Knowledge-based interpretation of serologic tests for hepatitis on the World Wide Web.

HEPAXPERT is a knowledge-based system that interprets the results of routine serologic tests for infection with hepatitis A and B viruses. The following tests are included: hepatitis A virus antibodies, IgM antibodies to the hepatitis A virus, hepatitis A virus in stool, hepatitis B surface antigen and antibodies, antibodies to hepatitis B core antigen, and hepatitis B envelope antigen and antibodies. HEPAXPERT/WWW, an implementation of HEPAXPERT-III for the World Wide Web, can be reached by URL http://www.med-expert.co.at/hepax. After selecting HEPAXPERT/WWW, serologic test results can be entered and will be transferred as an E-mail message for subsequent interpretation, which is done off-line with HEPAXPERT-III. The textual interpretation is sent back via E-mail. Each qualitative test for hepatitis A and B antibodies and antigens may produce one of four possible results: positive, negative, borderline, and not tested. To cover the resulting 64 (A) and 57,344 (B) combinations of findings, the knowledge base of HEPAXPERT/WWW contains 16 rules of hepatitis A and 131 rules for hepatitis B serology interpretation. This basic knowledge is structured such that all possible combinations of findings can be interpreted, and there is no overlap in the premises underlying the rules. The reports that the system automatically generates include the transferred results of the tests; a detailed analysis of the results, including virus exposure, immunity, stage of illness, prognosis, infectiousness, and vaccination recommendation; and, as an option, an identification, to distinguish the origin of the interpretation requests.

A WWW-accessible knowledge base for the interpretation of hepatitis serologic tests.

HEPAXPERT is a knowledge-based system that interprets the results of routine serologic tests for infection with hepatitis A and B viruses. The following tests are included: hepatitis A virus anti-bodies (anti-HAV), IgM antibodies to the hepatitis A virus (IgM anti-HAV), hepatitis A virus (HAV in stool, hepatitis B surface antigen (HBsAg) and antibodies (qualitative anti-HBs, quantitative anti-HBs titre), antibodies to hepatitis B core antigen (anti-HBc and IgM anti-HBc), and hepatitis B envelope antigen (HBeAg) and antibodies (anti-HBe). HEPAXPERT/WWW--an implementation of HEPAXPERT-III for WWW--can be reached by URL http://www.swun.com/hepax of the World Wide Web. After selecting HEPAXPERT/WWW, serologic test results can be entered and will be transferred as an e-mail message for subsequent interpretation which is done off-line with HEPAXPERT-III. The textual interpretation is sent back via e-mail. Each qualitative test for hepatitis A and B antibodies and antigens may produce one of four possible results: positive, negative, borderline, and not tested. To cover the resulting 64 (A) and 57344 (B) combinations of findings, the knowledge base of HEPAXPERT/WWW contains 16 rules for hepatitis A and 131 rules for hepatitis B serology interpretation. This basic knowledge is structured such that all possible combinations of findings can be interpreted and there is no overlap in the premises underlying the rules. The reports that the system automatically generates include: (a) the transferred results of the tests; (b) a detailed analysis of the results, including virus exposure, immunity, stage of illness, prognosis, infectiousness, and vaccination recommendation; and (c) optional: an ID to distinguish the origin of the interpretation requests.

Development and retrospective evaluation of Hepaxpert-I: a routinely-used expert system for interpretive analysis of hepatitis A and B serologic findings.

Hepaxpert-I is an expert system that interprets the results of routine serologic tests for infection with hepatitis A or B virus. The tests measure antibody to the hepatitis A virus (anti-HAV), IgM antibody to the hepatitis A virus (IgM anti-HAV), hepatitis A virus (HAV) in the stool, hepatitis B surface antigen (HBsAg) and antibody (anti-HBs), antibody to hepatitis B core antigen (anti-HBc and IgM anti-HBc), and hepatitis B envelope antigen (HBeAg) and antibody (anti-HBe). The knowledge base of Hepaxpert-I contains 13 If-Then rules for hepatitis A and 106 If-Then rules for hepatitis B serology. Formally, knowledge acquisition was done by forming a partition of each of the two sets of possible serologic finding patterns that contain patterns of serologic test results, 64 for hepatitis A and 4096 for hepatitis B, respectively. After entering an input pattern of serologic test results in Hepaxpert-I, a rule pattern matching algorithm based on indexing is internally employed as efficient access method for providing the respective interpretive text. Since 1 September 1989, Hepaxpert-I has been routinely applied at the Hepatitis Serology Laboratory of the 2nd Department of Gastroenterology and Hepatology at the University of Vienna Medical School (Vienna General Hospital). Beforehand, a retrospective evaluation of the expert system based on 23,368 hepatitis A and 24,071 hepatitis B serology requests was carried out.

