Hepatitis A virus-associated acute acalculous cholecystitis in an adult-onset Still’s disease patient:A case report and review of the literature

BACKGROUND Acute acalculous cholecystitis(AAC)is inflammation of the gallbladder without evidence of calculi.Although rarely reported,its etiologies include hepatitis virus infection(e.g.,hepatitis A virus,HAV)and adult-onset Still’s disease(AOSD).There are no reports of HAV-associated AAC in an AOSD patient.CASE SUMMARY Here we report a rare case of HAV infection-associated AAC in a 39-year-old woman who had a history of AOSD.The patient presented with an acute abdomen and hypotension.Elevated hepatobiliary enzymes and a thickened and distended gallbladder without gallstones on ultrasonography suggested AAC,but there were no signs of anemia nor thrombocytopenia.Serological screening revealed anti-HAV IgM antibodies.Steroid treatment did not alleviate her symptoms,and she was referred for laparoscopic cholecystectomy.The resected gallbladder was hydropic without perforation,and her clinical signs gradually improved after surgery.CONCLUSION AAC can be caused by HAV in AOSD patients.It is crucial to search for the underlying etiology for AAC,especially uncommon viral causes.

Seroepidemiology of hepatitis A virus in Kuwait

AIM: To fi nd the current seroepidemiology of hepatitis A virus (HAV) in Kuwait.METHODS: A total of 2851 Kuwaitis applying for new jobs were screened.RESULTS: HAV-positive cases were 28.8%; 59% were males and 41% were females. The highest prevalence was in the Ahmadi area. High prevalence was among the group of non-educated rather than educated parents. This is the fi rst study in Kuwait demonstrating the shifting epidemiology of HAV.CONCLUSION: This study reflects the need of the Kuwaiti population for an HAV vaccine.

Genetic Variation of the VP1 Gene of the Virulent Duck Hepatitis A Virus Type 1(DHAV-1) Isolates in Shandong Province of China

To investigate the relationship of the variation of virulence and the external capsid proteins of the pandemic duck hepatitis A virus type 1(DHAV-1) isolates,the virulence,cross neutralization assays and the complete sequence of the virion protein 1(VP1) gene of nine virulent DHAV-1 strains,which were isolated from infected ducklings with clinical symptoms in Shandong province of China in 2007-2008,were tested.The fifth generation duck embryo allantoic liquids of the 9 isolates were tested on 12-day-old duck embryos and on 7-day-old ducklings for the median embryonal lethal doses(ELD 50 s) and the median lethal doses(LD 50 s),respectively.The results showed that the ELD 50 s of embryonic duck eggs of the 9 DHAV-1 isolates were between 1.9 × 10 6 /mL to 1.44 × 10 7 /mL,while the LD 50 s were 2.39 × 10 5 /mL to 6.15 × 10 6 /mL.Cross-neutralization tests revealed that the 9 DHAV-1 isolates were completely neutralized by the standard serum and the hyperimmune sera against the 9 DHAV-1 isolates,respectively.Compared with other virulent,moderate virulent,attenuated vaccine and mild strains,the VP1 genes of the 9 strains shared 89.8%-99.7% similarity at the nucleotide level and 92.4%-99.6% at amino acid level with other DHAV-1 strains.There were three hypervariable regions at the C-terminus(aa 158-160,180-193 and 205-219) and other variable points in VP1 protein,but which didn't cause virulence of DHAV-1 change.

False positive anti-hepatitis A virus immunoglobulin M in autoimmune hepatitis/primary biliary cholangitis overlap syndrome:A case report

BACKGROUND Autoimmune hepatitis(AIH)is an immune-mediated liver disease affecting all age groups.Associations between hepatitis A virus(HAV)and AIH have been described for many years.Herein,we report a case of an AIH/primary biliary cholangitis(PBC)overlap syndrome with anti-HAV immunoglobulin M(IgM)false positivity.CASE SUMMARY A 55-year-old man was admitted with manifestations of anorexia and jaundice along with weakness.He had marked transaminitis and hyperbilirubinemia.Viral serology was positive for HAV IgM and negative for others.Autoantibody screening was positive for anti-mitochondria antibody but negative for others.Abdominal ultrasound imaging was normal.He was diagnosed with acute hepatitis A.After symptomatic treatment,liver function tests gradually recovered.Several months later,his anti-HAV IgM positivity persisted and transaminase and bilirubin levels were also more than 10 times above of the upper limit of normal.Liver histology was prominent,and HAV RNA was negative.Therefore,AIH/primary biliary cholangitis(PBC)overlap syndrome diagnosis was made based on the“Paris Criteria”.The patient was successfully treated by immunosuppression.CONCLUSION This case highlights that autoimmune diseases or chronic or acute infections,may cause a false-positive anti-HAV IgM result because of cross-reacting antibodies.Therefore,the detection of IgM should not be the only method for the diagnosis of acute HAV infection.HAV nucleic acid amplification tests should be employed to confirm the diagnosis.

