HAV Infection Research Articles

Long-term immunogenicity and immune persistence of live attenuated and inactivated hepatitis a vaccines: a report on additional observations from a phase IV study

Both live attenuated (HA-L) and inactivated (HA-I) hepatitis A vaccine were licensed for routine use in China. Although phase 1, 2 and 3 clinical studies of both vaccines have been completed, further systematic evaluation of their immunogenicity and immunological persistence under phase 4 clinical studies in a wide range of conditions and involving large populations is necessary. A phase IV clinical trial (NCT02601040) was performed in 9000 participants over 18 months of age. Geometric mean concentrations (GMCs) and seroconversion rates (SRs) were compared at five time points during 3 years for 1800 individuals among them. The SRs of HA-L and HA-I were 98.08% (95% CI 95.59%–99.38%) and 99.64% (95% CI 98.93%–100.00%) respectively 28 days after administration of the first dose, and remained at 97.07% (95% CI 94.31%–98.73%) or above and 96.73% (95% CI 94.07%–98.42%) or above respectively during the following 3 years. The GMCs for both the HA-L and HA-I groups showed that both vaccines elicited high anti-HAV titres, considerably more than the threshold of protection needed against HAV infection in humans, and these titres were sustained. Hence, both HA-I and HA-L vaccines could provide an excellent long-term protective effect, and supported the routine use of both vaccines.

The Prevalence of Hepatitis A Among Blood Donors in Golestan Province in the Northeast of Iran

Background: Hepatitis A is a virus with linear and positive strand RNA. As HAV has no envelope, it is more resistant to environmental stress than other hepatitis viruses, and it can be transmitted by water and food. HAV infection is acquired commonly by the fecal-oral route and in adults, it can leave very serious complications, including fulminate hepatitis. The virus is infectious for one to two weeks in the bloodstream before symptoms appear. In the acute phase of the disease, when the virus is presented in the bloodstream, it is possible to transfer via blood transfusion and plasma products. Objectives: This study was designed to determine the frequency of antibodies against HAV and the acute phase of the disease among blood donors in Golestan province in the northeast of Iran. Methods: Sera of 400 blood donors in Golestan province who were negative for anti-HIV, HBs Ag, and anti-HCV were tested for the total anti-HAV antibody, anti-HAV IgM, and HAV-RNA. Total antibodies (IgG+IgM) and IgM were determined by the ELISA method using commercial kits. HAV-RNA was detected by nested RT-PCR. Results: Overall, 91% of the analyzed specimens were anti-HAV seropositive and all blood donors were negative for anti-HAV IgM. HAV-RNA was not found in any serum samples. Conclusions: The prevalence of HAV was high among blood donors in Golestan province and due to high anti-HAV seroprevalence rates, the blood donors are safe in terms of virus transfer.

Changing epidemiological characteristics of Hepatitis A and warning of Anti-HAV immunity in Beijing, China: a comparison of prevalence from 1990 to 2017

ABSTRACTBackgroud: Beijing was hyper-endemic for hepatitis A until the 1990s and has been vaccinating against hepatitis A since 1994. The objective is to study the epidemiology and changes of antibody level of hepatitis A from 1990 to 2017.Methods: A multistage randomized cluster sampling serological cross-sectional study was conducted in individuals over one year old in 1992, 2006 and 2014 in Beijing. Venous blood samples were collected to test anti-HAV antibody. The incidence data of hepatitis A were obtained from National Notifiable Disease Reporting System (NNDRS) and CDC statistics in Beijing. The vaccination data of hepatitis A immunization were acquired from Beijing Immune Information System.Results: From 1990 to 2017, the reported incidence rate of HAV in Beijing declined from 59.41/100,000 in 1990 to 0.80/100,000 in 2017. The average age of HAV infection was postponed from individuals under 20 years old to individuals over 20 years old. After hepatitis A vaccine was introduced to Beijing, the outbreak of hepatitis A decreased sharply. Adjusted anti-HAV positive rate in general population was 68.23%, 81.73% and 82.47% respectively in 1992, 2006 and 2014. Due to hepatitis A vaccination conducted in children, the anti-HAV positive rate in individuals under 20 years old increased from 1992 to 2014, while in individuals over 20, this rate was barely changed. The coverage rate in target population was higher than 99% after hepatitis A vaccine was integrated into Expanded Program on Immunization (EPI).Conclusion: Incidence rate of hepatitis A in Beijing has decreased dramatically from 1990 to 2017. Hepatitis A vaccine plays an important role in protecting individuals under 20 years old. A higher proportion of adults will be susceptible to hepatitis A virus due to the decay of antibodies as they grow up from childhood to adulthood, which may result in possible outbreak of hepatitis A.