HEPAXPERT-III: knowledge-based interpretation of serologic tests for hepatitis A, B, C, and D.

1. The HEPAXPERT-III SYSTEM. HEPAXPERT-III--the successor of HEPAXPERT-I[1] and HEPAXPERT-II [2]--is a routinely-used, integrated medical database and knowledge-based system that stores and interprets the results of serologic tests for infection with hepatitis A, B, C, and D viruses. The following tests are included: Anti-HAV, IGM anti-HAV, and HAV in stool; HBsAg, anti-HBs, anti-HBc, IGM anti-HBc, HBeAg, anti-HBe, and anti-HBs titre; Anti-HCV, HCV-immunoblot, and HCV-PCR; Delta-Ag and anti-delta. HEPAXPERT-III provides the following functions: a) screen input of patient's personal data (patient ID, surname, first name, name at birth, date of birth, and sex), administrative data (department requiring the tests and date of specimen sample), and medical data (results of serologic tests); and/or b) automatic transfer of patient's personal, administrative, and medical data by connecting HEPAXPERT-III to a laboratory information system, a hospital information system, or an automated laboratory analyzer; and c) automatic generation of interpretive reports of the obtained serologic findings, including an analysis of possible virus exposition, immunity, disease stage, prognosis, and degree of infectiousness. HEPAXPERT-I and HEPAXPERT-II have been routinely used at the Vienna General Hospital, the teaching hospital of the University of Vienna Medical School. The interpretive reports are well-accepted and lead to several improvements in patient care [3]. HEPAXPERT-III will not only extend the scope of interpretation to hepatitis C and D serologic tests, but will also offer a state-of-the-art graphical user interface. 2. HARDWARE AND SOFTWARE. IBM-compatible personal computer (minimum 80386 SX processor), 8 MB RAM (OS/2) and 4 RM RAM (MS-Windows), resp., graphic adapter (minimum 640x480) and printer supported by OS/2 and MS-Windows 3.1, resp., IBM OS/2-2.1 or higher and MS-Windows 3.1 or higher, resp., and for the OS/2 version IBM Database 2 (DB2/2).

[The knowledge base of the Hepaxpert I System: automatic interpretation of Hepatitis A and B serology]. / Die Wissensbasis des Hepaxpert-I-Systems: Automatische Interpretation der Hepatitis-A und -B-Serologie.

The knowledge base of Hepaxpert-I, a medical expert system for interpretive analysis of hepatitis A and B serologic findings, contains 13 rules for hepatitis A and 106 rules for hepatitis B serology. Formally, the construction of the knowledge base was done by forming a partition of the sets of possible serologic finding patterns--64 for hepatitis A and 4096 for hepatitis B serology--induced by an equivalence relation, divides the elements of the sets into disjoint subsets, the equivalence classes. Each equivalence class is represented as one If-Then rule that assigns to every member of the equivalence class one interpretive text. The partition of the possible finding patterns into equivalence classes and the disposal of one and only one interpretive text for each equivalence class made the creation of a very practical and efficient computer program for the precise interpretation of any finding pattern of serologic tests for hepatitis A and B possible. The complete set of the provided If-Then rules is represented in this paper.

[Medical expert and consultation systems: review and examples for their use]. / Medizinische Experten- und Konsultationssysteme: Uberblick und Anwendungsbeispiele.

After a general introduction into the area of medical expert and consultation systems, a survey about different types of medical expert systems is given. The different objectives and modes of application of medical expert systems are presented and explained in detail. In the second part of this paper, the applicability of computer systems for fully automated interpretation of hepatitis serology findings in the clinical laboratory and for aiding differential diagnosis in internal medicine is described. With the examples given, it is demonstrated that expert systems for clinical decision aid can be of great benefit for the physician in the hospital or the doctor's office.

Hepatitis A and B in non-institutionalized mentally retarded patients.

