Hepatitis A Virus Isolates Research Articles

Male-Dominant Hepatitis A Outbreak Observed among Non-HIV-Infected Persons in the Northern Part of Tokyo, Japan.

Recently, we experienced an outbreak of acute hepatitis A virus (HAV) infection between 2018 and 2020. Herein, we describe this male-dominant HAV infection outbreak observed among non-human immunodeficiency virus (HIV)-infected persons in the northern part of Tokyo, Japan. Clinical information was collected from patient interviews and from medical record descriptions. In the present study, 21 patients were retrospectively analyzed. A total of 90.4 and 33.3% of patients were males, and men who have sex with men (MSM), respectively. The total bilirubin levels and platelet counts tended to be lower in the MSM group than in the non-MSM group. C-reactive protein (CRP) levels tended to be higher in acute liver failure (ALF) patients than in non-ALF patients. Prolonged cholestasis was observed in one patient (4.8%). We also found that 18 HAV isolates belonged to HAV subgenotype IA/subgroup 13 (S13), which clustered with the HAV isolate (KX151459) that was derived from an outbreak of HAV infection among MSM in Taiwan in 2015. Our results suggest that the application of antivirals against HAV, as well as HAV vaccines, would be useful for the treatment and prevention of severe HAV infection.

Monitoring of Foodborne Hepatitis A virus Outbreaks in the Fresh Foods

HEPATITIS A virus (HAV) is one of the most widespread foodborne pathogens and the cause of viral hepatitis. Fresh foods can be considered as a vector of transmission for HAV when contaminated by spoiled irrigation water or when prepared by infected food handlers. To improve microbiological detection and to increase insights into the contribution of fruit and vegetables to foodborne viral transmission, sensitive and standardized methods are needed. Two outlet drainage water samples from El-Mariotia and El-Gable Elasfar canals (Nile River) were collected in each month starting from March 2015 over a period of 12 months. As well as vegetables and fruit samples (lettuce, green onion and strawberry) were irrigated and washed with drainage water were also collected. Samples were extracted and concentrated for viral analysis. Strawberry and lettuce foods collected from El-Mariotia and lettuce from El-Gable Elasfar gave positive serological results by enzyme-linked immunosorbent assay (ELISA) test.Reverse transcription polymerase chain reaction (RT-PCR) was successfully used to detect the virus in strawberry and lettuce samples using HAV-specific primers, designed to amplify a 500 bp fragment covering VP1/2A gene in HAV. The VP1/2A gene was sequenced and the nucleotide sequence similarity was in the range of 95- 99.1% between HAV-Eg isolate and 30 HAV sequences retrieved from GenBank. Phylogenetic analysis revealed that HAV-Eg isolate was grouped into a clade comprising Egyptian HAV isolates sub-genotype IB. Phylogenetic tree of nucleotides sequence showed that HAV sub- genotype IB is the circulating strain.

Key Role of Sequencing to Trace Hepatitis A Viruses Circulating in Italy During a Large Multi-Country European Foodborne Outbreak in 2013.

BackgroundFoodborne Hepatitis A Virus (HAV) outbreaks are being recognized as an emerging public health problem in industrialized countries. In 2013 three foodborne HAV outbreaks occurred in Europe and one in USA. During the largest of the three European outbreaks, most cases occurred in Italy (>1,200 cases as of March 31, 2014). A national Task Force was established at the beginning of the outbreak by the Ministry of Health. Mixed frozen berries were early demonstrated to be the source of infection by the identity of viral sequences in patients and in food. In the present study the molecular characterization of HAV isolates from 355 Italian cases is reported.MethodsMolecular characterization was carried out by PCR/sequencing (VP1/2A region), comparison with reference strains and phylogenetic analysis.ResultsA unique strain was responsible for most characterized cases (235/355, 66.1%). Molecular data had a key role in tracing this outbreak, allowing 110 out of the 235 outbreak cases (46.8%) to be recognized in absence of any other link. The data also showed background circulation of further unrelated strains, both autochthonous and travel related, whose sequence comparison highlighted minor outbreaks and small clusters, most of them unrecognized on the basis of epidemiological data. Phylogenetic analysis showed most isolates from travel related cases clustering with reference strains originating from the same geographical area of travel.ConclusionsIn conclusion, the study documents, in a real outbreak context, the crucial role of molecular analysis in investigating an old but re-emerging pathogen. Improving the molecular knowledge of HAV strains, both autochthonous and circulating in countries from which potentially contaminated foods are imported, will become increasingly important to control outbreaks by supporting trace back activities, aiming to identify the geographical source(s) of contaminated food, as well as public health interventions.

