A case of acute hepatitis with positive autoantibodies who actually had hepatitis E virus infection.

Hepatitis E virus (HEV) is one of the major causative agents of acute hepatitis in many developing countries. On the other hand, recent intensive investigation has revealed the existence of non-imported cases in industrialized countries. We encountered a sporadic patient with hepatitis E in 1999, who had had no recent travel abroad. He was a 67-year-old Japanese, and his laboratory data were negative for serum markers of hepatitis A, B and C virus infection and positive anti-nuclear antibody, anti-smooth muscle antibody and high level of serum immunoglobulin G. He scored as probable autoimmune hepatitis (AIH) with the scoring system by the international AIH group. He was given a diagnosis of acute cryptogenic hepatitis including acute onset AIH in those days, but the recent retrospective examination with frozen stocked serum revealed his exact diagnosis. In conclusion, we must take HEV infection into consideration for the diagnosis of cryptogenic acute hepatitis even in the developed countries, and some patients with hepatitis E could demonstrate positive for autoantibodies similar to clinical features of AIH. This case demonstrated the needs for further studies about clinical feature of acute hepatitis E virus infection.     

肝炎患者重度黄疸原因分析

目的观察重度黄疸肝炎病人的原因及转归。方法采用7170A血清生化仪进行检测肝功能,采用SPECTRA酶标仪检测肝炎病毒血清标志物,对281例深度黄疸病人的临床资料进行分析。结果单纯感染肝炎病毒的患者187例,未感染肝炎病毒的患者24例,肝炎病毒重叠感染患者58例,病因未明12例;急性重症肝炎16例,亚急性重症肝炎21例,慢性重症肝炎198例,瘀胆型肝炎43例,其它3例;存活159例,死亡122例。结论嗜肝病毒感染是引发本组病人发病的主要原因,其中感染乙型肝炎病毒者占多数,慢性重症肝炎占70.5%,深度黄疸的患者死亡率高达43.4%。     

A case of acute hepatitis E with the travel history to an endemic area]

Hepatitis E is a self-limited and enterically transmitted acute viral hepatitis that occurs from epidemic outbreaks of developing countries and sporadic hepatitis in non-endemic areas. In endemic areas, hepatitis E virus (HEV) is one of the most common causes of acute hepatitis and hepatic failure in pregnancy. Its mortality rate has been reported up to 20%. In non-endemic areas, HEV infection without any travel history is very rare. In Korea, only one case of simple hepatitis E without any travel history to endemic areas was reported. Recently, we experienced a case of acute hepatitis. The patient who had a travel history to India, showed watery diarrhea and high fever. Transaminase level and total bilirubin were increased, and prothrombin time was prolonged. It was positive for IgM anti-HEV and IgG anti-HEV, and showed no evidence of other viral infections or drug ingestion history. In spite of absence of useful test such as seroconversion of IgM anti-HEV and HEV RNA PCR, we diagnosed the case as an acute hepatitis E from his symptom, travel history and initial serologic marker. We report this as a case of hepatitis E infected from endemic areas.     

Severe acute pancreatitis with pseudocyst bleeding due to hepatitis E virus infection

Coincidence of acute pancreatitis caused by hepatitis E virus (HEV) infection is rare. We report a case of severe acute pancreatitis in the course of acute hepatitis E in a 35-year-old man who presented with jaundice for 1 week. Serum was positive for IgM anti-HEV and negative for hepatitis A, B and C viruses. There was upper abdominal tenderness and fullness with absent bowel sounds. A diagnosis of acute pancreatitis was made and confirmed with elevated serum lipase 2,032 U/L and amylase 1,287 U/L. Two weeks after admission he had an increase in abdominal pain associated with oliguria and hemodynamic instability. Serum creatinine had increased and hemoglobin had dropped along with metabolic acidosis. Ultrasound showed hemorrhage into the pseudocyst, which was confirmed by contrast-enhanced computed tomography scan (which also ruled any pseudoaneurysm as the cause of bleed). He was hemodialysed and transfused blood. However, he developed refractory hypotension and did not respond to inotropes. After a rapid downhill course, he did not survive. Hepatitis E virus infection was complicated with the development of acute pancreatitis, which was severe with multiorgan failure and had a fatal outcome.     

Case of domestically infected hepatitis E with marked thrombocytopenia]

A 52-year-old man was admitted to our hospital for fever, jaundice, and general malaise. Laboratory data revealed elevated serum liver enzyme levels (AST 2377IU/L, ALT 2756IU/L) and bilirubin (T-Bil 3.7 mg/dl). Blood count showed a marked decrease of platelets (2.0 x 10(4)/microl). Serological and virological analysis showed positive results for HEV IgM and HEV RNA, indicating a diagnosis of acute hepatitis E. The serum ferritin level was also markedly elevated (23200 ng/ml). A diagnosis of virus associated hemophagocytic syndrome (VAHS) was strongly suggested. This is the first report of hepatitis E most likely accompanied by VAHS.     

