Nucleotide Substitutions of Hepatitis E Virus Genomes Associated with Fulminant Hepatitis and Disease Severity

Inoue, Jun; Takahashi, Masaharu; Mizuo, Hitoshi; Suzuki, Kazuyuki; Aikawa, Tatsuya; Shimosegawa, Tooru; Okamoto, Hiroaki

doi:10.1620/tjem.218.279

Cited by 31 publications

(37 citation statements)

References 23 publications

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“…On the other hand, successful in vitro cultivation of HEV-3 and HEV-4 strains with nucleotide substitutions associated with more severe illness was reported by Inoue and colleagues in Japan in 2009 (127). In a comparison of isolates from patients with milder and more severe hepatitis E, several substitutions in the RNA helicase and capsid protein-encoding domains, in particular, were found to be associated with severe hepatitis E leading to liver failure (127). Mutations identified in HEV-3 isolates collected from several severe hepatitis E cases across Japan, including another substitution affecting the helicase domain, also suggest that these mutations may affect the pathogenetic potential of HEV strains (126).…”

Section: Hypotheses Regarding Regional Differences In the Nature And mentioning

confidence: 98%

“…Cordoba and colleagues identified an attenuated swine HEV-3 strain from the United States with mutations in the sequences encoding the capsid protein that appeared to be associated with reduced viral replication (163). On the other hand, successful in vitro cultivation of HEV-3 and HEV-4 strains with nucleotide substitutions associated with more severe illness was reported by Inoue and colleagues in Japan in 2009 (127). In a comparison of isolates from patients with milder and more severe hepatitis E, several substitutions in the RNA helicase and capsid protein-encoding domains, in particular, were found to be associated with severe hepatitis E leading to liver failure (127).…”

Section: Hypotheses Regarding Regional Differences In the Nature And mentioning

confidence: 99%

“…In the relatively wealthy nations of Europe, North America, and East Asia, human infections with HEV-3 and HEV-4 are often asymptomatic (33,125), though more virulent strains appear to exist (126,127). In these settings, autochthonous HEV-3 appears to pose the greatest threat to people with chronic medical conditions that require immunosuppressive therapy or that directly compromise the immune system and/or liver (128)(129)(130).…”

Section: Epidemiologic Patterns Of Hepatitis E Virus Infectionmentioning

confidence: 99%

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Host Immune Status and Response to Hepatitis E Virus Infection

2014

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SUMMARY Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available.

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Section: Hypotheses Regarding Regional Differences In the Nature And mentioning

confidence: 98%

Section: Hypotheses Regarding Regional Differences In the Nature And mentioning

confidence: 99%

Section: Epidemiologic Patterns Of Hepatitis E Virus Infectionmentioning

confidence: 99%

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Host Immune Status and Response to Hepatitis E Virus Infection

2014

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“…In addition, HEV-4 infection was reported in 2010 in England in a patient who returned from a 2-month stay in India 1 month before presenting jaundice [28]. HEV-4 collected in Japan and France have been associated with higher liver cytolysis and a lower prothrombin index relative to HEV-3, and more severe illness was described in Japan for HEV-4 compared to HEV-3 [29,30]. However, further studies are needed to determine if differences in the hepatitis E presentation and outcome might be linked to the HEV genotypic patterns or the host or both.…”

Section: Figmentioning

confidence: 99%

Emergence of Autochthonous Infections with Hepatitis E Virus of Genotype 4 in Europe

et al. 2013

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In Europe, autochthonous hepatitis E is caused by genotype 3 hepatitis E virus (HEV) in almost all cases. A total of 15 infections with genotype 4 HEV were diagnosed in France from May 2009 to April 2012, and all but one of the HEV-4 strains implicated in these infections were genetically related and highly similar to HEV-4 sequences isolated from swine in Belgium. In addition, 5 autochthonous HEV-4 infections have been described in the region of Lazio, Italy, during March and April 2011, and these HEV sequences were 100% identical to one another but showed relatively low similarity (74-85%) to HEV-4 RNA samples collected in France. We report 6 additional HEV-4 infections that were diagnosed from May to July 2012 which represented 50% of the HEV infections diagnosed during this period in our clinical microbiology laboratory. Five of these HEV-4 strains were associated with autochthonous infections and were clustered together and with the majority of HEV-4 previously described in France, whereas the sixth strain was genetically divergent. Taken together with reports from other teams, these observations indicate that autochthonous infections with HEV-4 are emerging in Europe and have been transmitted by at least two distinct sources.

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“…Furthermore, HEV has been proposed to potentially trigger autoimmune hepatitis (27,28), and a case of acute hepatitis E associated with autoimmunity signs (i.e., ANA [titer, 1/320] and ASMA positivity) was recently reported (28). Finally, viral features, including mutations and genotype (29)(30)(31), and host features, including some patterns of the immune response and a polymorphism in the promoter region of the gene for tumor necrosis factor alpha (31)(32)(33), were proposed to be factors associated with the occurrence of fulminant acute hepatitis E. Here, the full-length viral genome was not analyzed, but genotype 3 HEV substantially differed from those previously identified in fulminant hepatitis E cases in France, which were mostly of subtype 3f (12,18,34), and in another recent report from our center (12) ( Table 1).…”

mentioning

confidence: 99%

Fatal Fulminant Hepatitis E Associated with Autoimmune Hepatitis and Excessive Paracetamol Intake in Southeastern France

Doudier¹,

Vencatassin²,

Aherfi³

et al. 2014

J Clin Microbiol

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We present, to our knowledge, the first case of fatal fulminant liver failure associated with hepatitis E virus infection, autoimmune hepatitis, and excessive paracetamol intake, which occurred in a 77-year-old woman. Hepatitis E testing should be performed in severe acute liver failure cases, even when another cause has been identified. CASE REPORTA 77-year-old woman was admitted to an emergency unit for jaundice and fever in Marseille, France, in January 2013. She had a past medical history of autoimmune hepatitis without hepatocellular failure. She was receiving an oral anticoagulant for atrial fibrillation (fluindione, 35 mg/day), insulin for diabetes mellitus, and antihypertensive drugs (rilmenidine [2 mg/day], losartan [100 mg/day], and hydrochlorothiazide [25 mg/day]). Diclofenac/misoprostol (50/0.2 mg/day), tramadol chlorhydrate (225 mg/day), and paracetamol (or acetaminophen; 6.6 g/day) were taken from 1 week until 2 days prior to admission for recent dorsal pain. Physical examination revealed jaundice, drowsiness, and digestive tract hemorrhage, which led to admission of the patient into the intensive care unit. She then developed hepatic encephalopathy and hypovolemic shock within a few hours. Laboratory tests showed severe anemia (a hemoglobin level of 6.9 g/dl), acute renal failure (her creatinine level rose to 227 mol/ liter), and acute liver failure with an alanine aminotransferase activity level of 1,668 IU/liter and a prothrombin index of 10% (Table 1). The serum paracetamol level was 3.5 mg/liter (normal value, Ͻ5 mg/liter), possibly because it was measured Ͼ2 days after the last drug intake. Serological and/or molecular markers of hepatitis A, B, and C virus; Epstein-Barr virus; cytomegalovirus; and human immunodeficiency virus (HIV) infection were negative or indicated past infections. The diagnosis of hepatitis E virus (HEV) infection was based on HEV RNA detection in the patient's serum with an in-house PCR assay (1). Subsequently, anti-HEV IgM and IgG were detected (Adaltis, Rome, Italy). The patient was positive for antinuclear autoantibodies (ANA; titer, 1/640) and anti-smooth-muscle antibodies (ASMA; titer, 1/160) but negative for anti-liver kidney microsomal antibodies. Cerebral and abdominal computed tomography scans revealed no abnormalities. The patient's condition deteriorated rapidly, with hemodynamic instability despite blood transfusions and hemodynamic support, which led to the patient's death 5 days later.The patient's family did not report any travel abroad or contact with travelers within the 10-week period prior to admission or a recent transfusion history. Consumption of cooked pork was reported, but consumption of uncooked pork, shellfish, or unsafe drinking water was not. The HEV strain was of genotype 3, as determined by phylogenetic analyses (1) (Fig. 1). The top BLAST hits against the NCBI GenBank nucleotide sequence database for fragments of HEV genome open reading frame 1 (ORF1) (accession no. KF921518) and ORF2 (KF921517) showed 92%

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Nucleotide Substitutions of Hepatitis E Virus Genomes Associated with Fulminant Hepatitis and Disease Severity

Cited by 31 publications

References 23 publications

Host Immune Status and Response to Hepatitis E Virus Infection

Host Immune Status and Response to Hepatitis E Virus Infection

Emergence of Autochthonous Infections with Hepatitis E Virus of Genotype 4 in Europe

Fatal Fulminant Hepatitis E Associated with Autoimmune Hepatitis and Excessive Paracetamol Intake in Southeastern France

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