Persistent Hepatitis a IgM Antibody: A Clue in the Diagnosis of Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is a condition characterized by persistent inflammation of the liver, associated with a T-cell mediated immune response directed against liver antigens. The presence of underlying genetic predisposition, failure of immune tolerance mechanisms, and the presence of exogenous precipitating stimulus have been linked to its pathophysiology. Hepatitis A (HAV) infection has been described as an environmental trigger associated with AIH development. We describe a patient with previously diagnosed acute HAV, presenting with persistent IgM antibody against Hepatitis A (anti-HAV IgM) who was subsequently diagnosed with AIH. A 56-year-old African-American lady presenting with two-week history of dark urine, pale stools, fatigue, lower extremity edema, and nocturnal pruritus. She had a well-documented prior history of HAV infection two years before, with subsequent resolution of symptoms and laboratory abnormalities. On physical examination, she appeared mildly ill with conjunctival icterus and jaundice. See Table 1 for laboratory results. Her MELD score was 21 upon presentation. Antinuclear antibody and anti-smooth muscle antibody titer were 1/640 and 1/1280, respectively. A liver biopsy demonstrated interface hepatitis with exuberant plasma cell infiltrate, and stage 4/4 fibrosis on trichrome stain, suggestive of AIH. The patient was diagnosed with AIH according to international diagnostic criteria for AIH (Score 17). She received treatment with oral steroids and azathioprine with later normalization of liver function and transaminases after three months of treatment. Anti-HAV IgM could be detected for up to three to six months after acute HAV infection. Our case illustrates the significance of late detection of Anti-HAV IgM more than six months after resolution of acute HAV infection. A study in children aged 6-14 years showed persistent Anti-HAV IgM in more than 20% of patients 12 to 18 months after initial infection. Several case reports (Table 2) have been published of AIH diagnosed seven to sixteen weeks after the initial acute HAV infection. In our case the time interval from initial acute HAV infection to the diagnosis of AIH is much longer, but the sustained anti-HAV IgM response indicates persistent antigenic stimuli, which could play a role in subsequent development of AIH, and facilitate its diagnosis.2265_A Figure 1. Laboratory values before and after treatment of AIH, including prior diagnosis of acute HAV and interval resolution2265_B Figure 2. Prior case reports of AIH diagnosed after documented acute HAV

Hepatitis A and B Vaccination Rates Among Patients With Chronic Liver Disease: A Phase 1 Quality Assessment Report

Introduction: According to the US Advisory Committee on Immunization Practices, patients with chronic liver diseases are recommended vaccination against Hepatitis A and B unless already immune. To this end, the New York State Department of Health has outlined the Viral Hepatitis Strategic Plan 2016 - 2020 to ensure access and coverage for hepatitis A, B, and C. In phase 1 of this quality assessment/improvement project, we aim to investigate whether patients with chronic liver disease are receiving adequate hepatitis A and B vaccinations. Methods: A total of 4,000 patients were identified by retrospective chart review from January 2015 to January 2018 that satisfied our inclusion criteria; 200 of those patients were randomly selected as a sample population. Descriptive statistics was used to compare continuous and categorical variables. Results: Of the 200 patients randomly identified, 31% were males. The median age was 62±12 years. The majority (46%, n=92) of patients were treated for acute/chronic hepatitis C. 27.5% (n=56) were never screened for HAV or HBV infection, 0.5% (n=1) was screened for HAV only, and 5.5% (n=12) screened for HBV only. Out of those patients who were screened for both HAV and HBV (n=131), 80.1% (105/131) were already immune to HAV while 18.3% (24/131) patients were already immune to HBV. On sub-analysis, 10.7% (14/131) of patients were non-immune to both HAV and HBV, while 16% (21/131) were immune to both HAV and HBV. Additionally, 19.1% (25/131) of patients were immune to HAV but infected with HBV while 8.4% (11/131) patients were non-immune to HAV but infected with HBV. 1 patient was coinfected with HAV and HBV. Approximately 53% (105/200) of patients did not have adequate immunization status. For those patients who needed either the HAV or HBV vaccine, 34 patients were never offered vaccines, and 67 patients were offered vaccines but did not receive it. Only 16% (n=17/105) of patients who were screened and needed HAV, HBV, or both vaccines were given the vaccine (2= HAV only, 7= HBV, 8= both HAV & HBV), and of those patients, only 53% (9/17) were re-checked for immunity after the vaccine was administered. Conclusion: Phase 1 of our quality assessment has revealed that patients with chronic liver disease are not receiving adequate vaccination against HAV and HBV. Phase 2 will focus on implementing educational interventions aimed at increasing physician awareness of vaccination guidelines.

