HEV Infection Research Articles

Low prevalence of IgG antibodies against antigens of HEV genotypes 1 and 3 in women with a high-risk pregnancy.

The aim of the study was to assess whether high-risk pregnant women have a higher prevalence of HEV during the perinatal period. This was a cross-sectional study of 428 patients: Group 1, 127 women with a high-risk pregnancy; Group 2, 97 asymptomatic people with reactivity to HCV or HBV; Group 3, 94 patients with clinical symptoms suggestive of HEV infection; and Group 4, 110 healthy blood donors from an urban area of Mexico City. ELISA was used to measure antibody to HEV genotypes 1 and 3. The prevalence rates of anti-HEV IgG antibodies were 0.79% in Group 1, 2.1% in Group 2, 7.4% in Group 3, and 0% in Group 4. Women with a high-risk pregnancy did not have a higher prevalence of HEV infection in this clinical setting.

Hepatitis E - A new era in understanding.

Hepatitis E virus [HEV], the last of the five hepatotropic viruses to be discovered, was originally considered to cause an acute, travel-associated self-limiting illness restricted to humans; however, new research shows that there are animal reservoirs and zoonotic transmission. Additionally, HEV is now considered as a major health burden worldwide, leading to significant morbidity and mortality; therefore, the topic of hepatitis E is of re-emerging importance, having brought to light important questions such as the transmission of HEV, especially in developed countries, as well as treatment and vaccination options. HEV belongs to the genus Hepevirus in the Hepeviridae family. The HEV genome sequence is relatively stable; however, there is a diversity of genotypes which are helpful in comprehending the epidemiological phenomena. HEV is classified based on the nucleotide sequences of the genome and is now characterised as a single serotype with four major genotypes [HEV 1-4]. Hepatitis E cases are not clinically distinguishable from other types of acute viral hepatitis, although diagnosis can be strongly suspected in certain epidemiological settings. It is imperative to raise awareness among physicians about the importance of HEV, with the aim of helping recognise, prevent and treat HEV infections. This review article highlights the current developments of HEV in microbiology, epidemiology, clinical features, treatment and prophylaxis.

HEV and transfusion-recipient risk

HEV infections are mainly food- and water-borne but transfusion-transmission has occurred in both developing and developed countries. The infection is usually asymptomatic but it can lead to fulminant hepatitis in patients with underlying liver disease and pregnant women living in developing countries. It also causes chronic hepatitis E, with progressive fibrosis and cirrhosis, in approximately 60% of immunocompromised patients infected with HEV genotype 3. The risk of a transfusion-transmitted HEV infection is linked to the frequency of viremia in blood donors, the donor virus load and the volume of plasma in the final transfused blood component. Several developed countries have adopted measures to improve blood safety based on the epidemiology of HEV.

Etiological characterizations of sporadic viral hepatitis in north east part of Bangladesh

These retrospective study was done to see common viral etiology of sporadic acute viral hepatitis in North East Part of Bangladesh. Consecutive patients attending in private chambers with acute or recent onset of jaundice with biochemical evidence of hepatocellular injury from January 2011 to December 2013 were enrolled. Epidemiological features and reports of viral markers i.e. HBsAg, Anti-HBc IgM, anti-HAV-IgM, Anti-HEV IgM, and Anti-HCV were retrieved. Data of 256 cases (male 195 and female 61, age ranging from 6 years to 89 years with mean 29.44 years were analyzed. Both HBsAg and anti-HBc-IgM were found positive in 98 (38.67%) cases (male 77 and female 21). Of them 39 were in 16-25 years age group. Anti-HAV IgM was found positive in 41 (16%) cases (male 30, female 11) and 27 of them were in the less than 16 years group. Anti HEV IgM was positive in 116 (45.31%) cases (male 87 and female 29). Majority (85 cases ) of HEV infection was found in 16 to 40 years age group. In this study HEV is the most frequent agent for acute sporadic viral hepatitis among adults followed by HBV. HAV is more prevalent cause of sporadic acute viral hepatitis among children.Bangladesh Med J. 2016 Sep; 45 (3): 138-140

HepatitisB, C, and E infection among HIV-infected patients in Franceville, Gabon: retrospective cross-sectional study.

