Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment

Abstract

The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients ( e.g ., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.

Human hepatitis viruses-associated cutaneous and systemic vasculitis

“…Acute HEV infection can be asymptomatic or manifest as fulminant hepatitis[ 21 ]. Neurological involvement is the most frequently encountered extrahepatic disorder, followed by hematological and gastrointestinal manifestations, possibly caused by autoimmune responses related to molecular mimicry[ 42 , 43 ].…”

“…Typically following HHV invasion into humans, there is rapid clearance of viruses by the host defense system, with a self-limiting disease course[ 4 ]. The morbidities associated with HAV and HEV infection, commonly transmitted via the fecal-oral route, occur shortly after their intrusion in the acute stage[ 19 - 21 ]. The infectious processes can persist for a long period of time in HBV, HCV, and HDV infection, progressing to chronic hepatitis and leading to liver fibrosis, irreversible cirrhosis, and hepatocellular carcinoma[ 22 - 24 ].…”

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 RNA consists of four open reading frames (ORF) and untranslated regions at the 5’ and 3’ ends. At the 5’ end is a 7-methylguanosine cap and at the 3’ end is a polyadenylated tail, just like eukaryotic messenger RNA (mRNA) [ 14 , 15 ], as shown in Figure 1 . During viral replication two viral RNA are generated: a full-length RNA of 7.2 kb and subgenomic RNA of 2.2 kb [ 13 , 14 ].…”

“…Transcription of ORF4 protein is controlled by an internal ribosome entry site (IRES)-like RNA structure, and it plays a vital role in HEV RNA polymerase’s proper functioning. The ORF4 protein promotes viral RdRp activity and viral replication [ 14 , 18 , 20 ].…”

“…Outbreaks of HEV-1 and HEV-2 occur periodically in several regions of Asia, Africa, Mexico, and the Middle East due to floods causing water supplies contamination with feces. The first HEV epidemic (1955–1956) infected 29,300 people in India [ 14 , 35 , 36 ]. In hyperendemic regions of the world, the infection is caused by HEV genotypes 1 and 2, most often in young adults, and extremely severe forms develop in pregnant women [ 17 , 37 , 38 ].…”