Sporadic Hepatitis Research Articles

Investigating the origin and global dispersal history of hepatitis E virus genotype 4 using phylogeographical analysis.

Hepatitis E virus (HEV) genotype 4 has mainly been isolated from sporadic hepatitis cases and swine in Asian countries. We analysed the origin and global dispersal history of genotype 4 using a Bayesian phylogeographical approach. The 412-nucleotide sequences of open reading frame 2 of genotype 4 (47 Japanese, 40 Chinese, 1 Indian, 8 Indonesian, 1 Korean, 1 Taiwanese, 2 Danish and 2 Italian), of which sampling date and location were known, were collected. Evolutionary rate, divergence time, demographic growth and phylogeography were co-estimated in the Bayesian statistical inference framework implemented in the BEAST package to model spatial dispersal on a time-scaled genealogy. The most probable origin of genotype 4 was Japan and the time of origin was 1909 (95% highest posterior density, 1871-1940). Seven lineages of genotype 4 migrated from Japan to China. The analysis also showed the migration of genotype 4 from Japan or China to India and Indonesia and from China to Indonesia, Taiwan, Korea and a few European countries. Swine trade between countries coincided with the migration time and direction of genotype 4 in some cases and was considered the primary cause of dispersal. However, there was no clear cause of dispersal for some cases, for which no records of pig trade were found. Future research should analyse additional nucleotide sequences paired with epidemiological data from various countries to improve our understanding of HEV dispersal.

Seroprevalence and risk factors of hepatitis E virus infection among children in China.

Hepatitis E virus (HEV) infection is an important public health concern worldwide, especially in developing countries, causing waterborne outbreaks as well as sporadic autochthonous hepatitis. China is usually considered to be a HEV-endemic area, but the prevalence of HEV infection in children in mainland China remains unclear. Between May 2013 and July 2014, a cross-sectional study was conducted to estimate the seroprevalence and potential risk factors associated with the acquisition of HEV infection by children in China. A total of 1,500 healthy children (range 1-18; 942 and 558 from urban and rural areas, respectively) were recruited to examine for the presence of anti-HEV IgG and IgM antibodies by enzyme-linked immunosorbent assay. Socio-demographic and behavioral characteristics from the examined children were obtained. The overall seroprevalence of HEV in the examined children was 14.93%. Of these, 174 (11.60%) were positive for only anti-HEV IgG antibodies, 50 (3.33%) were IgM positive and IgG negative, and 44 (2.93%) were positive for both anti-HEV IgG and IgM antibodies. Age, type of residence area, contact with pigs, and source of drinking water were found to be associated with HEV infection. These findings demonstrated the high prevalence of HEV and the considerable potential for the transmission of HEV infection in children in China.

P0599 : Role of non-hepatotropic viruses in acute sporadic viral hepatitis in adults: Should the screening strategies be changed?

P0599 : Role of non-hepatotropic viruses in acute sporadic viral hepatitis in adults: Should the screening strategies be changed?

Histopathology of chronic Hepatitis E

Background and aims: Sporadic hepatitis E is an emerging indigenous disease in Europe induced by the genotype 3 of the virus. Whereas in immunocompetent individuals it takes an acute self-limited course, under immunocompromised conditions the majority of cases develop chronic hepatitis. Histopathology of acute hepatitis has been published whereas histology of chronic hepatitis has noit been described so far.

Clinical analysis on 108 patients with sporadic hepatitis E for coastal regions

Objective To investigate and analyze the clinical features of hepatitis E in the north coastal regions.Methods The clinical manifestations,complications,treatment and outcome of 108 patients with hepatitis E were retrospectively observed and analyzed.Results Hepatitis was distributed throughout the year,in the first quarter as high incidence of 38.0％; more men than women (4.1∶1); with an average age of 59.2 years,elderly morbidity of 88.0％.Farmers was the majority (84.3％); basic diseases patients accounted for 88.9％.Elderly and overlapping HBV infection patients had the longer duration.ALT resumed rapidly after treatment,an average of 24.9 days of such confinement,the average hospitalization cost 8923.4 yuan.But the elderly group TBIL restored slower,an average of 28.9 days of such confinement,the average hospitalization cost 10325.9 yuan.Conclusion Hospital patients with hepatitis E are mostly the middle-aged and old male in the region of rural,generally combined with basic diseases,with the heavier clinical manifestation,the longer duration,the higher cost,but with better prognosis and lower fatality rate. Key words: Coastal regions; Hepatitis E; Clinical features

P45: Virological characteristics of hepatitis E and A infection in acute sporadic viral hepatitis and acute exacerbation of chronic liver disease patients

