Management of latent tuberculous infection in Norway in 2009: a descriptive cross-sectional study.

SETTING: Despite a steep increase in the number of individuals treated for latent tuberculous infection (LTBI), few data are available on how treatment is implemented. OBJECTIVE: To obtain baseline information on initiation and completion of treatment for LTBI in Norway in 2009. DESIGN: A descriptive cross-sectional study. RESULTS: All 721 patients treated for LTBI in 2009 in Norway were included, of whom 607 (84%) completed treatment. The treatment regimen generally consisted of 3 months of rifampicin and isoniazid. The three main reasons for starting treatment were: 1) countries of origin with high tuberculosis (TB) prevalence, 2) a positive tuberculin skin test, and 3) a positive interferon gamma release assay. The use of directly observed treatment varied by health region and age. The majority of the 34 medical specialists interviewed saw a need for new national guidelines to improve the selection of high-risk patients with LTBI. CONCLUSIONS: Management of LTBI is in accordance with current guidelines, with a high completion rate. More targeted selection of which patients should be offered preventive treatment is required, and new guidelines and tools to enhance risk assessment are necessary.

Relevance of a combined HIV antigen/antibody assay to detect early HIV infections in a low prevalence population: case reports.

The AxSYM HIV Ag/Ab Combo assay (Abbott) has proven to possess excellent sensitivity on seroconversion samples. Since its introduction in Sweden and Norway approximately one year ago, eight cases of acute HIV infections were found earlier compared to assays detecting only antibodies either to screen or to confirm an HIV infection. Data of the presented cases indicate that the early detection of primary HIV infection is of benefit to the individual patient and may reduce further spread of the disease. The impact of HIV combo assays on screening and diagnosis in a low prevalence population is discussed.

Liposome encapsulation of the internal control for whole process quality assurance of nucleic acid amplification-based assays.

A system intended for whole process quality assurance of nucleic acid amplification assays was developed based on the use of liposomes as cell-mimicking vehicles for the internal control, allowing introduction of the internal control directly into the crude biological specimens. By the proof of principle testing, the Roche Cobas Amplicor CT assay was chosen as model system and the Roche CT/NG Internal Control was thus loaded into the liposomes. The liposome/DNA particles were spiked into a Chlamydia trachomatis-positive urine specimen. A quantitative "in-house" duplex real-time C. trachomatis PCR assay showed that liposomes having Blue Dextran 2000 polysaccharide co-entrapped were the most suited particles as they were efficiently deposited by the centrifugation carried out according to the Roche urine specimen preparation procedure. Furthermore, it was demonstrated that the liposome/DNA particles might be used for whole process quality assurance of Amplicor assay without major modifications of the assay protocol. An additional feature of the use of these liposomes was that the pellet became blue coloured and that might facilitate a thorough removal of the urine supernatant without increasing the risk of disturbance of the pellet. Principally, the liposome/internal control system is versatile and seems to be applicable for whole process quality control of amplification-based assays for detection of various pathogens.

Hepatitis C in the general adult population of Oslo: prevalence and clinical spectrum.

BACKGROUND: The prevalence of hepatitis C (HCV) in Northern Europe has not been well described. This study aimed to estimate the prevalence and spectrum of hepatitis C infection in the general adult population of Oslo, Norway. METHODS: The study was part of the Oslo Health Study 2000-2001 and included a random selection of individuals older than 30 years living in Oslo County. Sera from 11,456 participants were screened for anti-HCV (EIA-3), positive samples were confirmed (RIBA-3) and examined for HCV RNA (PCR). All anti-HCV positive patients were offered clinical evaluation. Routine biochemical liver tests were performed. Candidates for HCV treatment were asked to undergo a percutanous liver biopsy. RESULTS: Among 11,456 participants HCV RNA was detected in 62 (0.5%) and HCV RNA with raised serum alanine aminotransferase (ALT) in 46 (0.4%). Anti-HCV was detected in 78 (0.7%) with a peak prevalence of 1.5% among subjects 40 and 45 years old. Being anti-HCV positive was associated with being unmarried, unemployed and having low education. Anti-HCV prevalence was higher among subjects with alcohol-related problems compared to those without (4.4% versus 0.6%, P < 0.001). It was also higher among smokers compared to non-smokers (2.0% versus 0.2%, P < 0.001). In 33 liver biopsies, bridging fibrosis was seen in 8 (24%) and cirrhosis in 1 (3%). The route of transmission was injecting drug use in 67%, transfusion in 6% and unknown in 27%. CONCLUSION: In this population-based survey the prevalence of chronic hepatitis C was 0.5% and ALT was raised in 80% of those with chronic infection.