Molecular analysis of hepatitis A virus strains obtained from patients with acute hepatitis A in Mongolia, 2004-2013.

Despite the high endemicity of hepatitis A virus (HAV) in Mongolia, the genetic information on those HAV strains is limited. Serum samples obtained from 935 patients with acute hepatitis in Ulaanbaatar, Mongolia during 2004-2013 were tested for the presence of HAV RNA using reverse transcription-PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 180 patients (19.3%) had detectable HAV RNA. These 180 isolates shared 94.6-100% identity and formed four phylogenetic clusters within subgenotype IA. One or three representative HAV isolates from each cluster exhibited 2.6-3.9% difference between clusters over the entire genome. Cluster 1 accounted for 65.0% of the total, followed by Cluster 2 (30.6%), Cluster 3 (3.3%), and Cluster 4 (1.1%). Clusters 1 and 2 were predominant throughout the observation period, whereas Cluster 3 was undetectable in 2009 and 2013 and Cluster 4 became undetectable after 2009. The Mongolian HAV isolates were closest to those of Chinese or Japanese origin (97.7-98.5% identities over the entire genome), suggesting the evolution from a common ancestor with those circulating in China and Japan. Further molecular epidemiological analyses of HAV infection are necessary to investigate the factors underlying the spread of HAV and to implement appropriate prevention measures in Mongolia.

Epidemiological and genetic analysis of a 2014 outbreak of hepatitis A in Japan

Hepatitis A virus (HAV) is one of the most common causes of feces-transmitted acute hepatitis worldwide. In Japan, most of HAV infections have been sporadic cases and a relatively low number of cases (approximately 100–150) of acute hepatitis A were reported in 2012 and 2013. However, in 2014, 342 cases were reported as of week 22. In order to characterize the viral agents causing this outbreak, we collected stool or sera (and both for three case) from patients with hepatitis A from many regions throughout Japan and performed genotyping of the VP1/P2A regions of HAV. We then used a multiple-alignment algorithm to compare the nucleotide sequences with those of reference strains. Phylogenetic tree analyses revealed that the 159 HAV isolates were divided into three subgenotypes: IA (137 cases), IB (4 cases), and IIIA (18 cases). The most unique feature of this outbreak was that for most subgenotype IA cases (103 out of 137 IA cases) the sequences analyzed shared 100% homology. Interestingly, the peak week for these IA infections was almost the same nationwide, suggesting that the epidemic of hepatitis A caused by this subgenotype IA strain may have expanded from a single source possibly because of one food-borne or waterborne source that was distributed nationwide at once.

Molecular epidemiology of hepatitis A virus infection in Northeast India.

The present study was undertaken to screen the molecular epidemiology of Hepatitis A virus (HAV) in Northeast India (NEI) who are ethnically distinct, tribal dominated and of lower socio-economic status with almost no information available from NEI on these aspects. Briefly, 3 ml blood was collected from 324 random liver disease cases with jaundice, receiving care at Central Hospital, N.F. Railway, Guwahati, Assam with informed consent. The patients detected with HAV-IgM positive status were included and were stratified as acute viral hepatitis (AVH) and fulminant hepatitis (FHF) based on clinical profile. Viral RNA was isolated and HAV-RNA was detected by Real-time PCR using primers for the VP3-VP1 region. HAV genotyping was studied by PCR-direct sequencing-phylogenetic analysis approach using the VP1/2A region of HAV isolates. Statistical analysis was performed using SPSS13.0 software. A total of 69 cases were HAV infected with two HBV co-infected cases (n = 69 + 2 = 71), 62 cases and two co-infected cases were AVH and others were FHF cases. HAV infection was predominant in especially in the young and adult age group. HAV-RNA was detected in 28 cases, out of which 19 cases could be genotyped (12 AVH, 7 FHF); which showed the prevalence of genotype IIIA or IA only. Although HAV genotype IIIA was the major genotype in both the AVH (10/12, 83.33%) and FHF (5/7, 71.43%) group, but the difference in distribution of genotypes in AVH and FHF cases was statistically non-significant (P = 0.550). HAV genotype IIIA is associated with the majority of HAV infected cases and severity in NEI.

Migration pattern of hepatitis A virus genotype IA in North-Central Tunisia.

