Clinical Characteristics of Acute Hepatitis E and Their Correlation with HEV Genotype 3 Subtypes in Italy

Genotype 3 (GT3) is responsible for most European autochthonous hepatitis E virus (HEV) infections. This study analyzed circulating genotypes and GT3 subtypes in the Lazio region, Italy, between 2011 and 2019, as well as their pathogenic characteristics. Of the 64 evaluable HEV GT3 patient-derived sequences, identified subtypes included GT3f (n = 36), GT3e (n = 15), GT3c (n = 9), GT3a (n = 1) and three unsubtyped GT3 sequences. GT3c strains were similar to Dutch sequences (96.8–98.1% identity), GT3e strains showed high similarity (96.8%) with a United Kingdom sequence, while the most related sequences to GT3f Italian strains were isolated in France, Belgium and Japan. One sequence was closely related to another Italian strain isolated in raw sewage in 2016. The liver functioning test median values for 56 evaluable GT3 patients were: alanine aminotransferase (ALT), 461 (range 52–4835 U/L); aspartate aminotransferase (AST), 659 (range 64–6588 U/L); and total bilirubin, 3.49 (range 0.4–33 mg/dL). The median HEV RNA viral load for 26 evaluable GT3 patients was 42,240 IU/mL (range 5680–895,490 IU/mL). Of the 37 GT3 patients with available clinical information, no correlation was observed between HEV clinical manifestations and GT3 subtype. HEV symptoms were comparable among GT3c/e/f patients across most analyzed categories except for epigastric pain, which occurred more frequently in patients with HEV GT3e (75%) than in patients with GT3c (50%) or GT3f (19%) (p = 0.01). Additionally, patients with HEV GT3c exhibited significantly higher median international normalized ratio (INR) than patients with GT3e and GT3f (p = 0.033). The severity of GT3 acute hepatitis E was not linked to HEV RNA viral load or to the GT3 subtype.

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An Epidemiologic Investigation of a Case of Acute Hepatitis E

Journal of Clinical Microbiology ◽

10.1128/jcm.01189-15 ◽

2015 ◽

Vol 53 (11) ◽

pp. 3547-3552 ◽

Cited By ~ 9

Author(s):

Souvik Sarkar ◽

Elenita M. Rivera ◽

Ronald E. Engle ◽

Hanh T. Nguyen ◽

Cathy A. Schechterly ◽

...

Keyword(s):

Acute Hepatitis ◽

Blood Donors ◽

Hepatitis E ◽

Transmission Risk ◽

Genotype 3 ◽

Modes Of Transmission ◽

Parenteral Transmission ◽

Potential Mode ◽

Acute Hepatitis E ◽

Animal Handlers

Hepatitis E virus (HEV) is considered a zoonotic infection in developed nations. A case of acute hepatitis E in a researcher following a scalpel injury while working on a pig prompted a seroepidemiologic study to identify potential modes of transmission and determine the seroprevalence of HEV among animal handlers at the institute. Sera from personnel (n= 64) in two animal facilities and age/sex-matched blood donors (n= 63) as controls were tested for IgG anti-HEV and, if positive, for IgM anti-HEV and HEV RNA. Sera and stool from pigs aged 6 to 12 weeks from the breeding farm and older pigs from animal facilities were tested similarly. The median age of personnel was 36 years, 74% were white, 56% were male, and 74% had direct exposure to pigs. The prevalence of anti-HEV was 3.1% among personnel compared to 3.2% among blood donors; none were positive for IgM anti-HEV or HEV RNA. IgG anti-HEV was detected in sera from 10% of pigs aged 6 to 8 weeks, 80% aged 10 weeks, 100% aged 12 weeks, and 76% aged >12 weeks. HEV RNA was detected in stool but not sera from three 12-week-old pigs. Sequencing revealed HEV genotype 3 with ∼10% difference between the patient and pig sequences. Parenteral transmission is a potential mode of acute HEV infection. The low and similar seroprevalence of anti-HEV between the at-risk group and age-matched blood donors suggests low transmission risk with universal precautions among animal handlers.

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Prognostic Significance of End-Stage Liver Diseases, Respiratory Tract Infection, and Chronic Kidney Diseases in Symptomatic Acute Hepatitis E

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.593674 ◽

2021 ◽

Vol 10 ◽

Author(s):

Huahao Fan ◽

Junfen Fan ◽

Suming Chen ◽

Yangzhen Chen ◽

Huiru Gao ◽

...

