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Es wurde ein Patient mit rheumatoider Arthritis (RA) vorgestellt, der unter der Therapie mit dem Januskinase-1/2-Inhibitor Baricitinib eine Infektion mit dem Hepatitis-E-Virus (HEV) entwickelte. Unser Patient hatte bei seiner vierteljährlichen Routineuntersuchung deutlich erhöhte Transaminasen bei einer unauffälligen körperlichen Untersuchung. Es fanden sich Antikörper der IgM- und IgG-Klasse gegen HEV und ein erhöhtes C‑reaktives Protein (CRP) sowie HEV-RNA mittels Real-Time-PCR, was auf eine frische HEV-Infektion hinwies. Baricitinib wurde sofort abgesetzt. Die ausführliche Anamnese ergab, dass der Patient Tage vor der Konsultation Rindertartar verzehrt hatte, ohne dass gastrointestinale Symptome oder Fieber aufgetreten waren. Im weiteren Verlauf erholte sich der Patient vollständig, und die Leberfunktionstests und das CRP normalisierten sich innerhalb von 3 Monaten. Baricitinib wurde daraufhin wieder eingenommen. Bisher wurden nur wenige Daten zu HEV-Infektionen bei RA-Patienten, die mit JAK-Inhibitoren behandelt wurden, publiziert. A patient with rheumatoid arthritis (RA) was presented, who developed an infection with the hepatitis E virus (HEV) under treatment with the Janus kinase (JAK) 1 and 2 inhibitor baricitinib. In the 3‑month routine check-up the patient had clearly elevated transaminase levels with an inconspicuous physical examination. The investigations detected antibodies of IgM and IgG classes against HEV and an elevated C‑reactive protein (CRP) level as well as HEV-RNA by real-time PCR, which is indicative of a recent HEV infection. Baricitinib was immediately discontinued. The extensive anamnesis revealed that the patient had eaten beef tartar some days before the consultation, without the occurrence of gastrointestinal symptoms or fever. In the further course the patient completely recovered and the liver function tests and the CRP levels normalized within 3 months. Baricitinib was then restarted. So far only few reports have been published on HEV infections in RA patients who have been treated with JAK inhibitors.

No vaccine against the hepatitis E virus (HEV) is currently licensed in Europe. In contrast, HEV-239 (Hecolin®, Xiamen Innovax Biotech Co., Xiamen, China), a vaccine against HEV genotype 4, has been available in China for 10 years. Challenges for the development of vaccines arise mainly from the differences between the genotypes with regard to distribution, transmission routes and risk groups. Other obstacles include the envelopment of HEV in blood by host membranes, replication in various organs outside the liver and weaker immune responses in vulnerable groups. This article reviews the current status of vaccines against HEV that are available and in advanced preclinical evaluation, with a focus on vaccine development strategies. Challenges and limitations are described.Current vaccine candidates focus on protein-based immunisation with the aim of inducing protective, neutralising antibody responses. The goal of the HEV-239 pivotal trial with more than 100,000 study participants was to prevent acute symptomatic infections. However, it is unclear to what extent asymptomatic infections were prevented by the vaccine and whether it is effective enough in patients at risk for a complicated course, such as patients with liver cirrhosis, immunosuppressed individuals and pregnant women. Efficient in vitro models are increasingly enabling the development of monoclonal neutralising antibodies for passive immunisation or therapy.Future vaccines should demonstrate clear protection against all genotypes in addition to a very good safety profile. The development of an efficient passive immunisation strategy, especially for immunosuppressed individuals, is desirable.In Europa ist aktuell kein Impfstoff gegen das Hepatitis-E-Virus (HEV) zugelassen. Demgegenüber steht in China bereits seit 10 Jahren mit HEV-239 (Hecolin®, Xiamen Innovax Biotech Co., Xiamen, China) ein Vakzin gegen den HEV-Genotyp 4 zur Verfügung. Herausforderungen für die Entwicklung von Impfstoffen ergeben sich v. a. aus den Unterschieden zwischen den Genotypen bezüglich Verbreitung, Übertragungswege und Risikogruppen. Weitere Hindernisse sind die Umhüllung von HEV im Blut durch Wirtsmembranen, die Replikation in verschiedenen Organen außerhalb der Leber sowie schwächere Immunantworten in vulnerablen Gruppen. In diesem Artikel wird der aktuelle Stand der verfügbaren und in fortgeschrittener präklinischer Evaluation befindlichen Vakzine gegen HEV mit Fokus auf Strategien der Impfstoffentwicklung dargestellt. Herausforderungen und Limitationen werden beschrieben.Aktuelle Impfkandidaten fokussieren auf proteinbasierte Immunisierungen mit dem Ziel der Induktion von schützenden, neutralisierenden Antikörperantworten. Das Ziel der HEV-239-Zulassungsstudie mit mehr als 100.000 Studienteilnehmern war die Verhinderung von akuten symptomatischen Infektionen. Es ist jedoch unklar, inwieweit asymptomatische Infektionen durch das Vakzin verhindert wurden und ob es in Risikopatienten für einen komplizierten Verlauf, wie Patienten mit Leberzirrhose, Immunsupprimierten und Schwangeren, effektiv genug wirkt. Effiziente In-vitro-Modelle ermöglichen zunehmend die Entwicklung von monoklonalen neutralisierenden Antikörpern zur passiven Immunisierung oder Therapie.Zukünftige Vakzine sollten neben einem sehr guten Sicherheitsprofil eine eindeutige Protektion gegenüber allen Genotypen demonstrieren. Die Entwicklung einer effizienten passiven Immunisierungsstrategie, insbesondere für immunsupprimierte Personen, ist wünschenswert.