Journal of Viral HepatitisVolume 21, Issue s2 p. 46-46 Poster SessionFree Access P45: Virological characteristics of hepatitis E and A infection in acute sporadic viral hepatitis and acute exacerbation of chronic liver disease patients First published: 08 October 2014 https://doi.org/10.1111/jvh.12333_44AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume21, Issues2Special Issue: Abstracts for the Viral Hepatitis Congress 2014, 9–11 October 2014, Frankfurt, GermanyOctober 2014Pages 46-46 RelatedInformation

Clinical and molecular analyses of sporadic acute hepatitis A and E and the specific viral genotypes isolated in Iwate and three neighboring prefectures in the northern part of Honshu, Japan, between 2004 and 2013.

To examine the prevalence and characteristics of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in the northern part of Honshu, Japan, during the last decade. Using the registration system of a prospective cohort study for acute liver injury (ALI) in Iwate and three neighboring prefectures, we examined the prevalence of sporadic acute hepatitis (AH) with HAV (AH-A) and HEV (AH-E) and the distribution of viral genotypes in 487 patients diagnosed with ALI between 2004 and 2013. Among all 487 patients, 135 (28%) had ALI with viral infection. In the cases with viral ALI, the prevalence of hepatitis B virus-related AH was highest (55.6%). AH-E was seen in 23 patients (17.0%) and its prevalence was higher than that of AH-A (10 patients, 7.4%). There were no appreciable differences in the prevalence of AH-A and AH-E between 2004-2008 and 2009-2013. However, subgenotype IIIA HAV homologous to Korean strains has recently emerged, and the number of AH-E cases seems to be increasing. HEV genotype 3 was predominant throughout the observation period, but HEV genotype 4 was found in three patients after 2010. The transmission routes of HAV and HEV infections were unknown in approximately 60% of the patients. In the northern part of Honshu, Japan, HEV has been more frequently implicated in the development of AH than HAV, and HEV genotype 4 has been recently increasing. To provide an effective prophylactic management for HAV and HEV infections, further clarification of the transmission routes is needed.

An Analysis of Epidemiological Characteristics and the Clinical Features of 394 Cases of Sporadic Acute Hepatitis E in Southwest China from 2008 to 2010

Abstract Background and Aims Recently, epidemiology studies of hepatitis E in different areas are attracted more attention. Extensive studies of prevalent status and clinical manifestations could help us to broaden our knowledge, so as to excellently prevent and treat hepatitis E. The study analyzed the epidemiological characteristics and clinical features of 394 cases of sporadic acute hepatitis E (AHE) in Southwest of China from 2008 to 2010. Methods The clinical data of 394 cases with sporadic AHE in Southwest of China from 2008 to 2010 were reviewed. Results In the 394 cases with sporadic AHE, the ratio of male/female was 1.432 : 1, and the mean age was (31.53 ± 18.12) years. Totally, 94 (23.86%) patients aged under 18, 271 (68.78%) patients aged between 18 and 60, and 29 (7.36%) patients aged above 60. The incidence rate was significantly increased in summer (P = 0.000), especially in May (14.72%) and July (13.71%). In addition, the characteristics of occupation and ethnic group distribution were migrant laborers (106/394, 26.90%) and Han people (365/394, 92.64%). The length of stay, incidence of jaundice, the peak value of total bilirubin and alanine aminotransferase in male patients were all higher than those in female patients significantly (P < 0.05). The prolonged length of stay, decreased levels of ALT/ALB/CHE, increased levels of TBil, and increased incidence of jaundice and fatigue were associated with older age significantly (P < 0.05). The differences in peak values of total bilirubin (TBil), total bile acid (TBA), glutamyltransferase (GGT), cholinesterase (CHE) between AHE group and the groups of AHE accompanied respectively by chronic hepatitis B (CHB), acute alcoholic fatty liver (AFL), nonalcoholic fatty liver disease (NAFLD) were significant (P < 0.05). In addition, no significant difference was found in length of stay and biochemical indexes among anti-HEV-IgG positive group, anti-HEV-IgM positive group and anti- HEV-IgM/IgG both positive group (P > 0.05). Conclusions Four epidemiological characteristics, including aged between 18 and 60, male, summer and migrant laborers, are found to be associated with acute hepatitis E. The prognosis of AHE in the majority of patients was favorable, but aged above 60 years and coexistence with CHB, AFL and NAFLD could be considerede as the factors inducing the infaust prognosis.

