Torkil Moestrup

Continued transmission of hepatitis B and C viruses, but no transmission of human immunodeficiency virus among intravenous drug users participating in a syringe/needle exchange program.

The virological efficacy of a syringe/needle exchange program was evaluated in a cohort incidence study. Of 698 intravenous drug users (IVDUs) initially recruited, 15 (2.1%) were HIV-positive at baseline. Adequate follow-up was possible in 515 (74%) and showed no new cases of HIV infection during a median of 31 months. Most IVDUs had been previously exposed to HBV (anti-HBc-positive 70.1%) and HCV (anti-HCV-positive 90.7%). Of those 159 IVDUs negative at baseline for anti-HBc and/or anti-HCV, 56 (35%) seroconverted to one or both viruses during follow-up, corresponding to 11.7 seroconversions/100 y at risk for HBV and 26.3 seroconversions/100 y for HCV. Multiple logistic regression analysis showed hepatitis seroconversion to correlate with imprisonment during the study (OR 2.2; 95% CI 1.04-4.74), absence of drug-free periods (OR 5.7; CI 1.44-22.3) and frequent syringe/needle exchanges (OR 1.31; CI 1.02-1.7). The absence of HIV spread was probably partly due to the low prevalence of HIV-infected IVDUs in the city. Despite free syringes and needles, both HBV and HCV continued to spread at high rates. Nevertheless, syringe/needle exchange programs, coupled with monitoring of serostatus provide good surveillance and are valuable for further assessment of remaining risks.The virological efficacy of a syringe/needle exchange program was evaluated in a cohort incidence study. Of 698 intravenous drug users (IVDUs) initially recruited, 15 (2.1%) were HIV-positive at baseline. Adequate follow-up was possible in 515 (74%) and showed no new cases of HIV infection during a median of 31 months. Most IVDUs had been previously exposed to HBV (anti-HBc-positive 70.1%) and HCV (anti-HCV-positive 90.7%). Of those 159 IVDUs negative at baseline for anti-HBc and/or anti-HCV, 56 (35%) seroconverted to one or both viruses during follow-up, corresponding to 11.7 seroconversions/100 y at risk for HBV and 26.3 seroconversions/100 y for HCV. Multiple logistic regression analysis showed hepatitis seroconversion to correlate with imprisonment during the study (OR 2.2; 95% CI 1.04-4.74), absence of drug-free periods (OR 5.7; CI 1.44-22.3) and frequent syringe/needle exchanges (OR 1.31; CI 1.02-1.7). The absence of HIV spread was probably partly due to the low prevalence of HIV-infected IVDUs in the city. Despite free syringes and needles, both HBV and HCV continued to spread at high rates. Nevertheless, syringe/needle exchange programs, coupled with monitoring of serostatus provide good surveillance and are valuable for further assessment of remaining risks.

Clinical aspects of delta infection.

The clinical features of delta infection were analysed retrospectively in 191 hepatitis B surface antigen (HBsAg) carriers and 592 cases of acute hepatitis B seen over 11 years in the Swedish town of Malmö (population 250 000). With a few exceptions delta infections occurred exclusively in drug addicts. In the chronic HBsAg-carriers the most common clinical manifestation was an episode of acute hepatitis, which in some individuals became severe with a pronounced rise in serum alanine aminotransferase activity for many months. During the period of delta infection the HBsAg titre was lowered and in three out of 26 cases the patient lost HBsAg altogether and developed hepatitis B surface antibodies (anti-HBs). In one patient the acute hepatitis due to delta infection was fulminant and fatal. In patients with acute hepatitis B the clinical picture did not distinguish between those with and without simultaneous delta infection. The frequency with which acute hepatitis B was succeeded by a chronic carrier state was the same whether or not the patient was infected simultaneously with the delta agent. The discovery of the delta agent has improved understanding of the natural history of chronic hepatitis B infection in drug addicts. Thus, instances of acute hepatitis in a chronic carrier, previously termed hepatitis non-A, non-B, may actually be episodes of delta infection.

Increased occurrence of hepatitis A with cyclic outbreaks among drug addicts in a Swedish community