Need for recognizing atypical manifestations of childhood sporadic acute viral hepatitis warranting differences in management.

Various atypical manifestations have been described in acute viral hepatitis (AVH). We evaluated the prevalence, clinical features, response to treatment and outcome of various atypical manifestations of AVH in children. Consecutive children (≤ 18years) with AVH due to hepatitis A, B, or E were studied while patients with acute or acute on chronic liver failure were excluded. Diagnosis of atypical manifestations was based on standard criteria. A total of 477 children with AVH (median age 7.0 (5-11) years, 74% boys) were seen; 22% (n = 106) had atypical manifestations. Prolonged cholestasis was the most common (11%), followed by ascites (7%), intravascular hemolysis (3%), relapsing hepatitis (2%), acute pancreatitis (1.3%), and thrombocytopenia (0.7%). Atypical manifestations were more common in HAV as compared to HBV (30% vs. 3%, p = 0.00) and HEV (30% vs. 15%, p = 0.07). Prolonged cholestasis was significantly more common in older children (20% in > 10years vs. 9% in 6-10years ; p = 0.009 and 5% in 0-5years of age [p < 0.000]). Ascites was more common in younger children, although not significant. All patients recovered with supportive treatment.Conclusions: Twenty-two percent of children with AVH have atypical manifestations, more often with HAV infection, and prolonged cholestasis is most common. Recognition of these manifestations ensures correct diagnosis and treatment. What is Known: • Acute viral hepatitis is a major public health problem in developing countries. • There is limited information about atypical manifestations which may lead to unnecessary investigations, delayed diagnosis and morbidity. What is New: • Atypical manifestations are common in children, seen most often with HAV infection, and prolonged cholestasis is most common. • Prompt recognition of these manifestations helps in early diagnosis, appropriate management, and preventing unnecessary investigations. • Ensure follow-up until complete recovery and not to miss underlying chronic liver disease.

SCREENING AND VACCINATION AGAINST HEPATITIS A IN PEDIATRIC CHRONIC LIVER DISEASE PATIENTS

Background: Superadded HAV infection in patients with chronic liver disease (CLD) or cirrhosis may result in further deterioration of liver functions causing acute on chronic liver failure. The Center for disease control (CDC) strongly recommends to vaccinate all CLD patients against HAV. Methods: All pediatric patients with chronic liver disease for &gt;6 months, after informed consent from their parents were enrolled. HAV immunity was defined as the qualitative presence of HAV IgG antibody (?1.00 reactive) in the serum blood test. All patients with negative HAV IgG were subjected to HAV vaccination and adverse events were also noted. Results: A total of 30 pediatric CLD patients with a mean age of 9.3 ± 3.9 years were enrolled. Majority of participants were males n=19 (63.3%). The overall prevalence of positive HAV serology (IgG) was 86.7 %. Three participants with negative HAV serology received a series of two vaccines, 6 months apart and HAV IgG titers were checked at 4 weeks after the first and second dose of vaccination. Despite two doses of vaccine satisfactory titer levels could not be achieved. Conclusion: This is the first study from Pakistan in which pediatric CLD patients were evaluated for HAV exposure. Early vaccination is advisable in such patients as advanced liver disease patients may not achieve adequate titers.

Acute hepatitis A is the chief etiology of acute hepatitis in Egyptian children: a single-center study.

