Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hep...Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration.展开更多
BACKGROUND Genetic disorders affecting hepatobiliary transporters can be triggered by various factors,resulting in marked cholestasis.CASE SUMMARY We report two patients who experienced a severe episode of intrahepati...BACKGROUND Genetic disorders affecting hepatobiliary transporters can be triggered by various factors,resulting in marked cholestasis.CASE SUMMARY We report two patients who experienced a severe episode of intrahepatic cholestasis triggered by an acute hepatitis E virus infection.Following an extensive clinical examination that ruled out common causes of cholestatic liver damage,we conducted next-generation sequencing to determine the genetic profiles of the patients.The analysis revealed several known and unknown variants in genes associated with hepatobiliary transporters and bile salt regulation,including ATP8B1,ABCB11,ABCB4,MYO5B,and FXR.For a comprehensive understanding of the pathophysiology,we performed ClinVar analysis and utilized PolyPhen for bioinformatic prediction of functional impact.Both patients exhibited rapid symptom improvement and a decrease in hyperbilirubinemia when treated with either rifampicin or bezafibrate.CONCLUSION Our findings introduce hepatitis E viral infection as a novel trigger for intrahepatic cholestasis,and we categorize the significance of the various genetic variants based on the current state of research.展开更多
BACKGROUND Many causal factors influence acute liver failure(ALF),including the primary underlying cause,age,and socioeconomic conditions.ALF outcomes depend on etiology,coagulopathy,bilirubin,age,and understanding of...BACKGROUND Many causal factors influence acute liver failure(ALF),including the primary underlying cause,age,and socioeconomic conditions.ALF outcomes depend on etiology,coagulopathy,bilirubin,age,and understanding of hepatic encephalopathy(HE),and help us predict coma and death.AIM To evaluate the association between etiologies,clinical manifestations,and outcomes of adults admitted with ALF.METHODS This institution-based,prospective cross-sectional study was conducted in the Department of Gastroenterology and Hepatology at Jinnah Postgraduate Medical Center,Karachi,from July 2019 to December 2022.A total of 102 patients diagnosed with ALF were included using consecutive sampling and data were collected from patients who visited Jinnah Postgraduate Medical Center,Karachi,the gastroenterology and hepatology department,entered into Microsoft Excel,and analyzed using Statistical Package for the Social Sciences version 26.0.Diagnosis was based on King’s College criteria:Age,encephalopathy grade,bilirubin,prothrombin time,international normalized ratio,creatinine,and etiology.We assessed the association between socioeconomic status and various outcomes using chi-square tests with a level of significance was less than 0.05.RESULTS Mean age of the ALF cohort was 27.37±6.60 years.Of the 102 patients,71(69.6%)were female,including 55(77.5%)pregnant women with a mean gestational age of 34.56±3.80 weeks.Regarding HE severity,45(44.1%)had grade III,and 13(12.7%)had grade II.Among the patients admitted to the intensive care unit,51(72.9%)did not survive,while 14(43.8%)recovered.CONCLUSION This study observed a high mortality rate among ALF patients in a tertiary care hospital.Hepatitis E virus infection,HE severity,and sepsis were significantly associated with higher mortality.展开更多
BACKGROUND: Fulminant hepatic failure (FHF) is not uncommon in our clinical practice in Bangladesh. There was a rise in acute hepatitis E virus (HEV) in Bangladesh after the 2004 floods. At that time, most of the coun...BACKGROUND: Fulminant hepatic failure (FHF) is not uncommon in our clinical practice in Bangladesh. There was a rise in acute hepatitis E virus (HEV) in Bangladesh after the 2004 floods. At that time, most of the country was under water for more than a month, leading to sewage contamination of the water supply. The aim of this study was to investigate the etiology of FHF in Bangladesh. METHODS: In this retrospective study, 23 patients with FHF who presented with severe impairment of hepato- cellular function (i.e. encephalopathy, coagulopathy and jaundice) within 6 months of onset of symptoms were included. There were 17 men and 6 women, aged from 18 to 32 years. Four of the women were pregnant. Patients were tested for markers for common hepatotrophic viruses. A relevant history was taken and the Patient Record Book of the Unit was reviewed. RESULTS: 56.52% patients (13/23) had HEV infection, and all were anti-HEV IgM-positive tested by ELISA. HBV infection was detected in 34.78% patients (8/23), all of whom were tested positive for either HBsAg or anti-HBs IgM by ELISA. 8.7% patients (2/23) had a positive history for intake of alcohol and/or drugs. CONCLUSIONS: Acute HEV infection is the leading cause of FHF in Bangladesh. Sewage contamination of the water supply following floods contributes to a higher incidence of HEV infection. HBV infection is also important.展开更多
BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HA...BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.展开更多
Hepatitis E virus(HEV)represents a significant global cause of acute viral hepatitis.Annually,it is estimated to cause approximately 20.1 million infections worldwide,3.3 million of which result in symptomatic illness...Hepatitis E virus(HEV)represents a significant global cause of acute viral hepatitis.Annually,it is estimated to cause approximately 20.1 million infections worldwide,3.3 million of which result in symptomatic illness.In developing regions,genotypes HEV-1 and HEV-2 are the primary strains responsible for widespread outbreaks and epidemics of acute jaundice(icteric hepatitis),transmitted predominantly through the fecal-oral route via contaminated water and food(Devarbhavi et al.,2023).展开更多
Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global populat...Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.展开更多
Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive ...Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive patients,and those with hematological malignancies.It poses a risk of liver fibrosis and cirrhosis.Data sources:Relevant articles published till September 2024 were located using Pub Med searches.The further search terms utilized were:“immunocompromised”,“solid organ transplant”,“HIV”,“hematological malignancy”,and“hepatitis E virus”.A manual search of references from pivotal articles extended further publications.The search parameters encompass publications in English.Results:The epidemiology,clinical manifestations,diagnostic measures,and therapeutic modalities of chronic hepatitis E were discussed.Immunocompromised individuals who are infected with HEV are at an increased risk of developing chronic infections,which may progress to liver fibrosis and cirrhosis.Current understanding of HEV is still limited,and there is no medicine that specifically targets hepatitis E.Consequently,the prevention and management of hepatitis E continue to present a significant challenge.Conclusions:Chronic hepatitis E patients need special attention in clinical practice.The relevant risk factors must be identified to facilitate accurate diagnosis and the implementation of more effective preventive measures,thereby enhancing the monitoring,treatment,and prevention of immunocompromised individuals.展开更多
The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has...The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has introduced a new public health threat due to its potential for zoonotic transmission.This study investigated2?464 wild small mammals spanning four animal orders,eight families,21 genera,and 37 species in Yunnan Province,China.Using broadly reactive reverse transcription-polymerase chain reaction(RT-PCR),we systematically screened the presence and prevalence of Orthohepevirus and identified 192 positive specimens from10 species,corresponding to an overall detection rate of7.79%.Next-generation sequencing enabled the recovery of 24 full-length genomic sequences from eight host species,including Bandicota bengalensis,Eothenomys eleusis,and Episoriculus caudatus,representing newly reported host species for Orthohepevirus strains.Phylogenetic and sequence analyses revealed extensive genetic diversity within orthohepeviruses infecting rodents and shrews.Notably,among the identified strains,20 were classified as Rocahepevirus ratti C1,two as C3,and one as Rocahepevirus eothenomi,while the remaining strain exhibited significant divergence,precluding classification.Evolutionary analyses highlighted close associations between orthohepeviruses and their respective host taxa,with distinct phylogenetic clustering patterns observed across different host orders.These findings emphasize the critical roles of co-speciation and cross-species transmission in shaping the evolutionary trajectories of the genera Paslahepevirus and Rocahepevirus.展开更多
Hepatitis E virus(HEV)infection causes acute hepatitis,chronic hepatitis,particularly in compromised hosts,and various extrahepatic manifestations.HEV infection is reportedly associated with biliary-pancreatic disease...Hepatitis E virus(HEV)infection causes acute hepatitis,chronic hepatitis,particularly in compromised hosts,and various extrahepatic manifestations.HEV infection is reportedly associated with biliary-pancreatic diseases,such as gallstones,cholangitis,choledocholithiasis,and acute pancreatitis.Severe jaundice and prolonged cholestasis are also atypical manifestations of HEV infection.The mechanism and genes involved in cholestasis,namely sinusoidal uptake of blood,bile salt synthesis and secretion from hepatocytes to the canaliculus,have been elucidated.HEV infection triggers severe jaundice and prolonged cholestasis in patients with genetic variants in adenosine triphosphatase phospholipid transporting 8B1,adenosine triphosphate-binding cassette(ABC)protein B4,ABCB11,Myosin VB,and/or farnesoid X receptor(FXR/NR1H4).Although prolonged cholestasis associated with these gene mutations does not seem to be specific to HEV infection,these mutations may be risk factors related to the severity of HEV infection.The use of the pregnane X receptor agonist rifampicin and the peroxisome proliferator-activated receptor activator bezafibrate may be useful for the treatment of cholestasis.These studies provide new insights into under-standing the mechanisms of severe jaundice and prolonged cholestasis caused by HEV infection.展开更多
Background:Despite the insights into the role of aldehyde dehydrogenase 1 family member A1(ALDH1A1)in various liver diseases,the expression and its prognostic significance in patients with hepatitis E virus-related ac...Background:Despite the insights into the role of aldehyde dehydrogenase 1 family member A1(ALDH1A1)in various liver diseases,the expression and its prognostic significance in patients with hepatitis E virus-related acute liver failure(HEV-ALF)remain unclear.This study delved into the assessment of serum exosome-derived ALDH1A1 expression and its prognostic implications for HEV-ALF patients.Methods:Between January 2018 and December 2023,a total of 226 individuals with acute hepatitis E(AHE)and 210 patients with HEV-ALF were recruited from member units of Chinese Consortium for the Study of Hepatitis E.According to the number of organ failure,we categorized 210 HEV-ALF patients into three groups:two organs failure(n=131),three organs failure(n=46),and more than three organs failure(n=33).In addition,200 health controls from Suzhou Municipal Hospital were included.Results:The levels of serum exosome-derived ALDH1A1 in HEV-ALF patients were significantly higher than those in AHE patients and health controls(both P<0.05).Furthermore,the levels of serum exosome-derived ALDH1A1 were the highest in more than three organs failure group,followed by three organs failure group and two organs failure group(all P<0.001).Moreover,serum exosome-derived ALDH1A1 was positively correlated with total bilirubin in HEV-ALF patients(r=0.315,P<0.001).The comparisons of serum exosome-derived ALDH1A1 levels in treatment response showed that serum exosome-derived ALDH1A1 levels were decreased in the improvement group,while increased in the fluctuation and deterioration groups(all P<0.001).Moreover,serum exosome-derived ALDH1A1 was an independent risk factor for predicting the 30-day mortality(P<0.001).Furthermore,the area under the receiver operating characteristic curve was 0.943,with the sensitivity of 94.87%and specificity of 87.72%,indicating the robust decision-making ability.However,no significant differences were found in serum exosome-derived ALDH1A1 levels between patients aged<60 and≥60 years old(P=0.131).Conclusions:Serum exosome-derived ALDH1A1 can greatly predict the prognosis of HEV-ALF patients.展开更多