SummaryTo determine the prevalence of antibodies toHepatitis A virus (anti-HAV) among drug addicts, sera collected in a Swedish city during a ten-year period from 234 drug addicts with acute hepatitis B were tested for anti-HAV. The results were compared with the normal population, where only 3.8% of those born after 1950 were anti-HAV-positive. In individuals born between 1941 and 1965, 8.2% in the normal population and 30.2% of the drug addicts were anti-HAV-positive (p<0.001). The level of immunity to hepatitis A among drug addicts ranged from 7.7% to 60% during the ten-year period. Low levels of immunity were seen in the years preceeding outbreaks of hepatitis A among drug addicts. These outbreaks occurred in a cyclic pattern. Higher levels of immunity were seen after each outbreak.ZusammenfassungZur Bestimmung der Prävalenz vonHepatitis A Virus-Antikörpern (anti-HAV) bei Drogenabhängigen wurden Seren von 234 Drogenabhängigen mit akuter Hepatitis B, die in einer schwedischen Stadt während zehn Jahren gesammelt worden waren, auf anti-HAV getestet. Zum Vergleich wurde eine normale Bevölkerungsgruppe herangezogen, bei der nur 3,8% der nach 1950 Geborenen und 8,2% der Jahrgänge 1941–1965 anti-HAV positiv waren. Hingegen war bei 30,2% der Drogenabhängigen anti-HAV nachzuweisen (p<0,001). Die Rate von Drogenabhängigen mit Immunschutz variierte innerhalb von zehn Jahren zwischen 7,7% und 60%. In den Jahren von Hepatitis A-Ausbrüchen waren die Immunitätsraten jeweils niedrig. Die Ausbrüche traten zyklisch auf. Nach jedem Ausbruch war jeweils eine höhere Rate von Drogensüchtigen mit Immunschutz festzustellen.To determine the prevalence of antibodies toHepatitis A virus (anti-HAV) among drug addicts, sera collected in a Swedish city during a ten-year period from 234 drug addicts with acute hepatitis B were tested for anti-HAV. The results were compared with the normal population, where only 3.8% of those born after 1950 were anti-HAV-positive. In individuals born between 1941 and 1965, 8.2% in the normal population and 30.2% of the drug addicts were anti-HAV-positive (p<0.001). The level of immunity to hepatitis A among drug addicts ranged from 7.7% to 60% during the ten-year period. Low levels of immunity were seen in the years preceeding outbreaks of hepatitis A among drug addicts. These outbreaks occurred in a cyclic pattern. Higher levels of immunity were seen after each outbreak. Zur Bestimmung der Prävalenz vonHepatitis A Virus-Antikörpern (anti-HAV) bei Drogenabhängigen wurden Seren von 234 Drogenabhängigen mit akuter Hepatitis B, die in einer schwedischen Stadt während zehn Jahren gesammelt worden waren, auf anti-HAV getestet. Zum Vergleich wurde eine normale Bevölkerungsgruppe herangezogen, bei der nur 3,8% der nach 1950 Geborenen und 8,2% der Jahrgänge 1941–1965 anti-HAV positiv waren. Hingegen war bei 30,2% der Drogenabhängigen anti-HAV nachzuweisen (p<0,001). Die Rate von Drogenabhängigen mit Immunschutz variierte innerhalb von zehn Jahren zwischen 7,7% und 60%. In den Jahren von Hepatitis A-Ausbrüchen waren die Immunitätsraten jeweils niedrig. Die Ausbrüche traten zyklisch auf. Nach jedem Ausbruch war jeweils eine höhere Rate von Drogensüchtigen mit Immunschutz festzustellen.

Antibody to a hepatitis C virus related protein among patients at high risk for hepatitis B

Anti-HCV prevalence in treated hemophiliacs, their heterosexual partners, intravenous drug addicts and homosexual men was studied. In hemophiliacs and many of the intravenous drug addicts, greater than or equal to 2 sera drawn 1-18 or 1-17 years apart were available. Anti-HCV testing was performed by ELISA (Ortho). Among patients with severe and moderate hemophilia A, 87% (98/112) were positive for anti-HCV at least once and among patients with severe and moderate hemophilia B, 83% (24/29) were positive for anti-HCV. Seroconversion to anti-HCV was observed in 21% of hemophilia patients. In hemophilia A, HCV infection generally occurred during the first years of life and in hemophilia B somewhat later. Loss of anti-HCV antibody was seen in 12% (17 patients). The rest, 54% (76 patients) were seropositive in first and last samples. All 12 tested spouses to anti-HCV positive men were anti-HCV negative. 80% of the drug addicts (137/172) were seropositive for anti-HCV. In those with greater than 1 serum tested, 8% were consistently negative and 68% consistently positive. 21% seroconverted to anti-HCV while 3% lost antibody. 10% (22/211) of homosexual men were anti-HCV positive. Intravenous transmission of HCV thus seemed highly efficient whereas sexual transmission was much less efficient.

Relation between donor transaminase and recipient hepatitis non-A, non-B in Sweden

Abstract. The relation between donor alanine aminotransferase (ALT) and recipient post‐transfusion hepatitis (PTH) non‐A, non‐B was studied in patients tested before and 6 and 12 weeks after transfusion. The minimum ALT criterion for PTH was 105 IU/1 (> 2.5 times the upper normal of 42 IU/1). In 8.8% of donors, ALT was > 42 IU/1, and in 2.3% ALT was > 63 IU/1, i.e., 1.5 times elevated. PTH non‐A, non‐B occurred in 14 of 742 recipients. The PTH incidence increased when donor ALT was above 63 IU/1 (1.5 vs. 5.6%; p < 0.05). However, if the confounding factor of volume variations was compensated for, elevated donor ALT and PTH were only statistically linked among recipients < 70 years (p < 0.02; Mantel‐Haenszel test).