Viral hepatitis A to E describes various infectious inflammations of the liver parenchyma that are caused by the hepatitis viruses A to E (HAV, HBV, HCV, HDV, and HEV). Although the clinical pictures are similar, the pathogens belong to different virus families and differ in terms of pathogenesis, transmission routes, clinical course, prevention, and therapy options. In Germany, there is mandatory reporting according to the Infection Protection Act (IfSG) for direct or indirect laboratory evidence and for suspicion, illness, and death of viral hepatitis. The data are transmitted to the Robert Koch Institute.In this article, on the basis of published studies and notification data, we describe the epidemiology of hepatitis A to E as well as current challenges and prevention approaches. In particular, the latter contains the improvement of existing vaccination recommendations (hepatitis A and B); improvement of access to prevention, testing, and care including therapy with antiviral drugs (hepatitis B, C, and D) and the detection and prevention of foodborne infections and outbreaks; and improvements in the field of food safety (hepatitis A and E).Mit Virushepatitis A bis E werden verschiedene infektiöse Entzündungen des Leberparenchyms bezeichnet, die durch die Hepatitisviren A bis E (HAV, HBV, HCV, HDV und HEV) ausgelöst werden. Zwar ähneln sich die Krankheitsbilder, die Erreger gehören jedoch zu verschiedenen Virusfamilien und unterscheiden sich bezüglich der Pathogenese, der Übertragungswege, des klinischen Verlaufs und der Präventions- und Therapiemöglichkeiten. In Deutschland besteht eine namentliche Meldepflicht nach Infektionsschutzgesetz (IfSG) für den direkten oder indirekten Nachweis und für Verdacht, Erkrankung und Tod. Die Daten werden an das Robert Koch-Institut übermittelt.In diesem Beitrag wird die Epidemiologie der Hepatitiden A bis E anhand publizierter Studien und Meldedaten beschrieben und es werden aktuelle Herausforderungen und Präventionsansätze aufgezeigt. Letztere bestehen insbesondere in der verbesserten Umsetzung bereits bestehender Impfempfehlungen (Hepatitis A und B), dem verbesserten Zugang zu Prävention, Testung und Versorgung, einschließlich Therapie mit antiviralen Medikamenten (Hepatitis B, C und D), und der Erkennung und Verhinderung lebensmittelbedingter Infektionen und Ausbrüche und Verbesserungen auf dem Gebiet der Lebensmittelsicherheit (Hepatitis A und E).