Acute hepatic illness is an important health issue in children. Our work aimed to determine the prevalence of viral hepatitis in symptomatic children. It is a prospective cohort study of 268 children presented with acute hepatitis. Complete blood count, liver panel, and anti-hepatitis A virus (HAV) IgM were done initially. Cases negative for HAV were tested for anti-hepatitis E (HEV) IgM, anti-Epstein-Barr virus viral capsid antigen (EBV VCA) IgM, anti-cytomegalovirus virus IgM, hepatitis B surface antigen, anti-hepatitis B core IgM antibody, and anti-HCV antibody. Anti-HCV was repeated after 12weeks to exclude seroconversion. In cases with negative viral serology, ceruloplasmin, total immunoglobulin G, antinuclear antibody, and abdominal ultrasound were done. Follow-up visits were bimonthly till recovery, then after 6months. The mean age ± SD was 7.1 ± 3.7years (1.5-18), and 56% were males. Acute HAV infection was diagnosed in 260 (97%) of cases and acute EBV infection in one case (0.4%). HAV/HEV coinfection was excluded in 70 HAV-positive cases. Six (2.2%) children remain undiagnosed and one child lost follow-up. About 80% of HAV-cases had normal laboratory results within 45days. Unusual presentation of HAV infection was noticed in six children: four (1.5%) were relapsing, one had a cholestatic course, and one case had severe hemolytic anemia. Acute HAV infection was the chief etiology of acute hepatitis in our Egyptian children. The majority of the presentations were mild and children recover within a few weeks. An unusual pattern of HAV in children can be observed in endemic areas.

Seroprevalence of Hepatitis A Virus in Children and Adults

Hepatitis A is the most common form of acute viral hepatitis in the world. Major geographical differences in endemicity of hepatitis A are closely related to hygienic and sanitary conditions and other indicators of the level of socioeconomic development. In this study we aimed to investigate the seroprevalence of hepatitis A for adults and pediatric in university hospital- Gaziantep, and to demonstrate the relationship between various socio-demographic data and seropositivity. Serum samples were investigated by ELISA method for Anti HAV IgG and Anti HAV IgM. A total of 102 individuals, 55 male and 47 female, were included in the study. Anti HAV IgG positivity was detected in 87(85.3%), anti HAV IgM positivity was detected in 2 (2.0%). There weren't any significant gender differences in HAV IgG. By analysis according to the age, Anti-HAV IgG seropositivity increased with age. Although there was no significant difference in HAV IgG seropositivity according to the types of drinking water supply, HAV IgG seropositivity was detected in a less percentage in individuals who drink the commercial water. In Turkey HAV infection has been shifted to older ages than younger age. The disease is more complicated in advanced age than younger people. We recommend the importance of applying the vaccine.

European outbreak of Hepatitis A in Iceland in 2017. Common radiological changes of the gallbladder

IAim The incidence of hepatitis A (HAV) in Iceland is low with about one case per year in the last decades. Since 2016, there has been an ongoing outbreak of HAV in men who have sex with men (MSM). The aim of this study was to inves-tigate whether cases diagnosed in Iceland during 2017 had any link to the HAV outbreak in Europe. Methods All cases of HAV in Iceland during 2017 were reviewed retrospectively. Results Four of five cases diagnosed during 2017 were MSM and one was a female. Three cases presented the same week in the summer 2017. The age of the patients was between 25 and 39 years. All the male patients had had sex with men from Europe and/or had travelled to Europe prior to admission. All cases had typical signs and symptoms of HAV infection and in all cases recent infection was confirmed by positive serology and exclusion of other causes of acute hepatitis. Four of five patients had radiological signs of changes in the gallbladder with thickening of the wall and oedema and one underwent later an elective cholecystectomy. Conclusion The outbreak of HAV in MSM Europe reached Iceland in the summer 2017, emphasizing the importance of vaccination in this risk group as recommended by the Icelandic Health Authorities. The review of these cases indicate that changes such as thickening of the gallbladder wall without gallstones in patients with HAV are common. It is important to discrimi-nate patients with these changes associated with HAV from patients with acute acalculus cholecystitis.

A Seroepidemiologic Study of Hepatitis A in Seven to Eighteen-Year-Old School Children in Birjand: New Concerns and Opportunities

Background: Hepatitis A is globally spread and is an important public health problem. Objectives: This study aimed at investigating the seroepidemiology of hepatitis A in students aged seven to eighteen years in Birjand, during year 2016. Methods: This study was a descriptive-analytic research, in which 300 school children aged seven to eighteen years in Birjand city were selected through the cluster sampling method. Subsequently, participants and their parents were requested to fill the questionnaire and were referred to the laboratory for blood sampling in order to examine hepatitis A antibody titer. Data were analyzed using SPSS-21 software and the chi-square test. Results: Hepatitis A antibody test was positive for only 111 out of 300 participants (37%). Females (P = 0.009) and teenagers (P = 0.0001) had significantly higher levels of antibody against HAV. There was a significant difference between the presence of hepatitis A antibody, education level of the mothers of the studied individuals (P = 0.042), and the social level and size of the family (P = 0.041). However, no difference was seen regarding fathers’ literacy level (P = 0.284). Conclusions: The findings of the study showed that immunity against HAV was reduced during the past years. The reduced level of immunity against HAV along with several major risk factors for HAV infection, such as neighboring with Afghanistan and health hazards of hepatitis A for Iranian pilgrims visiting Karbala-based shrines in Iraq suggest anti-HAV vaccination as an essential priority.