The high incidence of hepatitis A and B in institutionalized patients with Down's syndrome is not fully understood. Under poor hygienic conditions immunological alterations might predispose to these infections. To minimize environmental influences, 125 patients with Down's syndrome (mean age 11.9 years) living at home with their families were studied for the occurrence of serological markers of Hepatitis A and B. 106 outpatients with mental retardation of other genesis (mean age 12.4 years), and 114 consecutive voluntary blood donors (mean age 18.0 years) from the same area served as controls. Evidence of previous hepatitis A virus infection was found in 5.6% of Down's patients, in 9.4% of other mentally retarded patients, and in 16.7% of healthy controls. Evidence of previous or ongoing hepatitis B virus infection was a common finding in both groups of mental retardation (Down's syndrome 20.0%, other mentally retarded patients 11.3%) in sharp contrast to healthy blood donors (0.9%, p less than 0.05). Patients with Down's syndrome, however, revealed a much higher incidence of HBs-antigenemia as compared with other mentally retarded patients (12.8% vs. 2.8%, p less than 0.01). All HBs antigen-positive cases had normal transaminase levels and no overt clinical signs of liver disease, suggesting an asymptomatic carrier state. These data indicate that hepatitis A is not a special risk for mentally retarded outpatients, while hepatitis B virus infection is hyperendemic even in not-institutionalized patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Efficacy and tolerance of hepatitis B vaccination in medical personnel and hemodialysis patients]. / Zur Wirksamkeit und Verträglichkeit der Hepatitis-B-Impfung bei medizinischem Personal und bei Hämodialysepatienten.

The efficacy and safety of a hepatitis B vaccine (Pasteur Institute) has been evaluated in 93 healthy members of the medical staff and in 28 patients undergoing chronic haemodialysis. Following 3 injections of vaccine (each 5 micrograms) at monthly intervals, 94% of the healthy subjects and 61% of the patients were already successfully immunized 4 months after commencement of the vaccination course. Those who did not respond initially received an additional dose at 6 months, which induced seroconversion in several more cases, resulting in the successful immunization of 98% of healthy subjects and 75% of haemodialysis patients. Immune response was sex- and age-dependent. Peak anti-HBs concentrations in responders at 6 months were 643, 325, and 194 mU/ml in healthy women, healthy men, and in patients, respectively. None of the staff members developed clinical or biochemical signs of hepatitis or of any other disease. Markers of hepatitis B virus infection were detected in 3 healthy subjects and in 6 dialysis patients.

[Iatrogenic and environmentally induced diseases of the liver in old age: viral hepatitis in old age]. / Iatrogene und umweltbedingte Erkrankungen der Leber im Alter: Virushepatitis im Alter.

Elderly people rarely develop hepatitis A, because of their acquired immunity, but they are more exposed to hepatitis-B and -nonAnonB infections. The course of viral hepatitis is usually more severe and more prolonged, the mortality of fulminant hepatitis is higher, and the risk of developing chronic hepatitis B is increased. There exists an association between chronic hepatitis B virus infection, old age, and the incidence of hepatoma. Exposed elderly persons should be vaccinated against hepatitis B but it might be necessary to give them additional booster doses in order to achieve sufficient antibody production.

[Extracorporeal liver perfusion in the treatment of hepatic coma]. / Die extrakorporale Leberperfusion zur Behandlung des Leberzerfallskoma.

Four patients with fulminant hepatic failure had extracorporal hemoperfusion. In selecting the patients, the following criteria were applied: Potential reversibility of the liver disease, prothrombin time under 10%, neurological coma stage III-IV. In total 11 treatments (9 treatments using baboon and 2 treatments using human livers) were performed lasting from 3 to 60 hours. One patient improved immediately after perfusion. 3 patients died; at post mortem severe oedema of the brain and acute yellow atrophy of the liver without tendency to regeneration was observed in these patients.

Autoantibodies to collagen in patients with chronic liver diseases.

Sera of patients with various liver diseases were investigated for the presence of autoantibodies to type I collagen with a sensitive radioimmunoassay employing 3H-labelled collagen type I. A high percentage (69%) of patients with chronic liver diseases, equally distributed between chronic active hepatitis and alcoholic liver disease, was found to possess antibodies to denatured type I collagen, while no antibodies against native collagen were found. These antibodies belonged predominantly to the IgA immunoglobulin class. None of the patients with acute hepatitis or cholestatic liver disease, nor the healthy individual investigated had IgA-anticollagen antibodies. These findings may be useful as a parameter for the detection of chronic liver disease.

