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Biomedical subjects

K Skaug

Publications and source records attributed to K Skaug.

At least 37 records · Page 2Linked to original sources

The effect of treatment with alpha-interferon on hepatitis G/GBV-C viraemia. The CONSTRUCT Group.

BACKGROUND: Hepatitis G virus (HGV) or GBV-C is frequently detected in patients co-infected with hepatitis C virus (HCV). This study investigated host and virologic factors influencing the response to HGV/GBV-C to alpha-interferon treatment. METHODS: HGV/GBV-C was detected and quantified by nested polymerase chain reaction. The influence of variables such as liver biopsy appearance, liver function abnormalities, and response of HCV to interferon treatment was monitored. RESULTS: Fourteen of the 25 HGV/GBV-C-infected patients treated with interferon (3-6 MIU three times a week for 6 months) became non-viraemic during treatment, although all relapsed after treatment withdrawal at 6 months, with no net change in virus load between 0 and 12 months. CONCLUSIONS: Predictive factors for clearance of HGV/GBV-C viraemia by interferon were pre-treatment severity of liver disease (median Knodell score of 4, compared with 7 for non-responders; P = 0.030) and alanine aminotransferase levels (median, 114, 182 for non-responders; P = 0.039). Clearance was associated with the treatment response of HCV. Nine of 13 who cleared HGV/GBV-C also cleared HCV, compared with 3 of 11 HGV/GBV-C non-responders; P = 0.05). The shared susceptibility of HGV/GBV-C and HCV to interferon treatment suggests a link between the mechanism of clearance of the two viruses.

Adult↗

Liver transplantation for endstage hepatitis C cirrhosis in a patient with primary hypogammaglobulinaemia.

Liver transplantation was performed in a patient with primary hypogammaglobulinaemia, chronic hepatitis C and hepatic failure. The immediate posttransplant period was uncomplicated. Owing to a stricture of the choledochojejunostomy the patient was reoperated with construction of a hepaticojejunostomy 11 months posttransplant. The patient remained hepatitis C virus (HCV) RNA-positive, with high and increasing levels of HCV. Liver biopsies demonstrated the recurrence of HCV. 14 months after the transplantation the patient developed severe diarrhoea caused by Cryptosporidium parvum. The infection did not respond to available therapeutic measures. He deteriorated with development of liver failure and died 18 months after the transplantation. The present case report illustrates the difficulties associated with organ transplantation in patients with primary hypogammaglobulinaemia.

Adult↗

A unique hepatitis A virus strain caused an epidemic in Norway associated with intravenous drug abuse. The Hepatitis A Study Group.

A major epidemic of hepatitis A virus (HAV), associated with intravenous drug abuser (IVDA) communities, was studied by molecular epidemiology using a 348 bp region of the VP1/2PA junction of the HAV genome. A total of 621 cases were notified during the 2-year epidemic, 492 of whom were IVDA. Serum samples, taken from 79 patients during the acute phase of infection, were selected for analysis of HAV RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing. A unique epidemic strain was detected among 49 cases thought to be associated with the epidemic, and among 10/30 patients with no apparent association to the epidemic. The other 20 HAV variants differed from the epidemic strain, and in several cases could be connected to the patient's destination of travel. These strains were mostly associated with smaller outbreaks that were soon eradicated. Our data indicate different dissemination routes of HAV, suggesting that needle sharing practises contribute to a wide spread of the virus in the IVDA communities. By early detection of an outbreak, by epidemic survey and sequence analysis, preventive measures can be applied, and thereby limit the epidemic at an early stage.

Disease Outbreaks↗

[An outbreak of hepatitis A among intravenous drug addicts in Oslo 1995-96].