Access to antiretrovirals has increased the life expectancy of patients living with HIV. However, HIV-viral hepatitis coinfections in countries endemic for these infections make management more difficult. To determine the extent of these coinfections in Gabon, we investigated markers of hepatitis B, C, and E viruses in 762 adults infected with HIV-1 by ELISA. We used real-time PCR to quantify plasma HBV DNA (HBV VL) and amplified HCV and HEV RNA by nested RT-PCR and PCR.The seroprevalence of chronic hepatitis B infection was 9.3%. Among patients with isolated HBcAc profiles, the prevalence of occult hepatitis B infection was 26.7%, for a real prevalence (detectable CV-HBV) of 17.3% of the total population. HCV seroprevalence was 8.8%. Of the 67 HIV-positive patients, 76.1% had replicative profiles (detectable HCV RNA), that is, 6.7% of the total population. For hepatitis E, seroprevalence was 3.5%. No case of chronic HEV infection was found. In conclusion, this study highlights a high rate of HIV-Hepatitis B, C and E coinfections in Gabon. In addition, we show the interest of looking for chronic infections (replicative profiles) in HIV-infected patients in Gabon. The establishment of technical platforms for this type of research, accessible to middle-income countries, is necessary.

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.

Meat consumption is a major risk factor for hepatitis E virus infection

BackgroundThe incidence of autochthonous hepatitis E virus genotype 3 (HEV gt3) infections in Western Europe is high. Although pigs are a major reservoir of the virus, the exact sources and transmission route(s) of HEV gt3 to humans remain unclear.MethodsTo determine the role of meat consumption at a population level, the seroprevalence of anti-HEV IgG antibodies was compared between Dutch blood donors with a vegetarian lifestyle and donors who consume meat on a daily basis.ResultsThe age-weighted anti-HEV IgG seroprevalence among donors not eating meat was significantly lower than among meat-eating donors (12.4% vs 20.5%, p = 0.002). For both groups the prevalence strongly increased with age and the difference in prevalence was apparent for all age groups.ConclusionsCompared with meat-eating donors, the incidence of HEV infection is significantly lower among donors not eating meat, indicating that meat consumption is a major risk factor for HEV infection.

MiRNA signatures can predict acute liver failure in hepatitis E infected pregnant females.

BackgroundAcute viral hepatitis E (AVH-E) can often result in acute liver failure (ALF) during pregnancy. microRNAs serve as mediators in drug induced liver failure. We investigated their role as a biomarker in predicting ALF due to HEV (ALF-E).MethodsWe performed next generation sequencing and subsequent validation studies in PBMCs of pregnant (P) self limiting AVH-E, ALF due to HEV (ALF-E) and compared with AVH-E in non-pregnant (NP) females and healthy controls.FindingsEleven microRNAs were significantly expressed in response to HEV infection; importantly, miR- 431, 654, 1468 and 4435, were distinctly expressed in pregnant self-limiting AVH-E and healthy females (p = 0.0005), but not in ALF-E. Sixteen exclusive microRNAs differentiated ALF-E from self limiting AVH-E in pregnant females. miR-450b which affects cellular proliferation and metabolic processes through RNF20 and SECB was predominanlty upregulated and correlated with poor outcome (ROC 0.958, p = 0.001).InterpretationOur results reveal that a specific microRNA profile can predict fatality in ALF-E in pregnancy. These microRNAs could be exploited as prognostic biomarkers and help in the development of new therapeutic interventions.

Racial differences in seroprevalence of HAV and HEV in blood donors in the Western Cape, South Africa: a clue to the predominant HEV genotype?

Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. This infection causes major water-borne outbreaks in low- and middle-income countries, whilst in industrialised countries this infection is zoonotic. These differences in epidemiology are related to different HEV genotypes. HEV genotype 3 is a zoonotic infection, whilst genotype 2 causes large outbreaks. This study determined the seroprevalence of HEV in blood donors from the Western Cape. Anti-hepatitis A virus (anti-HAV) antibody was detected in 184/300 (61%) donors. Antibody to HEV (anti-HEV) was detected in 78 of 300 donors (26%). It was highest in mixed race donors (62/100), followed by white donors (23/100) and lowest in black donors (19/100) P = 0.019. Since it is thought that genotypes 1 and 2 predominate both viruses would be acquired by the oro-faecal route, it is surprising that HEV seroprevalence does not mirror that of HAV. We postulate that this may reflect differences in socio-economic status and consumption of dietary meat. So the marked divergence between HEV and HAV seroprevalence may be the result of different routes of transmission. Further data are needed to explore the risk factors associated with HEV infection.

Cynomolgus monkeys are successfully and persistently infected with hepatitis E virus genotype 3 (HEV-3) after long-term immunosuppressive therapy.

Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs. HEV infected monkeys were followed up during 160 days post infection (dpi) by clinical signs; virological, biochemical and haematological parameters; and liver histopathology. The tacrolimus blood levels were monitored throughout the experiment. Immunosuppression was confirmed by clinical and laboratorial findings, such as: moderate weight loss, alopecia, and herpes virus opportunistic infection. In this study, chronic HEV infection was characterized by the mild increase of liver enzymes serum levels; persistent RNA viremia and viral faecal shedding; and liver histopathology. Three out of four immunosuppressed monkeys showed recurrent HEV RNA detection in liver samples, evident hepatocellular ballooning degeneration, mild to severe macro and microvesicular steatosis (zone 1), scattered hepatocellular apoptosis, and lobular focal inflammation. At 69 dpi, liver biopsies of all infected monkeys revealed evident ballooning degeneration (zone 3), discrete hepatocellular apoptosis, and at most mild portal and intra-acinar focal inflammation. At 160 dpi, the three chronically HEV infected monkeys showed microscopic features (piecemeal necrosis) corresponding to chronic hepatitis in absence of fibrosis and cirrhosis in liver parenchyma. Within 4-months follow up, the tacrolimus-immunosuppressed cynomolgus monkeys infected with a Brazilian swine HEV-3 strain exhibited more severe hepatic lesions progressing to chronic hepatitis without liver fibrosis, similarly as shown in tacrolimus-immunosuppressed solid organ transplant (SOT) recipients. The cause-effect relationship between HEV infection and tacrolimus treatment was confirmed in this experiment.

Decreased egg production in laying hens associated with infection with genotype 3 avian hepatitis E virus strain from China

To determine the relationship between decreased egg production and avian HEV infection, thirty healthy 23-week-old Hy-Line Variety Brown layer hens were randomly divided into 3 groups with 10 hens per group. Next, a genotype 3 avian HEV strain from China was used to inoculate laying hens via oronasal or intravenous routes using a 50% chicken infectious dose of 500. All hens were necropsied at 14 weeks postinoculation (wpi). Fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions showed that after intravenous (i.v.) and oronasal inoculation, the laying hens were successfully infected. Compared with the uninoculated group, the i.v. and oronasally inoculated groups exhibited egg production decreases at 1wpi and 2wpi, reaching peak production at 3wpi and 8wpi, respectively. In both groups, decreased production was evident for 12 weeks and overall decreases ranged from 10% to 30%. In addition, in the 7 field layer farms exhibiting decreased egg production, vaccination regimens had been completed against Newcastle disease, infectious bronchitis, avian influenza H9N2 and H5N1 and egg drop syndrome virus. However, circulating avian HEV was confirmed on these farms using tests to detect avian HEV IgG antibodies and RNA. Therefore, the experimental and field data indicate that avian HEV infection acting alone could account for observed decreases in egg production in laying hens.

The added value of hepatitis E diagnostics in determining causes of hepatitis in routine diagnostic settings in the Netherlands

ObjectivesHepatitis E virus (HEV) genotype 3 is endemic in Europe and an underdiagnosed and emerging (public) health issue. In recent years commercial enzyme immunoassays (EIAs) that detect antibodies to HEV more adequately, became available. We investigated the added value of this HEV serology in the diagnostic work flow to detect viral causes of recent hepatitis. MethodsDuring a 2-year period (May 2013 to May 2015), HEV serology was added to the hepatitis work flow, consisting of serological detection of hepatitis viruses A, B and C (HAV, HBV, HCV), Epstein–Barr virus (EBV) and cytomegalovirus (CMV). Samples positive for HEV IgM were also analysed using PCR to detect HEV RNA. If positive, HEV sequencing was performed for genotyping purposes. ResultsIn 235 out of 2521 patients (9.3%), a viral cause for hepatitis was found. Recent HAV, HBV, HCV, EBV or CMV infections were serologically diagnosed in 3, 34, 10, 69 and 42 patients, respectively. Seventy-eight patients (3.1%) had a recent HEV infection. In 49 of them, sufficient HEV RNA was present for genotyping. All patients were infected with HEV genotype 3. ConclusionsIn our region, an HEV infection is the most frequently diagnosed viral cause for recent hepatitis. These results indicate that, in a country where HEV is endemic, serological HEV diagnostics should be added to the standard work-up for viral hepatitis.

Persistent Hepatitis E Infection in a Patient with Tuberous Sclerosis Complex Treated with Everolimus: A Case Report.