The hepatitis E virus(HEV)is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s.Globally,it is one of the most frequent cause...The hepatitis E virus(HEV)is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s.Globally,it is one of the most frequent causes of acute viral hepatitis.The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus.Among the eight different genotypes identified to date,HEV genotype 1(HEV1),HEV2,HEV3,and HEV4 are the most frequent genotypes causing infections in humans.HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies.They are also responsible for severe hepatitis in pregnant patients and infants.In contrast,HEV3 and HEV4 are zoonotic,and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals.Their main reservoir is the pig,and they are mostly encountered in developed countries.The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women,infants,older people,immunocompromised individuals,patients with underlying chronic liver diseases,and workers that come into close contact with HEV-infected animals.In the clinical perspective,HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis,acute-on-chronic liver disease,chronic hepatitis,cirrhosis,and liver failure.Although HEV mainly results in acute selflimiting infection,chronic HEV infection may occur among immunocompromised patients(e.g.,solid-organ transplant recipients).Additionally,HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade,although the causal link for many of them still needs to be proven.Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success.However,ribavirin is contraindicated in pregnant patients,and interferon-alpha cannot be used in most transplant recipients.Therefore,there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirinresistant HEV.In this review article,a literature search using PubMed and MEDLINE databases was performed,up to March 2020.Only the articles published in English were reviewed.展开更多
AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B vi...AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.展开更多
Chronic hepatitis B(CHB)is a condition of globalprevalence and its sequelae include cirrhosis and hepatocellular carcinoma.The natural history of CHB isa complex interplay of virological,environmental andhost factors....Chronic hepatitis B(CHB)is a condition of globalprevalence and its sequelae include cirrhosis and hepatocellular carcinoma.The natural history of CHB isa complex interplay of virological,environmental andhost factors.The dynamic relationship between thevirus and host evolves over the duration of the infection and different phases of the disease have been observed and described.These have been conceptualizedin terms of the state of balance between the host immune system and the hepatitis B virus and have beengiven the labels immune tolerant,immune clearance,immune control and immune escape although othernomenclature is also used.Host factors,such as age atinfection,determine progression to chronicity.Virological factors including hepatitis B viral load,mutationsand genotype also have an impact on the adverseoutcomes of the infection,as do hepatotoxic cofactorssuch as alcohol.Our understanding of the natural history of CHB has evolved significantly over the past fewdecades and characterizing the phase of disease ofCHB remains an integral part of managing this virus in the clinic.展开更多
Each hepatitis virus—Hepatitis A,B,C,D,E,and G—poses a distinct scenario to the patient and clinician alike.Since the discovery of each virus,extensive knowledge regarding epidemiology,virologic properties,and the n...Each hepatitis virus—Hepatitis A,B,C,D,E,and G—poses a distinct scenario to the patient and clinician alike.Since the discovery of each virus,extensive knowledge regarding epidemiology,virologic properties,and the natural clinical and immunologic history of acute and chronic infections has been generated.Basic discoveries about host immunologic responses to acute and chronic viral infections,combined with virologic data,has led to vaccines to prevent Hepatitis A,B,and E and highly efficacious antivirals for Hepatitis B and C.These therapeutic breakthroughs are transforming the fields of hepatology,transplant medicine in general,and public and global health.Most notably,there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade.While attainable,there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local,national,and international scales.Herein,we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.展开更多
Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent year...Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent years,there are still points of conflict concerning the pathogenesis,immune response,development of new and more effective vaccines,therapies,and treatment.This review focuses on the most important research topics that deal with issues that are currently being solved,those that remain to be solved,and future research directions.For hepatitis A virus we will address epidemiology,molecular surveillance,new susceptible populations as well as environmental and food detections.In the case of hepatitis B virus,we will discuss host factors related to disease,diagnosis,therapy,and vaccine improvement.On hepatitis C virus,we will focus on pathogenesis,immune response,direct action antivirals treatment in the context of solid organ transplantation,issues related to hepatocellular carcinoma development,direct action antivirals resistance due to selection of resistanceassociated variants,and vaccination.Regarding hepatitis D virus,we describe diagnostic methodology,pathogenesis,and therapy.Finally,for hepatitis E virus,we will address epidemiology(including new emerging species),diagnosis,clinical aspects,treatment,the development of a vaccine,and environmental surveillance.展开更多
INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 a...INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .展开更多
AIM： To study the significance of serum anti-hepatitis E virus （HEV） IgA in patients with hepatitis E. METHODS： A new method was established to assay anti-HEY IgA, which could be detected in the middle phase of th...AIM： To study the significance of serum anti-hepatitis E virus （HEV） IgA in patients with hepatitis E. METHODS： A new method was established to assay anti-HEY IgA, which could be detected in the middle phase of the infection. We compared anti-HEV IgA assay with anti-HEV IgM and anti-HEV IgG assay in sera from 60 patients with positive HEV-RNA. RESULTS： The 60 patients with positive HEV-RNA had both anti-HEV IgA and anti-HEV IgM and 410 patients with negative HEV-RNA were used as control. Periodic serum samples obtained from 60 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, anti-HEV IgA and anti-HEV IgG. Their HEV-RNA was detectable in the serum until 20 ±11 d. We used anti-HEV IgM and anti-HEV IgA assay to detect HEV infection and positive results were found in 90 ± 15 d and 120 ±23 d respectively, the positive rate of anti-HEV IgA was higher than that of anti-HEV IgM and HEV-RNA （P 〈0.05）. CONCLUSION： The duration of anti-HEV IgA in serum is longer than that of anti-HEV IgM, and anti-HEV IgA assay is a good method to detect HEV infection.展开更多
AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of to...AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of tobacco （Nicotiana tabacum cv. SR1）, to investigate the transgene expression and pE2 accumulation in plastids, and to evaluate the antigenic effect of the plastid-derived pE2 in mice. METHODS： Plastid-targeting vector pRB94-E2 containing the E2 fragment driven by rice psbA promoter was constructed. Upon delivery into tobacco plastids, this construct could initiate homologous recombination in psaB-trnfM and trnG-psbC fragments in plastid genome, and result in transgene inserted between the two fragments. The pRB94-E2 was delivered with a biolistic particle bombardment method, and the plastid-transformed plants were obtained following the regeneration of the bombarded leaf tissues on a spectinomycin-supplemented medium. Transplastomic status of the regenerated plants was confirmed by PCR and Southern blot analysis, transgene expression was investigated by Northern blot analysis, and accumulation of pE2 was measured by ELISA. Furthermore, protein extracts were used to immunize mice, and the presence of the pE2-reactive antibodies in serum samples of the immunized mice was studied by ELISA. RESULTS： Transplastomic lines confirmed by PCR and Southern blot analysis could actively transcribe the E2 mRNA. The pE2 polypeptide was accumulated to a level as high as 13.27 μg/g fresh leaves. The pE2 could stimulate the immunized mice to generate pE2-specific antibodies. CONCLUSION： HEV-E2 fragment can be inserted into the plastid genome and the recombinant pE2 antigen derived is antigenic in mice. Hence, plastids may be a novel source for cost-effective production of HEV vaccines.展开更多
The study aimed to describe the epidemiological,virological and clinical features of sporadic HEV infection in eastern China.A total of 6112 patient sera were tested for anti-HEV IgG or anti-HEV IgM during one consecu...The study aimed to describe the epidemiological,virological and clinical features of sporadic HEV infection in eastern China.A total of 6112 patient sera were tested for anti-HEV IgG or anti-HEV IgM during one consecutive year(between August 2018 and July 2019).HEV RNA presence was evaluated by RT-PCR and HEV sequences were phylogenetically analyzed.Clinical features of confirmed HEV-infected patients were delineated.The sero-positivity rate of anti-HEV IgG maintained stable around 40%,while an obvious winter spike of anti-HEV IgM prevalence was observed.A total of 111 patients were confirmed of HEV viremia by molecular diagnosis.Subtype 4d was predominant.Phylogenetic analyses suggest that certain strains circulate across species and around the country.Subjects with confirmed current HEV infection had a high median age(58 years)and males were predominant(62.2%).Most patients presented with jaundice(75.7%)and anorexia(68.0%).Significantly elevated levels of liver enzymes and bilirubin were observed.Remarkably,the baseline bilirubin level was positively correlated with illness severity.Pre-existing HBV carriage may deteriorate illness.The clinical burden caused by locally acquired HEV infection is increasing.Surveillance should be enforced especially during the transition period from winter to spring.Patients with higher level of bilirubin at disease onset had slower recovery from HEV infection.展开更多
基金supported by a Borden Scholars awardDuke Claude D.Pepper Older Americans Independence Center Pilot Award(P30AG028716)by the NIH/NIA(R01AG081393)。
文摘Advanced age impairs bone fracture healing;the underlying mechanism of this phenomenon remains unknown.We determined that apolipoprotein E(ApoE)increases with age and causes poor fracture healing.After deletion of hepatic ApoE expression(ΔApoE),24-month-oldΔApoE mice displayed a 95%reduction in circulating ApoE levels and significantly improved fracture healing.ApoE treatment of aged BMSCs inhibited osteoblast differentiation in tissue culture models;RNA-seq,Western blot,immunofluorescence,and RT-PCR analyses indicated that the Wnt/β-catenin pathway is the target of this inhibition.Indeed,we showed that ApoE had no effect on cultures with stabilizedβ-catenin levels.Next,we determined that Lrp4 serves as the osteoblast cell surface receptor to ApoE,as expression of Lrp4 is required in ApoE-based inhibition of Wnt/β-catenin signaling and osteoblast differentiation.Importantly,we validated this ApoE-Lrp4-Wnt/β-catenin molecular mechanism in human osteoblast differentiation.Finally,we identified an ApoE-neutralizing antibody(NAb)and used it to treat aged,wildtype mice 3 days after fracture surgery resulting in fracture calluses with 35%more bone deposition.Our work here identifies novel liver-to-bone cross-talk and a noninvasive,translatable therapeutic intervention for aged bone regeneration.
文摘BACKGROUND Genetic disorders affecting hepatobiliary transporters can be triggered by various factors,resulting in marked cholestasis.CASE SUMMARY We report two patients who experienced a severe episode of intrahepatic cholestasis triggered by an acute hepatitis E virus infection.Following an extensive clinical examination that ruled out common causes of cholestatic liver damage,we conducted next-generation sequencing to determine the genetic profiles of the patients.The analysis revealed several known and unknown variants in genes associated with hepatobiliary transporters and bile salt regulation,including ATP8B1,ABCB11,ABCB4,MYO5B,and FXR.For a comprehensive understanding of the pathophysiology,we performed ClinVar analysis and utilized PolyPhen for bioinformatic prediction of functional impact.Both patients exhibited rapid symptom improvement and a decrease in hyperbilirubinemia when treated with either rifampicin or bezafibrate.CONCLUSION Our findings introduce hepatitis E viral infection as a novel trigger for intrahepatic cholestasis,and we categorize the significance of the various genetic variants based on the current state of research.