Hepatitis A Virus PCR Analysis and <i>E. coli</i>Detection in Oysters at Oualidia Lagoon and Their Correlation

The present study aims to evaluate hepatitis A virus (HAV) prevalence and faecal contamination indicators Escherichia coli (E. coli) in oysters from Oualidia lagoon (Moroccan Atlantic coast) and to study the correlation between the two parameters. The survey was carried out on 87 samples of oysters (Crassostrea gigas) collected monthly between November 2015 and February 2017 from three sites corresponding to different oyster farms in the lagoon. Sanitary status of bivalve molluscs was assessed by E. coli enumeration using ISO 16649-3. Detection of hepatitis A virus, was carried out by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) according to ISO 15216-2 method. The prevalence of samples for which E. coli contamination exceeds the threshold of 230 E. coli/100g of flesh and intravalvular fluid (FIF) is 43%. HAV RNA was detected in 2% of the samples analyzed. This RNA was even detected in a sample meeting the bacterial criteria. Viral health surveillance of bivalve molluscs is therefore necessary before their delivery for human consumption.

Artificial intelligence and machine learning could support drug development for hepatitis A virus internal ribosomal entry sites

Hepatitis A virus(HAV)infection is still an important health issue worldwide.Although several effective HAV vaccines are available,it is difficult to perform universal vaccination in certain countries.Therefore,it may be better to develop antivirals against HAV for the prevention of severe hepatitis A.We found that several drugs potentially inhibit HAV internal ribosomal entry site-dependent translation and HAV replication.Artificial intelligence and machine learning could also support screening of anti-HAV drugs,using drug repositioning and drug rescue approaches.

Molecular evolution of hepatitis A virus in a human diploid cell line

AIM： To investigate the hoLspoLs, direction, and the time course of evolution of hepatitis A virus in the process of consecutive cell culture passage in human KMB17 diploid cells.METHODS： Wild type hepatitis A virus H2w was serially propagated in KMB17 cells until passage 30, and the fulllength genomes of H2w and its six chosen progenies were determined by directly sequencing RT-PCR products amplified from viral genomic RNA. Alignment comparison of sequences from H2w with its six progenies and phylogenetic analysis of the whole VP1 region from H2w, progenies of H2w, and other cell culture adapted hepatitis A virus were then carried out to obtain data on the molecular evolution of hepatitis A virus in the process of consecutive passage in KMB17 cells.RESULTS： Most of the mutations occurred by passage 5 and several hotspots related to adaptation of the virus during cell growth were observed. After that stage, few additional mutations occurred through the remaining duration of passage in KMB17 cells except for mutation in the virulence determinants, which occurred in the vicinity of passage 15. The phylogenetic analysis of the whole VP1 region suggested that the progenies of H2w evolved closely to other cell culture adapted hepatitis A virus, i.e. MBB, L-A-l, other than its progenitor H2w.CONCLUSION： Hepatitis A virus served as a useful model for studying molecular evolution of viruses in a given environment. The information obtained in this study may provide assistance in cultivating the next generation of a seed virus for live hepatitis A vaccine production.

Current perspectives of viral hepatitis

Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.

Genetic analysis of wild-type hepatitis A virus strains

Objective To clarify the distribution of hepatitis A virus (HAV) genotype in geographical regions of China Methods Seventeen representative HAV strains were isolated from the stool or serum of hepatitis A patients in different geographical regions Viral RNA was recovered from stool or serum by proteinase K digestion and phenol chloroform extraction, followed by ethanol precipitation prior to reverse transcription and polymerase chain reaction (RT PCR) amplification The nucleotide sequences of VP1/2A junction region were tested by using a direct sequencing technique Results A pairwise comparison of sequences within 168 bases at the VP1/2A junction revealed that all the sequences clustered within genotype Ⅰ About 53% of strains clustered in genotype ⅠB, with less than 6% variability; while the others clustered in genotype ⅠA, with less than 5 3% variability Sequence homology between genotype ⅠA and ⅠB varied from 88 7% to 92 3% Conclusion Epidemic or sporadic HAV strains in China may belong to HAV genotype ⅠA or ⅠB Epidemiologically related strains may be identical or closely related in sequence

Animal models for the study of hepatitis C virus infection and replication

Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates. Recent work has focused modification of animals to permit HCV entry, replication and transmission. In this review, we highlight the currently available models for the study of HCV including chimpanzees, tupaia, mouse and rat models. Discussion will include methods of model design as well as the advantages and disadvantages of each model. Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies. Research within animal models is critically important to establish a complete understanding of HCV infection, which will ultimately form the basis for future treatments and prevention of disease.

Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of patients.The remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the illness.Nearly a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular carcinoma.The indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity levels.The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

The infectivity and pathogenicity of hepatitis A virus live-attenuated vaccine strain H2 in type I interferon receptor-deficient mice

Hepatitis A virus(HAV)live-attenuated vaccine H2 strain has been approved for clinical use for decades with ideal safety profiles in nonhuman primate models and humans.Recently,type Ⅰ interferon(IFN)receptor-deficient mice were shown to be susceptible to HAV infection.Herein,we sought to determine the infection and replication dynamics of the H2 in Ifnar^(-/-)mice that lack type Ⅰ IFN receptor.Following intravenous injection,the H2 failed to cause obvious clinical symptoms in Ifnar^(-/-)mice,and no significant upregulation in serum alanine aminotransferase(ALT)levels was observed.Notably,the histopathological examination showed that there were significant focal infiltrations of lymphocytes and neutrophils in the portal area,but no focal necrosis was observed in liver tissues.Viral RNAs sustained in the liver,and the infectious virus could be recovered from the liver tissue until 42 days post-infection.More importantly,H2 infection induced obvious viremia and persistent viral shedding in feces.In addition,robust HAV-specific humoral immune responses were induced in Ifnar^(-/-)mice.Overall,our study revealed the safety profile of H2 in Ifnar^(-/-)mice,which not only helps understand the attenuation mechanism of H2,but also expands the application of the Ifnar^(-/-)mouse model for HAV studies.

Comparison of concentration methods for detection of hepatitis A virus in water samples

Hepatitis A virus is a pathogen associated with water pollution.Contaminated drinking water can cause hepatitis A outbreaks,lead to economic losses,and even threaten human lives.It is difficult to detect low levels of hepatitis A virus in water,so the virus must be concentrated in order to quantify it accurately.Here,we present a simple,rapid,efficient technique for the concentration and detection of hepatitis A virus in water.Our data showed that adding phosphate-buffered saline to the water,pre-filtering the water,and adding Trizol reagent directly to the filtration membrane can significantly improve concentration efficiency.Of three types of filtration membranes studied(mixed cellulose ester membrane,polyvinylidene fluoride membrane,and nylon membrane),the concentration efficiency using mixed cellulose ester membrane with a 0.1-μm pore size was the highest,reaching 92.62 ± 5.17%.This method was used to concentrate hepatitis A virus in water samples from Donghu Lake.Using SYBR Green real-time reverse transcription polymerase chain reaction analysis,the detection sensitivity of this method reached 10~1 copies/μL and its concentration efficiency reached 79.45 ± 9.88%.

Community-based cross-sectional seroprevalence study of hepatitis A in Bangladesh

AIM： TO elucidate the age-distribution of anti-hepatitis A virus （HAY） seroprevalence across different socioeconomic status （SES） categories in Bangladesh which, despite scarce data, is generally deemed to have high endemicity. METHODS： Blood samples of 818 subjects from a stratified samp#e of schools and hospitals, comprising different age categories and SES were collected. They were assayed for total anti-HAV antibodies. Social and medical history data were obtained using a questionnaire. RESULTS： Overall anti-HAV seroprevalence was 69.6%, increasing with age from 1-5 years （40.4%） to 〉 30 years （98.4%）. Seroprevalence was lowest （49.8%） in the high SES group and highest （96.5%） in the rural lower-middle SES group. Among subjects aged 6-20 years, anti-HAV seroprevalence was lowest in urban private school children （43.0%）, followed by urban government school children （76.2%） and rural school children （96.5%） （P 〈 0.01）. Within the high SESgroup, anti-HAV seroprevalence was 32.3% in subjects 〈 10 years and 51.7% in those aged 11-20 years. Until now Bangladesh has been deemed to have high endemicity for HAV. CONCLUSION： The transition from high to intermediate HAV endemicity may be underway; high SES adolescents and adults remain particularly at risk of symptomatic illness. Preventive measures need consideration.

