Hepatitis E virus: has anything changed?

PURPOSE OF REVIEW: Infection with hepatitis E virus (HEV) is a global health concern, yet a clinically underdiagnosed cause of acute and chronic hepatitis. The WHO estimates that 20 million people are infected with HEV annually, yet the epidemiology, diagnosis and prevention remain elusive in many clinical settings. RECENT FINDINGS: Orthohepevirus A (HEV-A) genotypes 1 and 2 cause acute, self-limited hepatitis through faecal-oral transmission. In 2022, the first-ever vaccine campaign was implemented as a response to an HEV outbreak in an endemic region. HEV-A genotypes 3 and 4 are zoonotic infections that primarily cause chronic HEV infection in immunosuppressed populations. Pregnant women and immunocompromised persons are at high risk for severe illness in some settings. Another recent advance in our knowledge of HEV is the zoonotic transmission of Orthohepevirus C (HEV-C) to humans, presumably from contact with rodents and/or their excrement. Previously, HEV infection in humans was presumed to be limited to HEV-A only. SUMMARY: Clinical recognition and accurate diagnosis are essential to the management of HEV infection and understanding the global burden of the disease. Epidemiology affects clinical presentations. Targeted response strategies in HEV outbreaks are needed for the prevention of disease, and vaccine campaigns may prove to be an effective part of these strategies.

Optimization of the molecular diagnosis of the acute hepatitis E virus infection.

To evaluate the diagnostic value of the combination of two broad-range PCR assays targeting two different and conserved regions of the viral genome for the diagnosis of acute Hepatitis E virus (HEV) infection. Patients with acute hepatitis were prospectively recruited. In all, HEV-IgM antibodies were tested together with evaluation of HEV viraemia by two PCR assays (ORF3 and ORF1). The number of individuals exhibiting negative IgM antibody results but carrying viral RNA was calculated by each PCR assay. Four-hundred and seventy individuals were included, of whom 145 (30.8%) were diagnosed as having acute HEV. Of them, 122 (84.1%) exhibited HEV-IgM antibodies, and 81 (55.8%) had detectable viral RNA for at least one PCR. Using the ORF3 molecular assay, 70 (48.3%) individuals were identified with HEV infection. When the ORF1 molecular assay was applied, 49 (33.8%) individuals were identified. The ORF3 assay detected viral RNA in 32 patients not detected by the ORF1 assay. In contrast, the ORF1 assay could amplify viral RNA in 11 patients who were not detected by the ORF3 assay. The parallel use of two broad-range PCR assays significantly increased the performance of the molecular diagnosis of HEV.

Hepatitis E in Bangladesh: Insights From a National Serosurvey.

BACKGROUND: Hepatitis E virus (HEV) genotypes 1 and 2 are a major cause of avoidable morbidity and mortality in South Asia. Despite the high risk of death among infected pregnant women, scarce incidence data has been a contributing factor to global policy recommendations against the introduction of licensed hepatitis E vaccines, one of the only effective prevention tools. METHODS: We tested serum from a nationally representative serosurvey in Bangladesh for anti-HEV immunoglobulin G and estimated seroprevalence. We used Bayesian geostatistical models to generate high-resolution maps of seropositivity and examined variability in seropositivity by individual-level, household-level, and community-level risk factors using spatial logistic regression. RESULTS: We tested serum samples from 2924 individuals from 70 communities representing all divisions of Bangladesh and estimated a national seroprevalence of 20% (95% confidence interval [CI], 17%-24%). Seropositivity increased with age and male sex (odds ratio, 2.2 male vs female; 95% CI, 1.8-2.8). Community-level seroprevalence ranged widely (0-78%) with higher seroprevalence in urban areas, including Dhaka, with a 3.0-fold (95% credible interval, 2.3-3.7) higher seroprevalence than the rest of the country. CONCLUSIONS: Hepatitis E infections are common throughout Bangladesh. Strengthening surveillance for hepatitis E, especially in urban areas, can provide additional evidence to appropriately target interventions.

Acute hepatitis E in an immunocompromised patient with seropositive rheumatoid arthritis on rituximab and long-term methotrexate.

We report the case of a 61-year old female with a 20-year history of seropositive rheumatoid arthritis (RA) who developed acute hepatitis. Her arthritis had been treated with methotrexate (MTX) since 2003 and, following an increase in disease activity, Rituximab (RTX) was commenced in January 2017. In May 2020, routine blood tests showed a new elevation in her liver profile, although synthetic function was preserved. A standard liver screen found no cause for her acutely abnormal lab values. Upon additional serological testing, the patient was confirmed to have acute hepatitis E virus (HEV). Her primary complaint at the time was fatigue. Within a month, her liver blood tests spontaneously improved and her symptoms resolved with conservative management.