Hepatitis E as a Cause of Acute Jaundice Syndrome in Northern Uganda, 2010–2012

Hepatitis E virus (HEV) is a common cause of acute viral hepatitis in developing countries; however, its contribution to acute jaundice syndrome is not well-described. A large outbreak of hepatitis E occurred in northern Uganda from 2007 to 2009. In response to this outbreak, acute jaundice syndrome surveillance was established in 10 district healthcare facilities to determine the proportion of cases attributable to hepatitis E. Of 347 acute jaundice syndrome cases reported, the majority (42%) had hepatitis E followed by hepatitis B (14%), malaria (10%), hepatitis C (5%), and other/unknown (29%). Of hepatitis E cases, 72% occurred in Kaboong district, and 68% of these cases occurred between May and August of 2011. Residence in Kaabong district was independently associated with hepatitis E (adjusted odds ratio = 13; 95% confidence interval = 7–24). The findings from this surveillance show that an outbreak and sporadic transmission of hepatitis E occur in northern Uganda.     

Similarities,differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice

Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.     

Viral RNA but no evidence of replication can be detected in the peripheral blood mononuclear cells of hepatitis E virus–infected patients

Summary. Hepatitis E virus (HEV) infection is an important cause of acute viral hepatitis in several developing countries but has recently been shown to cause chronic hepatitis in immunosuppressed persons. Other hepatotropic viruses that cause chronic infection have been shown to infect peripheral blood mononuclear cells (PBMCs) and to persist in those cells. We therefore decided to look for evidence of replication of HEV in PBMCs obtained from patients with acute hepatitis E, using strand‐specific assays for positive and negative HEV RNA. Of the 44 patients with acute hepatitis E during an outbreak in India, including 27 with detectable IgM anti‐HEV and 19 with detectable serum HEV RNA, 11 had detectable HEV RNA in their PBMCs. However, of the six PBMC specimens with strong HEV RNA signal, none had detectable negative‐strand HEV RNA, a marker of viral replication. These findings indicate the presence of HEV RNA but the absence of its replication in PBMCs from patients with acute hepatitis E.     

Autochthonous Hepatitis E Virus Infection in Germany with Sequence Similarities to Other European Isolates

Abstract Hepatitis E virus (HEV) is a common cause of acute hepatitis in endemic areas. Yet reports on autochthonous cases in other areas such as middle Europe are increasing. Here we report on a patient, who obviously acquired his HEV infection in Germany. Sequence analysis of the virus gained from his serum revealed homologies to other European isolates and swine isolates. J. C. Preiss and A. Plentz contributed equally to this work.     

Current status of hepatitis e virus infection in Korea

Hepatitis E virus (HEV) is an emerging pathogen associated with acute viral hepatitis, and HEV is becoming increasingly recognized. Approximately 2% of acute viral hepatitis is caused by HEV, and 18 cases of hepatitis E have been reported in Korea. Of these cases, only two have involved a history of travel from India, which suggests that they were imported cases. The remaining reported cases include a sporadic case of acute hepatitis E with genotype 4 HEV isolates and identification of the full genome sequence, as well as another case of genotype 4 HEV hepatitis that developed after ingestion of the raw bile juice of a wild bear living on a mountain in southern Korea. Moreover, genotype 3 HEV, which shows close genetic homology with swine HEV in Korea, has been detected in collected human serum samples. Therefore, genotypes 3 and 4 HEV are currently circulating in the Korean community and may be related to zoonotic transmission and food-borne infection. The reported anti-HEV seroprevalence of 17% to 27% in the Korean population suggests that HEV infection has been autochthonously circulating, thereby resulting in subclinical infection in Korea. Given the discrepancies among anti-HEV assays, the diagnosis of hepatitis E should be made with caution using adequate antibody assays, and HEV RNA should be preferably detected from the stool. Further virological characterization and epidemiological study of the virus are warranted.     