Hepatitis A surveillance using commercial laboratory data

ObjectiveTo evaluate the use of commercial laboratory data for monitoring trends in HAV infections over time and identifying geographic and demographic characteristics of HAV case clusters for the purpose of targeting interventions.IntroductionHepatitis A virus (HAV) infections have persisted in the United States despite the availability of an effective vaccine. Recent outbreaks of HAV infections among unvaccinated adults attributed to consumption of HAV-contaminated food, or person-to-person contact in certain populations (e.g., men who have sex with men) or settings (e.g., homeless shelters) have emphasized the importance of targeted vaccination of at-risk adults.MethodsWe used commercial laboratory data from Quest Diagnostics (Quest) and Laboratory Corporation of America (LabCorp) to identify unique individuals within each database who tested positive for HAV IgM antibody (indicative of acute HAV infection) from January 2011 through June 2017. Though de-depulication across the two laboratories was not possible, comparison of case characteristics indicated limited possible overlap of cases (&lt;0.5%) and thus data from the two laboratories were combined. Demographic characteristics associated with the first positive test were used to classify cases by age, gender, state of residence, insurance type, and provider specialty. Persons co-infected with hepatitis B and/or hepatitis C were identified based on positive test results for hepatitis B surface antigen and hepatitis C RNA, respectively.ResultsA total of 6,702,256 HAV IgM test results from Quest and 7,043,555 HAV IgM test results from LabCorp were processed. Of those, 24,697 (0.4%) and 13,785 (0.2%) tests, respectively, had a ‘Reactive’, or positive result, indicating acute HAV infection. From these test results, we identified 15,415 unique individuals from Quest and 10,622 unique individuals from LabCorp with an acute HAV infection between January 2011 and June 2017. Among the 26,037 acute cases, the majority were female (14,056; 54.0%), were aged 50 or older (13,940; 53.5%), resided in large central or fringe metropolitan areas (17,842; 68.5%), and had tests ordered by family or internal medicine providers (12,358; 47.5%; Table). We identified 330 cases (1.3%) among incarcerated persons. Although data could not be de-duplicated across labs, we estimated a minimum of 630 persons (2.4%) were co-infected with hepatitis B and 852 persons (3.3%) were co-infected with hepatitis C. From 2011 to 2015, there were 7,370 cases of acute HAV reported to CDC, whereas Quest and LabCorp test results indicated 19,822 cases over the same time period. Trends in cases by month revealed seasonal increases in cases in late summer and early fall months (Figure 1). Mapping of acutely-infected individuals demonstrated a range of cases from 0 to 1,119 cases by county over the study period (Figure 2).ConclusionsHAV IgM test results over a 6-year period from two commercial laboratories serving the United States suggest continuing hepatitis A transmission. Most cases occur among older adults, and appear to cluster geographically in metropolitan areas. Commercial laboratory data is a useful tool for supplementing case-based surveillance and informing prevention efforts.

Monitoring human enteric viruses in wastewater and relevance to infections encountered in the clinical setting: a one-year experiment in central France, 2014 to 2015.

