Sten Iwarson

Trigger factors and HL-A antigens in chronic active hepatitis.

Forty-six patients with histologically verified chronic active hepatitis (CAH) were divided into three groups according to whether the CAH was virus-induced, drug-induced, or cryptogenic. The frequency of the HL-A antigens 1 and 8 was increased in the cryptogenic group while the other groups did not differ significantly from healthy controls. Autoantibodies were often found in high titres in the drug-induced and cryptogenic groups but were infrequent in the virus-induced group.

The Epidemiological Pattern of Hepatitis A, B, and Non-A, Non-B in Sweden

In a clinical series of 148 patients with acute hepatitis, serological analysis of hepatitis A and hepatitis B markers revealed 16% of the cases as hepatitis type non-A, non-b. Hepatitis A was diagnosed in 27% of the patients with drug addicts as the predominating category, while serological evidence of hepatitis B infection was found in 57%, again with drug addicts in the majority. Drug addicts also predominated among the non-A, non-B cases, and possibly this category of patients is today the main reservoir not only of hepatitis B but also of hepatitis A and non-A, non-B.

Hepatitis B vaccination with short dose intervals — A possible alternative for post-exposure prophylaxis?

SummaryTo achieve a more rapid antibody response following hepatitis B (HB) vaccination, vaccine injections were given to medical students at considerably shorter intervals than usually recommended. They received 10 µg of the Merck Sharp & Dohme recombinant HB vaccine at time 0, 2 and 6 weeks (27 vaccinees) or were vaccinated according to the recommended schedule for pre-exposure HB prophylaxis (0, 1 and 6 months) (26 vaccinees). The short interval regimen resulted in a significantly higher frequency of protective antibody levels (≥10 IU/l) two weeks after the second dose of vaccine (48% vs. 4%; p<0.001), and all short interval vaccinees had seroconverted within two months (i. e. two weeks after the third dose). The recommended interval regimen resulted in a slower development of antibodies but significantly higher peak antibody levels after the completed three doses (p<0.001). The results indicate that protective antibody levels against hepatitis B virus (HBV) can be achieved more rapidly in humans through vaccination with short intervals. This short interval vaccination regimen, which has proved effective for post-exposure prophylaxis in chimpanzees, should possibly also be considered for post-exposure prophylaxis in humans, for instance after accidental exposure to HBV-contaminated blood.ZusammenfassungUm die Antikörperantwort nach Hepatitis-B(HB)-Impfung zu beschleunigen, wurden die Impfstoffinjektionen bei einer Gruppe von Medizinstudenten in erheblich kürzeren Abständen vorgenommen, als üblicherweise empfohlen wird. Die Applikation der rekombinanten HB-Vakzine (Merck Sharp & Dohme) erfolgte zum Zeitpunkt 0, 2 und 6 Wochen (27 Geimpfte) oder nach dem für die Prä-Expositionsprophylaxe für HB empfohlenen Schema (0, nach 1 und 6 Monaten) (26 Geimpfte). Die Dosis betrug jeweils 10 µg des Impfstoffs. Bei Anwendung des Applikationsschemas mit kurzen Dosierungs-intervallen waren zwei Wochen nach der zweiten Impfdosis signifikant häufiger protektive Antikörperspiegel (≥10 IU/1) nachzuweisen (48% gegenüber 4%; p<0,001); alle nach diesem Schema Geimpften hatten innerhalb von zwei Monaten (d. h. zwei Wochen nach der dritten Dosis) serokonvertiert. Bei dem empfohlenen Applikationsschema kam die Antikörperproduktion langsamer in Gang, erreichte aber nach Gabe aller drei Dosen signifikant höhere Antikörper-Spitzenspiegel (p<0,001). Mit einer Impfstoffapplikation in kürzeren Zeitabständen läßt sich folglich beim Menschen die Bildung protektiver Antikörperspiegel gegen Hepatitis-B-Virus (HBV) beschleunigen. Dieses Impfschema mit kurzen Dosierungsintervallen, das sich in der Prophylaxe nach Exposition bei Schimpansen bewährt hat, sollte eventuell auch beim Menschen als Schema für die Prophylaxe nach Exposition erwogen werden, beispielsweise nach versehentlicher Exposition gegenüber mit HBV kontaminiertem Blut.To achieve a more rapid antibody response following hepatitis B (HB) vaccination, vaccine injections were given to medical students at considerably shorter intervals than usually recommended. They received 10 µg of the Merck Sharp & Dohme recombinant HB vaccine at time 0, 2 and 6 weeks (27 vaccinees) or were vaccinated according to the recommended schedule for pre-exposure HB prophylaxis (0, 1 and 6 months) (26 vaccinees). The short interval regimen resulted in a significantly higher frequency of protective antibody levels (≥10 IU/l) two weeks after the second dose of vaccine (48% vs. 4%; p<0.001), and all short interval vaccinees had seroconverted within two months (i. e. two weeks after the third dose). The recommended interval regimen resulted in a slower development of antibodies but significantly higher peak antibody levels after the completed three doses (p<0.001). The results indicate that protective antibody levels against hepatitis B virus (HBV) can be achieved more rapidly in humans through vaccination with short intervals. This short interval vaccination regimen, which has proved effective for post-exposure prophylaxis in chimpanzees, should possibly also be considered for post-exposure prophylaxis in humans, for instance after accidental exposure to HBV-contaminated blood. Um die Antikörperantwort nach Hepatitis-B(HB)-Impfung zu beschleunigen, wurden die Impfstoffinjektionen bei einer Gruppe von Medizinstudenten in erheblich kürzeren Abständen vorgenommen, als üblicherweise empfohlen wird. Die Applikation der rekombinanten HB-Vakzine (Merck Sharp & Dohme) erfolgte zum Zeitpunkt 0, 2 und 6 Wochen (27 Geimpfte) oder nach dem für die Prä-Expositionsprophylaxe für HB empfohlenen Schema (0, nach 1 und 6 Monaten) (26 Geimpfte). Die Dosis betrug jeweils 10 µg des Impfstoffs. Bei Anwendung des Applikationsschemas mit kurzen Dosierungs-intervallen waren zwei Wochen nach der zweiten Impfdosis signifikant häufiger protektive Antikörperspiegel (≥10 IU/1) nachzuweisen (48% gegenüber 4%; p<0,001); alle nach diesem Schema Geimpften hatten innerhalb von zwei Monaten (d. h. zwei Wochen nach der dritten Dosis) serokonvertiert. Bei dem empfohlenen Applikationsschema kam die Antikörperproduktion langsamer in Gang, erreichte aber nach Gabe aller drei Dosen signifikant höhere Antikörper-Spitzenspiegel (p<0,001). Mit einer Impfstoffapplikation in kürzeren Zeitabständen läßt sich folglich beim Menschen die Bildung protektiver Antikörperspiegel gegen Hepatitis-B-Virus (HBV) beschleunigen. Dieses Impfschema mit kurzen Dosierungsintervallen, das sich in der Prophylaxe nach Exposition bei Schimpansen bewährt hat, sollte eventuell auch beim Menschen als Schema für die Prophylaxe nach Exposition erwogen werden, beispielsweise nach versehentlicher Exposition gegenüber mit HBV kontaminiertem Blut.

