Hepatitis Syndrome Research Articles

β-arrestin2 deficiency ameliorates S-100-induced autoimmune hepatitis in mice by inhibiting infiltration of monocyte-derived macrophage and attenuating hepatocyte apoptosis.

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. β-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether β-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and β-arrestin2 knockout (Arrb2 KO) mice, and the experimentsidentified that liver β-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, β-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. β-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that β-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas β-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, β-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3β pathway. These results suggest that β-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, β-arrestin2 may act as an effective therapeutic target for AIH.

Pathogenicity and molecular characteristics of fowl adenovirus serotype 4 with moderate virulence in Guangxi Province, China.

The GX2020-019 strain of fowl adenovirus serotype 4 (FAdV-4) was isolated from the liver of chickens with hydropericardium hepatitis syndrome in Guangxi Province, China, and was purified by plaque assay three times. Pathogenicity studies showed that GX2020-019 can cause typical FAdV-4 pathology, such as hydropericardium syndrome and liver yellowing and swelling. Four-week-old specific pathogen-free (SPF) chickens inoculated with the virus at doses of 103 median tissue culture infectious dose (TCID50), 104 TCID50, 105 TCID50, 106 TCID50, and 107 TCID50 had mortality rates of 0, 20, 60, 100, and 100%, respectively, which were lower than those of chickens inoculated with other highly pathogenic Chinese isolates, indicating that GX2020-019 is a moderately virulent strain. Persistent shedding occurred through the oral and cloacal routes for up to 35 days postinfection. The viral infection caused severe pathological damage to the liver, kidney, lung, bursa of Fabricius, thymus, and spleen. The damage to the liver and immune organs could not be fully restored 21 days after infection, which continued to affect the immune function of chickens. Whole genome analysis indicated that the strain belonged to the FAdV-C group, serotype 4, and had 99.7-100% homology with recent FAdV-4 strains isolated from China. However, the amino acid sequences encoded by ORF30 and ORF49 are identical to the sequences found in nonpathogenic strains, and none of the 32 amino acid mutation sites that appeared in other Chinese isolates were found. Our research expands understanding of the pathogenicity of FAdV-4 and provides a reference for further studies.

Occurrence and phylogenetic analysis of fowl adenovirus E in broiler flocks from Gaza Strip Palestine.

Inclusion-body hepatitis (IBH) and hydropericardium syndrome (HPS) are highly infectious diseases caused by fowl adenoviruses (FAdVs). IBH and HPS cause major economic losses in poultry production. IBH is caused by multiple FAdV serotypes such as FAdV-11, FAdV8a, and FAdV8b; while HPS is mainly caused by the FAdV-4 serotype. In 2018, we detected FAdVs in West Bank - Palestine for the first time. This study aims to monitor the emergence of new FAdVs in broiler farms in Gaza Strip-Palestine in 2022. The clinical signs, necropsy, and histopathological findings associated with IBH in the suspected birds were recorded. Polymerase chain reaction (PCR) was performed using primers matching the virus-encoded L1 loop of the hexon gene. The sequences of the L1 loop were analyzed and a phylogenetic tree was constructed and compared with the related FAdV field isolates and reference strains from different regions of the world available in GenBank. The infected broiler displayed FAdVs-induced clinical symptoms and pathological lesions with mortality rates ranging from 20-46%. The L1 loop sequences from the infected flocks were submitted to GenBank with accession numbers ON638995, ON872150, and ON872151. The identified L1 loop gene has high nucleotide homology (96.7-97.9%) to the highly pathogenic FAdV E serotype 8b strain FAdV_isolate_04-53357-122_Canada_2007 (GenBank: EF685489) and 94.5-94.6% to FAdV_10_Belgium_2010 isolate 11-15941 (GenBank: AF339924.1). Furthermore, the phylogenetic analysis indicated that they belong to FAdV-E serotype 8b. Our study reports the emergence of FAdV-E causing IBH disease in broiler chickens for the first time in Gaza in Palestine.

Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome

Introduction and objectivesPrimary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC overlap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. Materials and methodsThe Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. ResultsAmong the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis (95% vs. 32.5% of those subjects without cancer, p≤0.001), smoking (55% vs. 12.3%, p≤0.001), CREST syndrome (30% vs 7.6%, p=0.003) and prior azathioprine (30% vs 8%, p= 0.005) and prednisone (35% vs 14%, p= 0.018) use, whereas patients with EHM had a higher prevalence of smoking (42.3% vs 12.4% of those subjects without cancer, p= <0.001), AMA positivity (96.6% vs 80.1%, p≤0.001), azathioprine therapy (21% vs 7.9%, p= 0.01) and concurrent other autoimmune diseases. In multivariate analysis, cirrhosis, obesity and prior azathioprine therapy were independent risk factors for HCC, while Sjogren syndrome and psoriasis were associated with EHM. Fibrates reduced EHM risk. ConclusionsThe prevalence of EHM is higher when compared to HCC in PBC patients. Cirrhosis, obesity, prior azathioprine use, and concurrent autoimmune diseases were significantly associated with cancer in PBC.

HIV-Indicator Condition Guided Testing in a Hospital Setting.

Late diagnosis is still a major issue in HIV infection management, leading to important consequences for both patients and community. In this perspective, HIV screening targeted on some clinical conditions (HIV indicator conditions-HIVICs) emerged as a useful strategy, also involving patients not considered at high behavioral risk. We organized an in-hospital HIVICs guided screening campaign named ICEBERG in Milan, Italy, between 2019 and 2021. Among the 520 subjects enrolled, mainly presenting with viral hepatitis or mononucleosis-like syndrome, 20 resulted HIV positive (3.8% prevalence). A significant proportion of them had multiple conditions and advanced immunosuppression, with 40% being AIDS-presenters. As adherence to the screening campaign was modest for non-ID specialists, educational interventions to raise clinicians' sensitivity are urgently needed. HIV-ICs guided testing was confirmed as a useful tool, but a combined approach with other screening strategies seems to be essential for early HIV diagnosis.

An Updated Review on Advances in Hydrogel-Based Nanoparticles for Liver Cancer Treatment

More than 90% of all liver malignancies are hepatocellular carcinomas (HCCs), for which chemotherapy and immunotherapy are the ideal therapeutic choices. Hepatocellular carcinoma is descended from other liver diseases, such as viral hepatitis, alcoholism, and metabolic syndrome. Normal cells and tissues may suffer damage from common forms of chemotherapy. In contrast to systemic chemotherapy, localized chemotherapy can reduce side effects by delivering a steady stream of chemotherapeutic drugs directly to the tumor site. This highlights the significance of controlled-release biodegradable hydrogels as drug delivery methods for chemotherapeutics. This review discusses using hydrogels as drug delivery systems for HCC and covers thermosensitive, pH-sensitive, photosensitive, dual-sensitive, and glutathione-responsive hydrogels. Compared to conventional systemic chemotherapy, hydrogel-based drug delivery methods are more effective in treating cancer.

Design and Identification of a Novel Antiviral Affinity Peptide against Fowl Adenovirus Serotype 4 (FAdV-4) by Targeting Fiber2 Protein.

Outbreaks of hydropericardium hepatitis syndrome caused by fowl adenovirus serotype 4 (FAdV-4) with a novel genotype have been reported in China since 2015, with significant economic losses to the poultry industry. Fiber2 is one of the important structural proteins on FAdV-4 virions. In this study, the C-terminal knob domain of the FAdV-4 Fiber2 protein was expressed and purified, and its trimer structure (PDB ID: 7W83) was determined for the first time. A series of affinity peptides targeting the knob domain of the Fiber2 protein were designed and synthesized on the basis of the crystal structure using computer virtual screening technology. A total of eight peptides were screened using an immunoperoxidase monolayer assay and RT-qPCR, and they exhibited strong binding affinities to the knob domain of the FAdV-4 Fiber2 protein in a surface plasmon resonance assay. Treatment with peptide number 15 (P15; WWHEKE) at different concentrations (10, 25, and 50 μM) significantly reduced the expression level of the Fiber2 protein and the viral titer during FAdV-4 infection. P15 was found to be an optimal peptide with antiviral activity against FAdV-4 in vitro with no cytotoxic effect on LMH cells up to 200 μM. This study led to the identification of a class of affinity peptides designed using computer virtual screening technology that targeted the knob domain of the FAdV-4 Fiber2 protein and may be developed as a novel potential and effective antiviral strategy in the prevention and control of FAdV-4.

