Research progress in extrahepatic manifestations and pathogenic mechanisms of hepatitis E
[Background]Hepatitis E,classified as a zoonotic viral infectious disease,is caused by the hepatitis E virus(HEV)and primarily transmitted through the fecal-oral route.There are four main genotypes(types 1 to 4)of HEV that infect humans and cause diseases,among which genotypes 1 and 2 are more common in humans.The diagnosis of hepatitis E relies on the detection of anti-HEV IgM and IgG antibodies,which are essential for identifying HEV infections.Hepatitis E is endemic in many countries and poses a heavy disease burden,becoming a major public health problem that threatens human health.Globally,an estimated 20 million new infections of hepatitis E occur each year,resulting in approximately 44 000 deaths.China is a highly endemic area of hepatitis E,with an average reported incidence rate of 1.95 per 100 000 from 2011 to 2021.HEV infection not only leads to liver diseases but also manifests in various extrahepatic conditions,such as neurological disorders,urinary system diseases,and hematological disorders.Currently,some studies have been conducted to explore the mechanism of extrahepatic manifestations.However,the underlying pathophysiological mechanisms are still not fully understood.This article systematically reviews the progress in research on the HEV related extrahepatic clinical manifestations and the possible underlying pathogenic mechanisms.[Progress]Based on the epidemiological characteristics and clinical symptoms,an increasing number of studies have reported HEV-related extrahepatic diseases.These include neurological disorders such as Guillain-Barré syndrome and neural muscular atrophy,urinary system diseases such as glomerulonephritis,hematological disorders such as thrombocytopenia,and other diseases including acute pancreatitis,myocarditis,thyroid disease,arthritis,lymphoproliferative disease,purpura and infertility.This review also summarizes the association between HEV infection and extrahepatic manifestations,including possible underlying pathogenic mechanisms.At present,a common mechanistic theory suggests that viral infection may trigger multiple host defense mechanisms,which may not be limited to the primary site of infection,and may also cause cross-reactivity between viral epitopes and autoantigens,resulting in extrahepatic multisystem manifestations.Another hypothesis is that HEV not only replicates in the liver but also in other tissues,directly causing extrahepatic symptoms.[Perspective]Although related research has been conducted,the understanding of the complex associations between HEV infection and extrahepatic diseases remains limited.More epidemiological studies are needed to evaluate the impact of HEV infection in different population and differetn genotypes on extrahepatic manifestations.Further studies are necessary to explore the pathogenic mechanisms,especially the direct and immune-mediated effects of HEV infection on extrahepatic organs.Based on these research results,more effective prevention,diagnosis,and treatment strategies should be developed for hepatitis E and related diseases,which is crucial to address this increasingly important public health challenge.Fully understanding and mitigating the effects of HEV requires a concerted effort across multiple disciplines and research approaches.Further studies can be conducted in epidemiological fields to provide a macro view of the public health impact of HEV,and in molecular perspectives to provide microscopic insights into the effects of the virus on the non-liver tissues.In addition,efforts to develop new treatments and preventive measures based on these comprehensive research sites that may change the course of hepatitis E management and control will also be important.In conclusion,as our understanding of hepatitis E deepens,the extrahepatic manifestations and potential mechanisms caused by hepatitis E have gained attention.In the management of patients with confirmed hepatitis E,early detection,diagnosis and treatment of extrahepatic diseases caused by HEV are of great significance for a comprehensive understanding and for the prevention and control of hepatitis E.This is conducive to reducing the disease burden and health hazards,effectively addressing this public health challenge.
hepatitis Ehepatitis E virusextrahepatic manifestationpathogenic mechanism
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