An outbreak of hepatitis A among homosexuals linked to a family outbreak.

Several outbreaks of hepatitis A occurred in Norway in 1995-8. Molecular epidemiology was used to follow the spread of hepatitis A virus in the population. Distinct strains of hepatitis A virus (HAV) were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent sequencing in serum from patients in different communities at risk of infection. Two HAV strains were detected in an outbreak among 26 men having sexual contact with other men. One of these strains was also detected in a geographically limited family outbreak. The family outbreak was first believed to be acquired abroad. The sequence information linked the two outbreaks, and epidemiological and serological analyses revealed the transmission route. This study demonstrates the importance of molecular epidemiology in outbreak investigation, surveillance and monitoring of hepatitis A in the population.

Raised serum ferritin predicts non-response to interferon and ribavirin treatment in patients with chronic hepatitis C infection.

BACKGROUND/AIM: Previous studies have indicated that response to interferon therapy is inversely proportional to the amount of body iron stores. We have studied the relationship between serum ferritin, transferrin saturation, liver iron, presence of HFE-C282Y gene mutation and response to treatment in patients with chronic hepatitis C infection. METHODS: Two hundred and fifty-six naive, HCV-RNA positive patients (60% males, median age 38 years, range 21-70) were treated with interferon and ribavirin for 6 months. Iron indices and the presence of the C282Y mutation were measured. In 242 (94%) patients iron deposition were determined by Perls staining method. Patients with negative HCV-RNA at 6 months after the end of treatment were defined as sustained viral responders. RESULTS: Non-responders (n = 127) had significantly higher median s-ferritin values compared with sustained viral responders (130 microg/L vs. 75 microg/L P < 0.001). There was no difference in transferrin saturation among the two response groups. Only 23% (4/7) of patients with Perls grade 1 in liver biopsies responded to treatment vs. 54% (122/225) patients without iron deposition (P = 0.02), however, 10/13-non-responders had HCV genotype one. Two patients (0.8%) were homozygous for the C282Y mutation, 36 patients were heterozygous (14%). Among mutation carriers 26/38 achieved sustained response compared with 102/216 non-carriers (68% vs. 48%, P = 0.02). In a multivariate analysis s-ferritin (P = 0.030) and C282Y carrier status (P = 0.012) remained independent predict of sustained response. CONCLUSIONS: Raised s-ferritin values predicate non-response to interferon-ribavirin therapy in hepatitis C patients. Response rate in C282Y mutation carriers seems greater than in non-carriers.

Effect of interferon-alpha induction therapy on genotype 2b/3a and low viral load hepatitis C virus infection. A randomized multicentre study.

BACKGROUND: Interferon monotherapy for chronic hepatitis C virus (HCV) infection leads to sustained viral eradication in a minority of patients. However, in selected groups of patients, sustained virological response is observed in as many as 50% of patients. High initial interferon dose (induction therapy) has been reported to increase the initial response rate. We have studied the effect of interferon induction therapy in patients infected with HCV genotype 2b/3a, low viral load and no cirrhosis. METHODS: A total of 71 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis, with genotype 2b or 3a, viral load < or = 3 million copies per ml and no cirrhosis were randomized to receive either standard interferon therapy (3 MIU interferon-alpha-2a thrice weekly) for 26 weeks or 6 MIU interferon-alpha-2a daily for 4 weeks (induction group) followed by the standard dose (3 MIU thrice weekly) for 22 weeks. Those with persistent HCV RNA at 4 weeks stopped treatment. Patients were monitored for HCV RNA during and following treatment, and data were interpreted according to intention-to-treat analysis. RESULTS: Viral clearance occurred more rapidly (after 4 weeks) in the induction group (33/36 = 92%) compared to the standard interferon group (21/35 = 60%) (P = 0.01). Among the initial responders, 23/33 (induction group) compared to 16/21 (standard group) were persistently HCV RNA-negative at the end of treatment. At 52 weeks (6 months' follow-up), 22/36 (61%) (induction group) compared to 10/35 (29%) (standard group) were HCV RNA-negative. Among initial responders, 22/33 (induction group) and 10/21 (standard group) achieved a sustained virological response. Among end-of-treatment responders, 22/24 (induction group) and 10/16 (standard group) were HCV RNA-negative at 6 months' follow-up (P = 0.013). CONCLUSIONS: In patients infected with HCV genotype 2b/3a, low viral load and without cirrhosis, IFN induction therapy increases the initial viral clearance and reduces the risk of relapse in end-of-treatment responders. A sustained virological response was achieved in 61% of the patients receiving IFN induction therapy.