IntroductionThe incidence of hepatitis E (HEV) genotype 3 is rising in developed countries. HEV infections are usually self-limiting, but can become chronic in immunocompromised patients. This might lead to rapid fibrosis development even resulting in cirrhosis. Chronic HEV is mainly described in patients after solid-organ or hematological transplantations. We present the first case of HEV infection in a patient with tuberous sclerosis complex (TSC) treated with everolimus, a mammalian target of rapamycin (mTOR) inhibitor.CaseA 46-year-old male with TSC was referred to the infectious diseases department with an acute rise of liver enzymes during routine laboratory check-up. He was diagnosed with an acute HEV infection. His current treatment for TSC was everolimus. After awaiting a spontaneous clearance for 3 months, everolimus was discontinued. Hereafter, the infection was cleared within another 3 months.DiscussionDue to a favorable side-effect profile, everolimus is gaining popularity as an immunosuppressive therapy. However, in vitro experiments suggest that inhibition of mTOR leads to a significant increase in HEV replication. Thus far, there have been no clinical reports of HEV infections in patients treated with everolimus.ConclusionDue to higher dosing of everolimus in TSC patients, they are more vulnerable to the development of chronic HEV infection. Periodic assessment of transaminases in these patients is advised.

Evaluation of two VIDAS ®prototypes for detecting anti-HEV IgG

BackgroundHigh performance anti-hepatitis E virus (HEV) IgG assays are crucial for epidemiology. ObjectiveTo evaluate the performance of 2 prototypes developed for the VIDAS® automatic system for detecting anti-HEV IgG, one based on the ORF2 antigen (ORF2 prototype) and the other on the ORF2 and ORF3 antigens (ORF2/3 prototype), with reference to the Wantai anti-HEV IgG assay. Study designThe sensitivity of each assay was determined by testing 113 blood samples, 63 from immunocompetent and 50 from immunocompromised patients, with a proven HEV infection defined by detecting HEV RNA. Their specificity was assessed with 103 blood samples that the Wantai assay indicated was negative for anti-HEV IgM and IgG, and negative for HEV-RNA. Cross reactivity was assessed using samples that were positive for hepatitis A virus IgG (n=16), hepatitis C virus antibodies (n=15), hepatitis B virus antigen and anti-HBc antibodies (n=16), rheumatoid factor (n=14), and negative for anti-HEV IgG with the Wantai assay. ResultsThe sensitivities in immunocompetent patients were: 95.2% (ORF2), 96.8% (ORF2/3), and 93.6% (Wantai); in immunocompromised patients they were: 66% (ORF2), 72% (ORF2/3), and 68% (Wantai). Both VIDAS prototypes detected low concentrations of anti-HEV IgG. The overall specificity was 100% (ORF2 prototype) and 98.1% (ORF2/3 prototype). Both VIDAS prototypes cross-reacted in five samples (9.6%), mainly those containing HCV antibodies or rheumatoid factor. ConclusionBoth VIDAS® prototypes performed very well and appear to be suitable for routine detection of anti-HEV IgG.

Molecular Epidemiology and Strain Comparison between Hepatitis E Viruses in Human Sera and Pig Livers during 2014 to 2016 in Hong Kong.

Hepatitis E virus (HEV) causes substantial morbidity and mortality in developing countries and is considered an emerging foodborne pathogen in developed countries in which it was previously not endemic. To investigate genetic association between human HEV infection and HEV-contaminated high-risk food in Hong Kong, we compared local virus strains obtained from hepatitis E patient sera with those surveyed from high-risk food items during 2014 to 2016. Twenty-four cases of laboratory-confirmed human HEV infections were identified from January 2014 to March 2016 in our hospitals. Five types of food items at risk of HEV contamination were purchased on a biweekly basis from April 2014 to March 2016 in two local market settings: supermarkets (lamb, oyster, and pig liver) and wet markets (oyster, pig blood curd, pig large intestine, and pig liver). HEV RNA detection was performed by a real-time reverse transcription-PCR assay. HEV RNA was detected in pig liver, pig intestine, and oyster samples with prevalences of 1.5%, 0.4%, and 0.2%, respectively. Neighbor-joining phylogenetic inference showed that all human and swine HEV strains belonged to genotype 4. HEV subtype distributions in humans and swine were highly comparable: subtype 4b predominated, while subtype 4d was the minority. Local human and swine HEV genotype 4 strains shared over 95% nucleotide identity and were genetically very similar, implicating swine as an important foodborne source of autochthonous human HEV infections in Hong Kong. Action should be taken to raise the awareness among public and health care professionals of hepatitis E as an emerging foodborne disease.

Seroprevalence of Hepatitis E Among Boston Area Travelers, 2009-2010.