BackgroundHepatitis A virus (HAV) epidemiology in Tunisia has changed from high to intermediate endemicity in the last decades. However, several outbreaks continue to occur. The last reported sequences from Tunisian HAV strains date back to 2006. In order to provide an updated overview of the strains currently circulating in Tunisia, a large-scale molecular analysis of samples from hepatitis A cases was performed, the first in Tunisia.ResultsBiological samples were collected from patients with laboratory confirmed hepatitis A: 145 sera samples in Tunis, Monastir, Sousse and Kairouan from 2008 to 2013 and 45 stool samples in Mahdia in 2009. HAV isolates were characterised by nested RT-PCR (VP1/2A region) and sequencing. The sequences finally obtained from 81 samples showed 78 genotype IA and 3 genotype IB isolates.A Tunisian genotype IA sequence dataset, including both the 78 newly obtained IA sequences and 51 sequences retrieved from GenBank, was used for phylogenetic investigation, including analysis of migration pattern among six towns. Virus gene flow from Sfax and Monastir was directed to all other towns; in contrast, the gene flows from Sousse, Tunis, Mahdia and Kairouan were directed to three, two, one and no towns, respectively.ConclusionsSeveral different HAV strains co-circulate in Tunisia, but the predominant genotype still continues to be IA (78/81, 96% isolates). A complex gene flow (migration) of HAV genotype IA was observed, with Sfax and Monastir showing gene flows to all other investigated towns. This approach coupled to a wider sampling can prove useful to investigate the factors underlying the spread of HAV in Tunisia and, thus, to implement appropriate preventing measures.

Evolution and genetic characterization of hepatitis A virus isolates in China

Hepatitis A virus (HAV), transmitted mainly through the fecal-oral route, is one of the major causes of acute viral hepatitis worldwide. HAV is endemic in China. This study performed genetic and evolutionary analysis of HAV isolates circulated in the country. Clinical samples were collected and HAV nucleotide and deduced amino acid sequences were analyzed. 70 representative sequences of HAV VP3-VP1-2A regions sampled from 1988 to 2014 were compared and characterized using the Bayesian Markov Chain Monte Carlo approach (BEAST software, Version1.7.5). All isolates from China in this study belonged to genotype I, with most of the samples clustering in subgenotype IA, while several unique amino acid variants were observed. The estimated mean substitution rate was 5.56×10(-4) substitutions / site / year, the time to the most recent common ancestor of genotype I isolates in China was calculated to be around 180 years ago. Skyline plots showed the incidence of HAV went down gradually from the mid-1990s. The evolution estimations were consistent with the laboratory and epidemiological results. Several isolates from China showed amino acid changes close to the immunodominant sites, which needs to be further analyzed. The study results have indicated the effectiveness of improving economic and sanitation levels together with HAV vaccination to control HAV-related infections in China.

Clinical significance of genetic diversity of hepatitis A virus

Aim: to identify features of the clinical course of hepatitis A (HA) caused by viruses of different subtypes. Patients and methods: In the study there were included 195 patients with hepatitis A (130 males and 65 females) at the age from 15 to 72 years residing in the territories with various manifestations of the epidemic process of HA (Moscow, the Khabarovsk region, the Republic of Sakha (Yakutia), the Republic of Tajikistan and Ukraine). All patients were examined for the presence of Hepatitis A virus (HAV) RNA in blood, with following determination of the genotype of the virus by PCR. Biochemical blood tests (concentration of total and direct bilirubin, ALT activity) were performed from 2 to 9 times depending on the duration of hospital stay and severity of infection. The dynamics of biochemical indices was evaluated in accordance with the period of the disease: the first period -from the 1 st to 10 th day, the second -from 11 th to 20 th day, the third -from the 21 st day and later. Results: A direct moderate correlation (The Spearman correlation coefficient r = 0,3; p = 0,002) between the duration of jaundice and patients ’ age has been revealed. A significant relationship was observed in the group ofpatients with subtype IIIA (r = 0,4; p = 0,003) and was absent in patients with subtype IA. There were no statistically significant differences between the groups of patients with subtypes IA and IIIA, in dependence on the duration of hospitalization, the variant of the course ofprejaundice period, severity of the course disease, duration of the persistent jaundice and symptoms of intoxication. Absolute values and the dynamics of the reduction of total and direct bilirubin, as well as the dynamics of decrease of ALT activity in groups of patients with various subtypes were not differed significantly. Cholestatic forms of HA were observed only in patients with HAV isolates belonging to subtype IIIA. Conclusion: HAV subtype has no effect on the severity of the course of the disease neither major clinical symptoms and laboratory indices in patients from different age groups. A direct correlationship between the duration ofjaundice syndrome and age in patients with subtype IIIA may indicate a trend towards the formation of cholestatic forms of HA in patients with this subtype of the virus in older age groups.

