Hepatitis E Virus Infection In Patients Research Articles

Incidence and risk factors of de novo hepatitis E virus infection after receiving liver transplantation.

Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.

Aggravating Effects of Hepatitis E Virus Infection on Patients with Chronic Liver Disease in Ibn-Sina Hospital Sudan

Background: Hepatitis E virus (HEV) is one of the most common causes of acute hepatitis. Sudan is considered as hyper-endemic for HEV. HEV infection in patients with preexisting chronic liver diseases (CLDs) has been reported to result in severe clinical manifestations and poor outcomes. However data on the role of HEV infection in worsening of pre-existing CLD are limited.
 Objective: To determine hepatitis E virus (HEV) infection and its effect on severity of CLD.
 Methods: A descriptive cross-sectional study that consecutively enrolled 87 CLD patients in Ibn-Sina Specialized Hospital was carried out during the period from August 2020 to December 2020. Data regarding demographics, CLD causes, clinical manifestations and comorbidities were collected. The screening for anti-HEV antibodies was performed in all patients by using enzyme linked immuno-sorbent assay (ELISA).
 Results: Hepatitis B virus (HBV) was the commonest etiology of chronic liver diseases being detected in 45/87(51.7%) patients. On the other hand;among all subjects; 43/87(49.4%) patients were HEV seropositive with anti-HEV Ig-G being detected in 32(36.8%) and concurrent anti-HEV Ig-M and Ig-G in 11(12.6%) patients. Jaundice (OR= 3.8, CI95%: 1.5-9.4; P. value=0.004), HCC (OR= 4.1, CI95%: 1.4-11.9; P. value=0.008), child-Pugh class-C (OR= 26, CI95%: 5.4-94.0; P. value=0.000) and child-Pugh class-B (OR= 5.3, CI95%: 1.6-17.0; P. value=0.000) were associated independently with anti-HEV positivity.
 Conclusion: The frequency of hepatitis E virus (HEV) among Sudanese patients with chronic liver disease (CLD) was considerably high (mainly past infection- Ig-G). Furthermore, HEV was associated with advanced liver failure statuses (child-Pugh class-B & C), jaundice, and hepatocellular carcinoma.

Prevalence of Hepatitis A Virus and Hepatitis E Virus Infection in the Patients Presenting with Acute Viral Hepatitis in Eastern India: A Cross-sectional Study

Introduction: Enterically transmitted Hepatitis A Virus (HAV) and Hepatitis E Virus (HEV) are the most common cause of Acute Viral Hepatitis (AVH) and a major health concern in developing nations like India. Both viruses cause AVH and are spread predominantly through the faecal-oral pathway, most commonly through contaminated water. Aim: To estimate the prevalence of HAV and HEV infection in patients presenting with AVH. Materials and Methods: An analytical cross-sectional study was undertaken in Indira Gandhi Institute of Medical Sciences, Bihar. The study was conducted over a period of 24 months from November 2019 to October 2021. All patients presenting with AVH were included as study participants. The blood samples were subjected to test anti-HAV and anti-HEV positivity. Prevalence of HAV and HEV was calculated taking total cases of AVH as denominator. Patients with confirmed infection with HCV, HBV and any other cause of hepatitis were excluded from the study. Templates were generated in an Microsoft Excel spreadsheet and analysis of data was done using Statistical Package of the Social Sciences software (SPSS) version 20.0. Quantitative data were presented as frequency and percentages. Results: A total of 682 patients presented with acute hepatitis. The AVH patients comprised 467 males (68.5%) and 215 (31.5%) females with the mean age 39.6±18.87 years. The current study reports the seroprevalence of 9.18% HAV and 8.35% of HEV. A total of 4 patients tested positive for coinfection with HAV and HEV. Most of the HAV patients belonged to an age group less than or equal to 12 years (25,58.1%) and none were more than 60 years. However, none of the HEV patients were children and most of them were aged between 13 to 60 years (46,92%). A male preponderance among HAV (28,65.1%), and HEV (38,76%) was noted. Conclusion: Low seroprevalence was noted, with infection more common in younger age group and male patients. Further studies and vaccination along with surveillance system strengthening are warranted.