Intravenous drug abuse is a well-known risk factor for acquiring hepatitis A infection. Among drug abusers most cases are sporadic, but epidemic outbreaks may occur occasionally. In this article we describe an epidemic outbreak including 144 serologically proved cases of hepatitis A among intravenous heroin and amphetamine abusers in Oslo. The outbreak lasted for 11 months. 59 (41%) of the patients were admitted to hospital. One of them died and seven developed severe but reversible acute hepatitis. We also registered 26 cases of hepatitis A among close contacts, 14 of whom were associated with a nosocomial outbreak that affected nurses, fellow patients and relatives. We do not know how the hepatitis A virus was introduced into the abuser population, but the further spread was probably dominated by a combination of faecal-oral transmission and parenteral transmission secondary to sharing needles. Although we were unable to detect hepatitis A virus in confiscated drug samples by means of polymerase chain reaction we cannot exclude that some abusers were infected by injection of contaminated amphetamine.

Adult↗

Characterisation of an epidemic of hepatitis A virus involving intravenous drug abusers--infection by needle sharing?

An epidemic of hepatitis A virus (HAV) among intravenous drug abusers in Oslo involved 144 serologically confirmed cases. Another 26 patients (non-drug abusers), of whom 14 were derived from a single nosocomial outbreak, were associated with the epidemic. Sequencing of the VP1/P2A junction revealed that viruses associated with the epidemic were completely identical, whereas other HAV samples collected during the same period differed by up to 10%. HAV was detected in the serum of 48 of 100 patients by a nested PCR. Viremia was observed as early as 25 days before the onset of clinical hepatitis, and up to 30 days after. The large number of patients within the drug abuser group, and the few secondary cases, raised the question of whether the virus could be transmitted by the use of needles. To establish whether viral contamination of drugs did contribute appreciably to maintaining the epidemic, we examined heroin and amphetamine confiscated during the period, using immunomagnetic separation coupled to nested PCR, but failed to detect any virus. Antibodies against hepatitis B virus and hepatitis C virus were common among the HAV infected drug abusers (43% and 81%, respectively), suggesting widespread sharing of needles. This observation and the large number of patients with a demonstrable viremia suggest that needle sharing may contribute to the dissemination of HAV.

Amphetamine↗

False-negative results of a ligase chain reaction assay to detect Chlamydia trachomatis due to inhibitors in urine.

The aim of this study was to assess the presence of inhibitors in urine specimens causing false-negative results in a commercial Chlamydia trachomatis gap-filling ligase chain reaction (Gap-LCR) assay. On testing of urine samples by the Gap-LCR assay and urethral swab specimens by cell culture, 73 (19%) Chlamydia trachomatis positive subjects were detected among 382 men attending a clinic for sexually transmitted diseases. In 56 subjects, the agent was detected in both the urine and the urethral samples, while 309 subjects were negative in both tests. In seven subjects urine samples were Gap-LCR positive (confirmed by a different Gap-LCR assay), but the corresponding urethral swab samples were cell culture-negative. In another ten subjects the urethral swab samples were cell culture positive, but their urine samples were Gap-LCR negative. Subsequent re-analysis of the urine samples including the addition of external Chlamydia trachomatis DNA indicated full or partial inhibition in nine of the cell culture-positive Gap-LCR negative subjects. When urine preparations were freeze-thawed and diluted prior to testing, Chlamydia trachomatis was detected in six of the ten initially Gap-LCR-negative samples. Gap-LCR inhibitors were present in at least nine (12%) of the 73 urine preparations from the Chlamydia trachomatis positive individuals. Identification of samples containing Gap-LCR inhibitors and subsequent processing to reduce the inhibition increased the sensitivity of the test from 86% to 95%.

Adult↗

Interferon-alpha 2b therapy in low-activity hepatitis C: a pilot study.

BACKGROUND: Many patients with chronic hepatitis C have long periods of normal or near-normal liver enzyme levels, even though histologic alterations have been confirmed. The recommendation today is not to treat this patient group. METHODS: In a pilot study 23 hepatitis C virus (HCV) RNA-positive patients with alanine aminotransferase (ALAT) levels less than 1.5 times upper normal limits for at least 6 months on more than three occasions and with histologic liver abnormalities compatible with chronic hepatitis C were treated with 3 MU of interferon-alpha 2b three times a week for 6 months. RESULTS: Nine patients (39%) became HCV RNA-negative in serum during treatment, but only two (8.7%) remained so after 6 months' follow-up. Significantly more patients with genotype other than type 1 became HCV RNA-negative than patients with genotype 1 during treatment (P = 0.005). CONCLUSIONS: Patients with low-activity chronic hepatitis C have a response to interferon-alpha treatment similar to that of patients with increased ALAT levels. Genotype seems to influence the rate of response.

