Extrahepatic manifestations related to hepatitis E virus infection and their triggering mechanisms

Wu, Jian; Xiang, Ze; Zhu, Chunxia; Yao, Yiwen; Bortolanza, Mariza; Cao, Hong; Li, Lanjuan

doi:10.1016/j.jinf.2021.07.021

Cited by 28 publications

(26 citation statements)

References 96 publications

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“…The level of sTim-3 in patients infected with HEV was higher than that in patients infected with HBV, possibly because hepatitis caused by HEV is a systemic disease. Recently, studies have systematically explained the many extrahepatic manifestations of HEV infection, which are mainly related to diseases such as the kidney system, autoimmune system, and pancreatitis ( 28 ). Moreover, studies have shown that sTim-3 plays an important immunoregulatory role in kidney disease ( 17 , 29 ), pancreatitis ( 30 ), and autoimmune diseases ( 31 ), resulting in its high serum levels.…”

Section: Discussionmentioning

confidence: 99%

Increase in Serum Soluble Tim-3 Level Is Related to the Progression of Diseases After Hepatitis Virus Infection

Chen

Dai

et al. 2022

Front. Med.

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BackgroundViral hepatitis is a widespread and serious infectious disease, and most patients with liver cirrhosis and hepatocellular carcinoma are prone to viral infections. T cell immunoglobulin-and mucin-domain-containing molecule-3 (Tim-3) is an immune checkpoint molecule that negatively regulates T cell responses, playing an extremely important role in controlling infectious diseases. However, reports about the role of serum soluble Tim-3 (sTim-3) in hepatitis virus infection are limited. Therefore, this study explored changes in sTim-3 levels in patients infected with hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV).MethodsThis study applied high-sensitivity time-resolved fluorescence immunoassay for the detection of sTim-3 levels. A total of 205 cases of viral hepatitis infection (68 cases of HBV infection, 60 cases of HCV infection, and 77 cases of HEV virus infection) and 88 healthy controls were quantitatively determined. The changes in serum sTim-3 level and its clinical value in hepatitis virus infection were analyzed.ResultsPatients with HBV infection (14.00, 10.78–20.45 ng/mL), HCV infection (15.99, 11.83–27.00 ng/mL), or HEV infection (19.09, 10.85–33.93 ng/mL) had significantly higher sTim-3 levels than that in the healthy control group (7.69, 6.14–10.22 ng/mL, P < 0.0001). Patients with hepatitis and fibrosis infected with HBV (22.76, 12.82–37.53 ng/mL), HCV (33.06, 16.36–39.30 ng/mL), and HEV (28.90, 17.95–35.94 ng/mL) had significantly higher sTim-3 levels than patients with hepatitis without fibrosis (13.29, 7.75–17.28; 13.86, 11.48–18.64; 14.77, 9.79–29.79 ng/mL; P < 0.05).ConclusionsTim-3 level was elevated in patients infected with HBV, HCV, or HEV and gradually increased in patients with either hepatitis or hepatitis with hepatic fibrosis. It has a certain role in the evaluation of the course of a disease after hepatitis virus infection.

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Section: Discussionmentioning

confidence: 99%

Increase in Serum Soluble Tim-3 Level Is Related to the Progression of Diseases After Hepatitis Virus Infection

Chen

Dai

et al. 2022

Front. Med.

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“…Importantly, after only a few years of chronic HEV infection, progressive liver fibrosis and cirrhosis is commonly found [18]. In addition to this, HEV may cause a variety of extrahepatic manifestations such as neurologic diseases, acute pancreatitis, membranous glomerulonephritis, acute thyroiditis or hematologic abnormalities [19,20].…”