文摘BACKGROUND Many causal factors influence acute liver failure(ALF),including the primary underlying cause,age,and socioeconomic conditions.ALF outcomes depend on etiology,coagulopathy,bilirubin,age,and understanding of hepatic encephalopathy(HE),and help us predict coma and death.AIM To evaluate the association between etiologies,clinical manifestations,and outcomes of adults admitted with ALF.METHODS This institution-based,prospective cross-sectional study was conducted in the Department of Gastroenterology and Hepatology at Jinnah Postgraduate Medical Center,Karachi,from July 2019 to December 2022.A total of 102 patients diagnosed with ALF were included using consecutive sampling and data were collected from patients who visited Jinnah Postgraduate Medical Center,Karachi,the gastroenterology and hepatology department,entered into Microsoft Excel,and analyzed using Statistical Package for the Social Sciences version 26.0.Diagnosis was based on King’s College criteria:Age,encephalopathy grade,bilirubin,prothrombin time,international normalized ratio,creatinine,and etiology.We assessed the association between socioeconomic status and various outcomes using chi-square tests with a level of significance was less than 0.05.RESULTS Mean age of the ALF cohort was 27.37±6.60 years.Of the 102 patients,71(69.6%)were female,including 55(77.5%)pregnant women with a mean gestational age of 34.56±3.80 weeks.Regarding HE severity,45(44.1%)had grade III,and 13(12.7%)had grade II.Among the patients admitted to the intensive care unit,51(72.9%)did not survive,while 14(43.8%)recovered.CONCLUSION This study observed a high mortality rate among ALF patients in a tertiary care hospital.Hepatitis E virus infection,HE severity,and sepsis were significantly associated with higher mortality.
文摘BACKGROUND: Fulminant hepatic failure (FHF) is not uncommon in our clinical practice in Bangladesh. There was a rise in acute hepatitis E virus (HEV) in Bangladesh after the 2004 floods. At that time, most of the country was under water for more than a month, leading to sewage contamination of the water supply. The aim of this study was to investigate the etiology of FHF in Bangladesh. METHODS: In this retrospective study, 23 patients with FHF who presented with severe impairment of hepato- cellular function (i.e. encephalopathy, coagulopathy and jaundice) within 6 months of onset of symptoms were included. There were 17 men and 6 women, aged from 18 to 32 years. Four of the women were pregnant. Patients were tested for markers for common hepatotrophic viruses. A relevant history was taken and the Patient Record Book of the Unit was reviewed. RESULTS: 56.52% patients (13/23) had HEV infection, and all were anti-HEV IgM-positive tested by ELISA. HBV infection was detected in 34.78% patients (8/23), all of whom were tested positive for either HBsAg or anti-HBs IgM by ELISA. 8.7% patients (2/23) had a positive history for intake of alcohol and/or drugs. CONCLUSIONS: Acute HEV infection is the leading cause of FHF in Bangladesh. Sewage contamination of the water supply following floods contributes to a higher incidence of HEV infection. HBV infection is also important.
文摘BACKGROUND For decades,hepatitis A virus(HAV)has been a leading cause of acute hepatitis among children and was less prevalent among adults.However,recently a paradigm shift has been observed in the epidemiology of HAV,as evident by cases of acute hepatitis due to HAV among adults.AIM To estimate frequency of HAV in acute viral hepatitis and compare characteristics in HAV and hepatitis E virus(HEV)infection.METHODS This was a trend analysis conducted at Aga Khan University Hospital Karachi(Sindh,Pakistan)from February 2024 to May 2024.Individuals aged 18 years and older diagnosed with acute viral hepatitis attributed to hepatotropic viruses in 2024 were reviewed.To compare the trend patients admitted with acute hepatitis during 2019-2023 were also reviewed.Data regarding clinical and laboratory parameters were recorded.The yearly trend of acute hepatitis due to HAV and HEV was analyzed,and comparative analysis was done between HAV and HEV cases among adults.RESULTS A total of 396 patients were found to have acute hepatitis during our study duration.HAV was diagnosed in 234 patients(59%)while 157 patients(39.6%)were found to have acute HEV infection.Additionally,acute hepatitis B virus infection was identified in 3 patients(0.7%),whereas acute hepatitis C virus infection was found in 2(0.5%)cases of acute hepatitis.Yearly trends showed increasing occurrence of HAV infection among adults over last 5 years.The patients with acute HAV were younger than patients with HEV(28 years±8 years vs 30 years±8 years;P<0.01).Higher levels of total bilirubin were seen in HEV infection,while higher levels of alanine transaminase were seen in HAV infection.However,a higher proportion of acute liver failure(ALF),coagulopathy,and mortality were observed in HEV.CONCLUSION An increase in acute hepatitis A cases among adults shows less severity than hepatitis E,highlighting the need for better sanitation,hygiene,and adult hepatitis A vaccination programs.
文摘Hepatitis E virus(HEV)represents a significant global cause of acute viral hepatitis.Annually,it is estimated to cause approximately 20.1 million infections worldwide,3.3 million of which result in symptomatic illness.In developing regions,genotypes HEV-1 and HEV-2 are the primary strains responsible for widespread outbreaks and epidemics of acute jaundice(icteric hepatitis),transmitted predominantly through the fecal-oral route via contaminated water and food(Devarbhavi et al.,2023).
