The Hepatitis E Virus Open Reading Frame 2 Protein: Beyond Viral Capsid

Hepatitis E virus (HEV) is a zoonotic pathogen causing hepatitis in both human and animal hosts, which is responsible for acute hepatitis E outbreaks worldwide. The 7.2 kb genome of the HEV encodes three well-defined open reading frames (ORFs), where the ORF2 translation product acts as the major virion component to form the viral capsid. In recent years, besides forming the capsid, more functions have been revealed for the HEV-ORF2 protein, and it appears that HEV-ORF2 plays multiple functions in both viral replication and pathogenesis. In this review, we systematically summarize the recent research advances regarding the function of the HEV-ORF2 protein such as application in the development of a vaccine, regulation of the innate immune response and cellular signaling, involvement in host tropism and participation in HEV pathogenesis as a novel secretory factor. Progress in understanding more of the function of HEV-ORF2 protein beyond the capsid protein would contribute to improved control and treatment of HEV infection.

Acute Hepatitis E Virus Superinfection Increases Mortality in Patients with Cirrhosis

Background: Although acute hepatitis E is not fatal in healthy individuals, it is unclear whether hepatitis E superinfection increases mortality in patients with pre-existing liver disease. Thus, we investigated the prognosis of patients with acute hepatitis E according to their cirrhosis diagnosis, and the prognosis according to the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis and chronic liver disease (CLD). Methods: This study included 74 consecutive patients who were diagnosed with acute viral hepatitis E between January 2007 and December 2019. Of them, 39 patients without CLD, 13 patients with non-cirrhotic CLD, and 22 patients with cirrhotic CLD were analyzed. Results: Among the 74 patients with HEV infection, 7 (9.5%) died within 180 days: 5 with underlying cirrhosis (71.4%) and 2 without cirrhosis (28.6%). The 180-day mortality was significant higher for patients with cirrhosis than for patients without cirrhosis (22.7% vs. 3.8%, P = 0.013). The age- and sex-adjusted proportional-hazard model revealed an approximately 8-fold increase in 180-day mortality risk in patients with cirrhosis compared to patients without cirrhosis. In addition, development of hepatitis E virus-related ACLF due to acute liver function deterioration in patients with pre-existing CLD or cirrhosis worsened the 180-day mortality rate. Conclusions: Our findings suggest that the acute hepatitis E mortality rate was low in heathy individuals but higher in patients with cirrhosis, and especially high in those with ACLF.

Sooner than later: a little effort may avert postpartum haemorrhage in patients with acute hepatitis E

Background: The incidence of postpartum hemorrhage (PPH) in pregnancies with hepatitis E varies from 14-42%. Management of labor and PPH in these women with acute liver injury makes it a real obstetric challenge due to associated coagulopathies and contraindication for many drugs. Prophylactic insertion of condom balloon tamponade along with active management of the third stage of labour (AMTSL) prevent primary PPH in these women. Simultaneous use of injection tranexemic acid further gives reliable results. The present study was conducted to study the effectiveness of condom balloon tamponade in preventing PPH in pregnant women with acute hepatitis E in labor.Methods: The present study was conducted in the Department of Obstetrics and Gynecology, Pt. Jawaharlal Nehru Medical (JNM) College and associated Dr. Bhim Rao Ambedkar Memorial (BRAM) Hospital, Raipur, Chhattisgarh over period of two year from September 2018 to September 2020.Results: During the study period 32 women presented with hepatitis E in labor. Condom balloon tamponade was inserted prophylactically in all hepatitis E virus (HEV) positive cases immediately after delivery of placenta along with vaginal packing, irrespective of amount of bleeding. Inspite of so many odds in the form of unscanned pregnancies, multiparity, multifetal gestation, abruption, intrauterine fetal death (IUFD), prolonged labor, deranged liver and coagulation profiles, anemia and thrombocytopenia, our study showed high effectiveness of prophylactic condom balloon tamponade by encountering only one case of PPH.Conclusions: Prophylactic condom balloon tamponade insertion just after the removal of placenta is promising in averting PPH.