The long-term outcome of hepatitis B

SummaryAmong 466 hospitalized patients with serologically verified acute hepatitis B, 440 individuals (94.4%) could be followed up until normalization of liver function had occured, or for at least one year. In 90.2% of the patients followed-up liver function (including galactose tolerance) returned to normal within four months after onset of illness. Chronic persistent hepatitis (CPH) developed in 28 patients (6.4%) with persistence of hepatitis B surface antigen (HBs Ag) for at least one year in 14 patients (50%). Liver biopsy was performed in 20 of these 28 cases about a year after onset of illness and was consistent with CPH in all cases. Histological signs of chronic aggressive hepatitis developed in 15 patients (3.4%) and persistence of HBs Ag was observed in 11 of these patients (73%). No histological follow-up was performed in patients with normal liver function within four onths after onset of illness. Corticosteroid treatment in 56 patients with prolonged symptoms did not seem to predispose to persistence of HBs AG in the serum.ZusammenfassungVon insgesamt 466 stationären Patienten mit serologisch verifizierter akuter Hepatitis B konnten 440 (94,4%) bis zur Normalisierung der Leberfunktion oder mindestens ein Jahr nachbeobachtet werden. Bei 90,2% der nachbeobachteten Patienten normalisierte sich die Leberfunktion (einschließlich Galaktosetoleranz) binnen 4 Monaten nach Ausbruch der Krankheit. Chronisch persistierende Hepatitis entwickelte sich bei 28 Patienten (6,4%) mit Persistenz des Hepatitis-B-Oberflächenantigens (HBS AG) für die Dauer von mindestens einem Jahr bei 14 Patienten (50%). Bei 20 dieser 28 Fälle wurde ungefähr ein Jahr nach Ausbruch der Krankheit eine Leberbiopsie durchgeführt, die in allen Fällen dem Bild der chronisch persistierenden Hepatitis entsprach. Histologische Zeichen der chronisch aggressiven Hepatitis entwickelten sich bei 15 Patienten (3,4%) und bei 11 von ihnen (73%) wurde Persistenz des HBsAg festgestellt. Bei Patienten mit normaler Leberfunktion binnen 4 Monaten nach Ausbruch der Krankheit wurde keine histologische Kontrolluntersuchung vorgenommen. Die Kortikosteroidbehandlung von 56 Patienten mit langfristigen Symptomen schien nicht für die Persistenz von HBs AG im Serum zu prädisponieren.