Hepatitis E is an autochthonous disease in industrialized countries. Analysis of 23 patients in South-West France over a 13-month period and comparison with hepatitis A

OBJECTIVES: Hepatitis E virus (HEV) is responsible for acute hepatitis predominantly in developing countries. In Western Europe and in the US, cases of acute HEV infection are uncommon and occur primarily in travelers returning from endemic countries. The aim of this study was to describe patients with acute hepatitis E in South West France and compare them with patients with acute hepatitis A. METHODS: 23 consecutive patients over 13 months were analysed. Acute hepatitis E was diagnosed on the presence of specific serum antibodies or viral RNA detection in serum or stools. Real time PCR products from viraemic patients were sequenced. RESULTS: All the HEV sequences belonged to genotype 3. Two patients (8%) died during their hospital stay, both suffered from severe underlying disease. Only 3 patients (13%) had travelled outside of Europe, within 3 months of the onset of disease. When compared to 23 patients with acute hepatitis A at the same hospital and during the same time frame, HEV-infected patients were older (54.4 +/- 16.6 vs 24.5 +/- 16.6, P<0.05), had lower ALT levels (55.4 X upper normal limit +/- 48.6 vs 107.8 X upper normal limit +/- 82.8, P<0.05) and had lower incidence of recent travel outside of Europe (13% in the hepatitis E group vs 60% in the hepatitis A group, P<0.05). CONCLUSIONS: Hepatitis E can be considered an autochthonous infection in South West France. All strains sequenced were related to genotype III. When compared to hepatitis A, HEV-infected patients were older, had lower ALT levels and had a lower incidence of travel outside of Europe.     

Icteric acute hepatitis E with no response of immunoglobulin M class anti‐hepatitis E virus antibody

A 68‐year‐old Japanese man developed icteric acute hepatitis during periodic care after undergoing gastrectomy due to early gastric cancer. The routine serological markers for hepatitis A, B and C viruses were all negative. Although the liver enzymes spontaneously recovered without any specific therapy, cholestasis was relatively prolonged and successfully treated with prednisolone. Determination of serum hepatitis E virus (HEV) RNA revealed the transient infection of HEV, and both immunoglobulin (Ig)A and IgG class anti‐HEV antibodies were detected after the disease onset, whereas those were negative when measured 3 weeks prior to the onset. In addition, the titer of serum IgA class antibody was associated with the clinical signs of hepatitis. In contrast, no IgM class antibody was detected throughout the course. This case suggests that screening only with IgM class antibody is not sufficient to detect acute HEV infection.     

Hepatitis E: virología molecular,epidemiología y patogénesis

Hepatitis E represents a significant proportion of enteric transmitted liver diseases and poses a major public health problem, mainly associated with epidemics due to contamination of water supplies, especially in developing countries. Hepatitis E virus (HEV) is responsible for self-limiting acute liver oral-faecal infections. In industrialised countries, acute hepatitis E is sporadic, detected in travellers from endemic areas but also in sporadic cases with no risk factors. HEV is a non-enveloped virus with a single-stranded RNA genome classified into 4 genotypes and a single serotype. Genotypes 1 and 2 only infect humans, and are predominant in the developing countries, while 3 and 4 are predominant in industrialised countries, and also infect other species of mammals, especially pigs, and multiple evidence classifies HEV as a zoonotic agent. Some HEV chronic infections have recently been reported in kidney and liver transplant patients. The mortality rate of HEV infection is greater than hepatitis A. In addition to faecal-oral transmission, parenteral transmission of HEV has also been reported. Several vaccines are currently in development. The severity of this infection in some groups of patients, especially pregnant women, and the occurrence of chronic hepatitis, even with progression to cirrhosis, have raised interest in the application of interferon and/or ribavirin therapy.     

Hepatitis E： An overview and recent advances in vaccine research

Hepatitis E virus (HEV) is an unclassified, small, non-enveloped RNA virus, as a causative agent of acute hepatitis E that is transmitted principally via the fecal-oral route. The virus can cause large water-born epidemics of the disease and sporadic cases as well. Hepatitis E occurs predominantly in developing countries, usually affecting young adults, with a high fatality rate up to 15-20% in pregnant women. However, no effective treatment currently exists for hepatitis E, and the only cure is prevention. But so far there are no commercial vaccines for hepatitis E available in the world. Although at least four major genotypes of HEV have been identified to date, only one serotype of HEV is recognized. So there is a possibility to produce a broadly protective vaccine. Several studies for the development of an effective vaccine against hepatitis E are in progress and the best candidate at present for a hepatitis E vaccine is a recombinant HEV capsid antigen expressed in insect cells from a baculovirus vector. In this article, the recent advances of hepatitis E and the development of vaccine research for HEV including recombinant protein vaccine, DNA vaccine and the recombinant hepatitis E virus like particles (rHEV VLPs) are briefly reviewed.     

Acute pancreatitis associated with acute hepatitis E infection.

A 45-year-old male presented with severe abdominal pain, hyperamylasaemia and a bulky pancreas. In addition, he had deep jaundice and markedly raised serum transaminases, and his serum was positive for IgM anti-hepatitis E virus (HEV) antibodies. The common aetiologies of acute pancreatitis were excluded. The patient ran a benign course for both acute viral hepatitis and acute pancreatitis, and recovered completely. Acute pancreatitis caused by HEV infection has been reported only occasionally.