基金supported by a grant from the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(2019ZB101)。
文摘Hepatitis E virus(HEV)is the primary cause of acute viral hepatitis globally and is prevalent in many developing countries.Serological epidemiology studies[1,2]suggest that approximately onethird of the global population has been infected with HEV.There are an estimated 20 million new cases of HEV infection worldwide annually.World Health Organization(WHO)reported that HEV caused approximately 44000 deaths in 2015,which accounted for3.3%of deaths from viral hepatitis[3,4].Clinically,most cases of acute hepatitis E have a self-limiting course.However,co-infection with other viruses can increase the risk of acute or subacute liver failure.Hepatitis B virus(HBV)and HEV are highly prevalent in many regions worldwide,and these areas have high rates of coinfection with both viruses.The rate of co-infection with HEV among patients with chronic hepatitis B(CHB)is high,resulting in more severe health outcomes and a significantly elevated risk of liver failure and death.
基金supported by grants from the National Natural Science Foundation of China(82272396)Gusu Health Project of Suzhou(GSWS2022076 and GSWS2023004)。
文摘Background:Hepatitis E virus(HEV)may induce acute self-limiting illnesses or persistent infections.Chronic hepatitis E frequently occurs in immunocompromised persons,including organ transplant recipients,HIV-positive patients,and those with hematological malignancies.It poses a risk of liver fibrosis and cirrhosis.Data sources:Relevant articles published till September 2024 were located using Pub Med searches.The further search terms utilized were:“immunocompromised”,“solid organ transplant”,“HIV”,“hematological malignancy”,and“hepatitis E virus”.A manual search of references from pivotal articles extended further publications.The search parameters encompass publications in English.Results:The epidemiology,clinical manifestations,diagnostic measures,and therapeutic modalities of chronic hepatitis E were discussed.Immunocompromised individuals who are infected with HEV are at an increased risk of developing chronic infections,which may progress to liver fibrosis and cirrhosis.Current understanding of HEV is still limited,and there is no medicine that specifically targets hepatitis E.Consequently,the prevention and management of hepatitis E continue to present a significant challenge.Conclusions:Chronic hepatitis E patients need special attention in clinical practice.The relevant risk factors must be identified to facilitate accurate diagnosis and the implementation of more effective preventive measures,thereby enhancing the monitoring,treatment,and prevention of immunocompromised individuals.
基金supported by the National Natural Science Foundation of China (U2002218,81874274)Yunnan Health Training Project of High Level Talents (L-2017027)+3 种基金Project of Cross-border Control and Quarantine Innovation Group of Zoonosis of Dali University (ZKPY2019302)to Y.Z.ZOpen Project of Yunnan Key Laboratory of Biodiversity Information (BIKF22-02)Youth Innovation Promotion Association of the Chinese Academy of SciencesYunnan Revitalization Talent Support Program Young Talent Project to X.L.Y。
文摘The family Hepeviridae has seen an explosive expansion in its host range in recent years,yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown.The emergence of rat hepatitis E virus(HEV)has introduced a new public health threat due to its potential for zoonotic transmission.This study investigated2?464 wild small mammals spanning four animal orders,eight families,21 genera,and 37 species in Yunnan Province,China.Using broadly reactive reverse transcription-polymerase chain reaction(RT-PCR),we systematically screened the presence and prevalence of Orthohepevirus and identified 192 positive specimens from10 species,corresponding to an overall detection rate of7.79%.Next-generation sequencing enabled the recovery of 24 full-length genomic sequences from eight host species,including Bandicota bengalensis,Eothenomys eleusis,and Episoriculus caudatus,representing newly reported host species for Orthohepevirus strains.Phylogenetic and sequence analyses revealed extensive genetic diversity within orthohepeviruses infecting rodents and shrews.Notably,among the identified strains,20 were classified as Rocahepevirus ratti C1,two as C3,and one as Rocahepevirus eothenomi,while the remaining strain exhibited significant divergence,precluding classification.Evolutionary analyses highlighted close associations between orthohepeviruses and their respective host taxa,with distinct phylogenetic clustering patterns observed across different host orders.These findings emphasize the critical roles of co-speciation and cross-species transmission in shaping the evolutionary trajectories of the genera Paslahepevirus and Rocahepevirus.
基金Supported by the Japan Agency for Medical Research and Development(AMED),No.JP24fk0210132(Kanda T,Sasaki-Tanaka R and Terai S)the JSPS KAKENHI,No.JP23K15055(Sasaki-Tanaka R).
文摘Hepatitis E virus(HEV)infection causes acute hepatitis,chronic hepatitis,particularly in compromised hosts,and various extrahepatic manifestations.HEV infection is reportedly associated with biliary-pancreatic diseases,such as gallstones,cholangitis,choledocholithiasis,and acute pancreatitis.Severe jaundice and prolonged cholestasis are also atypical manifestations of HEV infection.The mechanism and genes involved in cholestasis,namely sinusoidal uptake of blood,bile salt synthesis and secretion from hepatocytes to the canaliculus,have been elucidated.HEV infection triggers severe jaundice and prolonged cholestasis in patients with genetic variants in adenosine triphosphatase phospholipid transporting 8B1,adenosine triphosphate-binding cassette(ABC)protein B4,ABCB11,Myosin VB,and/or farnesoid X receptor(FXR/NR1H4).Although prolonged cholestasis associated with these gene mutations does not seem to be specific to HEV infection,these mutations may be risk factors related to the severity of HEV infection.The use of the pregnane X receptor agonist rifampicin and the peroxisome proliferator-activated receptor activator bezafibrate may be useful for the treatment of cholestasis.These studies provide new insights into under-standing the mechanisms of severe jaundice and prolonged cholestasis caused by HEV infection.