Risk factors and molecular characterization of acute sporadic symptomatic hepatitis E virus infection in Thailand

ObjectiveTo report clinical outcomes and viral genotypes of acute symptomatic hepatitis E virus (HEV) infection in Thailand. MethodsForty patients with acute symptomatic HEV infection were recruited during 2009-2013. Clinical, demographic and laboratory data were collected. Diagnosis was accomplished by detection of anti-HEV IgM and/or HEV RNA in the serum or stool. HEV genotypes were classified by direct sequencing of RT-PCR products and phylogenetic analysis. ResultsThe high risk group, comprising immune-compromised, liver cirrhosis and very elderly (>80 years) patients (17 cases), had higher levels of serum alkaline phosphatase at presentation compared with the low risk group. Two fatal cases resulted from acute hepatitis E in the high risk group. Initial clinical presentation did not show statistically significant differences. In six cases (6/40), the virus could be detected in serum or stool by RT-PCR and sequencing. Upon molecular characterization, the viruses were classified as HEV genotype 3f and were in the same cluster as Thai swine HEV. ConclusionsOur data showed that acute HEV infection has various clinical presentations and outcomes. Higher levels of serum alkaline phosphatase were observed in high risk patients. All isolated viruses were identified as HEV genotype 3f possibly originating from swine.

Occurrence of hepatitis E virus infection in acute hepatitis in Thailand

Hepatitis E virus (HEV) infection is one of the enterically transmitted types of hepatitis. The present study was undertaken to estimate the occurrence of HEV infection in sporadic acute hepatitis in Thailand. Serum samples were obtained from 614 suspected acute hepatitis patients at two large hospitals in Bangkok during 2008, 2009, and 2011. Acute hepatitis E was identified by the presence of anti-HEV IgM (4.8%) using indirect ELISA kits and/or HEV RNA (4.5%) by a semi-nested reverse transcription-polymerase chain reaction assay. HEV IgM was the most common marker for detection (77%) at diagnosis, either by positive HEV IgM alone or together with HEV RNA, whereas HEV RNA alone was detected in 23% of patients. Overall, 4.2% of cases (26 out of 614) were acute HEV infection with the highest attack rate in the elderly age group. In addition, nucleotide sequence analysis of five HEV samples revealed 92.8-99.8% homology. All viruses were clustered into HEV genotype 3 and were similar genetically to swine HEV strains previously detected in the same area. Therefore, the occurrence of HEV infection with closely related to swine genotype 3 was approximately 4-5% of acute hepatitis cases in Thailand. Anti-HEV IgM was the most common marker at diagnosis.

Transmission, diagnosis, and management of hepatitis E: an update.

Hepatitis E virus (HEV) infection is an important public health concern in many developing countries, causing waterborne outbreaks as well as sporadic autochthonous hepatitis. HEV is mainly transmitted by the fecal–oral route in endemic areas through drinking of contaminated water. However, zoonotic transmission from animal reservoirs to humans has also been suggested. Three additional routes of HEV transmission have been proposed to occur: blood borne, human to human, and vertical transmission from mother to child. Acute HEV infection is usually diagnosed by detecting specific anti-HEV antibodies. However, the performance of the available assays in different settings is not optimal. Analysis of HEV ribonucleic acid in biologic specimens such as stools, serum, and liver biopsy by using nucleic acid amplification techniques is also employed. Nonetheless, additional consensus regarding the best technologies suitable for serosurveys and diagnosis of acute HEV infection is also needed. This review article summarizes the current status of HEV infection end epidemiology with particular emphasis in transmission, diagnosis, and clinical management.

Prevalence of hepatitis E virus infection in West Bengal, India: a hospital-based study.

India is an endemic zone for hepatitis E virus (HEV), which is associated with both epidemic and sporadic infections. In West Bengal, only two hepatitis E outbreaks have been studied to date. However, sporadic cases of HEV infection also occur during inter-epidemic periods. The aim of this hospital-based study was to detect the prevalence of HEV infection in patients with acute sporadic hepatitis in West Bengal, India. Blood samples and clinical information were collected from 285 patients of both sexes and different ages with acute viral hepatitis (AVH) at Calcutta Medical College, Kolkata, a tertiary-care centre. Samples were tested for hepatitis B virus (HBV) surface antigen, anti-hepatitis C virus antibodies, anti-hepatitis A virus IgM and anti-HEV antibodies (IgM and IgG) by ELISA. Only those patients with AVH who were in their first week of illness and negative for all hepatotropic viral antibodies were tested for HEV RNA by reverse transcriptase nested PCR. HEV was identified as the most common cause of AVH (41.8% of patients), followed by HBV (21.4%), hepatitis A virus (17.2%) and hepatitis C virus (4.6%). Co-infections with more than one virus were found in 22 patients, with HBV-HEV the most common co-infection (3.8%). Only 14.7% of patients had no viral marker. To the best of our knowledge, this is the first documented epidemiological study of acute sporadic hepatitis with HEV in the state of West Bengal, India, indicating that this state is an endemic zone for HEV infection.