Role of endocrine PACAP in age-related diseases.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a conserved neuropeptide, which confers diverse anti-aging endocrine and paracrine/autocrine effects, including anti-apoptotic, anti-inflammatory and antioxidant action. The results of the in vivo and in vitro experiments show that increasing emphasis is being placed on the diagnostic/prognostic biomarker potential of this neuropeptide in a wide array of age-related diseases. After the initial findings regarding the presence and alteration of PACAP in different body fluids in physiological processes, an increasing number of studies have focused on the changes of its levels in various pathological conditions associated with advanced aging. Until 2016 - when the results of previous human studies were reviewed - a vast majority of the studies had dealt with age-related neurological diseases, like cerebrovascular and neurodegenerative diseases, multiple sclerosis, as well as some other common diseases in elderly such as migraine, traumatic brain injury and post-traumatic stress disorder, chronic hepatitis and nephrotic syndrome. The aim of this review is to summarize the old and the new results and highlight those 'classical' and emerging clinical fields in which PACAP may become subject to further investigation as a diagnostic and/or prognostic biomarker in age-related diseases.

A seasonal idiopathic hepatitis syndrome in horses presented to a Midwestern veterinary teaching hospital.

To report history, clinical examination findings, clinicopathologic findings, diagnostic test results, treatment, and outcome in horses with a novel idiopathic hepatitis syndrome. 13 client-owned horses. Medical records of horses that were presented with fever and increased blood liver enzyme activity over a 16-month period were reviewed (December 1, 2020, to April 1, 2022). Collected data included signalment, history, clinical and clinicopathologic findings, diagnostic test results, treatment, clinical progression, and short-term outcome. Affected horses were presented between December and April of each of the 2 seasons investigated. The majority of horses developed cyclic fevers over the course of 3 weeks, during which time histologic evidence of hepatitis was observed. Histologic lesions included hepatic necrosis, neutrophilic to lymphohistiocytic inflammation, biliary epithelial injury, and portal fibrosis. Systemic inflammation was evidenced by increased serum amyloid A concentration and leukon changes. No horse developed signs of hepatic insufficiency, and all horses clinically recovered. Return of serum activity of GGT to within the reference range occurred within 16 weeks in most horses. Histologic lesions remained evident up to 27 weeks after initial presentation in 1 horse. Although an etiologic agent has not been identified, an apparently seasonal equine hepatitis syndrome was characterized by fever, systemic inflammation, increased liver enzyme activity, and histologic evidence of hepatitis. An infectious cause is suspected on the basis of histology and outcome.

Efficacy and safety of ursodeoxycholic acid in children with cholestasis: A systematic review and meta-analysis.

Ursodeoxycholic acid (UDCA) is the main therapeutic drug for cholestasis, but its use in children is controversial. We conducted this study to evaluate the efficacy and safety of ursodeoxycholic acid in children with cholestasis. We searched Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, WanFang Data and VIP from the establishment of databases to July 2022. Eligible studies included Chinese or English randomized controlled trials (RCTs) comparing the efficacy and safety of no UDCA (placebo or blank control) and UDCA in children with cholestasis. This study had been registered with PROSPERO (CRD42022354052). A total of 32 RCTs proved eligible, which included 2153 patients. The results of meta-analysis showed that UDCA could improve symptoms of children with cholestasis (risk ratio 1.24, 95% CI 1.18 to 1.29; moderate quality of evidence), and serum levels of alanine aminotransferase, total bilirubin, direct bilirubin and total bile acid (low quality of evidence). For some children with specific cholestasis, UDCA could also effectively drop serum levels of aspartate aminotransferase (parenteral nutrition-associated cholestasis) and γ-glutamyl transferase (infantile hepatitis syndrome, parenteral nutrition-associated cholestasis). The most common adverse drug reactions (ADRs) of UDCA in children were gastrointestinal adverse reactions, with an incidence of 10.63% (67/630). There was no significant difference in the incidence of ADRs between UDCA and placebo/blank control groups (risk difference 0.03, 95%CI -0.01 to 0.06; moderate quality of evidence), and among children taking different UDCA doses (P = 0.27). The available short-term evidence showed that UDCA was effective and safe for children with cholestasis. Clinicians should use UDCA with caution (start with a low dose) until the long-term effect is further explored in future larger RCTs.