Hepatitis E infection in adults with primary immunodeficiency with or without immunoglobulin replacement therapy.

In a context of secondary immunodeficiency, hepatitis E virus (HEV) infection can be responsible for chronic liver disease. We investigated HEV infection in patients with primary immunodeficiency treated (or not) with immunoglobulin (Ig) replacement therapy (IgRT) in France, a country with a high seroprevalence of HEV. In a nationwide study of individuals with primary immunodeficiency, 533 patients (349 and 184 receiving IgRT or not, respectively) were tested for HEV RNA and anti-HEV antibodies. In addition, 23 batches of five different commercially available immunoglobulin preparations were screened for anti-HEV IgG. Three of the 533 patients displayed markers of a recent HEV infection (HEV RNA in one case, and anti-HEV IgG and IgM in two) but no evidence of chronic liver disease. The overall seroprevalence of HEV was 50% (266 out of 533), with values of 68% and 16% in patients receiving IgRT or not, respectively (p<0.001). Anti-HEV IgG were detected in all batches of immunoglobulin preparations, although the titer varied from 3 to 127 IU/g IgG. Seroconversion was observed in 15 of the 22 (68%) patients tested before and after IgRT. No cases of chronic HEV-related disease were detected among patients with primary immunodeficiency and hypogammaglobulinemia, whether they received IgRT or not. This confirms that patients with primary immunodeficiency have a low risk of chronic infection despite a seroprevalence close to that observed in the French general population and that IgRT, which confers a high HEV seroprevalence, might play a key role in protection against chronic infection.

Hepatitis E Virus Infection in Cancer Patients

Hepatitis E virus (HEV) infection in immunocompetent patients can lead to chronic hepatitis and liver failure. However, the burden of HEV infection in cancer patients is largely unknown. We studied the characteristics of HEV infection in patients at a tertiary care cancer center in the United States. This retrospective study included adult cancer patients with HEV infection diagnosed between September 2011 to September 2021. A total of 405 patients were tested for HEV, and 63 (16%) had detectable HEV IgG. Thirty-three patients (52%) were male, 43 were born in America (68%), 46 (73%) were screened for HEV because of pre-existing liver conditions, and 22 (35%) had hematological malignancies. Only 2 patients had detectable HEV RNA. The first patient had myelodysplastic syndrome and underwent allogeneic stem cell transplantation (HSCT). He developed elevated liver enzymes with HEV RNA 14,000 IU/mL (4.2 log IU/mL) 13 months after HSCT. After reducing immunosuppression, his HEV viremia resolved. The second patient had diffuse large B-cell lymphoma and underwent anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. She had elevated liver enzymes with HEV RNA 4,560,000 IU/mL (6.7 log IU/mL) 12 months after CAR T-cell therapy. She developed chronic HEV infection, and ribavirin treatment failed. Now she is being considered for salvage treatment with peginterferon alfa-2a and ribavirin. This study is the first report of chronic HEV infection in patients who received CAR T-cell therapy. HEV infection in cancer patients appears to be at least as common as in the general population. Cancer patients with hematologic malignancies may be at risk for HEV viremia and chronic infection refractory to antiviral treatment.

Prevalence of anti-hepatitis E virus IgG antibodies in sera from hemodialysis patients in Tripoli, Lebanon.

Hepatitis E virus (HEV) is an important global public health concern. Several studies reported a higher HEV prevalence in patients undergoing regular hemodialysis (HD). In Lebanon, the epidemiology of HEV among HD patients has never been investigated previously. In this study, we examine the seroprevalence of HEV infection among 171 HD patients recruited from three hospital dialysis units in Tripoli, North Lebanon. Prevalence of anti-HEV IgG antibodies was evaluated in participant’s sera using a commercial enzyme-linked immunosorbent assay (ELISA). The association of socio-demographic and clinical parameters with HEV infection in patients was also evaluated. Overall, 96 women and 75 men were enrolled in this study. Anti-HEV IgG antibodies were found positive in 37/171 HD patients showing a positivity rate of 21.63%. Among all examined variables, only the age of patients was significantly associated with seropositivity (P = 0.001). This first epidemiological study reveals a high seroprevalence of HEV infection among Lebanese HD patients. However, further evaluations that enroll larger samples and include control groups are required to identify exact causative factors of the important seropositivity rate in this population.