基金supported by grants from the National Nat-ural Science Foundation of China(82272396)Suzhou Med-ical and Health Science and Technology Innovation Project(SKY2022057)。
文摘Background:Despite the insights into the role of aldehyde dehydrogenase 1 family member A1(ALDH1A1)in various liver diseases,the expression and its prognostic significance in patients with hepatitis E virus-related acute liver failure(HEV-ALF)remain unclear.This study delved into the assessment of serum exosome-derived ALDH1A1 expression and its prognostic implications for HEV-ALF patients.Methods:Between January 2018 and December 2023,a total of 226 individuals with acute hepatitis E(AHE)and 210 patients with HEV-ALF were recruited from member units of Chinese Consortium for the Study of Hepatitis E.According to the number of organ failure,we categorized 210 HEV-ALF patients into three groups:two organs failure(n=131),three organs failure(n=46),and more than three organs failure(n=33).In addition,200 health controls from Suzhou Municipal Hospital were included.Results:The levels of serum exosome-derived ALDH1A1 in HEV-ALF patients were significantly higher than those in AHE patients and health controls(both P<0.05).Furthermore,the levels of serum exosome-derived ALDH1A1 were the highest in more than three organs failure group,followed by three organs failure group and two organs failure group(all P<0.001).Moreover,serum exosome-derived ALDH1A1 was positively correlated with total bilirubin in HEV-ALF patients(r=0.315,P<0.001).The comparisons of serum exosome-derived ALDH1A1 levels in treatment response showed that serum exosome-derived ALDH1A1 levels were decreased in the improvement group,while increased in the fluctuation and deterioration groups(all P<0.001).Moreover,serum exosome-derived ALDH1A1 was an independent risk factor for predicting the 30-day mortality(P<0.001).Furthermore,the area under the receiver operating characteristic curve was 0.943,with the sensitivity of 94.87%and specificity of 87.72%,indicating the robust decision-making ability.However,no significant differences were found in serum exosome-derived ALDH1A1 levels between patients aged<60 and≥60 years old(P=0.131).Conclusions:Serum exosome-derived ALDH1A1 can greatly predict the prognosis of HEV-ALF patients.
文摘The hepatitis E virus(HEV)is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s.Globally,it is one of the most frequent causes of acute viral hepatitis.The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus.Among the eight different genotypes identified to date,HEV genotype 1(HEV1),HEV2,HEV3,and HEV4 are the most frequent genotypes causing infections in humans.HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies.They are also responsible for severe hepatitis in pregnant patients and infants.In contrast,HEV3 and HEV4 are zoonotic,and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals.Their main reservoir is the pig,and they are mostly encountered in developed countries.The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women,infants,older people,immunocompromised individuals,patients with underlying chronic liver diseases,and workers that come into close contact with HEV-infected animals.In the clinical perspective,HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis,acute-on-chronic liver disease,chronic hepatitis,cirrhosis,and liver failure.Although HEV mainly results in acute selflimiting infection,chronic HEV infection may occur among immunocompromised patients(e.g.,solid-organ transplant recipients).Additionally,HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade,although the causal link for many of them still needs to be proven.Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success.However,ribavirin is contraindicated in pregnant patients,and interferon-alpha cannot be used in most transplant recipients.Therefore,there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirinresistant HEV.In this review article,a literature search using PubMed and MEDLINE databases was performed,up to March 2020.Only the articles published in English were reviewed.
基金Supported by the Key-Subject Construction Project of Ministry of Public Health of China,No.97030223the young researcher grant from Children's Hospital of Fudan University,No.QN2001-5 Co-first-authors: Jian-She Wang and Hui Chen
文摘AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.
文摘Chronic hepatitis B(CHB)is a condition of globalprevalence and its sequelae include cirrhosis and hepatocellular carcinoma.The natural history of CHB isa complex interplay of virological,environmental andhost factors.The dynamic relationship between thevirus and host evolves over the duration of the infection and different phases of the disease have been observed and described.These have been conceptualizedin terms of the state of balance between the host immune system and the hepatitis B virus and have beengiven the labels immune tolerant,immune clearance,immune control and immune escape although othernomenclature is also used.Host factors,such as age atinfection,determine progression to chronicity.Virological factors including hepatitis B viral load,mutationsand genotype also have an impact on the adverseoutcomes of the infection,as do hepatotoxic cofactorssuch as alcohol.Our understanding of the natural history of CHB has evolved significantly over the past fewdecades and characterizing the phase of disease ofCHB remains an integral part of managing this virus in the clinic.
文摘Each hepatitis virus—Hepatitis A,B,C,D,E,and G—poses a distinct scenario to the patient and clinician alike.Since the discovery of each virus,extensive knowledge regarding epidemiology,virologic properties,and the natural clinical and immunologic history of acute and chronic infections has been generated.Basic discoveries about host immunologic responses to acute and chronic viral infections,combined with virologic data,has led to vaccines to prevent Hepatitis A,B,and E and highly efficacious antivirals for Hepatitis B and C.These therapeutic breakthroughs are transforming the fields of hepatology,transplant medicine in general,and public and global health.Most notably,there is even an ambitious global effort to eliminate chronic viral hepatitis within the next decade.While attainable,there are many barriers to this goal that are being actively investigated in basic and clinical labs on the local,national,and international scales.Herein,we discuss pertinent clinical information and recent organizational guidelines for each of the individual hepatitis viruses while also synthesizing this information with the latest research to focus on exciting future directions for each virus.