The complete genomes of subgenotype IA hepatitis A virus strains from four different islands in Indonesia form a phylogenetic cluster

Despite the high endemicity of hepatitis A virus (HAV) in Indonesia, genetic information on those HAV strains is limited. Serum samples obtained from 76 individuals during outbreaks of hepatitis A in Jember (East Java) in 2006 and Tangerang (West Java) in 2007 and those from 82 patients with acute hepatitis in Solo (Central Java), Denpasar on Bali Island, Mataram on Lombok Island, and Makassar on Sulawesi Island in 2003 or 2007 were tested for the presence of HAV RNA by reverse transcription PCR with primers targeting the VP1-2B region (481 nucleotides, primer sequences at both ends excluded). Overall, 34 serum samples had detectable HAV RNA, including at least one viremic sample from each of the six regions. These 34 strains were 96.3-100 % identical to each other and formed a phylogenetic cluster within genotype IA. Six representative HAV isolates from each region shared 98.3-98.9 % identity over the entire genome and constituted a IA sublineage with a bootstrap value of 100 %, consisting of only Indonesian strains. HAV strains recovered from Japanese patients who were presumed to have contracted HAV infection while visiting Indonesia were closest to the Indonesian IA HAV strains obtained in the present study, with a high identity of 99.5-99.7 %, supporting the Indonesian origin of the imported strains. These results indicate that genetic analysis of HAV strains indigenous to HAV-endemic countries, including Indonesia, are useful for tracing infectious sources in imported cases of acute hepatitis A and for defining the epidemiological features of HAV infection in that country.

Hepatitis a virus: Structure-functional features of genome, molecular diagnostics, and cultivation

Recently published data on the following features of hepatitis A virus (HAV) are reviewed: structure-functional genome features, genotyping, clinical findings, and current means of diagnostics. The growing need to study the genetic diversity of HAV isolates and the search for its possible new antigenic variants are underlined. Results of cultivation of different HAV strains are considered and analyzed for possible application in creation and production of vaccines and diagnostic kits.

Full genome analysis of Philippine indigenous subgenotype IA hepatitis A virus strains from Japanese patients with imported acute hepatitis A

Hepatitis A virus (HAV) is the most common cause of infectious hepatitis worldwide. Although hepatitis A cases imported from South-East Asian countries, including the Philippines, have been reported in Japan, the molecular epidemiological data have been limited for these HAV-endemic countries. The full-length genomic sequences of HAV isolates were determined and subjected to the phylogenetic analyses. The HAV isolates (HA12-0796 and HA12-0938) obtained from two Japanese patients who developed acute hepatitis A in July 2012, 1 month after traveling to the Philippines, where they consumed undercooked shellfish, differed by only one nucleotide (nt) over the entire genome. These HAV isolates of genotype IA were 99.1-99.5% identical within 228-237 nt to those recovered from river water in the Philippines, suggesting that the HA12-0796 and HA12-0938 isolates represent HAV circulating in the Philippines. HAV isolates belonging to one of the two IA sublineages (IA-2) which were implicated in some of the mini-epidemics in 2010 in Japan are hypothesized to be connected with the Philippines. In support of this speculation, the present IA isolates (HA12-0796 and HA12-0938) shared 98.8% identity over the entire genome with one IA-2 isolate (HAJIH-Fukuo10) recovered from a Japanese female who developed a domestic HAV infection during the mini-epidemics. In the phylogenetic tree constructed based on the entire genome, these three isolates (HA12-0796, HA12-0938 and HAJIH-Fukuo10) segregated into a cluster with a bootstrap value of 100%. These results indicate that HAV isolates belonging to the IA-2 lineage might have been imported from the Philippines.

