HCV) infection is recognized as a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV non-structural protein 5A (NS5A) is a dimeric phosphoprotein with a hyperphosphorylated form to act as a switch that regulates HCV replication and assembly. NS5A inhibitors have been utilized as the scaffold for combination therapy of direct-acting antiviral agents (DAA). However, the mode of action of NS5A inhibitors is still unclear due to the lack of mechanistic detail regarding NS5A phosphorylation and dimerization in the HCV life cycle. It has been demonstrated that phosphorylation of NS5A at Ser235 is essential for RNA replication of the JFH1 strain. In this report, we found that NS5A phosphomimetic Ser235 substitution (Ser-to-Asp mutation) formed a dimer that was resistant to disruption by NS5A inhibitors as was the NS5A resistance-associated substitution Y93H. Phosphorylation of NS5A at Ser235 residue was required for the interaction of two NS5A-WT molecules in JFH1-based cell culture system but not absolutely required for dimerization of the NS5A-Y93H mutant. Interestingly, HCV nonstructural proteins from the subgenomic replicon NS3-5A was required for NS5A-WT dimerization but not required for NS5A-Y93H dimerization. Our data suggest that spontaneous Ser235 phosphorylation of NS5A and ensuing dimerization account for resistance of the JFH1/NS5A-Y93H mutant to NS5A inhibitors.