title: [Hepatitis caused by tick-borne meningoencephalitis virus (TBEV)--a rare clinical manifestation outside the central nervous system involvement].
abstract: OBJECTIVE
  North part of Croatia, especially the Koprivnica-Krizevci County has been a well-known endemic area of tick-borne encephalitis (TBE) for more than 50 years. To date, this disease caused by tick-borne encephalitis virus (TBEV) has retained the leading position among inflammatory diseases of the central nervous system (CNS), with an average morbidity of 19 patients per year. In 88% of patients the infection manifested with signs of meningitis or meningoencephalitis with a biphasic course. TBE may take a more severe course with different neurologic dysfunction or even lethal outcome. There have been isolated reports on some rare clinical manifestations outside CNS involvement caused by TBEV, including transient hepatitis, pancreatitis, and myocarditis. These manifestations have been most frequently detected during the initial stage of disease but also as a complication, or as an individually separate clinical entity. The incidence rate of these manifestations is not known. Until now, such clinical manifestations outside CNS have not been reported in the county. It was the reason to present the characteristics of liver failure in our patients suffering from TBE. Purpose of Work: To determine the frequency of elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with TBEV infection, to note the time from the detection to disappearance of elevated AST and to investigate and establish whether the degree of liver failure influences the course and outcome of TBE.
  
  
  METHODS
  The study was conducted from January 1991 until September 2004, and included patients with TBEV infection and elevated AST and ALT, examined at the Department of Infectious Diseases, Koprivnica General Hospital. Study patients were of all age groups and occupation. On their first examination detailed epidemiologic and patient history data were collected, with special reference to the history of alcohol abuse, disease of the liver or biliary tract, or any other apparent cause of liver failure. Clinical examination and laboratory tests were performed. Patients were classified into four groups as suffering from meningitis, meningoencephalitis, meningoencephalomyelitis, or abortive form of disease. The acute stage of meningoencephalitis was classified as mild, moderate or severe, depending on meningeal symptoms and severity of clinical signs of encephalitis, and presence of focal CNS signs. ELISA test was used to detect specific IgM and IgG antibodies. Serum samples were tested for other tick-borne diseases, including human monocyte and granulocyte ehrlichiosis. Oral consent was obtained from all patients enrolled in the study.
  
  
  CONCLUSIONS
  During the study, recent infection with TBEV was proven in 261 patients. Liver function tests were done in 115 (44%) patients. Elevated AST and ALT activity was found in 25 (22%) patients, without bilirubin and alkaline phosphatase increase. All these were County residents, with a male sex predominance, aged 28-70 (median 41) years, and none had received TBE vaccination. Elevated AST and ALT activities were detected during the first stage of TBE in 16 (64%) and during the second stage of meningoencephalitis in 9 (36%) patients suffering from TBE. Elevated activity of AST was observed in 76% and of ALT in 96% of study patients. The most frequently observed elevated AST and ALT activity was two- or threefold the usual normal values. The time of the first detection of elevated AST and ALT activity could not be precisely determined, since all laboratory findings were performed during the first examination of patients. In the initial stage of disease, patients were mostly tested between 2-5 days from the onset of disease, and during the first week in the second stage of meningoencephalitis. Elevated AST and ALT activities were transient and normalized in 3-4 weeks. The importance of elevated AST and ALT activity for the course and prognosis of TBE was not verified in this study.
  
  
  CONCLUSIONS
  The first patients with hepatitis as one of the possible manifestation outside CNS involvement caused by TBEV are described. The prevalence and new concepts on this type of the disease were investigated in the study.
authors.affiliation: Djelatnost za infektivne bolesti, Opća bolnica Koprivnica, Koprivnica, Hrvatska.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Misić-Majerus
authors.forename: Nevenka
authors.initials: N
authors.lastname: Bujić
authors.forename: Vesna
authors.initials: V
authors.lastname: Madarić
authors.forename: Tatjana
authors.initials: T
authors.lastname: Avsić-Zupanc
mesh_terms: D000328:Adult; D000368:Aged; D004796:Clinical Enzyme Tests; D004669:Encephalitis Viruses, Tick-Borne; D004675:Encephalitis, Tick-Borne / Q000150:complications*; D005260:Female; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged