Viral Hepatitis E and Chronicity: A Growing Public Health Concern

Abstract

Hepatitis E viral infection recently emerges as a global health concern. Over the last decade, the understanding of hepatitis E virus (HEV) had changed with the discovery of new genotypes like genotype-7 and genotype-8 with associated host and mode of infection. Diversification in the mode of hepatitis E infection transmission through blood transfusion, and organ transplants in contrast to classical feco-oral and zoonotic mode is the recent medical concern. The wide spectrum of infection ranging from self-limiting to acute liver failure is now overpowered by HEV genotype-specific chronic infection especially in transplant patients. This concern is further escalated by the extra-hepatic manifestations of HEV targeting the central nervous system (CNS), kidney, heart, and pancreas. However, with the development of advanced efficient cell culture systems and animal models simulating the infection, much clarity toward understanding the pathogenetic mechanism of HEV has been developed. Also this facilitates the development of vaccines research or therapeutics. In this review, we highlight all the novel findings in every aspect of HEV with special emphasis on recently emerging chronic mode of infection with specific diagnosis and treatment regime with an optimistic hope to help virologists and/or liver specialists working in the field of viral hepatitis.

Interplay between Hepatitis E Virus and Host Cell Pattern Recognition Receptors

“…The mechanisms underlying HEV pathogenesis during pregnancy are undermined and related mostly to hormonal imbalance and immunological alterations [5,6]. Chronic hepatitis E has been reported in immunocompromised patients such as organ transplant recipients, HIV-infected individuals, and patients with hematological malignancies (reviewed in [7]). Moreover, extrahepatic manifestations like neuronal and renal diseases and pancreatitis are also reported during the course of HEV infection [8,9].…”

“…Among the eight genotypes classified in Orthohepevirus A species, genotype 1 and 2 are found to be more virulent during pregnancy and responsible for an increased risk of miscarriage, preterm delivery, and stillbirth. The most prominent genotype (genotype 3) from industrialized countries has been exclusively reported in chronic hepatitis E cases [5][6][7]. HEV is a non-enveloped, spherical particle with a diameter of 27-34 nm when it is isolated from bile and feces whereas it also exists as a quasi-enveloped virus (~40 nm) in blood and cell culture supernatants [3].…”

Mechanism of Cross-Species Transmission, Adaptive Evolution and Pathogenesis of Hepatitis E Virus

“…Most chronic HEV infections are associated with HEV-3, with a single case of HEV-1 [ 101 ] or HEV-7 [ 49 ], which to date, are only anecdotal and unique; and HEV-4, which has been described in small numbers of reports [ 102 ]. Viral and host factors are likely the determinants of the chronicity of HEV infection [ 103 ]. Viral factors, such as genotype, zoonotic potential, specificity, and adaptability to a host play important roles in the establishment of persistent infection.…”

“…Meanwhile, host factors, such as the immune state and the nutritional health of the patient can also determine the course of HEV infection. The type of immunosuppressive drugs is reported to affect the progression to chronic infection, with patients treated with calcineurin inhibitors (e.g., tacrolimus, cyclosporin A) or mTOR inhibitors (e.g., everolimus, sirolimus), reported to be more prone to persistent HEV infection [ 3 , 103 ].…”

Towards the Improved Accuracy of Hepatitis E Diagnosis in Vulnerable and Target Groups: A Global Perspective on the Current State of Knowledge and the Implications for Practice

“…HEV is a major global health problem in developing and developed countries and is mostly zoonotic [ 11 , 26 , 27 ]. The World Health Organization (WHO) estimates that the incidence of HEV infections is 20 million annually, leading to approximately 3.3 million symptomatic cases of hepatitis E [ 28 ].…”