BACKGROUND: Establishing the safety and immunogenicity of a hepatitis E virus vaccine in multiple populations could facilitate broader access and prevent maternal and infant mortality.
METHODS: We conducted a phase 1, randomized, double-blinded, placebo-controlled (4:1 vaccine: placebo) trial of 30 µg HEV-239 (Hecolin®, Xiamen Innovax Biotech Company Limited, China) administered intramuscularly in healthy US adults aged 18-45 years. Participants were vaccinated on days 1, 29, and 180. Participants reported solicited local and systemic reactions for 7 days following vaccination and were followed through 12 months after enrollment for safety and immunogenicity (IgG, IgM).
RESULTS: Solicited local and systemic reactions between treatment and placebo group were similar and overall mild. No participants experienced serious adverse events related to HEV-239. All participants receiving HEV-239 seroconverted at one month following the first dose and remained seropositive throughout the study. HEV-239 elicited a robust hepatitis E IgG response that peaked one month following the second dose (Geometric Mean Concentration (GMC) 6.16; 95% CI 4.40-8.63), was boosted with the third dose (GMC 11.50; 95% CI 7.90-16.75) and persisted through 6 months.
CONCLUSIONS: HEV-239 is safe and elicits a durable immune response through at least 6 months after the third dose in healthy US adults.
BACKGROUND: NCT03827395. Safety Study of Hepatitis E Vaccine (HEV239) - Full Text View - ClinicalTrials.gov.

Hepatitis E is a disease associated with acute inflammation of the liver. It is related to several dysregulated metabolic pathways and alterations in the concentration of several metabolites. However, longitudinal analysis of the alterations in metabolites and lipids is generally lacking. This study investigated the changes in levels of metabolites and lipids over time in sera from men with acute hepatitis E compared to healthy controls similar in age and gender. Untargeted measurement of levels of various metabolites and lipids was done using mass spectrometry on 65 sera sequentially sampled from 14 patients with acute hepatitis E and 25 serum samples from five controls. Temporal changes in intensities of metabolites and lipids were determined over different times at 3-day periods for the hepatitis E virus (HEV) group. In carbohydrate metabolism, glucose levels, fructose 1-6-bisphosphate and ribulose-5-phosphate were increased in the HEV-infected persons compared to the healthy controls. HEV infection is significantly associated with decreased levels of inosine, guanosine, adenosine and urate in purine metabolism and thymine, uracil and β-aminoisobutyrate in pyrimidine metabolism. Glutamate, alanine and valine levels were significantly lower in the HEV group than in healthy individuals. Homogentisate of tyrosine metabolism and cystathionine of serine metabolism were increased, whereas kynurenate of tryptophan metabolism decreased in the HEV group. Metabolites of the bile acid biosynthesis, urea cycle (arginine and citrulline) and ammonia recycling (urocanate) were significantly altered. Co-enzymes, pantothenate and pyridoxal, and co-factors, lipoamide and FAD, were elevated in the HEV group. The acylcarnitines, sphingomyelins, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC and lysoPE tended to be lower in the HEV group. In conclusion, acute hepatitis E is associated with altered metabolite and lipid profiles, significantly increased catabolism of carbohydrates, purines/pyrimidines and amino acids, and decreased levels of several glycerophospholipids.

BACKGROUND: A novel equine parvovirus (EqPV-H) was recently discovered in the equine liver with Theiler\'s disease.
OBJECTIVE: To determine the prevalence of EqPV-H infection in naturally occurring Theiler\'s disease cases and in-contact horses in the absence of historical equine biologic product administration.
METHODS: Ten cases of Theiler\'s disease from 6 separate properties were included in the study, based on the criteria of acute onset of clinical signs of liver failure with laboratory or histopathologic findings characteristic of Theiler\'s disease and no history of receiving an equine biologic product within the preceding 4 months. In addition, 37 in-contact horses from 4 of the 6 properties were screened for EqPV-H infection and hepatitis.
METHODS: In prospective case series, cases were diagnosed with Theiler\'s disease by the attending veterinarian and were tested for EqPV-H by PCR of liver or serum. In-contact horses were assessed via serum chemistry and PCR at the attending veterinarian\'s discretion. Hepatitis was defined as serum gamma-glutamyltransferase activity above reference interval. The association of EqPV-H with hepatitis was determined by Fisher\'s exact test.
RESULTS: Nine of 10 (90%) Theiler\'s disease cases and 54% of tested in-contact horses were EqPV-H positive. Hepatitis was significantly associated with EqPV-H infection (P = .036).
CONCLUSIONS: Although further study is required to identify EqPV-H as the causative agent of Theiler\'s disease, EqPV-H appears strongly associated with cases of fatal Theiler\'s disease and subclinical hepatitis in horses in contact with those cases. The prevalence of EqPV-H infection on affected properties can be high.

Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis in both developed and developing countries. This infectious disease has a high prevalence and incidence in Europe. HEV infection has a greater clinical impact in vulnerable populations, such as immunosuppressed patients, pregnant women and patients with underlying liver disease. Therefore, the Study Group for Viral Hepatitis (Grupo de Estudio de Hepatitis Víricas, GEHEP) of the Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica, SEIMC) believed it very important to prepare a consensus document to help in decision-making regarding diagnosis, clinical and therapeutic management, and prevention of HEV infection.

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 12 weeks 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 6 months. The mean age ± SD was 7.1 ± 3.7 years (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 45 days. 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.

OBJECTIVE: Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy.
METHODS: Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA.
RESULTS: Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anaemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed.
CONCLUSIONS: Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viraemia may be the best regimen for this indication.

OBJECTIVE: The study was planned to evaluate the efficacy and safety of Livwin (polyherbal formulation) in acute viral hepatitis.
METHODS: In this study, there were 29 patients in each group, receiving either Livwin (containing Ashwagandha, Arjuna, Bhumyamalaki, Daruharidra, Guduchi, Kutki and Punarnava) or placebo capsules containing lactose powder (500 mg). Both drugs were given orally two capsules two times a day for eight weeks followed by treatment free period of four weeks. Recovery of patients was assessed by noting symptomatic recovery and by measuring levels of serum bilirubin, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), alkaline phosphatase at baseline, 2, 4, 8 and 12 weeks.
RESULTS: Significant earlier recovery of weakness was observed with Livwin as compared to placebo at 2, 4 and 8 weeks. Serum bilirubin and ALT was observed in normal range in significantly more number of patients with Livwin treatment as compared to placebo at 2, 4 and 8 weeks. AST was observed in normal range in significantly more number of patients with Livwin treatment as compared to placebo at 2 and 4 weeks.
CONCLUSIONS: Livwin is found effective in uncomplicated patients of acute viral hepatitis. Epigastric pain and diarrhea were reported with Livwin treatment.