BackgroundHuman enteric viruses are resistant in the environment and transmitted via the faecal-oral route. Viral shedding in wastewater gives the opportunity to track emerging pathogens and study the epidemiology of enteric infectious diseases in the community. Aim: The aim of this study was to monitor the circulation of enteric viruses in the population of the Clermont-Ferrand area (France) by analysis of urban wastewaters. Methods: Raw and treated wastewaters were collected between October 2014 and October 2015 and concentrated by a two-step protocol using tangential flow ultrafiltration and polyethylene glycol precipitation. Processed samples were analysed for molecular detection of adenovirus, norovirus, rotavirus, parechovirus, enterovirus (EV), hepatitis A (HAV) and E (HEV) viruses. Results: All wastewater samples (n = 54) contained viruses. On average, six and four virus species were detected in, respectively, raw and treated wastewater samples. EV-positive samples were tested for EV-D68 to assess its circulation in the community. EV-D68 was detected in seven of 27 raw samples. We collected data from clinical cases of EV-D68 (n = 17), HAV (n = 4) and HEV infection (n = 16) and compared wastewater-derived sequences with clinical sequences. We showed the silent circulation of EV-D68 in September 2015, the wide circulation of HAV despite few notifications of acute disease and the presence in wastewater of the major HEV subtypes involved in clinical local cases. Conclusion: The environmental surveillance overcomes the sampling bias intrinsic to the study of infections associated with hospitalisation and allows the detection in real time of viral sequences genetically close to those reported in clinical specimens.

Seroprevalence and disease burden of acute hepatitis A in adult population in South Korea.

BackgroundAdult seroprevalence of HAV is decreasing in developed countries including South Korea, due to general sanitation improvement. Although hepatitis A vaccination was introduced in South Korea more than 20 years ago, recent infection rates have not decreased. In this study, we investigate the seroprevalence of anti-HAV IgG, and estimate the national disease burden of acute hepatitis A in adult population.MethodsSeroprevalence data were collected from health promotion center of Korea University Guro Hospital, in Seoul, Korea from 2010 to 2014. Data from adults (≥20-years) being tested for anti-HAV IgG were included. In addition, epidemiological and clinical data of patients diagnosed with acute hepatitis A from 2009 to 2013, were collected from Korean Statistical Information Service (KOSIS) and the National Health Insurance Service (NHIS) database. Data were stratified and compared by age groups.ResultsA total of 11,177 subjects were tested for anti-HAV IgG from 2010 to 2014. Age-related seroprevalence showed relatively low seropositivity in young adults. Incidence of acute hepatitis A was highest in 2009 and lowest in 2013. When categorized by age group, adults in their 20s and 30s had more HAV infections and related-admissions than older adults. However, ICU admission rate and average insurance-covered cost was high in older adults.ConclusionThe anti-HAV IgG seropositivity in Korean younger adult population was low while the incidence of acute hepatitis A was high, especially in the 20–39 aged. However, a substantial number of older adults were infected, and required more intensive procedures and incurred higher insurance-covered medical costs.

An Assessment of Failure to Vaccinate Hepatitis C Patients for Both Hepatitis A and Hepatitis B

Introduction: Unlike hepatitis C (HCV), vaccines are available to prevent acquisition of hepatitis A (HAV) and hepatitis B (HBV) infection. HAV and HBV infection separately and together hasten liver injury for patients living with HCV. Current recommendations advise clinicians to vaccinate all patients living with HCV for both HAV and HBV (HAV/HBV). The aim of this study was to assess clinicians' failure to vaccinate HCV patients for HAV/HBV. Methods: A retrospective chart review was conducted of 307 HCV patients' vaccination history receiving care at 3 liver and infectious disease clinics. Measures of central tendency and frequency distributions were used for univariate analysis. HCV patients with and without HAV/HBV vaccination were compared using chi-square and Student's t-test. Results: Of 307 HCV patients, 53% (247/309) did not receive HAV/HBV vaccination. Compared to HCV patients who received HAV/HBV vaccination, those who did not receive HAV/HBV vaccination had a higher proportion of lifetime sex with a person who injects drugs (c2=4.49, p=0.034). Compared to HCV patients who did not receive HAV/HBV vaccination, those who did receive HAV/HBV vaccination had a higher proportion of lifetime (p=0.005), current major depressive disorder (p=0.014), and drug use paraphernalia HCV exposure history (p=0.035). HCV patients who did and did not receive HAV/HBV vaccination did not differ in other categories of exposure history, risky behaviors, or psychiatric disorders, and they did not differ in alcohol and drug use, stages of liver fibrosis, levels of HCV RNA, or liver enzymes. Conclusion: In this sample of HCV patients from 3 liver and infectious disease clinics, the frequency of failure for clinicians to comply with the HAV/HBV vaccination recommendation was alarming. Given HCV patients without HAV/HBV vaccination had higher frequencies of sex with a person who injects drugs, they were at increased risk of acquiring other forms of viral hepatitis. Research is needed to determine why clinicians are not following HAV/HBV vaccination guidelines, and research is needed to educate clinicians on the public health benefit of HAV/HBV vaccination with patients living with HCV. It is important for clinicians to comply with the HAV/HBV vaccination recommendation to reduce HCV patients' risk of acquisition of other forms of viral hepatitis that contribute to accelerated liver disease, morbidity, and mortality.