The hepatitis E virus (HEV) is an etiological agent of acute hepatitis in humans. In addition, chronic infections resulting in fatal liver cirrhosis currently emerge in immunosuppressed transplant patients. The number of notified hepatitis E cases in Germany has steeply increased in recent years. Here, genotype 3, which can be zoonotically transmitted from animals to humans, is predominant. The main reservoirs are pigs and wild boars, which show no signs of infection. In this article, the distribution of HEV in animals in Germany, possible transmission pathways, and especially the importance of food as a transmission vehicle are presented based on the current scientific literature.HEV is widely spread among domestic pigs and wild boars in Germany and the virus is mainly transmitted by direct contact or by consumption of food produced from those animals. However, if HEV RNA is detected in specific food it is often unclear whether the contained virus is still infectious or inactivated by the conditions during production. Recent studies indicate a high stability of HEV against different physicochemical conditions, whereas - among others - the virus can be efficiently inactivated by heating. Therefore, proper heating of pork meat and liver prior to consumption in general is recommended. For risk groups, avoiding shortly cured raw sausages is an additional suggestion.Further research is necessary to identify relevant risk food products, to investigate alternative transmission pathways, and to develop efficient measures in order to reduce or prevent zoonotic transmissions of the virus in future.Das Hepatitis-E-Virus (HEV) ist ein Erreger einer akuten Hepatitis beim Menschen. Darüber hinaus treten zunehmend auch chronische Infektionen mit fataler Leberzirrhose bei immunsupprimierten Transplantationspatienten auf. Die Zahl der gemeldeten Hepatitis-E-Fälle in Deutschland hat in den vergangenen Jahren stark zugenommen. Hier kommt vor allem der Genotyp 3 vor, der zoonotisch von Tieren auf den Menschen übertragen werden kann. Haus- und Wildschweine, die ohne die Ausbildung klinischer Symptome infiziert werden, stellen das Hauptreservoir dar. In diesem Artikel werden die Verbreitung von HEV in Tieren in Deutschland, mögliche Übertragungswege des Virus und insbesondere die Bedeutung von Lebensmitteln bei der Übertragung anhand der aktuellen wissenschaftlichen Literatur dargestellt.HEV ist in Haus- und Wildschweinen in Deutschland stark verbreitet und wird hauptsächlich über direkten Kontakt oder den Verzehr von Lebensmitteln, die aus diesen Tieren hergestellt wurden, auf den Menschen übertragen. Beim HEV-RNA-Nachweis in spezifischen Lebensmitteln bleibt allerdings oft unklar, ob das enthaltene Virus noch infektiös ist oder durch die Herstellungsbedingungen inaktiviert wurde. Neuere Studien weisen auf eine hohe Stabilität des HEV unter verschiedenen physikochemischen Bedingungen hin, wohingegen eine Inaktivierung unter anderem durch Erhitzung erreicht wird. Generell wird deshalb ein ausreichendes Erhitzen von Schweinefleisch und -leber vor dem Verzehr empfohlen und für Risikogruppen zusätzlich der Verzicht auf den Verzehr kurzgereifter Rohwürste.Weitere Forschungen sind nötig, um relevante Risikolebensmittel zu identifizieren, alternative Übertragungswege zu untersuchen und effiziente Maßnahmen zu entwickeln, die eine zoonotische Virusübertragung zukünftig verringern oder vermeiden.