Seroprevalence of Hepatitis E Virus in Pigs from Different Farming Systems in The Netherlands

Sporadic nontravel-related hepatitis E virus (HEV) infections have been reported in industrialized countries. These infections are caused by zoonotic HEV genotypes 3 and 4 that circulate in swine, wild boar, and deer. In The Netherlands, HEV RNA has been detected in >50% of the pig farms, and HEV-specific antibodies were detected in ∼70% of the slaughter pigs. In the current study, HEV seroprevalences were investigated in pigs raised on conventional, free-range, and organic farms in The Netherlands. Differences in seroprevalence may indicate different exposure routes or transmission dynamics within pig herds for HEV. In 2004, serum samples of 846 fattening pigs were obtained from farms that applied conventional (265 pigs at 24 farms), organic (417 pigs at 42 farms), and free-range (164 pigs at 12 farms) farming. HEV-specific antibodies were detected in samples from all conventional and free-range pig farms and in 41 of 42 organic pig farms, indicating that the probability of introducing HEV on a farm appeared to be equal for the different farming types. The estimated average within-herd seroprevalence was significantly higher for pigs raised on organic farms (89%) than for pigs raised on conventional farms (72%, P = 0.04) and nearly significant for pigs raised on free-range farms (76%, P = 0.06). Six of ten organic farms were estimated to have a withinherd seroprevalence of >95%, compared with 1 of 10 and 4 of 10 of the free-range and conventional pig farms, respectively. This suggests a higher force of infection with HEV for pigs reared on organic farms compared with pigs reared on conventional or free-range farms. This may be due to repetitive exposure to HEV caused by farming system-specific housing conditions, such as a greater contact frequency between pigs and more exposure to pig manure, increasing the transmission rate.

Aetiology of Sporadic Acute Viral Hepatitis in North-East India – Differences Exist from the Rest of India

Background: Acute viral hepatitis remains a major and mostly preventable cause of morbidity and mortality in India today. Aetiology of acute viral hepatitis cannot be differentiated clinically. Most reports on sporadic, epidemic, and fulminant cases of acute viral hepatitis from India implicate Hepatitis E as the major cause. Data from the North-eastern part of India is lacking.

Liver transplantation for acute liver failure related to autochthonous genotype 3 hepatitis E virus infection

Hepatitis E virus of genotype 3 (HEV-3) is an emerging cause of sporadic autochthonous acute hepatitis in Europe. Although spontaneous outcome of hepatitis E is usually favorable, fulminant liver failure has been described worldwide. In Europe, autochthonous hepatitis E associated with fulminant hepatic failure and leading to liver transplantation has been exceptionally reported. We report here four cases of fulminant and sub-fulminant hepatitis E proposed for liver transplantation in Marseille University hospitals between July 2006 and March 2010. HEV diagnosis relied on detection of anti-HEV IgM antibodies and HEV RNA in serum samples. All cases were men, with no travel history in hyperendemic areas. HEV sequence analyses revealed genotype 3 HEV in the four patients. Liver histology indicated severe acute hepatitis in all of them, pre-existing fibrosis being found in two cases. Two patients underwent liver transplantation, and the two other patients could not be transplanted due to septic complications and died. HEV testing should be performed for the initial evaluation of every acute liver failure regardless of the epidemiological and clinical context. With respect to the potentially fulminant evolution of HEV genotype 3 infections, treatment with ribavirin of severe acute hepatitis E should be considered.

Indigenous Hepatitis E Virus Genotype 1 Infection, Uruguay

Indigenous Hepatitis E Virus Genotype 1 Infection, Uruguay

Duration of viraemia in Chinese acute sporadic hepatitis E

Acute sporadic hepatitis E (ASHE) cases induced by hepatitis E virus genotype 4 (HEV-4) are increasing in China. Our study aimed to estimate the duration of HEV-4 viraemia in Chinese ASHE. A total of 619 serum specimens from 499 ASHE patients were examined for the presence of HEV RNA. The association between viraemia detection and serum sampling time was compared between subtypes. The cumulative probability of HEV viraemia detection was determined using Kaplan-Meier survival analysis, and the viraemia duration was estimated. A total of 42.7 % of serum specimens were positive for HEV RNA and all the isolated strains were identified as genotype 4 and subsequently assigned to five subtypes. Among the patients infected with subtypes 4d and 4i, the time interval from the initiation of clinical symptoms to serum specimen sampling was shorter than that among the patients with subtypes 4a, 4b and 4h. Kaplan-Meier analysis was conducted with 101 sequential specimens as well as with both 101 sequential specimens and 236 single negative specimens. The cumulative probability of HEV-4 viraemia detection was estimated to decline quickly to approximately 10 % within 32 days after the initiation of clinical symptoms and then to decline very slowly to 5 % by the 41st day and to zero by the 131st day. The majority of ASHE cases maintain detectable HEV-4 viraemia within one month after onset, whereas a small portion of cases maintain long-term viraemia and may act as a reservoir for further transmission.