AbstractWe determined the prevalence of IgG antibodies to hepatitis E virus (anti-HEV IgG) among travelers attending Boston-area travel health clinics from 2009 to 2010. Pre-travel samples were available for 1,356 travelers, with paired pre- and post-travel samples for 450 (33%). Eighty of 1,356 (6%) pre-travel samples were positive for anti-HEV IgG. Compared with participants who had never lived in nor traveled to a highly endemic country, the pre-travel prevalence odds ratio (POR) of anti-HEV IgG among participants born in or with a history of previous travel to a highly endemic country was increased (POR = 4.8, 95% CI = 2.3-10.3 and POR = 2.6, 95% CI = 1.4-5.0, respectively). Among participants with previous travel to a highly endemic country, anti-HEV IgG was associated with age > 40 years (POR = 3.7, 95% CI = 1.3-10.2) and travel history to ≥ 3 highly endemic countries (POR = 2.7, 95% CI = 1.2-5.9). Two participants may have contracted HEV infection during their 2009-2010 trip.

High seroprevalence against hepatitis E virus in patients with chronic hepatitis C virus infection

BackgroundHepatitis E virus (HEV) genotype 3 is endemic in Europe. Superinfection with HEV in patients with underlying chronic liver disease can cause hepatic decompensation leading to increased morbidity and mortality. ObjectivesThe prevalence of anti-HEV antibodies was investigated in 204 patients with chronic hepatitis C virus (HCV) infection and different stages of fibrosis. Study designSera were analyzed for anti-HEV IgG, IgM and HEV RNA. ResultsThe median age of the patients was 55 years (IQR 40–62 years); 126 (62%) were men. Ninety-eight (48%) patients had a METAVIR fibrosis stage F2 or higher. The prevalence of anti-HEV IgG was 30% (62/204), which was significantly higher than among Swedish blood donors (17%, p<0.01). The prevalence of anti-HEV antibodies was associated with higher age (OR 1.08 (1.05–1.11); p<0.01). It was also higher for patients with a prior history of blood transfusion (48%) as compared to intravenous drug use (IDU; 26%) as the risk factor for acquisition of the HCV infection (OR 2.72 (1.2–6.19); p<0.02). The prevalence of anti-HEV IgG was also significantly higher in patients with significant fibrosis, i.e. ≥F2 (38%; OR 2.04 (1.11–3.76); p=0.02) and/or neoplasm (72%; OR 7.27 (2.46–21.44); p<0.01). ConclusionsWhen adjusted for age, the prevalence of anti-HEV antibodies was significantly higher in patients with previous or current malignant liver disease compared to blood donors. The lack of significant correlation between HCV and HEV infections indicate low level of transmission of HEV by IDU. HEV infections warrant more attention, especially in patients with preexisting liver disease.

Familial Hepatitis E Outbreak Linked to Wild Boar Meat Consumption.

An HIV-infected patient was diagnosed with acute hepatitis E infection in our hospital. An epidemiological inquiry was performed to collect demographic, food and animal exposure variables in order to identify the potential route of transmission. The patient reported that his family traditionally hunted wild boar for food. All family members were analysed for hepatitis E virus infection. Additionally, route of transmission by wild boar meat consumption and prevalence of HEV infection among wild boar from the same hunting area were investigated. In all-family members (n=8), HEV-RNA was amplified. Two wild boar meat slices consumed was analysed, showing the presence of HEV. The virus isolated was consistent with genotype 3, revealing 100% homology between family members and meat. Additionally, we tested nine wild boar hunted in the same hunting area. All of them were RNA-HEV positive, isolating the same HEV genotype 3 viral strain. We demonstrated by phylogenetic analysis zoonotic transmission of HEV by wild boar meat consumption. The prevalence of HEV infection among wild boar found in our study suggests that this species is an important route of transmission to human.

THU-135 - Progesterone receptor mutations predisposes to HEV infection in the HIV-positive host

THU-135 - Progesterone receptor mutations predisposes to HEV infection in the HIV-positive host

Seroprevalence of Enterically Transmitted Hepatitis in North West India

Introduction: To ascertain the seroprevalence of enterically transmitted Hepatitis A (HAV) and Hepatitis E (HEV) in cases with acute/subacute hepatitis attending a tertiary care hospital in North West India. Methods: A total of 2936 cases were examined for the presence of current infection with HAV and HEV, determined by demonstration of HAV-IgM and HEV-IgM antibodies using ELISA. Results: Overall seroprevalence for enterically transmitted hepatitis was found to be 24.89%. HAV IgM was present in 7.35% and HEV IgM was present in 17.54% of total cases. HAV infection was predominantly found in pediatric age group while HEV infection was mostly seen among adults. Male preponderance was noted. Enteric hepatitis cases occurred throughout the year. No definitive seasonal pattern was observed. Conclusion: Our data demonstrated high seropositivity of enterically transmitted hepatitis indicating the need for improvement in personal and public hygiene, and development of HEV vaccine.