Precision medicine is also possible for infectious diseases as shown for the treatment of chronic viral hepatitis, especially if different options are available. In hepatitis B virus (HBV) infection, treatment indication as well as the choice of treatment and the decisions to stop treatment are based on viral markers and alanine aminotransferase (ALT) level. Future therapies for HBV infection aiming for functional cure or even virus elimination may be even more personalized and have to take into account the immune status of a given patient. Such treatment modalities might also increase the chance for successful treatment of chronic hepatitis delta where treatment options are still very limited. Some new therapeutic concepts targeting host receptors or host enzymes are promising, but may require individualized approaches. Chronic hepatitis C is a good example for precision medicine based on viral and host factors. However, the main reason for individualized direct-acting antiviral (DAA) treatment is to save costs. As DAAs are effective in more than 95% of patients, elimination of HCV seems to be possible at the level of a given country or even on a global scale. However, owing to high reinfection rates in high-risk groups and limited availability of antiviral therapy in many high endemic countries, it must still be decided whether an HCV vaccine or pre-exposure prophylaxis is required to achieve this goal. Hepatitis E is an emerging topic as this is the most frequent acute hepatitis virus infection. It can result in a chronic infection in immunosuppressed individuals. Treatment options are still limited and individualized management is based on tailoring immunosuppressive therapy and therapy with ribavirin. Thus, personalized therapy of hepatitis E virus infection is still limited.

History and initial findings | A patient with bilateral pain in his shoulders is presented at the emergency room. Investigations | There were strongly increased transaminases. Diagnosis | Serology and PCR led to the diagnosis of hepatitis E. Neurological examination revealed a neuralgic amyotrophy Treatment and course | The pain in the shoulders disappeared spontaneously after vanishing of HEV viremia. Conclusion | Patients with shoulder pain of unknown origin and elevated transaminases should be tested for hepatitis E.

The detection and estimation of hepatitis E have greatly changed in recent years. An increasing number of hepatitis E virus (HEV) infections, which were acquired in Europe and knowledge on chronic hepatitis E in immunosuppressed patients, give this infectious disease a new significance in industrial nations in contrast to the previous assumption of merely being a tropical disease with an acute course. Rheumatology patients under immunosuppressive therapy generally have an increased risk of infections.An HEV infection should always be taken into consideration for the differential diagnostics, particularly in cases of increased transaminase levels and/or diarrhea. In contrast to healthy individuals where the course of HEV infections is mostly innocuous, in immunocompromised patients isolated severe and also chronic courses have been described. Testing of these patients should initially also include PCR of HEV-RNA because serological markers are not always reliable. Therapy with ribavirin (cave: off-label) is a possible therapeutic option and should be considered in individual cases in cooperation with a hepatologist and/or specialist for infections. Whether a general screening for HEV before therapy with biologics is recommendable, cannot yet be conclusively assessed. Additionally, an HEV infection should be included in the differential diagnostics of unclear systemic diseases because the disease can have diverse extrahepatic manifestations.There are serological indications that hepatitis E can act as a trigger for autoimmune diseases, such as autoimmune hepatitis and cryoglobulinemia but this phenomenon and the underlying pathological mechanisms need further clarification.

We report about a 44-year old patient with severe acute hepatitis E after herbage walking-to ur. Transmission occurred with ingestion of contaminated herbs. Symptoms were jaundice, dark urine, rheumatic pains and distinctive fatigue. We could document a benign self-limiting course under regular clinical controls. Hepatitis Eisa worldwide common cause for acute hepatitis with jaundice. In Switzerland contamination of this autochthonic infection is aquired by consumption of pork and venison (seroprevalence up to 22%). Infection can be without symptoms but also can result in acute liver failure. Extrahepatic symptoms are not uncommon.