Section: Introductionmentioning

confidence: 99%

Serological Evidence of Hepatitis E Virus Infection in Semi-Domesticated Eurasian Tundra Reindeer (Rangifer tarandus tarandus) in Norway

et al. 2021

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Hepatitis E virus (HEV) is a common cause of viral hepatitis in humans. In developing countries, HEV-infections seem to be mainly associated with pigs, but other animal species may be involved in viral transmission. Recently, anti-HEV antibodies were detected in Norwegian wild reindeer. Here, we investigated anti-HEV seroprevalence in Norwegian semi-domesticated reindeer, animals in closer contact with humans than their wild counterparts. Blood samples (n = 516) were obtained from eight reindeer herds during the period 2013–2017 and analysed with a commercial enzyme-linked immunosorbent assay designed for detecting anti-HEV antibodies in livestock. Antibodies were found in all herds and for all sampling seasons. The overall seroprevalence was 15.7% (81/516), with adults showing a slightly higher seroprevalence (18.0%, 46/256) than calves (13.5%, 35/260, p = 0.11). The seroprevalence was not influenced by gender or latitude, and there was no temporal trend (p > 0.15). A positive association between the presence of anti-HEV antibodies and antibodies against alphaherpesvirus and pestivirus, detected in a previous screening, was found (p < 0.05). We conclude that Norwegian semi-domesticated reindeer are exposed to HEV or an antigenically similar virus. Whether the virus is affecting reindeer health or infects humans and poses a threat for human health remains unknown and warrants further investigations.

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“…Other extrahepatic manifestations related with HEV infection include hematological disorders, acute pancreatitis, myocarditis, arthritis, and autoimmune thyroiditis. [25] Diagnosis, prevention, and treatment of hepatitis E: Incubation period of hepatitis E varies from 15 to 60 days, and HEV RNA can be detected in feces and serum sample from patients 3 weeks after infection. HEV RNA detection and quantification in blood, stool, or other body fluids remains the golden standard for current HEV infection.…”

mentioning

confidence: 99%

“…Renal disorders including membranoproliferative glomerulonephritis and cryoglobulinemia have also been found to be associated with HEV infection. Other extrahepatic manifestations related with HEV infection include hematological disorders, acute pancreatitis, myocarditis, arthritis, and autoimmune thyroiditis [25] …”

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confidence: 99%

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Updates on hepatitis E virus

Liang

Wang

2022

Chinese Medical Journal

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Hepatitis E virus (HEV) is the causative agent of hepatitis E. Globally, it is estimated that 20 million HEV infections with 3.3 million symptomatic cases occur annually, and the mortality rate is 0.5% to 3% in general population.Although hepatitis E is commonly considered as an acute, self-limited disease, HEV infection can be chronic in immunocompromised patients and related with high mortality rate and poor pregnancy outcomes in pregnant women. [1] Characteristics of HEV: HEV is a single-stranded, positive sense RNA virus with genomic length ranging from 6.6 to 7.2 kb with three open reading frames (ORFs): ORF1 encodes non-structural protein associated with HEV RNA replication; ORF2 encodes the capsid protein and a secreted form of ORF2 protein [2] ; and ORF3 encodes a small protein related with the release of HEV. [3] The virus particle is icosahedral and has a diameter of 27 to 32 nm. HEV is non-enveloped in feces and bile but contains a lipid envelope in blood and cell culture supernatant, and hence HEV is declared to be a quasi-enveloped virus. [2] Robust cell culture system for HEV is still lacking, and suitable animal models for HEV include non-human primates, swine, rabbits, and human liver chimeric mice. Given the small size and zoonotic potential for rabbit HEV, rabbits could be an important model in HEV studies.

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Extrahepatic manifestations related to hepatitis E virus infection and their triggering mechanisms

Cited by 28 publications

References 96 publications

Increase in Serum Soluble Tim-3 Level Is Related to the Progression of Diseases After Hepatitis Virus Infection

Increase in Serum Soluble Tim-3 Level Is Related to the Progression of Diseases After Hepatitis Virus Infection

Serological Evidence of Hepatitis E Virus Infection in Semi-Domesticated Eurasian Tundra Reindeer (Rangifer tarandus tarandus) in Norway

Updates on hepatitis E virus

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