Hepatitis E: an emerging infection in developed countries
TL;DR: Patients with unexplained hepatitis should be tested for hepatitis E, whatever their age or travel history, and the source and route of infection remain uncertain, but it might be a porcine zoonosis.
Abstract: Hepatitis E is endemic in many developing countries where it causes substantial morbidity. In industrialised countries, it is considered rare, and largely confined to travellers returning from endemic areas. However, there is now a growing body of evidence that challenges this notion. Autochthonous hepatitis E in developed countries is far more common than previously recognised, and might be more common than hepatitis A. Hepatitis E has a predilection for older men in whom it causes substantial morbidity and mortality. The disease has a poor prognosis in the context of pre-existing chronic liver disease, and is frequently misdiagnosed as drug-induced liver injury. The source and route of infection remain uncertain, but it might be a porcine zoonosis. Patients with unexplained hepatitis should be tested for hepatitis E, whatever their age or travel history.
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TL;DR: HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16-65 years and no vaccination-related serious adverse event was noted.
620 citations
TL;DR: The findings strongly support the hypothesis of HEV infection through ingestion of raw figatellu, a traditional pig liver sausage widely eaten in France and commonly consumed raw, as a source ofHEV infection.
Abstract: Background. The source and route of autochthonous hepatitis E virus (HEV) infections are not clearly established in industrialized countries despite evidence that it is a zoonosis in pigs. We investigated the role of figatellu, a traditional pig liver sausage widely eaten in France and commonly consumed raw, as a source of HEV infection. Methods. A case-control study was conducted of 3 patients who presented autochthonous hepatitis E and 15 members of their 3 different families. Anti-HEV immunoglobulin G and immunoglobulin M antibody testing was performed with commercial assays. HEV RNA was detected in serum samples of patients and in pig liver sausages by means of real-time polymerase chain reaction and sequenced by means of in-house sequencing assays. Genetic links between HEV sequences were analyzed. Results. Acute or recent HEV infection, defined by detection of anti-HEV immunoglobulin M antibodies and/or HEV RNA, was observed in 7 of 13 individuals who ate raw figatellu and 0 of 5 individuals who did not eat raw figatellu (P = .041). Moreover, HEV RNA of genotype 3 was recovered from 7 of 12 figatelli purchased in supermarkets, and statistically significant genetic links were found between these sequences and those recovered from patients who ate raw figatellu. Conclusion. Our findings strongly support the hypothesis of HEV infection through ingestion of raw figatellu.
574 citations
Cites background from "Hepatitis E: an emerging infection ..."
...Pig Liver Sausage as HEV Source • JID 2010:202 (15 September) • 827 food, exposure to water, travel abroad, and transfusion within the 2–9 weeks preceding acute hepatitis, which corresponds to the incubation period of the disease [1]....
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...an emerging concern in industrialized countries [1, 2]....
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...genotypes 3 or 4 and have been found to be highly similar or even identical in some cases [1, 4, 8, 38, 45]....
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...unknown in most cases, it has been established that pigs are major HEV reservoirs [1, 2, 4]....
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...Nevertheless, despite these findings that indicate the possibility of zoonotic foodborne HEV infection, the source and manner of viral transmission in industrialized countries has not been documented in most cases [1, 2, 4]....
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TL;DR: The model was most sensitive to estimates of age‐specific incidence of HEV disease, which causes source‐originated epidemics of acute disease with a case fatality rate thought to vary by age and pregnancy status.
561 citations
TL;DR: A retrospective analysis of data from 17 centers from Europe and the United States that described the progression, outcomes, and factors associated with development of chronic HEV infection in recipients of transplanted solid organs found tacrolimus therapy is the main predictive factor for chronic hepatitis.
544 citations
Cites result from "Hepatitis E: an emerging infection ..."
...The data presented in the current report confirm and xtend previous observations in a much smaller number f solid organ transplant recipients and are 4-fold: (1) pproximately 60% of solid organ transplant patients nfected with HEV develop chronic hepatitis; (2) the use f tacrolimus rather than cyclosporin A as a main immuosuppressant and a low platelet count at diagnosis of EV infection are 2 independent predictive factors for he development of chronic HEV infection; (3) nearly ne-third of patients who are chronically infected with EV achieved sustained viral response after dose reducion of immunosuppressive therapy, and this was mainly ue to the reduction of therapy-targeting T cells; and (4) o reactivation was observed after HEV clearance....
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TL;DR: In this comprehensive review, the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries are summarized.
Abstract: Hepatitis E virus (HEV) infection is a worldwide disease. An improved understanding of the natural history of HEV infection has been achieved within the last decade. Several reservoirs and transmission modes have been identified. Hepatitis E is an underdiagnosed disease, in part due to the use of serological assays with low sensitivity. However, diagnostic tools, including nucleic acid-based tests, have been improved. The epidemiology and clinical features of hepatitis E differ between developing and developed countries. HEV infection is usually an acute self-limiting disease, but in developed countries it causes chronic infection with rapidly progressive cirrhosis in organ transplant recipients, patients with hematological malignancy requiring chemotherapy, and individuals with HIV. HEV also causes extrahepatic manifestations, including a number of neurological syndromes and renal injury. Acute infection usually requires no treatment, but chronic infection should be treated by reducing immunosuppression in transplant patients and/or the use of antiviral therapy. In this comprehensive review, we summarize the current knowledge about the virus itself, as well as the epidemiology, diagnostics, natural history, and management of HEV infection in developing and developed countries.
499 citations
Cites background from "Hepatitis E: an emerging infection ..."
...However, in most cases, the source of infection remains uncertain (18)....
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...HEV3 has a worldwide distribution (18)....
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References
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TL;DR: Current available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis.
1,813 citations
TL;DR: The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.
Abstract: Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.
1,139 citations
TL;DR: The discovery of swine HEV not only has implications for HEV vaccine development, diagnosis, and biology, but also raises a potential public health concern for zoonosis or xenozoonosis following xenotransplantation with pig organs.
Abstract: A novel virus, designated swine hepatitis E virus (swine HEV), was identified in pigs. Swine HEV crossreacts with antibody to the human HEV capsid antigen. Swine HEV is a ubiquitous agent and the majority of swine ≥3 months of age in herds from the midwestern United States were seropositive. Young pigs naturally infected by swine HEV were clinically normal but had microscopic evidence of hepatitis, and developed viremia prior to seroconversion. The entire ORFs 2 and 3 were amplified by reverse transcription–PCR from sera of naturally infected pigs. The putative capsid gene (ORF2) of swine HEV shared about 79–80% sequence identity at the nucleotide level and 90–92% identity at the amino acid level with human HEV strains. The small ORF3 of swine HEV had 83–85% nucleotide sequence identity and 77–82% amino acid identity with human HEV strains. Phylogenetic analyses showed that swine HEV is closely related to, but distinct from, human HEV strains. The discovery of swine HEV not only has implications for HEV vaccine development, diagnosis, and biology, but also raises a potential public health concern for zoonosis or xenozoonosis following xenotransplantation with pig organs.
1,088 citations
TL;DR: Findings on the genetic organization and expression strategy of HEV suggest that it is the prototype human pathogen for a new class of RNA virus or perhaps a separate genus within the Caliciviridae family.
1,016 citations