157 - A case of autoimmune hepatitis and primary biliary cholangitis overlap syndrome

157 - A case of autoimmune hepatitis and primary biliary cholangitis overlap syndrome

Pathogenicity of duck circovirus and fowl adenovirus serotype 4 co-infection in Cherry Valley ducks

Duck circovirus (DuCV) is one of the most prevalent infectious viruses in the duck industry in China. Although the clinical symptoms vary, it often causes immunosuppression in the host and leads to secondary infection with other pathogens. Fowl adenovirus serotype 4 (FAdV-4) mainly infects chickens and causes hydropericardium hepatitis syndrome. However, the incidence of infection in ducks has increased in recent years, and the phenomenon of mixed infection with DuCV is very common, resulting in more severe clinical morbidity. However, there is no systematic study evaluating the presence of mixed infection. To explore the synergistic pathogenicity of DuCV and FAdV-4 co-infection in Cherry Valley ducks, a comparative experiment was established between DuCV and FAdV-4 co-infection and single infection animal models. It was found that DuCV and FAdV-4 co-infected ducks showed more pronounced clinical signs of pericardial effusion, hepatitis and immunosuppression; more severe tissue damage in target organs; and more significant levels of viral load, biochemical indicators and immune indicators in various organs compared with Cherry Valley ducks infected with just one virus. The results showed that co-infection with DuCV and FAdV-4 may promote greater viral replication, causing more severe tissue damage and immunosuppression than infection with just one virus. Therefore, the monitoring and prevention of the two viruses should be strengthened clinically, with a particular focus on the potential harm of DuCV as it carries the highest infection rate.

Effects of triterpenoids in fatty products on liver condition of laboratory animals with acute toxic hepatitis

One of the principles of prevention and non-medicamentous treatment of liver diseases, including hepatitis of different etiology, is the normalization of the diet through the consumption of food with physiologically active ingredients, in particular betulin, which helps to eliminate the causes of metabolic and oxidative disorders within liver cells. The aim of the research was to assess in vivo the influence of triterpene alcohol betulin extracted from Betula pendula Roth. birch bark in fat-containing products (for example mayonnaise) on the blood biochemical parameters and liver morphological structure of rats with initiated acute toxic hepatitis. Material and methods. Hepatoprotective and antioxidant activities of betulin as part of mayonnaise samples has been investigated in vivo on the model of toxic hepatitis initiated by carbon tetrachloride in male Wistar rats weighing 210-265 g. The animals were divided into 4 groups of 10 animals each: CG-1 - intact, CG-2 and MG - with carbon tetrachloride initiated toxic hepatitis. rats of the main groups were orally administered mayonnaise once a day at a dosage of 1 ml for 21 days after the formation of the model pathology: OG-1 with the added betulin (1 mg per 1 kg of body weight), OG-2 without betulin. Disorders of metabolic and oxidative processes in liver cells of animals were evaluated by biochemical indicators of blood plasma: the level of glucose, albumin, total cholesterol, triglycerides and urea and the activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyltransferase. Oxidative stress in rats was estimated by the activity of catalase and superoxide dismutase in blood hemolysate (at a dilution of 1:200 and 1:10, respectively); the total prooxidant (in blood plasma) and total antioxidant (in blood hemolysate at a dilution of 1:10) activity were determined spectrophotometrically (colored complexes of TWIN-80 oxidation products with thiobarbituric acid). The morphological structure of rats' liver was estimated by microscopy of prepared cuts of hepatic tissue. Results. Based on biochemical parameters of rat blood plasma, it has been established that the administration of mayonnaise with betulin prevents the development of cytolic syndrome and suppresses the process of peroxidation by directly neutralizing free radicals. Aspartate aminotransferase and alkaline phosphatase activity in blood plasma of the experimental animals of the main group MG-1 reduced by 20.7 and 35.2% compared with indicators of the rats of the main group MG-2. Glucose concentration normalized to the level of the control group CG-1. The concentration of bilirubin and triglycerides decreased by 22.9 and by 48.1%, which indicates a significant reduction in the indicators of cholestatic syndrome in the group of animals OG-1 compared to OG-2. The total prooxidant activity and the concentration of thiobarbiturate-reactive products decreased compared to the CG-2 and MG-2 groups, which indicates the suppression of oxidative stress and, as a result, an improvement in liver conditions of animals with toxic hepatitis even when taking a fat-containing product. In liver histopeparates of animals receiving mayonnaise with betulin, necrobotic changes were less pronounced in comparison with the group MG-2. They were estimated at 1 point: small-drip dystrophy spots were found, haemorrhages in the interregional septum with inflammatory infiltration in the course of hemorrhages against the presence of necrosis hepatocytes with pronounced adipose dystrophy in the centres of the lobules, step necrosis with signs of replacing the damaged hepatocytes of the connective tissue, accompanied by centrolobular hemorrhages in MG-2 rats. Conclusion. Introduced into the composition of mayonnaise betulin, reduces the development of cytolic syndrome in toxic hepatitis and suppresses the process of peroxidation, on the basis of which fat-containing foods with betulin can be recommended for clinical examination as specialized products in acute and chronic liver diseases, including complicated cholestasis.