Genotypes of hepatitis a virus in Turkey: first report and clinical profile of children infected with sub-genotypes IA and IIIA

BackgroundHepatitis A virus (HAV) is a food and water-borne virus causing clinical (mainly hepatitis) and subclinical disease in humans. It is important to characterize circulating strains of HAV in order to prevent HAV infections using efficacious vaccines. The aim of this study was the detection and characterization of the circulating strains of HAV in Turkey by performing serology, RT-PCR, sequencing and phylogenetic analysis.MethodsIn this study, 355 HAV suspected cases were analysed by ELISA for the presence of antibodies to HAV. RNA was extracted from 54 HAV IgM positive human sera. None of the suspect cases were vaccinated against HAV and they never received blood transfusions. Samples found positive by RT-PCR using primers targeting the VP1/VP2A junction and VP1/VP3 capsid region of HAV, were subjected to sequencing and phylogenetic analyses.ResultsIgM type antibodies to HAV were detected in 54 patients. Twenty one of them were students. The age of IgM positive cases was between 3 and 60 years. IgM positivity differed in age groups and was higher in the age group 3 to 10 years. Phylogenetic analysis showed that the majority of HAV strains detected in this study belong to the “HAV 1B” cluster. In addition, the HAV sub-genotypes IA (KT874461.1) and IIIA (KT222963.1) were found in 2 children. These sub-genotypes were not previously reported in Turkey. The child who carried sub-genotype IIIA travelled to Afghanistan and presented with abdominal pain, icterus and vomitus. He was positive for anti-HAV IgM and IgG but negative for hepatitis B and C. Liver enzymes like aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase and lactate dehydrogenase were severely elevated. Bilirubin levels were also increased. White blood cells, neutrophils and hemoglobin were decreased while lymphocytes and monocytes were increased. Similar clinical signs and laboratory findings were reported for the child infected with sub-genotype IA but aspartate aminotransferase and alanine aminotransferase were not severely elevated.ConclusionsThe results indicate that molecular studies determining the HAV genotype variation in Turkey are timely and warranted. The majority of IgM positive cases in 3–10 year old patients indicate that childhood vaccination is important. Sub-genotype IB is the most prevalant genotype in Turkey. Surprisingly, sub-genotype IA and IIIA are also present in Turkey; future diagnostic efforts need to include diagnostic methods which can identify this emerging HAV genotypes. Our results also show that one important risk factor for contracting hepatitis A virus is international travel since genotype IIIA was detected in a child who had travelled to Afghanistan.

A waterborne outbreak involving hepatitis A virus genotype IA at a residential facility in the Republic of Korea in 2015

BackgroundHepatitis A virus (HAV), a major cause of acute hepatitis, has had the highest occurrence among group 1 nationally notifiable infectious diseases in Korea since 2010.Recently,the annual increase in the HAV infection rate among young adults has become a public health concern. ObjectivesThe aim of this study was to describe an outbreak of acute hepatitis in a residential facility in April 2015 and to identify potential sources of this outbreak. Study designSera from all exposed residents were tested for anti-HAV IgM or IgG antibodies by ELISA. Clinical (sera and stool) and environmental samples were screened for the presence of HAV RNA using one-step RT-PCR and nested PCR. The VP3-VP1 regions of HAV were analyzed using the BLAST database and MEGA7 software. ResultsOf the 82 persons in the facility, 12 (14.6%, including 10 residents and 2 health care workers) were diagnosed with hepatitis A. Clinical symptoms were evident in 9 individuals, one of whom died, and the remaining four patients were asymptomatic. Traceback investigation revealed that HAV-RNA (genotype IA) was detected in the patients’ stools and the groundwater used in the facility. ConclusionsWe described an HAV outbreak in a facility for the disabled due to using a water supply that was mixed with contaminated groundwater. Therefore, HAV vaccination and periodic water inspections in group facilities should be emphasized to prevent HAV infection.