Die Hepatitis-E-Virus-Infektion (HEV-Infektion) ist eine in Entwicklungsländern endemisch auftretende und in Industrieländern selten diagnostizierte Erkrankung, der bis 2008 ausschließlich ein akuter Verlauf vergleichbar mit einer Hepatitis-A-Virus-Infektion zugeschrieben wurde. Durch die Erstbeschreibung chronischer Infektionsverläufe bei Patienten nach Organtransplantation und die rasche Progredienz der viralen Hepatitis in eine Leberfibrose bzw. Leberzirrhose hat die Bedeutung der HEV-Infektion weltweit deutlich zugenommen. In Deutschland liegen bisher nur wenige Daten zur Prävalenz der HEV-Infektion sowie zu möglichen Risikofaktoren vor. Um retrospektiv die Inzidenz der akuten sowie chronischen HEV-Infektion bei Patienten, die zwischen 2001 und 2006 am Campus Virchow-Klinikum der Charité- Universitätsmedizin Berlin ein Lebertransplantat erhielten, zu bestimmen, erfolgte in der vorliegenden Arbeit bei 406 Patienten (PCR-Kohorte) zu den Zeitpunkten Monat 6 nach orthotoper Lebertransplantation (OLT) sowie zu einem 6 Monate späteren Zeitpunkt ein RNA-Screening unter Einsatz einer Real-Time PCR. Um die Seroprävalenz zu bestimmen sowie den Antikörperverlauf nach Lebertransplantation zu beobachten, erfolgte in einer Subkohorte von 150 Patienten (ELISA-Kohorte) die Durchführung eines sequentiellen RNA- und anti- HEV IgG-Screenings zu den Zeitpunkten vor OLT sowie Monat 6, 12 und 36 nach OLT. Weiterhin sollten mit Hilfe eines selbstkonzipierten Fragebogens Risikofaktoren für den Erwerb einer HEV-Infektion identifiziert werden. Die Inzidenz der HEV-Infektion bei Patienten nach Lebertransplantation war niedrig, jedoch bestand das Risiko eines chronischen Verlaufes: Bei 2 von 406 Patienten (0,5%) konnten zu mindestens einem Untersuchungszeitpunkt HEV-RNA nachgewiesen werden; ein Patient entwickelte einen chronischen Infektionsverlauf. Die in der ELISA-Subkohorte (n=150) ermittelte anti-HEV IgG-Seroprävalenz betrug 21% (n=31). Darüber hinaus zeigte das Antikörperscreening, dass die Mehrzahl der seropositiv getesteten Patienten bereits zum Zeitpunkt vor OLT anti-HEV IgG positive Serumproben aufwies (n=28). 20 Patienten wurden zu allen Untersuchungszeitpunkten seropositiv getestet, während 7 der 28 zum Zeitpunkt vor OLT positiv getesteten Patienten zu den Untersuchungszeitpunkten nach Lebertransplantation im ELISA ein negatives Testergebnis aufwiesen. Patienten, die durchgehend anti-HEV IgG positiv blieben (n=20), wiesen zum Untersuchungszeitpunkt vor OLT einen signifikant höheren Antikörpertiter auf als Patienten, die ausschließlich zum Zeitpunkt vor OLT anti-HEV IgG positiv getestet wurden und danach negativ (n=7). Zusätzlich gab es 3 Patienten (2%), die erstmalig zu einem Verlaufszeitpunkt nach OLT anti-HEV positiv getestet wurden. Die Serumprobe eines Patienten war vor OLT anti-HEV IgG negativ und ab Monat 6 seropositiv. Für diesen Patienten konnte eine akute Infektion nachgewiesen werden. Die übrigen 2 Patienten wurden ausschließlich zu Monat 12 nach OLT anti-HEV IgG positiv getestet, ohne dass zu einem Untersuchungszeitpunkt der Nachweis von HEV-RNA oder anti-HEV IgM gelang. Im Rahmen der Patientenbefragung konnten der häufige Verzehr von Innereien (mehr als 1 Mal pro Monat) sowie häufig wechselnde Sexualpartner (mehr als 10 bis zum Transplantationszeitpunkt) als Risikofaktoren für den Erwerb einer HEV-Infektion herausgestellt werden. Bei einem Patienten, welcher