Seroprevalence of hepatitis E virus infection in acute leukemia patients with allogeneic transplantation

Aim: Hepatitis E Virus (HEV) infection is an emerging threat in allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT) recipients. The aim of this study was to determine the prevalence of HEV infection in patients with acute leukemia before and after the transplantation.Material and Methods: The study was carried out with the serum samples taken before and after the transplantation from patients (n=42) with acute leukemia, who were 4 months to 64 years of age and who had allogenic transplant at Gazi University Hospital. All samples were tested in terms of HEV-specific anti-IgG and IgM positive value by using ELISA kit.Results: While 1 (2.3%) of the samples that were included in the study was positive anti-HEV IgG before transplantation, it was found negative after the transplantation (58th month). Positive anti-HEV IgM was not found before and after the transplantation in the collected samples. The average age of the seronegative group was determined as 30.8 ± 33.1 for male and female, respectively. There was no statistically significant difference in terms of anti-HEV IgM positivity and anti-HEV IgG positivity compared with seronegative cases of seropositive cases. Conclusions: This study was conducted to determine the prevalence of HEV infection in allogeneic stem cell patients. With this study, the incidence and importance of HEV can be determined in these patients before and after transplantation. This study can also create an important epidemiological data for our country.

Hepatitis E virus genotype 3 is associated with gallstone-related disease

Objective: Hepatitis E virus (HEV) genotype 3 is endemic in Northern Europe and despite a high seroprevalence of anti-HEV IgG antibodies among blood donors (≈17%), few clinical cases are notified in Sweden. Low awareness of hepatitis E and its possible symptoms may contribute to this discrepancy. The aim of this study was to investigate the prevalence of acute HEV infection among hospital admitted patients with abdominal pain and elevated liver enzymes.Materials and methods: During 2016–2017, 148 adult patients with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > twice normal levels were prospectively enrolled at surgical wards at three Swedish hospitals. Serum samples were analyzed for HEV RNA as well as anti-HEV IgM and IgG, and medical records were reviewed.Results: Six (6/148, 4.1%) patients were HEV infected confirmed by detectable HEV RNA, but only one of these patients had detectable anti-HEV antibodies. Four of the HEV infected patients were diagnosed with gallstone-related disease: three with biliary pancreatitis and one with biliary colic. The remaining two were diagnosed with bowel obstruction and pancreatic malignancy. Four HEV strains were typed by sequencing to genotype 3.Conclusions: This study identified acute HEV3 infection in 4% of the patients with elevated liver enzymes admitted to a surgical ward. HEV infection was not the solitary disease leading to hospitalization, instead it was found to be associated with other surgical conditions such as gallstone-related disease including biliary pancreatitis. Additionally, HEV RNA might be the preferential diagnostic tool for detecting ongoing HEV infection.

The Clinical Perspective on Hepatitis E.

Every year, there are an estimated 20 million hepatitis E virus (HEV) infections worldwide, leading to an estimated 3.3 million symptomatic cases of hepatitis E. HEV is largely circulating in the west and is associated with several hepatic and extrahepatic diseases. HEV Genotype 1 and 2 infections are waterborne and causative for epidemics in the tropics, while genotype 3 and 4 infections are zoonotic diseases and are mainly transmitted by ingestion of undercooked pork in industrialized nations. The clinical course of these infections differs: genotype 1 and 2 infection can cause acute illness and can lead to acute liver failure (ALF) or acute on chronic liver failure (ACLF) with a high mortality rate of 20% in pregnant women. In contrast, the majority of HEV GT-3 and -4 infections have a clinically asymptomatic course and only rarely lead to acute on chronic liver failure in elderly or patients with underlying liver disease. Immunosuppressed individuals infected with genotype 3 or 4 may develop chronic hepatitis E, which then can lead to life-threatening cirrhosis. Furthermore, several extra-hepatic manifestations affecting various organs have been associated with ongoing or previous HEV infections but the causal link for many of them still needs to be proven. There is no approved specific therapy for the treatment of acute or chronic HEV GT-3 or -4 infections but off-label use of ribavirin has been demonstrated to be safe and effective in the majority of patients. However, in approximately 15% of chronically HEV infected patients, cure is not possible.

