Chronic Hepatitis E Virus Infection in a Pediatric Female Liver Transplant Recipient

Abstract

cWe describe a case of chronic hepatitis E virus (HEV) infection in a 13-year-old female liver transplant recipient with recurrent increased aminotransferase levels and acute cellular rejection. This finding demonstrates that chronic HEV infection can occur and should be further investigated in immunocompromised patients in Latin America. CASE REPORTA 4-year-old girl who had undergone orthotopic liver transplantation in 2003 presented with increased aminotransferase levels and biopsy-confirmed acute cellular rejection in 2006. Liver enzyme levels were normalized after 3 days of methylprednisolone pulse therapy and increased tacrolimus dosage. In 2009, the alanine aminotransferase concentration reached 715 IU per liter and thereafter plateaued at nearly 2.5 times the upper limit of the normal range. Acute cellular rejection was additionally confirmed by biopsy. Results of serology and molecular testing for hepatitis A virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, and Epstein-Barr virus were negative. Results of molecular testing for cytomegalovirus and Epstein-Barr virus in liver tissue and testing for autoantibodies and antinuclear antibodies were also negative. Serum transaminase levels remained elevated, and in 2011, histological examination showed prominent inflammatory activity and fibrosis compatible with viral infection. Hepatitis E was diagnosed in February 2012 on the basis of positive results for anti-hepatitis E virus (HEV) IgG and IgM antibody testing (Mikrogen, Germany) and, later, in May 2013, HEV RNA detection (genotype 3b, Brazil h4; GenBank accession number KF152884), with a load of 4.5 log 10 copies per ml. The patient did not report any recent travel, and no potential route of HEV transmission other than consumption of pork was identified. The living organ donor tested negative for anti-HEV antibodies. No prior serum samples were available. However, retrospective examination of viral RNA extracted from paraffin-embedded formalin-fixed liver tissue (RNeasy FFPE kit; Qiagen, Germany) from 2009 showed the presence of HEV with Ͼ99% homology to the sequence found in the serum sample from 2013, thus characterizing chronic hepatitis E infection (Brazil h4.1; GenBank accession number KM502569). At the time of HEV RNA detection, the alanine aminotransferase concentration was 120 IU per liter. The patient received ribavirin treatment (500 mg/day) for 10 months, and her HEV RNA load became undetectable (Ͻ100 copies per liter) in August 2013.Infections caused by HEV can become chronic, with persistently elevated aminotransferase levels and persistent viremia in immunocompromised adults and children; certain chronic cases have been described in pediatric patients with HIV or hematological malignancies and in pediatric patients who have received solid-organ transplants (1-4).Increased levels of aminotransferases are frequently observed after solid-organ transplantation (5). In certain patients, after ruling out viral and alcohol-, toxin-, and drug-related causes, no etiology is established. I...

Hepatitis E virus in the countries of the Middle East and North Africa region: an awareness of an infectious threat to blood safety

“…No infectivity data, however, are available for anti-HEV IgM-positive donations in the MENA region. HEV-RNA on the other hand does not persist for long (1-2 months) and in some patients may persist for a longer period [8] where in immunocompromised patients the persistence extends to several years [124].…”

Hepatitis E virus infection in Brazil: results of laboratory-based surveillance from 1998 to 2013

“…Examination of viral RNA extracted from paraffi n-embedded formalin-fi xed liver tissue (RNeasy FFPE kit; Qiagen, Germany) from 3 years prior showed the presence of HEV sharing >99% homology with the sequence found in the serum sample from 2013, thus indicating chronic hepatitis E infection (KM502569). The patient was treated with ribavirin for 10 months, and her HEV RNA load became undetectable (<100 copies/L) in August 2013 (3) . 2.0-4.3% (4) .…”

<b>Detecção e quantificação do vírus da hepatite E (HEV) por RT-PCR em tempo real e estudo experimental em primatas neotropicais (<i>Aotus azarai infulatus</i>) infectados pelo genótipo 3 do HEV</b>

“…No presente, um número até então limitado de publicações tem indicado a ocorrência somente de isolados do genótipo 3 do HEV no Brasil em seres humanos (DOS SANTOS et al, 2010;PASSOS et al, 2013;PASSOS-CASTILHO et al, 2014), e suínos (PAIVA et al, 2007, DOS SANTOS et al, 2009DE SOUZA et al, 2012;GARDINALI et al, 2012;LANA et al, 2014) Estima-se que a taxa de letalidade da hepatite E em grávidas possa chegar a 20% em regiões endêmicas (KUMAR et al, 2004;AGGARWAL, 2011; As partículas do HEV são não-envelopadas, com tamanho de 27-34 nm e apresentam simetria icosaédrica (BRADLEY et al, 1987 A ORF1 viral contém sete domínios principais -metiltransferase, domínio y, cisteíno-protease tipo papaína, região hipervariável, domínio x, helicase, RNA-dependente de RNApolimerase -e codifica uma poliproteína de 1693 aminoácidos (aa) da qual são produzidas proteínas não-estruturais envolvidas na replicação viral; a ORF2 é responsável pela codificação de uma proteína formada por 660 aa que compõe o capsídeo viral; e a ORF3, codifica uma fosfoproteína multifuncional de 114 aa que apresenta atividade moduladora direta e indireta na replicação viral (EMERSON et al, 2006;PURCELL, 2013;CAO et al, 2012).…”

“…A primeira evidência de circulação do HEV no Brasil foi atribuída à detecção de anticorpos anti-HEV IgG entre 6,1% de trabalhadores de mineração saudáveis na bacia amazônica do Estado do Mato Grosso (PANG et al, 1995), mas casos humanos de hepatite E confirmados a partir da detecção molecular, sequenciamento nucleotídico e análise filogenética do HEV, até o momento, indicaram apenas a ocorrência do genótipo 3 do vírus em cinco casos: em um paciente com hepatite aguda autóctone no Estado do Rio de Janeiro (DOS SANTOS et al, 2010); e em quatro casos crônicos no Estado de São Paulo, sendo três pacientes transplantados receptores de rins e uma paciente receptora de fígado (PASSOS-CASTILHO et al, 2014).…”

“…Esta particularidade no perfil epidemiológico da hepatite E em regiões não endêmicas, causadas por infecções pelo genótipo 3 do vírus, pode ter relação com as baixas prevalências sorológicos e moleculares observadas em diversas populações no Brasil (DE PAULA et al, 2001;TRINTA et al, 2001;ASSIS et al, 2012;DOS SANTOS et al, 2010;ECHEVARRIA et al, 2013;PASSOS et al, 2013;PASSOS-CASTILHO et al, 2014;MARTINS et al, 2014;VITRAL et al, 2014), porém, devido ao fato do HEV já ter sido descrito em suínos em diversas regiões geográficas do Brasil, algumas populações como veterinários, criadores e/consumidores de suínos podem estar expostos a um maior risco de infecção, reforçando a necessidade de pesquisas relacionadas ao diagnóstico laboratorial do HEV em humanos e animais no país (PAIVA et al, 2007, DOS SANTOS et al, 2009DE SOUZA et al, 2012;GARDINALI et al, 2012;LANA et al, 2014;VASCONCELOS et al, 2015;HELDT et al, 2016).…”