Adult↗

Genotype, viral load and age as independent predictors of treatment outcome of interferon-alpha 2a treatment in patients with chronic hepatitis C. Construct group.

Patients with chronic hepatitis C respond differently when treated with interferon. We randomized 116 patients with chronic hepatitis C in order to compare two dosage regimens of recombinant interferon alpha 2a:3 MIU x 3 per week for 6 months (arm A) or 6 MIU x 3 per week for 3 months and then 3 MIU x 3 per week for 3 months (arm B). There were no significant differences concerning outcome between the two dose regimens: sustained clearance of HCV viremia 6 months after the end of treatment was obtained in 12/59 (20%) in group A compared with 18/57 (32%) in group B (p = 0.24). In patients with genotype 1a, 4/31 (13%), in genotype 1b, none of 9 (0%), 9/15 (60%) in genotype 2, and 17/58 (29%) in genotype 3, showed sustained clearance of HCV viremia 6 months after the end of treatment (p = 0.002). In a stepwise logistic regression analysis, only pretreatment viral load (p = 0.0001), genotype (p = 0.001) and age (p = 0.04) were identified as independent predictors of sustained clearance of HCV viremia. Liver histology as assessed by Knodell index was significantly improved in patients with sustained HCV RNA response 6 months after the end of treatment (5.2 +/- 2.2 vs 2.6 +/- 2.2, p < 0.001), but not in responders with relapse or in non-responders. In conclusion, stepwise logistic regression analysis showed that viral load, HCV genotype and age were the only independent predictors for sustained HCV RNA response.

Age Factors↗

Comparison of the sensitivity of four rapid assays for the detection of antibodies to HIV-1/HIV-2 during seroconversion.

OBJECTIVES: To compare the sensitivity of four rapid assays for the detection of antibodies against HIV-1 during early seroconversion. METHODS: Four rapid assays for the detection of antibodies to HIV-1/HIV-2 (SUDS HIV 1 + 2, TestPack HIV-1/HIV-2, HIV-SPOT and CAPILLUS HIV-1/HIV-2) were evaluated on 38 sera derived from 14 HIV-1 seroconverters, formerly tested with Abbott second- and third-generation HIV-1/HIV-2 enzyme immunoassay (EIA) and Diagnostic Biotechnology HIV blot 2.2. EIA-negative sera had also been investigated by HIV-1 antigen testing and polymerase chain reaction (PCR) analysis detecting HIV-1 proviral DNA. RESULTS: On 16 sera which were Abbott second-generation EIA negative, the SUDS assay rated highest with six positive results. Four sera were TestPack positive. No specimens in this group were HIV-SPOT positive or CAPILLUS positive. Of the remaining 22 sera (Abbott second- and third-generation EIA positive), all but two were positive in all tests. CONCLUSIONS: The study revealed differences in the sensitivities of the rapid assays in the early phase of seroconversion. The most sensitive assay, SUDS, was even more sensitive than the Abbott third-generation EIA, while TestPack and the EIA were equally sensitive. Based on these findings, we suggest the inclusion of these assays in the supplemental testing for detection of antibodies to HIV.

HIV Antibodies↗

Risk of toxoplasmic encephalitis in AIDS patients: indications for prophylaxis.