Infectious Hepatitis: A 3-Year Retrospective Study at a Tertiary Care Hospital in India

AbstractContext: Acute viral hepatitis (AVH) is predominantly caused by hepatitis A virus (HAV) and hepatitis E virus (HEV), the prevalence of which varies in different geographical regions. Aims: This study aimed to determine the prevalence of HAV and HEV infections in patients with AVH, the rate of HAV-HEV co-infection and the prevalence of HEV infection among pregnant women with hepatitis. Settings and Design: It was a retrospective observational study conducted over 3 years from January 2015 to December 2017, after obtaining clearance from the institutional ethics committee. Subjects and Methods: A total of 675 serum samples were collected from patients with a clinical diagnosis of AVH, between January 2015 and December 2017. The study population included outdoor and hospitalised patients between 3 and 70 years of age who presented with signs and symptoms of hepatitis. The presence of IgM anti-HAV and IgM anti-HEV antibodies in serum were assessed by enzyme-linked immunosorbent assay. Statistical Analysis Used: Chi-square test. Results: The prevalence of HAV, HEV and HAV-HEV co-infection was found to be 6.96%, 9.63% and 2.07%, respectively. Among males, this was 7.3%, 8.8% and 2.6%, respectively and in females 6.7%, 10.2% and 1.7%, respectively. However, these differences in the prevalence rates were of no statistical significance. The prevalence of HEV infection in pregnant women with hepatitis was 9.4%. HAV and HEV infections showed a seasonal trend with predominance during summer and rainy seasons (May to September). Conclusions: A higher seroprevalence of HEV as compared to HAV together with a co-infection rate of 2.07% mandates screening for HEV in all suspected cases of acute hepatitis, particularly pregnant women in whom the outcomes of HEV infection are poor. Health and civic authorities should make necessary efforts to counter epidemic or outbreak situations, thus reducing morbidity, mortality and economic burden.

Prevalence of Viral Liver Disease and Oral Lichen Planus in Patients Who Visited Dental Clinics: A Study by the Ehime Dental Association

Background: The association between hepatitis C virus (HCV) infection and oral lichen planus (OLP), an extrahepatic manifestation, is well known. There are still patients with viral liver disease in this country who are not receiving appropriate treatment. This prospective study aimed to evaluate the prevalence of OLP and untreated hepatitis virus infection in patients who visited dental clinics in Ehime prefecture, in western Japan. Methods: Patients who visited 35 dental clinics in Japan from March 2018 to June 2018 were analyzed. The items examined are as follows: (1) the number who visited the dental clinics, (2) the numbers of OLP patients, HCV-infected patients, and hepatitis B virus (HBV)-infected patients, (3) the numbers of OLP patients, HCV-infected patients and HBV-infected patients encouraged to be examined for liver diseases. Results: There were 19,077 patients in total and the numbers of OLP, HCV-infected and HBV-infected patients were 42, 69 and 76, respectively. Of the OLP patients, 66.7% (28/42) were encouraged to be examined for liver disease and 47.6% (20/42) had complications of liver disease. The most common complication was HCV-related liver disease (70%, 14/20) and 78.6% had not eliminated HCV (p=0.0287). The dentists encouraged 33.3% of the HCV-infected patients and 36.8% of the HBV-infected patients to be investigated by physicians for liver disease. Of the 69 patients with hepatitis C, the rate of persistent infection was significantly higher than that with viral clearance (72.5%, p=0.0001). Conclusions: Among the various dental clinics in Ehime prefecture, half of OLP patients had complication of liver disease, many of them with persistent HCV infection. Dentists need to have knowledge of liver disease and infection control measures and provide information through medical cooperation.