Keyword(s):

Acute Hepatitis ◽

Liver Diseases ◽

Kidney Diseases ◽

Clinical Manifestations ◽

Hepatitis E ◽

Meld Score ◽

Co Morbidity ◽

Acute Hepatitis E ◽

Symptomatic Acute Hepatitis ◽

End Stage

Symptomatic hepatitis E virus (HEV) infection is sporadic, and usually occurs in a limited number of infected patients, which hinders the investigation of risk factors for clinical outcomes in patients with acute HEV infection. A retrospective cohort study enrolling 1913 patients with symptomatic acute hepatitis E in Beijing 302 Hospital from January 1, 2001 to December 31, 2018 was conducted. The baseline characteristics, clinical features and laboratory data of these HEV infection cases were analyzed. Albumin (ALB), platelet (PLT), alanine aminotransferase (ALT), total bilirubin (T-BiL), international normalized ratio (INR) and serum creatinine (SCR) levels, along with the model for end-stage liver disease (MELD) score, hospitalization days, co-morbidity number and mortality were taken as major parameters for comparing the clinical manifestations in our study. We found that not all pre-existing chronic liver diseases exacerbate clinical manifestations of acute hepatitis E. Alcoholic hepatitis, fatty liver hepatitis, hepatic cyst, drug-induced hepatitis and hepatocellular carcinoma were not significantly associated with mortality of HEV patients. Among all of the comorbidities, end-stage liver diseases (ESLDs, including ascites, cirrhosis, hepatic coma and hepatorenal syndrome), respiratory tract infection and chronic kidney diseases (CKDs, including renal insufficiency and renal failure) were found to remarkably increase the mortality of patients with symptomatic HEV infection. Furthermore, the severity evaluation indexes (SEI), such as MELD score, duration of hospital stay, and co-morbidity number in HEV patients with underlying comorbidities were much worse than that of their counterparts without relevant comorbidities.

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Hepatitis E virus in Italy: molecular analysis of travel-related and autochthonous cases

Journal of General Virology ◽

10.1099/vir.0.031278-0 ◽

2011 ◽

Vol 92 (7) ◽

pp. 1617-1626 ◽

Cited By ~ 45

Author(s):

Giuseppina La Rosa ◽

Michele Muscillo ◽

Valentina Spuri Vennarucci ◽

Anna Rosa Garbuglia ◽

Patrizia La Scala ◽

...

Keyword(s):

Acute Hepatitis ◽

Hepatitis E Virus ◽

Hepatitis E ◽

The Body ◽

Industrialized Countries ◽

Genotype 3 ◽

Serum Samples ◽

Specific Primers ◽

Body Of Knowledge ◽

Acute Hepatitis E

Human hepatitis E virus (HEV) is considered an emerging pathogen in industrialized countries. The aim of the present study was to contribute to the body of knowledge available on the molecular epidemiology of acute hepatitis E in Italy. Three sets of HEV-specific primers targeting the ORF1 and ORF2 were used to examine serum samples collected from acute hepatitis patients positive for anti-HEV IgG and/or IgM, between 2007 and 2010. Seventeen patients (39.5 %) tested HEV RNA-positive: 12 infections, due to genotype 1, were associated with travel to endemic areas (Bangladesh, India and Pakistan), while five infections, due to genotype 3, were presumably autochthonous. Risk factors identified in this group included exposure to raw seafood, pork liver sausages and wild boar. Results from the present study confirm that human HEV infection in Italy is caused by different genotypes, depending on whether the infection is travel-related or autochthonous.

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Association of poor virus specific immunoglobulin G antibody responses with higher viral load is seen in Bangladeshi pregnant women having acute Hepatitis E Genotype 1 infection

10.1101/2020.06.12.148528 ◽

2020 ◽

Author(s):

Rosy Sultana ◽

Md Tarikul Islam ◽

Golam Sarower Bhuyan ◽

Farjana Akther Noor ◽

Suprovath Kumar Sarker ◽

...

Keyword(s):