Molecular Characterization of Hepatitis A Virus Isolates from Nigeria

Objective: Despite the endemicity of hepatitis A virus (HAV) in Nigeria, genetic information on the HAV genotypes/subgenotypes circulating in the country remains unknown. The objective of this study was to investigate HAV strains using molecular epidemiological and genetic analyses among apparently healthy adult Nigerian subjects. Methods: Testing for HAV-RNA was performed on 114 serum samples by the reverse transcription-polymerase chain reaction and sequenced with primers encompassing the VP1/P2A junction. Results: Twelve serum samples tested were found to be HAV-RNA positive. Phylogenetic analysis revealed that all 12 HAV isolates were classified as subgenotype IA exhibiting 98.3% nucleotide identity. Interestingly, the Nigerian HAV/IA subgenotype consisted of two distinct genomic sublineages with a unique majority (n = 11) corresponding to strains endemic in Cameroon and the other (n = 1) shows a probable link with European sequences. Predicted conserved amino acid sequences and the few deduced substitution in the VP1/P2A junction might play a role in the development of a novel Nigerian-Cameroon sublineage within the HAV/IA subgenotype and might explain the stability of HAV/IA in this subregion. Conclusion: This study reveals the development of a new HAV/IA sublineage in the Nigerian-Cameroon subregion. The presence of a single subgenotype indicates that this HAV strain has been predominantly circulating in Nigeria.

Increased circulation of hepatitis A virus genotype IIIA over the last decade in St Petersburg, Russia

The current study, covering the period 2004-2009, is a part of long-term monitoring for hepatitis A virus (HAV) strains circulating in St Petersburg, Russia. The HAV RNA was isolated directly from the sera of hepatitis A patients and RT-PCR was carried out using primer pairs for VP1/2A and VP1 genomic regions. PCR products were sequenced and 324 nucleotides from VP1/2A and 332 from the VP1 region were used for phylogenetic analysis. The results show that the IA subtype was the most common circulating subtype during the follow-up period, as found in the previous study: almost 90% of the isolated HAV strains belonged to the IA subtype. The large hepatitis A food-borne outbreak in St Petersburg in 2005 was caused by HAV IA. However, the proportion of HAV isolates belonging to subtype IIIA significantly increased in the period 2001-2009 (7.9%) compared to the period 1997-2000 (none found). The subtype IIIA was first found in St Petersburg in 2001 among a group of intravenous drug users. The increase in its circulation during the decade suggests that this previously unusual genotype has been permanently introduced into the general population of St Petersburg. These results indicate the usefulness of molecular epidemiological methods for studying changes in the circulation of HAV strains.

Genetic analysis of hepatitis A virus variants circulating among children presenting with acute diarrhea in Cameroon

Molecular investigation was undertaken of circulating hepatitis A virus (HAV) associated with cases of acute diarrhea among children under 5 years of age in Kumba-Cameroon. Reverse transcription PCR, sequencing, and phylogenetic analysis of a 371 bp segment of the VP1/P2A junction of six isolates obtained from stool samples showed the exclusive emergence of genetically related HAV subgenotype IA. All the isolates clustered within a unique lineage exhibiting a 99.5% nucleotide identity suggesting infection from a common source. The Cameroonian HAV isolates did not intermix or cluster with those from other regions of Africa and the rest of the world. Tajima's neutralization tests using the six sequences suggested HAV/IA population expansion (D = -1.37; P = 0.016). This is the first description of indigenous HAV genotypes circulating in Cameroon revealing a community-wide spread and predominance of HAV/1A infection in the Kumba area. These findings stress the need for routine molecular tracking of HAV infection as a contributory cause of acute diarrhea in Cameroonian children.

Comparative analysis of disease severity between genotypes IA and IIIA of hepatitis A virus

Although hepatitis A is a major health problem worldwide, it has not yet been clarified whether or not viral factors affect the clinical characteristics. This study aimed to investigate if a genotype of hepatitis A virus (HAV) affects disease severity among adolescent and adult populations. Clinical data and specimens were collected from patients ≥16-years-of-age with acute hepatitis A at two university hospitals in Korea during the two study periods: 1998 and 1999 (n = 45), and 2009 (n = 66). Nucleotide sequencing of the complete VP1 region of the HAV isolates was performed for phylogenetic analysis and genotyping. Clinical parameters related to disease severity were compared by HAV genotype to determine its clinical relevance. Of the 87 patients, 47 were male and the mean age was 29.8 ± 8.1 years. The genotype IIIA (93.0%, 53/57) was predominant in the year 2009, whereas IA (93.3%, 28/30) was the major genotype in 1998 and 1999. When comparing disease severity between the two HAV genotypes, the patients with genotype IIIA were older and had higher alanine aminotransferase (ALT) levels, prolonged prothrombin times and lower serum albumin levels. In a multivariate logistic regression model, higher ALT levels ≥ 1,000 IU/L (odds ratio [OR] 11.7, 95% confidence interval [CI] 2.5-54.0) and longer hospitalization (OR 22.49, 95%CI 4.6-132.5) were associated independently with genotype IIIA. In conclusion, this study indicates that HAV genotype might be one of the viral factors responsible for the disease severity of hepatitis A.

