Tag Archives: Hepatitis E

Effective and Durable Hepatitis E Vaccine (Phase III Study)

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Background (from MedPage Today): HEV is a leading cause of acute viral hepatitis worldwide, resulting in an estimated 20 million infections worldwide and 70,000 deaths every year. HEV primarily occurs in Africa, Central America, and Asia…U.S. incidence of HEV infection is largely unknow in part because of a lack of surveillance or an FDA-approved, commercially available HEV assay. However, an analysis of seroprevalence of HEV among blood donors in the U.S. showed approximately 10% seropositivity for HEV immunoglobulin G (IgG), reflecting past infection, and 0.58% for HEV IgM, indicating recent infection.

Genotypes HEV-1 and HEV-2 are transmitted via contaminated water and are specific to humans. However, HEV-3 and HEV-4 are zoonotically transmitted, often by eating uncooked or undercooked meat and offal of boar, deer, and pig. 

Safety data of the vaccine were reported in an earlier study, showing no serious adverse effects attributed to the vaccine (though data is scarce in vulnerable populations including pregnant women and children)

S Huang et al. The Lancet 2024: DOI:https://doi.org/10.1016/S0140-6736(23)02234-1. Long-term efficacy of a recombinant hepatitis E vaccine in adults: 10-year results from a randomised, double-blind, placebo-controlled, phase 3 trial

In this randomized placebo-controlled study with 112 604 healthy Chinese adults aged 16–65 years, the key findings:

  • During the 10-year study period, there were 13 infections in the vaccine group (0·2 per 10 000 person-years) and 77 in the placebo group (1·4 per 10 000 person-years), corresponding to a vaccine efficacy of 83·1% in the modified intention-to-treat analysis and 86·6% in the per-protocol analysis.
  • In a subset of patients, 254 (87·3%) of 291 vaccinees had vaccine-induced antibodies detectable at the 8·5-year mark.

My take: This HEV vaccine markedly decreases the likelihood of acquiring HEV infection.

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View from Ram Head Trail, St John

Shorts: Hep E in Urine, Genetics in Autoimmune Enteropathy, EndoFlip Findings in EoE

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D Ying et al. Hepatology 2023; 77: 1722-1734. Urine is a viral antigen reservoir in hepatitis E virus infection

Key findings:  HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10‐fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model.

F Charbit-Henrion et al. Clin Gastroenterol Hepatol 2023; 21: 1368-1371. Open Access! Genetic Diagnosis Guides Treatment of Autoimmune Enteropathy

Background: Autoimmune enteropathy (AIE) is a severe form of enteropathy characterized by chronic diarrhea refractory to any exclusion diet and associated with autoimmunity…In a recent cohort of 40 AIE patients, anti-enterocyte antibodies were reported in only 14% (4/28) of the cases, likely caused by the high frequency of patients with primary hypogammaglobulinemia…30%–50% of adult AIE can display anti-transglutaminase antibodies. The common histopathologic presentation of AIE includes intestinal villous atrophy with variable lymphocytic infiltration and various features of follicular lymphoid hyperplasia, cryptitis, graft-versus-host disease-like lesions, and loss of Paneth and goblet cells.

Key findings: Pathogenic variants were identified in 20/48 adult patients (41.6%); most common variants: CTLA4, LRBA, STAT3, and STAT1; 12/20; 60% of those with variants. Thus, specific therapeutics were available for more than half of the patients who received a molecular diagnosis

Representative endoscopic aspects in patients with CTLA4 variants and AIE.

NV Hoffmann et al. Clin Gastroenterol Hepatol 2023; 21: 1188-1197. Esophageal Distensibility Defines Fibrostenotic Severity in Pediatric Eosinophilic Esophagitis

Key finding: In this prospective pediatric cohort (n=59) with EoE, distensibility index (DI) <4.5 mm2/mmHg predicted grade 2 rings on endoscopy. Lower DI was associated with increased risk of food impaction but did not correlate with eosinophilic count. DI was “superior to diameter in assessing fibrostenotic severity.”

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Seronegative Villous Atrophy

Liver Briefs 2017

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Briefly noted:

RJ Fontana et al. Hepatology 2016; 64: 1870-80.  In this study of 681 adults with acute liver failure in U.S., only 3 had detectable anti-HEV IgM and all three were negative for HEV-RNA.  In addition, other putative causes of acute liver failure were present in all three.  My take: Hepatitis E is very rare explanation for acute liver failure in the U.S.

RA Rosencrantz et al. Hepatology 2016; 64: 2253-6. Case report of 2.5 yr old with autoimmune sclerosing cholangitis with Kawasaki disease. This was a well-described case with MRCP and liver histology. My take: In patients with Kawasaki with protracted liver disease, another etiology to consider.

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