Study on the in vitro activity of Hehuan Yin aqueous extract against hepatitis C 2a virus

Objective:To study the anti-HCV activity and mechanism of Hehuan Yin aqueous extract.Methods:Huh7.5.1 cells were used to establish the HCV2a virus infection model.Cell survival rate(%)and Renilla Luciferase Assay Kit(%)were calculated by Celltiter-GLO Assay for evaluating CC50,EC50 and SI values.To observe the drug resistance of the virus to different concentrations of Hehuan Yin within 72 hours by detecting luciferase activity,western-blot was used to detect the protein expression levels of NS5A,NS3 and NS5B.Results:the CC50,EC50 and SI of Hehuan Yin against HCV2a were 132.50g/ml,1.90g/ml and 67.90 respectively.The EC50 after 24h,48h and 72h administration were 18g/ml,5.8g/ml and 2.3g/ml respectively.Within the range of drug concentration,the aqueous extract Hehuan Yin had inhibitory effect on the expression of NS5A and NS5B proteins in a dose-effect relationship,but had no obvious effect on the expression of NS3 protein.Conclusion:The aqueous extract of Hehuan Yin may inhibit the replication of HCV2a virus by changing the protein expression levels of NS5A and NS5B,and the virus has no tolerance to the aqueous extract of Hehuan Yin.

Viral hepatitis update: Progress and perspectives

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.

Hepatitis A vaccine associated with autoimmune hepatitis

To describe a case of probable relapsing autoimmune hepatitis associated with vaccination against hepatitis A virus （HAV）. A case report and review of literature were written concerning autoimmune hepatitis in association with hepatitis A and other hepatotropic viruses. Soon a^er the administration of formalin-inactivated hepatitis A vaccine, a man who had recently recovered from an uncharacterized but self-limiting hepatitic illness, experienced a severe deterioration （AST 1687 U/L, INR 1.4）. Anti-nuclear antibodies were detectable, and liver biopsy was compatible with autoimmune hepatitis. The observation supports the role of HAV as a trigger of autoimmune hepatitis. Studies in helper T-cell activity and antibody expression against hepatic proteins in the context of hepatitis A infection are summarized, and the concept of molecular mimicry with regard to other forms of viral hepatitis and autoimmunity is briefly explored.

Update on the management and treatment of viral hepatitis

This review aims to summarize the current evidence on the treatment of viral hepatitis,focusing on its clinical management.Also,future treatment options and areas of potential research interest are detailed.PubMed and Scopus databases were searched for primary studies published within the last ten years.Keywords included hepatitis A virus,hepatitis B virus(HBV),hepatitis C virus,hepatitis D virus(HDV),hepatitis E virus,and treatment.Outcomes reported in the studies were summarized,tabulated,and synthesized.Significant advances in viral hepatitis treatment were accomplished,such as the advent of curative therapies for hepatitis C and the development and improvement of hepatitis A,hepatitis B,and hepatitis E vaccination.Drugs that cure hepatitis B,going beyond viral suppression,are so far unavailable;however,targeted antiviral drugs against HBV(immunomodulatory therapies and gene silencing technologies)are promising approaches to eradicating the virus.Ultimately,high vaccination coverage and large-scale test-and-treat programmes with high screening rates may eliminate viral hepatitis and mitigate their burden on health systems.The development of curative hepatitis C treatment renewed the enthusiasm for curing hepatitis B,albeit further investigation is required.Novel therapeutic options targeting HDV life cycle are currently under clinical investigation.

Innate and adaptive immune responses against picornaviruses and their counteractions: An overview

Picornaviruses, small positive-stranded RNA viruses, cause a wide range of diseases which is based on their differential tissue and cell type tropisms. This diversity is reflected by the immune responses, both innate and adaptive, induced after infection, and the subsequent interactions of the viruses with the immune system. The defense mechanisms of the host and the countermeasures of the virus significantly contribute to the pathogenesis of the infections. Important human pathogens are poliovirus, coxsackievirus, human rhinovirus and hepatitis A virus. These viruses are the beststudied members of the family, and in this review we want to present the major aspects of the reciprocal effects between the immune system and these viruses.

Hepatotropic viruses:Is Roma population at risk?

Roma people make up a significant ethnic minority in many European countries,with the vast majority living in Central and Eastern Europe.Roma are a vulnerable population group in social,economic,and political terms.Frequent migrations,life in segregated communities,substandard housing,poverty,and limited access to quality health care,including low immunization coverage,affect their health status and predispose them to various diseases,including viral hepatitis.Hepatitis A,B,and E are highly prevalent among Roma and mainly associated with low socioeconomic status.In contrast,hepatitis C does not seem to be more frequent in the Roma population.Enhanced efforts should be directed towards the implementation of screening programs,preventive measures,and treatment of viral hepatitis in Roma communities throughout Europe.