Post-transfusion hepatitis type non-A, non-B in southern Sweden: occurrence and clinical significance

Two prospective studies of the occurrence and clinical significance of post-transfusion hepatitis non-A, non-B were performed in Malmö, Sweden. In both studies, patients of a broad clinical spectrum were followed up 6 and 12 weeks after transfusion. In a 7 week study from 1983, hepatitis non-A, non-B occurred in 9/173 transfused patients (5.2%) versus 1/203 untransfused controls (0.5%) (p less than 0.01). In a 6 month study from 1984-85, the incidence of hepatitis non-A, non-B had declined to 2.4% (18/739 transfused patients). The mean number of transfused units was about 5 in both studies and most patients had subclinical disease. Despite similar transfusion volumes to patients above or below 70 years of age, hepatitis non-A, non-B was predominantly seen among patients less than 70 years. In the 1984-85 study, hepatitis non-A, non-B incidence was 1.2% in recipients greater than or equal to 70 years, 3.4% in recipients less than 70 years and 4.5% in recipients less than 40 years. One year after the initial hepatitis non-A, non-B episode, 4/18 patients (22%) had biochemical signs of chronic hepatitis.

Antibody to Hepatitis-C-Virus-Related Proteins in Sera from Alanine-Aminotransferase-Screened Blood Donors and Prospectively Studied Recipients

Abstract. A prospective study of posttransfusion non‐A, non‐B hepatitis was conducted in Malmö, Sweden, in 1984–1985, in which donors were alanine aminotransferase (ALT) screened but not ALT selected. Among 741 patients studied at 0, 6, and 12 weeks after transfusion, 13 developed non‐A, non‐B hepatitis, and these were further followed up. Stored sera from the 13 hepatitis patients and their 123 donors were tested for anti‐hepatitis C virus (HCV) by ELISA and, if positive, analyzed by recombinant immunoblot assay (RIBA). All ALT‐elevated blood units (n = 301) and a similar number of ALT‐normal units were also tested. Only 4/13 patients with non‐A, non‐B hepatitis seroconverted to anti‐HCV, all with ALT peaks >10 times the upper normal. All seroconversions occurred within 5 months after transfusion and could be confirmed by RIBA. Hepatitis C in recipients occurred both after transfusion of blood that was strongly positive, weakly positive, and/or negative for anti‐HCV by ELISA. In donors grouped by ALT levels, the anti‐HCV prevalence varied between 0.4 (normal ALT) and 14% (ALT elevated ≥ 2 times). Of the total of 9 donor units positive by ELISA, only 5 were confirmed by RIBA. Of the 5 recipients of the RIBA‐positive blood units, 3 went into hepatitis, 1 remained normal at 10.5 weeks, and 1 showed a slight, transient ALT elevation at week 12. The recipients of ELISA‐positive but RIBA‐negative blood remained healthy.

HTLV-I and -II in Intravenous Drug Users from Sweden and Denmark

693 IVDU (intravenous drug user) sera from Copenhagen, Malmö and Stockholm were tested, 247 retro- and 446 prospectively, for antibodies to human T-lymphotropic virus (HTLV), types I and II, by means of a commercial whole-virus EIA and/or an HTLV-I/-II peptide-based EIA. Positive EIA reactions were checked and typed by electrophoretic immunoblotting, a differential peptide-based EIA and nucleic acid amplification/hybridization with HTLV-I and -II specific primers and probes. 3 (0.7%) of the prospectively tested IVDUs from Malmö, none of 100 from Stockholm and none of 45 from Copenhagen were HTLV-seropositive. The 3 Malmö IVDU cases were a female immigrant from South America, her male native Swedish spouse (both HTLV-I), and a male immigrant Italian heroinist (HTLV-II). We conclude that HTLV was uncommon among intravenous drug users, a sentinel population, in Sweden and Denmark during 1986 and 1989. However, the occurrence of 3 HTLV-positive cases in Malmö 1993 indicates that the situation can change rapidly.

Long term follow up of chronic hepatitis B virus infection in intravenous drug abusers and homosexual men.

Long term follow up of 16 homosexual men and 78 intravenous drug abusers who were chronic carriers of hepatitis B surface antigen (HBsAg) showed fundamental differences between the two groups. Viral replication, expressed by the presence of hepatitis B e antigen, lasted for four years or more in 10 out of 14 (71%) of the homosexual men whereas it was not present in 43 out of 73 (59%) of the drug addicts within one year. This shows a difference in the immunological response between homosexual HBsAg carriers and addicts that is not related to infection with human T cell lymphotropic virus type III. Severe histological damage such as chronic aggressive hepatitis, cirrhosis, or primary liver cancer was found in more than half of the homosexual men who underwent biopsy examinations. In drug addicts chronic persistent hepatitis was a regular finding in the absence of markers of delta infection, but in those addicts infected with the delta agent the degree of liver damage was comparable with that found in homosexual men.