Seroepidemiology of a recent outbreak of Hepatitis E in urban Shimla, Himachal Pradesh, India

Hepatitis E, a major public health problem, continues to cause epidemics in different geographic areas in India and poses multi-sectoral challenges. The aim of the study was to determine the seroepidemiology of the hepatitis outbreak in the urban areas of district Shimla, Himachal Pradesh. Patients presenting with clinical features of acute viral hepatitis during and after the epidemic period were tested for seromarkers; IgM anti-HEV and IgM anti-HAV by enzyme linked immunosorbant assay. The weekly reporting under Integrated Disease and Surveillance Programme (IDSP) for cases of jaundice from Shimla from December 2015 to April 2016 was reviewed. The outbreak of hepatitis due to contamination of drinking water supply in urban Shimla beginning December 12, 2015 was confirmed by IDSP. A total of 425 serum samples (males: 292; females: 133) were tested for IgM anti-HAV and IgM anti-HEV by ELISA. Liver enzymes where deranged in all cases. Serological evidence of infection with HAV and/or HEV was seen in 64%. HEV infection alone was detected in 62.13%. All ages were affected, with one case of HEV infection below ten years. HEV infection alone was 5 times more common than HAV infection and co-infection was detected in 69 cases (m: 47; f:22). Six antenatal mothers were anti-HEV positive and the maternal mortality of 50% (n=3) due to fulminant hepatitis. Since HAV and HEV have a similar faecal-oral route of transmission, this study highlights periodic surveillance of HAV/HEV exposure pattern to improve levels of personal and food hygiene and inter-sectoral collaboration for provision of safe water supply and safe sewage disposal.

O07 National response to an outbreak of hepatitis a associated with men who have sex with men in england, 2016/2017

IntroductionHepatitis A virus (HAV) is a vaccine-preventable infection, mainly travel-associated in the UK. Since July 2016 Public Health England has detected an increase in hepatitis A laboratory notifications in men who have sex with men (MSM). We described the outbreak characteristics to inform implementation of nation-wide control measures.MethodsA confirmed case was defined as a HAV infection with one of three outbreak strains and symptom onset after 31//6/16. Demographics, travel history and sexual behaviours were collected using a questionnaire.ResultsBy February 2017, 73 confirmed cases were detected across England. Of these 58 identified as MSM (median age 36 years) and 28 reported travel within the incubation period, primarily to Spain. 25% reported &gt;1 casual partner in the previous 8 weeks. In addition to supporting the local public health response, PHE collaborated with national STI, HIV and liver associations to refine immunisation recommendations for at-risk MSM and alert front-line clinicians, and worked with the NHS and sexual health charities to raise awareness and promote personal hygiene and immunisation among MSM via social media, posters and leaflets.DiscussionThe outbreak is likely associated with other MSM outbreaks with the same strains in other UK and European countries. The investigation suggests initial multiple importations from abroad followed by secondary sexual transmission within the MSM population in England. This outbreak highlights the need for MSM and healthcare professionals to consider the potential of HAV as a sexually transmitted infection, and the need to consider immunisation of MSMs where recommended.

Incidence of acute hepatitis A among HIV-positive patients during an outbreak among MSM in Taiwan: Impact of HAV vaccination.

An unprecedented outbreak of acute hepatitis A has occurred among MSM in Taiwan since June 2015. We aimed to describe the seroepidemiology of HAV infection and to investigate the relationship between HAV vaccination and the incidence of acute hepatitis A among HIV-positive patients at the largest designated hospital for HIV care during the outbreak. Between 2012 and 2016, the HAV serostatus, vaccination history and clinical characteristics of HIV-positive patients were retrospectively reviewed. A case-control study was performed to identify the factors associated with acute hepatitis A. The trends of HAV vaccination rate and incidence of acute hepatitis A among HAV-seronegative patients were examined during the outbreak. During the 4.5-year period, 2088 HIV-positive patients with a mean age of 37.7years and 90.2% being MSM were included. The overall HAV seroprevalence was 34.3%, which was significantly higher in older and non-MSM patients. The estimated incidence rate of acute hepatitis A was 52.6 cases per 1000 person-years of follow-up during the outbreak. The associated factors with acquiring acute hepatitis A were recent syphilis and having not received HAV vaccines. The HAV vaccination rate during the outbreak increased from 4.7% to 70.6% and the incidence rate of acute hepatitis A declined when up to 65% of the patients were immunized or tested positive for HAV. The seroprevalence of HAV infection was low in the younger HIV-positive individuals. Prevention of acute hepatitis A was achieved among HIV-positive, HAV-seronegative patients through HAV vaccination and increased herd immunity during the ongoing outbreak.