Molecular Diagnosis of Adeno Virus Associated with Hydropericardium Hepatitis Syndrome of the Broiler Chickens in Nineveh Province, Iraq

Molecular Diagnosis of Adeno Virus Associated with Hydropericardium Hepatitis Syndrome of the Broiler Chickens in Nineveh Province, Iraq

HLA-DR+ CD38high Expression in T Cells Is Excellent in Quantifying the Amplitude of T-Cell Activation in a Spectrum of Hyperinflammatory Disorders Including HLH

Introduction: T cell activation is the hallmark of several hyperinflammatory states such as HLH and immune dysregulation disorders like LRBA deficiency. Identifying T-cell activation and quantifying the amplitude of T-cell activation is critical for diagnosis, management, and monitoring treatment response in patients with hyperinflammatory and immune regulatory disorders. Soluble Interleukin 2 Receptor (sIL2R) is one of the established systemic T-cell activation markers for diagnosing and monitoring HLH and other hyperinflammatory disorders. However, the clinical availability of sIL2R testing is limited, and it may not be a reliable marker of T-cell activation in patients with eosinophilia and T-cell lymphoma. A recent study by Chaturvedi et.al has demonstrated the utility of flow-based T-cell activation assessment in differentiating HLH from sepsis. However, its utility in defining and quantifying T-cell activation across the hyperinflammatory spectrum and its correlation with sIL2R has not yet been established. Methods: A total of 125 samples were collected either at disease onset (n = 81) or at follow-up (n = 44) from 85 human subjects. Paired plasma sIL2R and T-cell activation markers were prospectively evaluated in patients with suspected HLH (n = 79) or immune dysregulation disorders (n = 46). Out of 85 patients, 21 patients were diagnosed with either primary HLH (p-HLH), Epstein-Barr virus infection-associated HLH (EBV-HLH), malignancy-associated HLH (m-HLH), or macrophage activation syndrome (MAS). The rest of the patients were diagnosed with either sepsis, multisystem inflammatory syndrome in children (MIS-C), hyperinflammatory conditions, hepatitis, or acute liver failure. Flow cytometry-based T-cell activation was evaluated in different T-cell sub-compartments by the co-expression of HLA-DR and CD38 surface markers. Plasma sIL2R levels and CXCL9 (a chemokine driven by IFN-g) were determined independently in CLIA certified clinical diagnostic laboratory. Research personnel who analyzed the flow cytometry data were blinded to the corresponding sIL2R test results and clinical diagnosis. Longitudinal follow-up was performed for a subset of patients with HLH or immune dysregulation with evidence of T-cell activation. We also evaluated T-cell activation in 30 healthy controls (HC) to establish a reference range. In addition, the correlation between T-cell activation markers with plasma levels of sIL2R and CXCL9 was also investigated. Results: Evaluation of T-cell activation measured by HLADR+CD38high in HCs and different hyperinflammatory/ immune regulatory disorders revealed that HCs have less than 8% of T-cell activation in CD8+ T effector memory (TEM) and less than 4% for activation in the CD4+ TEM compartments. In patients with suspected hyperinflammatory/ immune regulatory disorders, we identified significant correlation of direct T-cell activation with plasma sIL2R level in different T-cell subsets, CD3 (r = 0.44, p < 0.0001), CD4 (r = 0.41, p < 0.0001), CD8 (r = 0.45, p <0.001), CD4 TEM (T effector memory) (r =0.53, p < 0.001), and CD8 TEM (r =0.53, p < 0.0001). The strongest correlation between HLADR+CD38high with sIL2R level was noted in CD4+ TEM and CD8+ TEM compartments (Figure 1). The correlation is even more robust at disease onset (r = 0.69, p <0.0001 for CD4+ TEM and r = 0.64, p < 0.0001 for CD8+ TEM). However, at follow up, only activation in CD8+ TEM correlated with sIL2R levels (r = 0.4, p = 0.0069). Moreover, T-cell activation in CD8+ TEM correlated well with CXCL9 and ferritin levels. Among the cohort of patients with the confirmed final diagnosis, we found that both p-HLH and EBV-HLH have CD8+ TEM activation > 70%, whereas MAS and m-HLH have a median T cell activation of 37.8% (10.5-67) and 48.1% (4.9-80.6) respectively. Immune dysregulation patients had T-cell activation range from 8.0 to 46.0 % and sepsis group has 0% to 10.8% (Figure 2). A similar trend was also validated using corresponding plasma sIL2R levels in different hyperinflammatory states. Conclusions: Flow cytometry-based direct assessment of HLADR+CD38high in T cells subsets can reliably quantify T-cell activation and strongly correlate with sIL2R level across a spectrum of different hyperinflammatory and immune dysregulations disorders. If validated, this could be used as a real-time assessment of T-cell activation at disease onset and monitoring response to therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Chronic non-communicable diseases: Hainan prospective cohort study