[Primary liver cell carcinoma, aetiology and clinical picture (author's transl)]. / Das primäre Leberzellkarzinom, Atiologie und Klinik.

Geographic area, age and sex influence the epidemiology of hepatoma. Aetiological factors are aflatoxins, sex hormones, thorotrast, alpha 1-antitrypsin deficiency, immunosuppression, vinylchloride, parasites, cirrhosis of the liver, and the hepatitis-B virus. Early diagnosis of the tumour is possible using alpha 1-fetoprotein estimations and modern morphological methods, particularly scintiscanning. Tumour resection is therapeutically desirable, while selective chemotherapy remains palliative and liver transplantation failed to prolong survival.

[Serum concentrations of alpha-1-fetoprotein suggestive of, or pathognomonic for hepatoma (author's transl)]. / Hepatom-suspekte und -pathognomonische Serumkonzentrationen von alpha-1-Fetoprotein.

A short review of alpha-1-fetoprotein (AFP), is followed by a presentation of the serum AFP concentrations obtained in healthy subjects and in patients with hepatoma, cirrhosis of the liver or metastatic liver cancer, measured by radioimmunoassay (RIA). A calculation is made from these results of the upper limit of normal (9 ng/ml), a limit which is suggestive of hepatoma (215 ng/ml) and a limit which is pathognomonic for hepatoma (7500 ng/ml). It is concluded that the quantitative determination of AFP by RIA represents a sensitive method which provides valuable clinical information for the early diagnosis of hepatoma.

[Aetiology of chronic aggressive hepatitis in Vienna, a contribution (author's transl)]. / Zur Atiologie der chronisch aggressiven Hepatitis in Wien.

In 32 patients with clinically, biochemically and histologically proven chronic aggressive hepatitis, HBsAg, HBsAb, HBcAb and HA-Ab were determined by radioimmunoassays and HBeAg and HBeAb were estimated by immunodiffusion. HBsAg was positive in 18 patients [57%], HBcAb were found in 23 patients [72%], HBsAg and/or HBcAb were detected in 26 patients (82%). The incidence of HA-Ab was 88%, similar to the frequency of HA-Ab found in healthy blood-donors. The aetiology of chronic aggressive hepatitis was associated with hepatitis B in 82%, and with autoantibodies in 6% of our patients, while in 12% the aetiology remained cryptogenetic.

[Plasmaperfusion through activated charcoal and amberlite XAD-7 in dogs with liver failure induced by yellow phosphorus (author's transl)]. / Plasmaperfusion über Aktivkohle und Amberlite XAD-7 bei der phosphor-induzierten Lebernekrose des Hundes.

Various sorbents were tested in-vitro for their ability to support hepatic excretory and detoxification functions, and their in-vivo perfusion with plasma was studied in an animal experiment. Amino acids, particularly phenylalanine and tyrosine, were strongest bound by activated charcoal, while Amberlite XAD-7 removed conjugated and unconjugated bilirubin and bile acids from plasma. Using a cell-separator plasma of dogs, in whom acute liver failure was induced by yellow phosphorus, was perfused through a combination of charcoal and Amberlite XAD-7 without major complications. Platelet counts remained nearly unchanged, platelet aggregation was inhibited reversibly, and circulating platelet aggregates occurred late only. It is concluded that using the method described, therapeutic trials in patients with fulminant hepatic failure can be performed.

[Immunological markers of hepatitis-A and -B in blood donors from Vienna]. / Immunologische Marker der Hepatitis A und B bei Blutspendern im Raum Wien.

In 1076 sera of healthy volunteer blood donors from Vienna and surroundings HBSAg was positive in 1,7%, HBSAb in 9,5%, HBCAb in 5,7% by radioimmunoassays. HA-Ab was more frequently positive in the rural than in the urban population, its incidence was higher than it was observed by others in Switzerland and in the USA, but lower than in Belgium, Israel, Yugoslavia and Taiwan. 4% of the blood units were positive for HBCAb but negative for HBSAg. The possibility to decrease the incidence of posttransfusion hepatitis by screening for HBCAb is discussed.