Viral Load ◽

Acute Hepatitis ◽

Pregnant Women ◽

South Asian ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Genotype 1 ◽

Asian Countries ◽

Igg Antibody ◽

Acute Hepatitis E

AbstractAlthough Hepatitis E viral illness is usually self-limiting, higher rates of morbidity and mortality are frequently observed during pregnancy in South Asian countries including Bangladesh. Of the four common variants, hepatitis E virus genotype 1 is mainly prevalent in South Asian countries. Pregnant women usually suffer from a state of immunosuppression. It is yet to be known whether virus specific immunoglobulin G (IgG) immune responses have any association with the vulnerability of pregnant women to acute hepatitis with E virus. The study aimed to compare the viral load and IgG responses of hepatitis E-infected pregnant women with that of non-pregnant women with same infection. Real Time –quantitative reverse transcription Polymerase Chain Reaction and Sanger sequencing were performed to determine the viral load and genotype, respectively, whereas Enzyme Linked Immunosorbent Assay method was used to determine hepatitis E virus specific serum IgG antibody index along with IgG avidity index. Although significant negative correlations were observed between log viral copy number and log IgG antibody index in the late acute phases of jaundice for both pregnant (r= −0.7971, p=0.0002) and non-pregnant women (r= −0.9117, p=0.0002), serum log viral copy number of pregnant women was significantly higher than that of the non-pregnant counterpart (p=0.0196) in the late acute stage of jaundice. In addition, log hepatitis E virus IgG antibody index of pregnant women was significantly lower than the non-pregnant women in the late phase of jaundice induced by hepatitis E virus (p=0.0303). Moreover, pregnant women with acute hepatitis E had higher cross-reactive IgG than in the non-pregnant women (p=0.0017). All the patients got infected with hepatitis E virus were in Genotype 1 variety. The study demonstrates that virus-specific poor IgG responses might be responsible for vulnerability of pregnant women to acute hepatitis with hepatitis E virus.Author SummaryAcute hepatitis caused by hepatitis E virus (HEV) Genotype 1 is a public health problem in Asian countries and especially it poses a potential health threat to pregnant women causing 19% to 25% mortality, particularly in South Asian countries including Bangladesh. The study aimed to explore whether HEV IgG immune responses were compromised during pregnancy, which might contribute to higher viral load and disease severity. Accordingly, pregnant and non-pregnant women with acute hepatitis (clinically presented with nausea, loss of appetite and /or jaundice) were enrolled from different tertiary care hospitals in Dhaka city. All these patients were screened and hepatitis E were differentiated from other hepatitis (caused by A, B, C) using Enzyme Linked Immunosorbent Assay (ELISA) methods. HEV IgG antibody/avidity indices and viral loads were measured using ELISA and real time quantitative polymerase chain reaction (RT-qPCR), respectively. The study showed that pregnant women with acute hepatitis E had lower IgG indices with higher viral load than their non-pregnant counterpart. Overall, the study revealed that virus-specific poor IgG responses might render pregnant women vulnerable to acute hepatitis E of varying degree of severity which might be associated with higher viral load.

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Th1/Th2 Cells and Associated Cytokines in Acute Hepatitis E and Related Acute Liver Failure

Journal of Immunology Research ◽

10.1155/2020/6027361 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Jian Wu ◽

Yurong Guo ◽

Xuan Lu ◽

Fen Huang ◽

Feifei Lv ◽

...

Keyword(s):

Viral Load ◽

Liver Failure ◽

Acute Liver Failure ◽

Acute Hepatitis ◽

Hepatitis E ◽

Th2 Cells ◽

Upward Trend ◽

Significant Difference ◽

Acute Hepatitis E ◽

Ifn Γ

Background and Aims. The involvement of cellular immunity in the development of hepatitis E virus (HEV) infection is rare. We aimed to study the roles of viral load and Th cell responses in acute hepatitis E (AHE) and HEV-related acute liver failure (HEV-ALF). Methods. We evaluated viral load and Th1/Th2 cytokine levels in 34 patients with HEV infection, including 17 each with AHE or HEV-ALF. Seventeen healthy controls (HCs) were also included who were negative for anti-HEV IgM and IgG. Results. There was no significant difference in viral load and HEV RNA in the AHE and HEV-ALF groups (both P > 0.05 ). The Th lymphocyte levels (CD3+, CD4+) in the AHE and HEV-ALF groups were significantly higher than those in the HC group (both P < 0.05 ), but there was no significant difference between the AHE and HEV-ALF groups ( P > 0.05 ). Both IFN-γ and IL-10 showed gradual upward trend from the HC group to the AHE (both P < 0.01 ), but IFN-γ showed a sharp downward trend from the AHE group to the HEV-ALF group ( P < 0.01 ) and IL-4 showed gradual upward trend from the AHE group to the HEV-ALF group ( P < 0.01 ).There was no significant difference in Th1 and Th2 cytokines between the HEV RNA(+) group and HEV RNA(-) group (all P > 0.05 ). Th2 bias was observed from the AHE ( ratio = 58.65 ) to HEV-ALF ( ratio = 1.20 ) groups. The level of IFN-γ was associated with the outcome of HEV-ALF patients. Conclusions. HEV viral load was not associated with aggravation of AHE, and the HEV-ALF patients showed significant Th2 bias, which may be involved in the aggravation of AHE.