Guillain-Barré Syndrome After Acute Hepatitis E Infection: A Case Report and Literature Review

Introduction Guillain-Barré syndrome precipitated by hepatitis E virus infection is rare, yet its incidence is increasing. Clinical Findings A 57-year-old man was transferred from another facility with fatigue, orange urine, and progressive weakness over 4 to 6 weeks. Initial laboratory results included total bilirubin, 9.0 mg/dL; direct bilirubin, 6.4 mg/dL; aspartate aminotransferase, 1551 U/L; alanine aminotransferase, 3872 U/L; and alkaline phosphatase, 430 U/L. Immunoglobulin M and quantitative polymerase chain reaction test results were positive for hepatitis E virus. Contrast-enhanced magnetic resonance imaging of the brain and spine showed no gross abnormalities. Analysis of cerebrospinal fluid obtained by lumbar puncture revealed the following (reference values in parentheses): total white blood cell count, 15/μL (0–5/μL), with 33% neutrophils and 54% lymphocytes; protein, 0.045 g/dL (0.015–0.045 g/dL); and glucose, 95 mg/dL (within reference range). Neurological examination revealed weakness in both upper extremities, with proximal strength greater than distal strength. The patient could not elevate either lower extremity off the bed and had areflexia and reduced sensation throughout all extremities. Diagnosis Guillain-Barré syndrome secondary to acute hepatitis E virus infection was diagnosed on the basis of clinical characteristics, serum and cerebrospinal fluid analyses, and nerve conduction studies. Conclusions Nurses and clinicians should obtain a thorough history and consider hepatitis E virus infection as a precipitating factor in patients with sensory and motor disturbances consistent with Guillain-Barré syndrome. The case gives insight into the diagnostic process for Guillain-Barré syndrome and highlights the vital role of bedside nurses in evaluating and treating these patients.

Limited Value of Single Sampling for IgM Antibody Determination as a Diagnostic Approach for Acute Hepatitis E Virus Infection

In immunocompetent patients with a suspicion of hepatitis E virus (HEV) infection, single IgM antibody testing is typically applied. In this prospective study, we aimed to evaluate the accuracy of three different HEV screening approaches in patients with acute hepatitis, including approaches based on IgM determination, HEV RNA detection, and the combination of both.

Hepatitis E Outbreak in the Central Part of Italy Sustained by Multiple HEV Genotype 3 Strains, June–December 2019

In European countries, autochthonous acute hepatitis E cases are caused by Hepatitis E Virus (HEV) genotype 3 and are usually observed as sporadic cases. In mid/late September 2019, a hepatitis E outbreak caused by HEV genotype 3 was recognized by detection of identical/highly similar HEV sequences in some hepatitis E cases from two Italian regions, Abruzzo and Lazio, with most cases from this latter region showing a link with Abruzzo. Overall, 47 cases of HEV infection were finally observed with onsets from 8 June 2019 to 6 December 2019; they represent a marked increase as compared with just a few cases in the same period of time in the past years and in the same areas. HEV sequencing was successful in 35 cases. The phylogenetic analysis of the viral sequences showed 30 of them grouped in three distinct molecular clusters, termed A, B, and C: strains in cluster A and B were of subtype 3e and strains in cluster C were of subtype 3f. No strains detected in Abruzzo in the past years clustered with the strains involved in the present outbreak. The outbreak curve showed partially overlapped temporal distribution of the three clusters. Analysis of collected epidemiological data identified pork products as the most likely source of the outbreak. Overall, the findings suggest that the outbreak might have been caused by newly and almost simultaneously introduced strains not previously circulating in this area, which are possibly harbored by pork products or live animals imported from outside Abruzzo. This possibility deserves further studies in this area in order to monitor the circulation of HEV in human cases as well as in pigs and wild boars.