Hepatitis E Virus Infection after Haploidentical Hematopoietic Stem Cell Transplantation:Incidence and Clinical Course

Introduction: Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic hematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients treated with haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients.Methods: From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV infection using HEV serology. HEV RNA were performed when HEV-IgG and/or IgM antibodies were positive.Results: Acute HEV infection was identified in seven of these patients (3.9%), none of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17.5 (range, 6-55) months. Median peak alanine transaminase during HEV infection was 716 (range, 164-1763) U/L. In 7 cases, HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n=5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n=2). None patients died of HEV infection directly. Two patients with HEV infection died showing signs of ongoing hepatitis and the median duration of HEV infection was 2.7 months. Five patients cleared HEV and the median duration of HEV infection was 1.5 (range, 1.0-5.7) months.Conclusions: In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV infection in haplo-HSCT. DisclosuresNo relevant conflicts of interest to declare.

Absence of Persistent Hepatitis E Virus Infection in Antibody-Deficient Patients Is Associated With Transfer of Antigen-Neutralizing Antibodies From Immunoglobulin Products.

Persistent hepatitis E virus (HEV) infection is described in a number of immunosuppressive conditions. We aimed to determine the risk of persistent HEV infection in patients with primary or secondary antibody deficiency. Two hundred forty-five antibody-deficient patients receiving regular immunoglobulin replacement therapy were tested for HEV RNA and anti-HEV immunoglobulin G (IgG). Immunoglobulin products and plasma specimens obtained from 9 antibody-deficient patients before and after intravenous immunoglobulin (IVIG) therapy, 5 recently treated patients with persistent HEV infection, and 5 healthy patients recovered from acute HEV infection were analyzed for anti-HEV IgG and for antibody reacting with HEV antigen. No antibody-deficient patient had detectable plasma HEV RNA. Anti-HEV IgG was detected in 38.8% of patients. All 10 immunoglobulin products tested contained anti-HEV capable of neutralizing HEV antigen. Plasma samples collected following IVIG infusion therapy demonstrated a higher anti-HEV IgG level and neutralizing activity, compared with samples collected before IVIG therapy. Neutralizing activity was similar to that in healthy patients with recent acute HEV infection. The risk of persistent HEV infection in patients with antibody deficiency appears extremely low. This may be due to passive seroprotection afforded by the ubiquitous presence of anti-HEV in immunoglobulin replacement products.

Sero - Epidemiology of Hepatitis E and D Infections among HIV - Infected and HIV/HCV - Coinfected Patients in Jahrom, Southern Iran

Background: Co - infection of hepatitis E virus (HEV) and hepatitis D virus (HDV) in human immunodeficiency virus (HIV) infected patients can develop and increase hepatic complications in the world, particularly in developing countries. Objectives: The purpose of this study was to assess and compare the sero - virological prevalence of HEV and HDV in patients bearing HIV infection and HIV/HCV co - infection, as well as their relation to clinical and demographic data. Methods: Cross - sectional study testing IgM/IgG anti - HEV and total antibodies HDV in serum samples belong to 73 HIV infected patients and co - infected HIV - HCV patients were evaluated. Demographic, lifestyle, and laboratory data such as CD4 counts and viral load were prospectively collected on each patient with the HIV infection. Results: There were 26 HEV infected patients IgG positive, two HEV infected patients IgM positive, two HDV infected patients total antibodies positive, and only one HDV infected patient IgM among the 73 HIV infected patients. The prevalence of HDV positive IgG and total anti - HDV among co - infected patients were 2.2% and 2.2%. In addition 18 (69.2%) and 2.2% were positive for anti - HEV IgG and IgM, respectively. Furthermore, HIV viral load among HIV co - infected patients with HEV or HDV were shown higher compared to patients solely infected with only HIV. Also, the numbers of HEV or HDV positive were high in low levels of CD4. Conclusions: According to the results, frequency of occurrence of hepatitis E was higher than hepatitis D in HIV infected patients. Severity of HIV infection and liver damage caused by HEV and HDV infections were in a direct relationship. Hence, HIV and HCV screening should be implemented in HIV - infected patients with liver damage.