Acute Hepatitis Non‐A, Non‐B following Administration of Factor VIII Concentrates

A retrospective survey on clinical hepatitis in patients with bleeding disorders was performed. Nine episodes of hepatitis non‐A, non‐B occurred in 8 out of 20 patients (40%) with mild hemophilia A or von Willebrands disease, who had been treated with commercial factor VIII concentrates. Only two episodes of hepatitis B occurred during the study period. The non‐A, non‐B attack rate after the first treatment was 40 % with factor VIII concentrate obtained from large plasma pools (=2,000 donors) including professional plasma donors as compared to 8 % after treatment with factor VIII concentrate obtained from smaller (100–250 donors) plasma pools from Scandinavian donors.

Genetic factors in the development of chronic active hepatitis.

In 14 of 16 patients with chronic active hepatitis (C.A.H.) who did not have HLA antigens B8 and/or B12 an external triggering factor (drug or virus) could be demonstrated at onset of symptoms. In contrast external factors were involved in only 11 of 25 cases of C.A.H. in patients with HLA-B8 and/or B12. In the latter group antinuclear antibodies were less common in cases possible triggered by external agents compared with cases in which no such factor was demonstrated. The results suggest that there are at least two pathogenetically different types of C.A.H.---one genetically determined type in which no external factor is involved and in which autoimmune phenomena are common, and another type triggered by environmental agents and not involving predisposing genetic factors.

POST-EXPOSURE PROPHYLAXIS FOR HEPATITIS B: ACTIVE OR PASSIVE?

After exposure to hepatitis B (HB) virus, passive immunisation with HB immune globulin is widely used for protection while active immunity is induced by conventional vaccination regimens. Protective antibody titres can be achieved much more quickly with accelerated vaccination, and the role of passive immunisation may need to be reconsidered.

Listeric meningitis in the non-compromised host

SummaryA small epidemic of listeric infection among non-compromised adults recently occurred in the western part of Sweden. All ten patients survived and the prognosis of listeric meningitis in non-compromised patients would seem to be considerably better than in the compromised host. A rapid initiation of ampicillin treatment (10–20 mg/kg of body weight daily) within 48 hours after onset of symptoms may have contributed to the excellent outcome in the present series besides a well-functioning intracellular killing mechanism which seems to be of the greatest importance in listeric infection.ZusammenfassungEine Listerien-Epidemie bei immunologisch intakten Erwachsenen trat vor einiger Zeit im westlichen Teil Schwedens auf. Alle zehn Patienten überlebten. Die Prognose der Listerien-Meningitis bei immunologisch nicht beeinträchtigten Patienten scheint beträchtlich besser zu sein als bei vorgeschädigten. Eine rasche Anwendung von Ampicillin (10–20 mg/kg/KG täglich) innerhalb der ersten 48 Stunden nach Einsetzen der klinischen Symptome mögen zu dem ausgezeichneten Ergebnis bei den beobachteten Fällen beigetragen haben, möglicherweise deswegen, weil ein gut funktionierender intrazellulärer Abtötungsmechanismus dieser Bakterien bei Listerien-Infektionen von größter Bedeutung sein kann.

Transfusion transmitted non-A, non-B hepatitis

Non‐A, non‐B of hepatitis (NANBH) may occur following blood transfusions or administration of blood products. The causative agent(s) is still not identified and the symptoms are usually mild. The only indication of infection may be increased serum alanine transferase levels. The incidence of posttransfusion NANBH has been reported as high as 4–12% in the US (average 7%) while in Sweden it is according to recent studies on the average 2%. An estimated 2–3% of Swedish blood donors are probably carriers of the NANBH agent(s). Of patients acquiring posttransfusion NANBH, 40–60% will develop chronic hepatitis which in 15–20% will progrediate to cirrhosis.

Determination of HBeAg by Radioimmunoassay: Prognostic Implications in Hepatitis B

A radioimmunoassay was used to determine the presence of the hepatitis B e antigen (HBeAg) and anti-HBe in the serum of 12 hepatitis B patients, who were follofed from an early phase of the illness into convalescence. The duration of detectable HBeAg in serum from these patients, in all ow whom the disease ran a normal course, was compared with the persistence of HBeAg in serum of nine patients with a protracted course and persistence of HBsAg in serum for more than 1 year. None of the hepatitis B patients with a normal course of the disease had HBeAg demonstrable for more than 9 weeks after the onset of illness (mean 5.4 weeks), whereas all patients developing chronic hepatitis had HBeAg in serum for more than 1 year after the onset of illness. These findings indicate that the detection of HBeAg in serum by radioimmunoassay for 10 weeks or more after the onset of illness implies a great risk of progression of the hepatitis B infection to chronic liver disease.