außerhalb der Studienkohorte auf HEV getestet wurde, konnte erstmals gezeigt werden, dass das Virus von einem Spender mit HEV-RNA infizierter Leber, jedoch serologisch okkultem HEV-Status, auf einen Empfänger übertragen werden und sich hieraus eine chronische HEV-Infektion entwickeln kann. In der vorliegenden Promotionsarbeit wurde die klinische Bedeutung der HEV-Infektion für Patienten nach Lebertransplantation in einem nichtendemischen Land evaluiert. Die ermittelte HEV-Seroprävalenzrate von 21% verdeutlicht, dass man in Deutschland von einer höheren Exposition gegenüber HEV ausgehen muss als bisher angenommen. Die Rate an Serokonversionen nach Lebertransplantation ist niedrig und das Risiko einer akuten oder chronischen HEV-Infektion für Patienten nach Lebertransplantation gering. Die Ergebnisse der serologischen Untersuchungen verdeutlichen zudem die Notwendigkeit der Verbesserung der zur Verfügung stehenden serologischen Testverfahren. Der erstmalig beschriebene Fall einer okkulten Transmission weist auf die Möglichkeit der Viruspersistenz in der Leber bzw. im Gallensystem hin und demonstriert die Möglichkeit der Reaktivierung von HEV bei Patienten mit Immunsuppression., Introduction: First reports of chronic HEV infection causing significant liver disease in immunocompromised patients such as organ transplant recipients have been published recently. Little is known about the HEV prevalence in Germany as well as relevant risk factors. The aim of our study was to evaluate the anti-HEV and HEV RNA prevalence in patients after liver transplantation (OLT). Patients and methods: 406 patients (median age at time point of OLT: 52 years; 64% male) who underwent liver transplantation between 2001 and 2006 at the Charité Campus Virchow-Klinikum in Berlin were included in our study. Stored serum samples were analyzed for the presence of HEV RNA by real-time PCR at month 6 after OLT as well as during the last follow-up evaluation. Additionally, a close monitoring for both, anti-HEV IgG and HEV RNA, was performed in a subgroup of 150 patients prior to OLT as well as at month 6, 12, and 36 after OLT. A survey was conducted in these patients to identify possible risk factors for HEV infection. Results: Out of the 150 patients who were systematically screened for the presence of anti-HEV and HEV RNA, 31 patients were tested positive for anti-HEV IgG indicating a seroprevalence of 21%. 28 patients (19%) were anti-HEV positive before OLT and 20 of them also remained positive for the entire observation period. HEV antibodies became detectable after OLT in further 3 patients (2%) and disappeared in 2 of them during further follow-up. In the remaining patient, HEV RNA and IgM anti-HEV antibodies could be transiently detected at month 6 after OLT. HEV RNA could not be detected in any other sample of the 150 patients, which were systemically screened. In the overall cohort (n=406), HEV RNA could be detected in 2 patients (0.5%). One patient developed chronic HEV infection defined by the presence of HEV RNA for more than six months. Conclusion: Anti- HEV seroprevalence is high in liver transplant recipients but seems not to be a risk factor for acute or chronic HEV reactivation. However, chronic HEV infection may occur in individual cases. Furthermore, the serological results of the present study indicate the need of further evaluation of the common serological screening tests.