Genotyping of acute hepatitis a virus isolates from China, 2003–2008

Hepatitis A virus (HAV) is usually transmitted by an oral-fecal route and is prevalent not only in developing countries but also in developed countries. In the present study, the phylogenetic characterization of the VP1/2A junction region (321 nucleotides) of China HAV isolates was examined. Anti-HAV IgM-positive serum samples were collected from 8 provinces, including 20 cities or counties in China from 2003 to 2008; 337 isolates from 406 HAV patients' serum samples were amplified by RT-PCR, sequenced at the VP1/2A junction region and aligned with the published sequences from GenBank to establish phylogenetic analysis. All China HAV isolates in this study belonged to genotype I, with 98.8% (333/337) of samples clustering in sub-genotype IA and 1.2% (4/337) in sub-genotype IB. In addition, sub-genotype IA isolates clustered into four groups (92.7-100% nucleotide identity), and the samples collected from all China HAV isolates in this investigation showed 87.5-100% nucleotide identity, but the amino acids in this region were more conserved (95.2-100% identity). Few unique amino acid changes could be deduced (VP1-253: Glu → Gly; 2A-34: Pro → Ala; 2A-33: Leu → Phe). Genetically identical or similar HAV strains existed in some investigated areas in China during different years, suggesting that an indigenous strain has been circulating in those regions. This report provides new data on the genetic relatedness and molecular epidemiology of HAV isolates from China as well as the distribution of sub-genotype IA and IB in this part of the world.

1957年"尾去沢肝炎"凍結保存53年目の血清から発掘したA型肝炎ウイルス准完全長ゲノム塩基配列

From June through January 1958, an etiology-unknown hepatitis was epidemic in a mineworkers' town Osarizawa, Akita-Prefecture, Japan, mainly affecting children. Twenty-two years later, a set of freeze-stored sera from patients involved in the Osarizawa Hepatitis 1957 tested positive for antibodies to hepatitis A virus (HAV) by a radioimmunoassay that was brand-new at the time. Further 31 years thereafter, our present study revealed that 8 out of 16 freeze-stored sera from the outbreak were positive for HAV RNA, and the nucleotide sequences from these samples segregated to a single cluster within genotype IA. Although the 5' terminus is yet to be determined, a nearly complete 7459-nt genome of HAV was obtained from one of these vintage samples (isolate name HA286-Aki1957, accession AB623053). To our knowledge, HA286-Aki1957 represents the oldest HAV isolates that have ever been sequenced/published to date.

What factors determine the severity of hepatitis A‐related acute liver failure?

The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were sub-genotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare sub-genotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes.

A unique HAV strain circulated in patients with acute HAV infection with different risk exposures in Tuscany, Italy

Background Acute Hepatitis A Virus (HAV) is reported to be an emergent problem in several developed countries. Objectives and study design The aim of this study was to analyse the HAV strains circulating among individuals with acute HAV infection, apparently transmitted by different routes, in several districts of Tuscany in central Italy, during the year 2008. Results An outbreak of acute HAV infection occurred from May to August 2008 in Arezzo; 32 individuals were admitted to the hospital, in 25 of them at least a linkage with an infected food handler and/or household contacts was reported and in 3 homosexuality was a possible risk factor. In Florence, from January 2008 to August 2008, 41 individuals mainly homosexual men were admitted to two hospitals with the diagnosis of acute HAV. The phylogenetic analysis of VP1/2A region of HAV was used to characterize these HAV isolates. All viral sequences were assigned to genotype IA. All clustered in the same branch (bootstrap 82%) of phylogenetic tree, thus indicating the same circulating isolate. Apart of one isolate from France and one from Germany which were similar with the “Tuscany” strain reported here, high heterogeneity with the other European HAV strains reported in the GenBank in the last years, was observed. Conclusion The detection of a unique HAV isolate circulating in different Tuscany districts, suggests sequential transmission of HAV infection in this geographical area through possible links among acute hepatitis cases. The application of safe food handling practices and vaccination of homosexual men may contribute to the prevention of HAV infection.