Hepatitis E virus infection and acute non-traumatic neurological injury: A prospective multicentre study

Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury. Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands. Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8-145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus. In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted. Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system.

The Epidemiology and Prevention of Hepatitis E Virus Infection

Hepatitis E virus (HEV) infections are a global public health problem. These viruses were originally identified as the cause of large waterborne outbreaks with increased mortality in pregnant women in developing countries in Asia and Africa in 1983. A decade later, locally acquired cases of acute hepatitis were reported in industrialized countries after food-borne transmission from an animal reservoir, especially swine, wild boar, and deer. However, the knowledge about the clinical features of HEV infection, the animal reservoirs, and virus characteristics has expanded substantially in recent years. HEV infections in patients who are immunosuppressed after a solid organ transplant and AIDS or cancer chemotherapy frequently develop chronic hepatitis. Some patients with chronic HEV infection develop extra-hepatic manifestations, especially neurologic symptoms. Clinical observations support the effectiveness of ribavirin therapy from chronic HEV. Recent research has found an expanded animal reservoir of Hepeviridae that are human pathogens and strains that are only animal pathogens. A consensus classification of Hepeviridae has been published recently. The risk of transfusion transmission of HEV has been quantified and selected donor screening implemented in two countries in the last few years. Recent research has greatly expanded scientific information on the diversity and zoonotic reservoirs of Hepeviridae as well as the epidemiology and clinical features of HEV infection in humans.

Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis.

Hepatitis E virus (HEV) infection can cause hepatic and extra-hepatic manifestations. Treatment of HEV infection has been thoroughly studied in solid-organ-transplant patients who have developed a chronic HEV infection. In this review, we report on our current knowledge regarding treatment of HEV infection.

Serum Levels of Soluble CD26, A Novel Prognostic Marker for Hepatitis E Infection.

Background:Even without treatment, most acute hepatitis E virus (HEV) infected patients resolve HEV but sometimes the disease leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of HEV pathogenesis appear to be substantially immune mediated. However, the immune responses to HEV are not precisely identified.Objectives:This study aimed to evaluate the Th1/Th2 ratio by investigating serum soluble markers from Th1 and Th2 cells in acute HEV infected patients.Patients and Methods:This case-control study included 35 acute HEV infected patients and 35 age and gender matched anti-HEV negative healthy controls. The serum levels of Interferon (IFN)-γ, IL-4, soluble CD26 (sCD26) and sCD30 were determined by the enzyme-linked immunosorbent assay.Results:The results showed a significant difference in IFN-γ and sCD26 (P < 0.0001 and P = 0.001) yet not IL-4 and sCD30 (P = 0.354 and P = 0.159) between acute HEV patients and controls, respectively. There was a positive direct correlation between serum levels of sCD26 and IFN-γ in acute HEV patients (r = 0.64, P = 0.001). In addition, the ratio of sCD26/sCD30 in the acute HEV group was more than two folds higher than in the HEV negative controls.Conclusions:Acute HEV infection shows a pattern of Th1-type immune response, and the direct significant positive correlation between the serum level of sCD26 and IFN-γ in acute HEV infected patients, suggests that the trend of sCD26 levels is a valuable marker for predicting hepatic inflammation in hepatitis E.

A Public Health initiative on hepatitis E virus epidemiology, safety and control in Portugal--study protocol.