Hepatitis E Virus (HEV) may cause acute hepatitis in humans. In industrialised countries, acute hepatitis E generally occurs only sporadically. However, in recent years an increase in the number of reported cases has been observed. Concerning autochthonous, non-travel-associated cases, a zoonotic transmission, particularly from the animal reservoirs of domestic pig and wild boar, and via undercooked meat is assumed. Meanwhile, HEV has been detected in domestic pig holdings as well as in wild boars in many regions of the world, including Europe and Germany. The samples from wild boars in the German investigations usually originated from different sub-regions with relatively small sample sizes per region--with no samples stemming from the territory of the federal state of Saxony-Anhalt. Therefore, in 2011 330 blood samples from wild boars were examined serologically for antibodies to HEV, genotype 3, in Saxony-Anhalt. An average seroprevalence of 33% and a non-homogeneous spatial distribution of positive samples with statistically significant clusters in the southwest and east of the state territory were found.

Infection with hepatitis viruses can lead to acute hepatitis with the risk of developing liver failure. Chronic viral hepatitis may evolve into liver cirrhosis and hepatocellular carcinoma. Thus, prevention of viral hepatitis and its sequels is essential. Vaccination against hepatitis A is successful in almost all individuals. Protective antibodies maintain for at least 20 years. Booster vaccinations are not necessary. Since the introduction of hepatitis A vaccines, the incidence of new HAV-infections has declined significantly. Hepatitis B vaccines are safe and highly effective. Special populations such as dialysis patients or immunocompromised patients require special vaccine schedules. New vaccines with improved adjuvants are currently being tested in clinical trials. So far there is no hepatitis C vaccine on the horizon. Prophylaxis of HCV-infections relies primarily on hygiene measures. Early therapy of acute hepatitis C can prevent chronic hepatitis C. HDV-infection can only be established if HBsAg is present. Thus, prevention of hepatitis B or elimination of HBsAg means prevention of hepatitis delta. Hepatitis E vaccines have been evaluated in phase III studies. The development of HEV vaccines becomes more relevant since chronic HEV infections have been reported in immunosuppressed individuals.

There is an increasing body of evidence that hepatitis E virus (HEV) triggers acute hepatitis not only in tropical and subtropical regions of Asia, Africa, and America with low sanitary standards but also in highly industrialized countries. We here report on two patients from Thuringia (Germany) with a HEV infection without a recent stay abroad. All other common causes of hepatitis were excluded. Transaminases were significantly increased in both cases, while icterus could be proven in one patient, only. Both patients fully recovered in the long-term course. Epidemiological and phylogenetic data from viral analyses suggest that HEV infection has to be considered as a zoonosis. It is likely that viral transmission from animals to humans occurs through insufficiently cooked meat or entrails, e. g., from pigs or wild animals. In summary, HEV infection is a relevant differential diagnosis in acute non-A/B/C viral hepatitis. Further studies are required for the identification of other transmission pathways, pathogen reservoirs as well as novel concepts for prophylaxis, especially for patients at risk for hepatic diseases.

Hepatitis E is an infectious disease caused by the hepatitis E virus (HEV). Hepatitis E is mainly a self-limiting travel-associated disease without chronic evolution. In recent years an increasing number of authochtonous HEV-infections has been described in industrialized countries. HEV-infections frequently take a mild clinical silent course of disease in immunocompetent individuals and thus HEV infection is largely underdiagnosed. Therefore, the anti-HEV-prevalence is much higher than anticipated with 2 - 20% in Western Europe. HEV genotype 3 infections must be considered as zoonotic infections with several animals including swines serving as reservoirs. Cases of HEV-transmissions by blood transfusion were described not only in Asia but also in France and the UK. HEV-infections may take severe courses in pregnant women and patients with chronic liver diseases, sometimes leading to acute liver failure. In addition several centres described cases of progressive chronic HEV-infection in organ transplant recipients and HIV-positive patients during the last two years. In this review we summarize the current state-of-the-art on the knowledge of HEV-infections in industrialised countries.

A 58-year-old female patient was transferred by her general practitioner with fatigue, nausea and icterus which had begun 2 weeks prior to admission. Laboratory results revealed acute hepatitis (ALAT [alanine aminotransferase] 3,871 U/l, ASAT [aspartate aminotransferase] 2,004 U/l, bilirubin 6.7 mg/dl, gamma-GT [gamma-glutamyl transferase] 503 U/l). The patient's medical history included genetic hemochromatosis (without cirrhosis). Hepatitis A to C, infection with herpesviruses or Leptospira interrogans were excluded by serologic and molecular biological tests. There was no diagnostic evidence for underlying autoimmune or additional metabolic liver disease. Due to a trip to Africa 5 months earlier, the patient was tested for hepatitis E, leading to positive anti-hepatitis E-IgM and negative anti-hepatitis E-IgG. PCR (polymerase chain reaction) detection of hepatitis E virus (HEV) was positive as well. In conclusion, acute HEV infection was diagnosed. After close reconsideration, the nonfitting incubation period precluded a travel-associated infection. Additionally, there was no evidence for current HEV infections within the patient's social environment, so that a zoonotic origin has to be discussed.

New findings have been made in recent years on the various forms of the hepatitis virus in terms of disease course, its etiopathogenetic link with comorbidities and the definition of new forms in Central Europe. Epstein-Barr virus (EBV)- and cytomegalovirus (CMV)-induced hepatitis may occur in the so-called sero-negative group of hepatitis and direct demonstration of the viral genome in paraffin liver tissues is required to confirm the diagnosis. Since diagnosis of autoimmune hepatitis in daily practice may be difficult, a scoring system with simplified criteria has recently been developed.

A 32-year-old woman of African origin in the third trimester of pregnancy was admitted to our hospital with jaundice, dark urine and mild abdominal pain. Symptoms had started one week before admission. During a routine pregnancy check-up six months previously, an HIV infection had been diagnosed and antiretroviral therapy was initiated. The patient had moved from Nigeria to Germany two years before and has not been abroad since then.Physical examination revealed marked scleral jaundice and a mild tenderness in the right upper abdominal quadrant. The laboratory tests showed highly elevated levels of liver enzymes and bilirubin. Ultrasonography of the abdomen indicated normal liver size and parenchyma.A hepatitis E virus (HEV) infection was identified as the cause of the acute hepatitis. Within the next few weeks the patient recovered spontaneously und a healthy boy was delivered by cesarean section at the expected date.In acute hepatitis during pregnancy concomitant or newly acquired liver diseases such as viral hepatitis should be considered, once ultrasound has excluded obstructive cholestasis or acute cholecystitis.

Acute liver failure is a rare disease that can cause death in the majority of untreated cases. Sudden loss of liver function in the absence of a preexisting liver disease is considered the true form and has to be distinguished from impaired function following exacerbation of an underlying liver disease (acute or chronic failure). Common causes include acute viral hepatitis, drug induced liver injury (DILI) and toxins. The loss of the excretory and synthetic function of the liver marks the clinical presentation and results in icterus, coagulopathy and encephalopathy. Additionally impairment of renal function and sepsis occur and contribute to the high mortality of this disease. The activation of cell death mechanisms (apoptosis) leading to a reductio of viable, functional liver tissue is considered to be an important pathophysiologic mechanism. Curative therapy of this disease includes liver transplantation that has been performed in Germany for the first time in 1969. In the year 2004 a total of 91 liver transplantation were performed for acute liver failure (10.3% of all transplants) in German transplant centers.

The diagnostic work-up of patients with liver diseases includes taking a past history, a physical examination, incl. an abdominal ultrasound examination or a duplex ultrasonography, general laboratory analyses, etiology-defining analyses, imaging studies and in special situations a percutaneous or transjugular liver biopsy or a laparoscopy. Following this algorithm it is possible to identify in most cases the etiology of the liver disease. The exact diagnosis is key for the understanding of the natural course and prognosis of the liver disease and for the indication for therapy, the choice of the optimal therapeutic strategy and the assessment of its response. Of particular importance is at the time of the first diagnosis of a liver disease to exclude or identify coexisting etiologies, e. g., alcohol use and HCV infection.

Hepatitis A virus (a picornavirus) and hepatitis E virus (so far unclassified) are small, non-enveloped and relatively stable RNA viruses with many similar, yet, not identical characteristics. Both viruses are transmitted preferentially by the fecal-oral route. Consequently, their spread is favoured by poor personal hygiene and inappropriate sanitary conditions. Infection can pass subclinically, take an acute and self limiting course, and can also manifest as fulminant hepatitis with liver failure. True chronic disease is unknown. Laboratory diagnosis is preferentially performed by serology, but can also be complemented by assay for viral RNA in stool or serum. Resolution of infection leads to immunity which, in the case of hepatitis A, is known to be fully protective and most likely lifelong. Available hepatitis A vaccines are able to induce a similar state of protection. Vaccines for hepatitis E are under development. Specific antiviral treatment is not yet available, neither for hepatitis A nor for hepatitis E.

Viral hepatitis is one of the most serious infections in pregnant women. There are now at least five hepatitis viruses. This educational review describes the various types of hepatitis, clinical manifestations, their impact on mother and fetus, prevention and treatment options, risks of perinatal transmission and differential diagnosis. Several open questions regarding vaccination as well as perinatal transmission have been addressed.