文摘Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent years,there are still points of conflict concerning the pathogenesis,immune response,development of new and more effective vaccines,therapies,and treatment.This review focuses on the most important research topics that deal with issues that are currently being solved,those that remain to be solved,and future research directions.For hepatitis A virus we will address epidemiology,molecular surveillance,new susceptible populations as well as environmental and food detections.In the case of hepatitis B virus,we will discuss host factors related to disease,diagnosis,therapy,and vaccine improvement.On hepatitis C virus,we will focus on pathogenesis,immune response,direct action antivirals treatment in the context of solid organ transplantation,issues related to hepatocellular carcinoma development,direct action antivirals resistance due to selection of resistanceassociated variants,and vaccination.Regarding hepatitis D virus,we describe diagnostic methodology,pathogenesis,and therapy.Finally,for hepatitis E virus,we will address epidemiology(including new emerging species),diagnosis,clinical aspects,treatment,the development of a vaccine,and environmental surveillance.
文摘INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .
文摘AIM： To study the significance of serum anti-hepatitis E virus （HEV） IgA in patients with hepatitis E. METHODS： A new method was established to assay anti-HEY IgA, which could be detected in the middle phase of the infection. We compared anti-HEV IgA assay with anti-HEV IgM and anti-HEV IgG assay in sera from 60 patients with positive HEV-RNA. RESULTS： The 60 patients with positive HEV-RNA had both anti-HEV IgA and anti-HEV IgM and 410 patients with negative HEV-RNA were used as control. Periodic serum samples obtained from 60 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, anti-HEV IgA and anti-HEV IgG. Their HEV-RNA was detectable in the serum until 20 ±11 d. We used anti-HEV IgM and anti-HEV IgA assay to detect HEV infection and positive results were found in 90 ± 15 d and 120 ±23 d respectively, the positive rate of anti-HEV IgA was higher than that of anti-HEV IgM and HEV-RNA （P 〈0.05）. CONCLUSION： The duration of anti-HEV IgA in serum is longer than that of anti-HEV IgM, and anti-HEV IgA assay is a good method to detect HEV infection.
基金Supported by a grant from the Hong Kong Research Grant Council, No. 7342/03M to YX Zhou and E Lam
文摘AIM： To cost-effectively express the 23-ku pE2, the most promising subunit vaccine encoded by the E2 fragment comprising of the 3＇-portion of hepatitis E virus （HEV） open reading frame 2 （ORF2） in plastids of tobacco （Nicotiana tabacum cv. SR1）, to investigate the transgene expression and pE2 accumulation in plastids, and to evaluate the antigenic effect of the plastid-derived pE2 in mice. METHODS： Plastid-targeting vector pRB94-E2 containing the E2 fragment driven by rice psbA promoter was constructed. Upon delivery into tobacco plastids, this construct could initiate homologous recombination in psaB-trnfM and trnG-psbC fragments in plastid genome, and result in transgene inserted between the two fragments. The pRB94-E2 was delivered with a biolistic particle bombardment method, and the plastid-transformed plants were obtained following the regeneration of the bombarded leaf tissues on a spectinomycin-supplemented medium. Transplastomic status of the regenerated plants was confirmed by PCR and Southern blot analysis, transgene expression was investigated by Northern blot analysis, and accumulation of pE2 was measured by ELISA. Furthermore, protein extracts were used to immunize mice, and the presence of the pE2-reactive antibodies in serum samples of the immunized mice was studied by ELISA. RESULTS： Transplastomic lines confirmed by PCR and Southern blot analysis could actively transcribe the E2 mRNA. The pE2 polypeptide was accumulated to a level as high as 13.27 μg/g fresh leaves. The pE2 could stimulate the immunized mice to generate pE2-specific antibodies. CONCLUSION： HEV-E2 fragment can be inserted into the plastid genome and the recombinant pE2 antigen derived is antigenic in mice. Hence, plastids may be a novel source for cost-effective production of HEV vaccines.
基金This study was funded by grants from the National Natural Science Foundation of China(No.81501733)the Shanghai Municipal Key Clinical Specialty(shslczdzk01103)Key Projects in the National Science&Technology Pillar Program during the Thirteenth Five-year Plan Period(2017ZX10203201-008,2018ZX09201016-003-001,2017ZX10202202-005-004).
文摘The study aimed to describe the epidemiological,virological and clinical features of sporadic HEV infection in eastern China.A total of 6112 patient sera were tested for anti-HEV IgG or anti-HEV IgM during one consecutive year(between August 2018 and July 2019).HEV RNA presence was evaluated by RT-PCR and HEV sequences were phylogenetically analyzed.Clinical features of confirmed HEV-infected patients were delineated.The sero-positivity rate of anti-HEV IgG maintained stable around 40%,while an obvious winter spike of anti-HEV IgM prevalence was observed.A total of 111 patients were confirmed of HEV viremia by molecular diagnosis.Subtype 4d was predominant.Phylogenetic analyses suggest that certain strains circulate across species and around the country.Subjects with confirmed current HEV infection had a high median age(58 years)and males were predominant(62.2%).Most patients presented with jaundice(75.7%)and anorexia(68.0%).Significantly elevated levels of liver enzymes and bilirubin were observed.Remarkably,the baseline bilirubin level was positively correlated with illness severity.Pre-existing HBV carriage may deteriorate illness.The clinical burden caused by locally acquired HEV infection is increasing.Surveillance should be enforced especially during the transition period from winter to spring.Patients with higher level of bilirubin at disease onset had slower recovery from HEV infection.