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Neurologic complications of acute hepatitis E virus infection

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000643 ◽

2019 ◽

Vol 7 (1) ◽

pp. e643 ◽

Cited By ~ 3

Author(s):

Paolo Ripellino ◽

Emanuela Pasi ◽

Giorgia Melli ◽

Claudio Staedler ◽

Monserrat Fraga ◽

...

Keyword(s):

Acute Hepatitis ◽

Hepatitis E Virus ◽

Elevated Serum ◽

Shoulder Girdle ◽

Hepatitis E ◽

Immunoglobulin M ◽

Genotype 3 ◽

Neurologic Symptoms ◽

Bilateral Involvement ◽

Acute Hepatitis E

ObjectiveTo assess the prevalence and clinical features of neurologic involvement in patients with acute hepatitis E virus (HEV) infection in Southern Switzerland.MethodsAmong 1,940 consecutive patients investigated for acute hepatitis E, we identified 141 cases of acute of HEV infection (anti-HEV immunoglobulin M and immunoglobulin G both reactive and/or HEV RNA positive) between June 2014 and September 2017. Neurologic cases were followed up for 6 months. We compared patients with and without neurologic symptoms.ResultsNeurologic symptoms occurred in 43 acute HEV cases (30.4%) and consisted of neuralgic amyotrophy (NA, n = 15, 10.6%) and myalgia (n = 28, 19.8%). All NA cases were immunocompetent. Men had higher odds (OR = 5.2, CI 1.12–24.0, p = 0.03) of developing NA after infection with HEV, and in 3 couples simultaneously infected with HEV, only men developed NA. Bilateral involvement of NA was predominant (2:1) and occurred only in men. Seven NA cases were viremic (all genotype 3), but HEV was undetectable in their CSF. In the acute phase of NA, 9 patients were treated with intravenous immunoglobulin and 4 with prednisone, reporting no side effects and improvement in pain and strength. Myalgia occurred both without (n = 16) or with (n = 12) concomitant elevated serum creatinine kinase. Seven cases with myalgia in the shoulder girdle did not have muscle weakness (“forme fruste” of NA).ConclusionsNeurologic symptoms occurred in one-third of acute HEV infections and consisted of NA and myalgia. NA seems to occur more frequently in men infected by HEV and has a predominant (but not exclusive) bilateral involvement.

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Four cases of sporadic acute hepatitis E in Mie, Japan who were infected with European type genotype 3 hepatitis E virus

Kanzo ◽

10.2957/kanzo.52.295 ◽

2011 ◽

Vol 52 (5) ◽

pp. 295-302 ◽

Cited By ~ 5

Author(s):

Hiroshi Okano ◽

Tatsunori Nakano ◽

Shimpei Matsusaki ◽

Tomohiro Sase ◽

Tomonori Saitou ◽

...

Keyword(s):

Acute Hepatitis ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Genotype 3 ◽

Sporadic Acute Hepatitis ◽

Acute Hepatitis E

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Severe Acute Hepatitis E in a Woman with an Autoimmune Background

Acta Médica Portuguesa ◽

10.20344/amp.10429 ◽

2020 ◽

Vol 33 (6) ◽

pp. 425

Author(s):

Maria S.J. Nascimento ◽

Madalena Almeida-Santos ◽

Maria Fernandes ◽

Fernando Maltez ◽

Sara Lino ◽

...

Keyword(s):

Acute Hepatitis ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Hepatic Necrosis ◽

Coagulation Disorder ◽

Genotype 3 ◽

Virus Genotype ◽

Younger Men ◽

Acute Hepatitis E ◽

Severe Acute Hepatitis

Hepatitis E virus genotype 3 infections are normally asymptomatic in immunocompetent individuals. Symptomatic cases of acute icteric hepatitis E are seldom observed among women, younger men and children but are particularly seen in middle-aged/elderly men. We report a case of severe acute hepatitis E caused by genotype 3 in an immunocompetent 40-year-old woman that required prolonged hospitalization. Her medical history included an autoimmune background, namely atrophic gastritis and Graves’ disease. She presented an extensive hepatic necrosis as revealed by the high levels of aminotransferases (ALT 4893 U/L; AST 3138 U/L). She showed also a coagulation disorder (prothrombin time; INR = 1.33). Serological markers for hepatitis viruses A, B and C were negative but serum was positive for hepatitis E virus RNA. Sequencing and phylogenetic analysis revealed that the hepatitis E virus strain belonged to subgenotype 3a. This is suggestive of an association between the severe acute hepatitis E virus genotype 3 infection and the autoimmune background.

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