PurposeThe Hainan Cohort was established to investigate the incidence, morbidity and mortality of non-communicable diseases and their risk factors in the community population.ParticipantsThe baseline investigation of the Hainan Cohort study...

Illumina high-throughput sequencing for the genome of emerging fowl adenovirus D species and C species simultaneously

In recent years, clinical cases of inclusion body hepatitis (IBH) and hydropericardium syndrome (HPS) have been emerging and increasing in chicken flocks worldwide. Mixed infections with 2 or more fowl adenovirus (FAdV) serotypes were common in these cases. Herein, we collected a clinical sample that was positive for FAdV from 40-day-old broilers with IBH and HPS symptoms in Shandong province of China and determined the complete genome of FAdVs on the Illumina HiSeq4000 platform. The results showed that the sample contained 2 FAdV strains of D species and C species and named SD1763-1 and SD1763-2 respectively. The genome of SD1763-1 strain was 43,913 nt in length, with a G+C content of 53.51%, whereas SD1763-2 strain was 43,721 nt in length, with a G+C content of 54.87%. Sequence alignment and phylogenetic analysis revealed that strain SD1763-1 was clustered together with serotype 2/11 of FAdV-D, and SD1763-2 was clustered together with FAdV-4. There is no recombination between the genomes of the 2 viruses of FAdV-D and FAdV-C in the present study. This is the first report of obtaining 2 genomic sequences of FAdV strains simultaneously by direct use of deep sequencing in one clinical individual chicken sample, which provided direct evidence for mixed infections of adenovirus serotypes in the clinic and enriched the genome data to explore the geographic biomarkers and virulence signatures of the genus Aviadenovirus.

Trends in liver transplantation for autoimmune liver diseases: a Canadian study.