To establish the indications for primary prophylaxis against toxoplasmic encephalitis in the Norwegian HIV-positive population, we estimated the incidence of toxoplasmic encephalitis, and related the degree of immunodeficiency and the presence of IgG antibodies against Toxoplasma gondii (T. gondii) to the development of toxoplasmic encephalitis. This retrospective study includes all HIV-positive patients at our hospital from April 1983 to October 1994 (n = 705). A total of 238 patients had AIDS, which represents almost 90% of all AIDS patients in Oslo. Autopsy was done in over 70% of the patients who died during this period; 19 patients developed toxoplasmic encephalitis (8.0%). The median CD4 cell count was 75 x 10(6) cell/I (range 0-280) at the time of diagnosis of toxoplasmic encephalitis. T. gondii serology was studied in 698 (99.0%) of the patients, and was found positive for 17.8%. Of the patients with toxoplasmic encephalitis 18/19 had IgG antibodies against T. gondii and of the 40 AIDS patients who had anti-T. gondii IgG, 18 (45%) developed toxoplasmic encephalitis. We conclude that there is indication for prophylactic treatment of HIV positive patients who have IgG antibodies against T. gondii and who have fewer than 200 x 10(6) CD4 cells/I.

AIDS-Related Opportunistic Infections↗

Prevalence of hepatitis C genotypes among patients with chronic hepatitis C in Norway. Construct Group.

Among 116 patients with biopsy-confirmed chronic hepatitis C (Riba 2 or Riba 3 positive) in a multicenter study in southern Norway on interferon, we determined hepatitis C virus genotype by restriction fragment length polymorphism (RFLP) of the 5' NCR. The RFLP method was supplemented by and compared with a serological typing method based on the detection of type-specific antibody to peptide from the NS-4 region. A total of 102/106 (96%) patient sera showed detectable type-specific antibody to NS-4 peptides and corresponded in all cases, except two, to the genotype detected by polymerase chain reaction. Combining the results from RFLP genotyping and serotyping, genotype 1 was found in 40 (35%) (27 with 1a and 10 with 1b, 3 subtypes not determined), genotype 2 in 15 (13%) (subtype 2b in 14 and 1 subtype not determined), and genotype 3 in 58 (50%) of patients. The low mean age of the patients (34 years), the low prevalence of cirrhosis (3.5%), the short duration of the disease, and a high prevalence of intravenous-drug abusers may account for the low prevalence of infection with genotype 1b (9%). The epidemiological features of hepatitis C patients are markedly different from patient groups described in southern Europe in terms of risk factors, age, and genotype distribution.

Adult↗

Screening urine samples by leukocyte esterase test and ligase chain reaction for chlamydial infections among asymptomatic men.

Urine samples from 358 asymptomatic males were screened for urethral inflammation by the leukocyte esterase (LE) test and for Chlamydia trachomatis by the ligase chain reaction (LCR). LE and LCR positivity rates were 7.5% (27 of 358 samples) and 2.8% (10 of 358 samples), respectively. Eight of the 10 LCR-positive samples were detected by the LE screening test. The urine LE prescreening test in combination with the LCR assay may be a reasonable approach for genitourinary chlamydial disease control.

Bacteriological Techniques↗

[New cases of HIV infection. Estimation of the time of transmission].

During 1991 and 1992, 107 HIV infections were diagnosed at Ullevål hospital, Oslo. Previously collected serum specimens from 53 of these persons were tested with different anti-HIV and HIV antigen tests. Some of the sera were also examined for HIV RNA using PCR. Based on these results, the intervals between the last HIV negative and the first positive samples, and between the first HIV positive sample and the HIV diagnosis, were calculated. 38 persons had delivered HIV negative samples before their first positive sample. In addition, eight persons had a sample with serological markers of recent infection. For these 46 persons, the median time between the last HIV negative sample and the diagnosis was one year. 36 of them were HIV negative three years before diagnosis. For 19 persons, markers of HIV infection were detected in samples taken before the disease was first diagnosed. For two persons HIV markers were present in samples taken as early as 1986.

AIDS Serodiagnosis↗

Three cases of acute hepatitis E virus infection imported into Norway.

We report 3 cases of acute hepatitis E virus (HEV) infection imported from Asia. All 3 patients had fever and upper abdominal discomfort preceding jaundice which lasted 2-3 weeks with maximum bilirubin levels of 141-254 mmol/l. The ALT values peaked between 1,347 and 3,690 U/l. Both values normalized within 1-2 months. During the acute phase of the disease, all patients had high levels of IgG and IgM antibodies against HEV (anti-HEV) recombinant and synthetic peptides. The duration of the anti-HEV IgM was about 1-2 months.