BackgroundThe discovery of autochthonous hepatitis E in industrialized countries has changed the understanding of hepatitis E virus (HEV) infection in these regions, now known to be mainly due to zoonotic transmission of genotype 3. The foodborne route of transmission via consumption of contaminated meat from HEV infected pigs is well documented as well as the direct occupational exposure to animal reservoirs. Accumulating evidence also points to an emerging potential threat to blood safety after the identification of viremic blood donors and the documentation of HEV-contaminated blood or blood products. Moreover, the origin of several iatrogenic cases remains unclear and porcine-derived pharmaceutic products have been suspected as a cause. Severe morbidity following HEV infection in patients receiving immunosuppressive therapy and in those with severe immunodeficiency from other causes has been recently recognized as a serious consequence of this infection in industrialized countries. In Portugal no large-scale HEV seroprevalence study has been undertaken, no professional risk groups have been identified, and the risk of blood donation from HEV silent infected donors is unknown. The present paper describes seroepidemiological and molecular approaches to answer these questions.Methods/designTo address these issues a study protocol was designed that will approach: i) the seroprevalence of HEV among the Portuguese general population; ii) HEV infection among butchers and slaughterhouse workers (occupational risk); iii) the silent HEV infection in Portuguese blood donors (HEV transfusion-associated risk); iv) the potential HEV contamination of porcine-derived pharmaceutical products. Commercial enzyme immunoassays and real-time/conventional RT-PCR assays will be used.DiscussionThis study is the first evaluation of the seroepidemiological status to HEV infection of the Portuguese population, the first to potentially identify professional risk groups, and to evaluate the safety of blood and blood products and porcine-derived pharmaceutics in Portugal. It will generate valuable data applicable for preventive and control measures against HEV infection (e.g., introduction of systematic screening of blood donors, control of blood products or porcine derived pharmaceutical products), thus helping to manage the burden of this viral disease.

Hepatitis E In Transplant Recipients: Why Is This Not A Problem In Japan?

Chronic hepatitis E virus (HEV) infection in immunosuppressed patients is increasingly recognized as a relevant clinical problem in European countries. However, it is unclear whether chronic hepatitis E is also a potential problem in eastern Asia. The study by lInagaki et al. published in this issue of EBioMedicine is therefore of major interest (Inagaki et al., 2015). The authors performed a large multi-center study examining the frequency and clinical relevance of chronic hepatitis E in Japanese liver transplant recipients. About 75% of all liver transplant centers participated in this study, comprising HEV-RNA testing of 1651 liver transplant recipients. Of note and very importantly, only two chronic HEV infections were detected, which is a surprisingly low rate of HEV infected patients (0.12%). The finding is remarkable considering that the median time from transplantation was 81 months (range 0–297 months) representing a long time of potential exposure post-transplantation. The findings in Japan are quite different from European experiences where many studies describe frequencies of chronic hepatitis E of more than 1% in liver transplant cohorts (Fig. 1) (Behrendt et al., 2014). In contrast, no case of chronic hepatitis E was found in India in a study on 205 renal transplant recipients (Naik et al., 2013). This has led to the hypothesis that HEV genotype 1, which is common in India, may not cause chronic infection. However, most reported cases of chronic hepatitis E are associated with HEV genotype 3 infections, and more rarely HEV genotype 4. In Japan, HEV genotypes 3 and 4 are endemic (Okano et al., 2014). The HEV subtype 3e is most frequently found in Japan (Okano et al., 2014), as in Central Europe. HEV genotypes or subtypes are therefore unlikely to explain the apparent differences in chronic HEV frequencies — even though it is still possible that distinct HEV strains circulating in Japan may be less likely to cause chronicity. Fig. 1 Chronic hepatitis E in Japanese liver transplant recipients is less common than in Europe (Behrendt et al., 2014). What then could explain the very low frequency of chronic hepatitis E in Japan (Fig. 1)? First, it is possible that distinct genetic factors in the Japanese population confer some level of resistance to chronic HEV infection. For other infections such as hepatitis C, differences in interferon-lambda 3 genotypes between Asians and Caucasians indeed explain, to some extent, distinct outcomes in these populations (Thursz et al., 2011). Second, there are obvious differences in food consumption habits between Japan and Europe. Regarding HEV infection, food products containing raw or undercooked pork meat are particular popular in some European countries and thus exposure to HEV may be more likely. Third, blood products may be less likely to carry HEV in Japan than in Europe (Hewitt et al., 2014). Of note, HEV-IgG antibodies have been shown to be lower in Japan (6%) than in Korean Chinese (51%), indigenous Chinese (48%), South Koreans (34%) or Koreans living in Japan (14%) (Taniguchi et al., 2009). In summary, Inagaki et al. demonstrated for the first time that chronic hepatitis E also occurs in Japan, albeit at a far lower frequency than in European transplant cohorts. The explanation for this difference still needs to be defined.