Genotype analysis of hepatitis E virus from sporadic hepatitis E cases in northern China

Hepatitis E is an important public health problem in many countries. However, there is no definite conclusion about the zoonotic reservoir, transmission patterns and risk factors of hepatitis E in the human population. The aim of this study was to analyze the epidemiological and viral genotype characteristics of hepatitis E cases in northern China. Surveillance was conducted in two hospitals in Liaoning and Hebei province from July 2010 to June 2012. Out of a total of 116 diagnosed patients, 88 (75.9%) were male and 28 (24.1%) were female and most (73%) were in the age group 40–70years. In both hospitals, cases were diagnosed more frequently in March than in other months. HEV RNA was amplified from 41 patients and characterized by nucleotide sequencing and phylogenetic analysis. Most of the isolates (37 strains, 90.3%) were genotype 4, including subgenotypes 4a, 4b, 4d, 4h, 4i and a new subgenotype. One subgenotype 3a strain was isolated from Baoding, Hebei province. Three genotype 1b strains were found from patients in Jinzhou, Liaoning province. Most of the genotype 4 strains and the genotype 3 strains were phylogenetically related to known swine isolates. In conclusion, the finding that HEV infects mostly middle-aged and elderly men and that the incidence spiked in March may reflect the zoonotic transmission characteristics of HEV infection. Pigs, but not rabbits, were the important reservoirs in this area, because genotype 4 HEV was found to be responsible for the majority hepatitis E cases. However, genotype 1 is still present in northern China. Also, the first isolation of genotype 3 HEV in this area indicates that alternative routes of HEV transmission might exist.

English

This study was carried out to evaluate the diagnostic value of nested reverse transcriptase-polymerase chain reaction (RT-PCR) for HEV (hepatitis E virus) RNA detection relative to anti-HEV immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays. One hundred and twenty six (126) patients with sporadic acute hepatitis E were included in this study. We focused on the popular genotype I and IV of HEV-positive patients in China, and selected the conserved region located in ORF2 for designing a set of nested RT-PCR primers. HEV RNA was detected in 53.2% (67/126) of patients, while all control subjects were negative for HEV RNA. The total agreement between IgM and nested RT-PCR detection was 80.9%, showing a fine coincidence. The results further suggested that there was a significant difference between nested RT-PCR detection and IgM ELISA: 3 cases with positive results for HEV RNA showed negative anti-HEV IgM at the early phrase, and presented positive IgM reaction in succession after the trail of detection. HEV RNA was detected in serum samples from sporadic acute hepatitis patient usually by day 1 to 12 after the onset of symptoms, but showed a decreasing sensitivity with the increasing disease course. From these experiments, we can conclude that HEV RNA detection is of great clinical significance, which has an obvious advantage in diagnosis of early infection of HEV. Key words: Hepatitis E virus, nested reverse transcriptase-polymerase chain reaction (RT-PCR), RNA, antibody.

A pediatric case of hepatitis B virus subgenotype A2 in Japan.

Hepatitis B virus (HBV) has been classified into 10 major genotypes, and HBV genotypes C and B are found in the majority of Japanese patients. However, the prevalence of genotype A has been increasing in patients with chronic or acute hepatitis. Here we report a pediatric case of HBV subgenotype A2. A 2-year-old girl was referred to our hospital for liver damage caused by HBV infection. During the pregnancy, her father had developed acute sporadic hepatitis B. The child was born without any complications. She did not receive HBV vaccination at birth because her mother was negative for HBs antigen at the pre-delivery screening; however, her mother developed acute hepatitis B 2months after delivery. At that time, HBs antigen was detected in the current patient. Phylogenetic full-length sequence analysis revealed HBV subgenotype A2. HBV sequencing was not performed for her parents; therefore, the intrafamilial transmission routes in these cases are unclear, although the authors speculate that, for the current patient, mother-to-child transmission may have occurred. This report illustrates the pitfalls of the selective vaccination strategy in Japan for preventing HBV infection. Universal vaccination to prevent HBV infection might be useful in Japan.