Acute Disease↗

Hepatitis C virus (HCV) RNA among anti-HCV-positive blood donors and their recipients.

Seven of 24 blood donors positive in Ortho's first-generation antibody to hepatitis C virus (anti-HCV) test (EIA-1) were also positive in Ortho's second-generation test (EIA-2). All 7 had at least two anti-HCV positive recipients, whereas only 1 of the 17 EIA-2-negative donors had an anti-HCV-positive recipient. This recipient was a multitransfused patient with von Willebrand's disease. Five of the 7 EIA-2-positive donors had detectable HCV RNA. We traced and tested 38 of the still living blood recipients from the 7 EIA-2-positive donors. Twenty-eight of these were EIA-2 positive and 22 were HCV-PCR positive. One patient with Waldenstroem's hypergammaglobulinemia was EIA-2 negative but HCV-PCR positive. All the EIA-2-positive sera showed reactivity in Ortho's recombinant immunoblot assay (RIBA-2), but 5 of the 28 recipients and 1 of the donors reacted with only one band (RIBA-2 indeterminate). Among 32 recipients who probably had received EIA-2-positive blood, 29 (91%) had markers of an HCV infection. Twenty-two (75%) of the HCV-infected recipients had detectable HCV RNA more than 6 months after transfusion and hence were chronic HCV carriers.

Base Sequence↗

[Chronic hepatitis C. Experience with 50 patients].

We studied 50 patients (36 males and 14 females) with chronic hepatitis C who were admitted consecutively to our medical department during the period 1987-91. Eight patients (16%) had had a blood transfusion, 17 (34%) had used intravenous drugs and 25 (50%) were "sporadic cases" with no identifiable risk factor except that at least five had been tattooed. Most of the patients had moderate symptoms, including tiredness and asthenia. Few were jaundiced. A percutaneous liver biopsy was performed in 27 patients and showed chronic persistent hepatitis in 12 of them, chronic active hepatitis in six and cirrhosis in nine. Three patients with cirrhosis died; one from hepatoma, one from an endstage cirrhosis with bleeding and coma hepaticum, and one from septicaemia.

Adult↗

Detection of HBV DNA by PCR in serum from an HBsAg negative blood donor implicated in cases of post-transfusion hepatitis B.

An HBsAg negative blood donor, and three of her recipients, who developed HBsAg positive post-transfusion hepatitis B, were all positive for serum HBV DNA by polymerase chain reaction (PCR), and by subtype discriminating PCR were found to harbour HBV specifying ayw. Thus HBV specifying ayw. Thus HBV DNA may be detected and sub-typed by PCR in infectious HBsAg negative individuals.

Base Sequence↗

Hepatitis B antibodies in HIV-infected homosexual men are associated with more rapid progression to AIDS.

OBJECTIVE: To study the influence of previous or present hepatitis B virus (HBV) infection on HIV disease progression. DESIGN: A prospective study of HIV-positive individuals from HIV diagnosis to diagnosis of AIDS or to the end of the follow-up period on 1 January 1991. Mean follow-up time was 62 months. SETTING: The study population was recruited from a primary health-care clinic for homosexual men and followed by linkage to the National AIDS Registry. PATIENTS, PARTICIPANTS: Of 876 individuals who were tested for HIV, 80 were HIV-positive and included for study. Two individuals were lost to follow-up. MAIN OUTCOME MEASURES: Differences in progression rates to AIDS according to HBV status at study entry. RESULTS: The adjusted relative risk of progression to AIDS for the 48 subjects who were HBV-antibody-positive at study entry was 3.6 [95% confidence interval (CI), 1.3-10.1]. A high frequency of receptive anal intercourse was also associated with more rapid HIV disease progression; adjusted relative risk 2.6 (95% CI, 1.1-5.9). CONCLUSIONS: Our results suggest that presence of HBV antibodies is associated with more rapid HIV-disease progression.

Acquired Immunodeficiency Syndrome↗