Background:To our knowledge, no analysis of data from liver transplantation registries exists in Canada. We aimed to describe temporal trends in the number of liver transplantation procedures, patient characteristics and posttransplantation outcomes for autoimmune liver diseases (AILDs) in Canada.Methods:We used administrative data from the Canadian Organ Replacement Register, which contains liver transplantation information from 6 centres in Canada. This study included transplantation information from 5 of the centres, as liver transplantation procedures in children were not included. We included adult (age ≥ 18 yr) patients with a diagnosis of primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH) or overlap syndrome (PBC–AIH or PSC–AIH) who received a liver transplant from 2000 to 2018.Results:Of 5722 primary liver transplantation procedures performed over the study period, 1070 (18.7%) were for an AILD: 489 (45.7%) for PSC, 341 (31.9%) for PBC, 220 (20.6%) for AIH and 20 (1.9%) for overlap syndrome. There was a significant increase in the absolute number of procedures for PSC, with a yearly increase of 0.6 (95% confidence interval 0.1 to 1.2), whereas the absolute number of procedures for PBC and AIH remained stable. The proportion of transplantation procedures decreased for PBC and AIH but remained stable for PSC. Recipient age at transplantation increased over time for males with PBC (median 53 yr in 2000–2005 to 57 yr in 2012–2018, p = 0.03); whereas the median age among patients with AIH decreased, from 53 years in 2000–2005 to 44 years in 2006–2011 (p = 0.03). The Model for Endstage Liver Disease score at the time of transplantation increased over time for all AILDs, particularly AIH (median 16 in 2000–2005 v. 24 in 2012–2018, p < 0.001). There was a trend toward improved survival in the PBC group, with a 5-year survival rate of 81% in 2000–2005 and 90% in 2012–2018 (p = 0.06).Conclusion:Between 2000 and 2018, the absolute number of liver transplantation procedures in Canada increased for PSC but remained stable for PBC and AIH; proportionally, PBC and AIH decreased as indications for transplantation. Posttransplantation survival improved only for the PBC group. An improved understanding of trends and outcomes on a national scale among patients with AILD undergoing liver transplantation can identify disparities and areas for potential health care improvement.

Epidemiology, pathology, prevention, and control strategies of inclusion body hepatitis and hepatitis-hydropericardium syndrome in poultry: A comprehensive review.

Infection with fowl adenoviruses (FAdVs) can result in a number of syndromes in the production of chicken, including inclusion body hepatitis (IBH), hepatitis-hydropericardium syndrome (HHS), and others, causing enormous economic losses around the globe. FAdVs are divided into 12 serotypes and five species (A–E; 1–8a and 8b−11). Most avian species are prone to infection due to the widespread distribution of FAdV strains. The genus aviadenovirus, which is a member of the adenoviridae family, is responsible for both IBH and HHS. The most popular types of transmission are mechanical, vertical, and horizontal. Hepatitis with basophilic intranuclear inclusion bodies distinguishes IBH, but the buildup of translucent or straw-colored fluid in the pericardial sac distinguishes HHS. IBH and HHS require a confirmatory diagnosis because their clinical symptoms and postmortem abnormalities are not unique to those conditions. Under a microscope, the presence of particular lesions and inclusion bodies may provide clues. Traditional virus isolation in avian tissue culture is more delicate than in avian embryonated eggs. Additionally, aviadenovirus may now be quickly and precisely detected using molecular diagnostic tools. Preventive techniques should rely on efficient biosecurity controls and immunize breeders prior to production in order to protect progeny. This current review gives a general overview of the current local and global scenario of IBH, and HHS brought on by FAdVs and covers both their issues and preventative vaccination methods.

Genetic testing and prenatal diagnosis for a Chinese pedigree affected with mitochondrial DNA depletion syndrome due to variant of MPV17 gene

To explore the genetic etiology of a Chinese pedigree affected with infantile hepatitis syndrome. Genes associated with liver diseases subjected to high-throughput sequencing. Candidate variants were validated by Sanger sequencing of the proband and his parents. The pathogenicity of the variants was analyzed through bioinformatic analysis. High-throughput sequencing revealed that the proband has harbored c.182T>C (p.F61S) and c.293C>T (p.P98L) variants of the MPV17 gene, which were verified by Sanger sequencing to be inherited from his parents. The variant c.182T>C (p.F61S) was unreported previously and predicted to be likely pathogenic by bioinformatic analysis. The proband was caused by the compound heterozygous variations of MPV17 gene including c.182T>C (p.F61S) and c.293C>T (p.P98L). Discovery of the novel variant has enriched the spectrum of pathogenic variants of the MPV17 gene.