Effect of combined interferon-alpha induction therapy and ribavirin on chronic hepatitis C virus infection: a randomized multicentre study.

BACKGROUND: The efficacy of interferon-alpha (IFN) induction in combination with ribavirin for chronic hepatitis C virus (HCV) infection is not known. METHODS: A total of 256 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis were enrolled in a randomized multicentre study. The patients received either standard combination therapy with 3 MIU interferon-alpha2b thrice weekly for 26 weeks or 6 MIU interferon-alpha2b daily for 4 weeks and 3 MIU 3/7 days for 22 weeks. All patients received ribavirin 1000 mg or 1200 mg (weight dependent) daily during the 26-week treatment period. Patients were monitored for HCV RNA during and following treatment. RESULTS: The sustained virological response rates (26 weeks after end of treatment) were 54% and 47% for patients receiving IFN induction/ribavirin and standard IFN/ribavirin, respectively (P = 0.35). Among patients infected with genotype 1a/1b, the sustained response rates were 32% and 35%. In patients infected with genotype 2b/3a IFN induction/ribavirin led to a sustained response rate of 80% as compared to 65% in the standard combination therapy group (P = 0.073). Steatosis was more frequently seen in liver biopsies from patients infected with genotype 3a as compared to genotypes la/lb. Among genotype 1a/1b infected patients. steatosis was a highly significant predictor of failure to achieve sustained virological response. Logistic regression analysis (multivariate analysis) showed that independent predictors of sustained virological response were low age, female gender, genotype 2b/3a and HCV RNA negativity at 2 weeks. CONCLUSIONS: IFN induction in combination with ribavirin does not increase the sustained virological response rate among patients infected with HCV. Absence of steatosis is an independent predictor of sustained virological response in patients infected with genotypes 1a/1b.

Treatment of chronic hepatitis C in injecting drug users: 5 years' follow-up.

AIM OF THE STUDY: To assess the long-term hepatitis C (HCV) treatment outcome in former injecting drug users (IDUs). MATERIALS AND METHODS: A long-term follow-up of 27 former IDUs who had been successfully treated for chronic hepatitis C was performed. These patients represented all IDUs who had obtained a sustained virological response in a Norwegian HCV treatment trial. The patients had been treated with interferon-alpha alone or in combination with ribavirin. At 5 years' follow-up the 27 IDUs were retested for HCV RNA and risk behaviour for HCV transmission after treatment was assessed. In the control group all 18 non-IDUs who had obtained a sustained virological response in the same treatment trial were included. RESULTS: At follow-up 13-82 months (median 64) after the end of treatment only one case of probable reinfection was seen among the 27 IUDs. No reoccurrence of HCV was observed in the control group. The IDU who was HCV RNA positive at follow-up had continued injecting drugs and reported frequent needle sharing. At follow-up HCV of genotype 1a was detected in contrast to genotype 1b before treatment indicating that this patient was reinfected with HCV. A return to injecting drug use occurred in 9 (33%) of 27 IDUs. CONCLUSION: The long-term outcome of HCV treatment in former IDUs was excellent. Despite frequent reinitiation of drug injection all but 1 remained HCV RNA negative.

[Immediate drug therapy of obstructive lung disease in hospital]. / Medikamentell straksbehandling i sykehus ved obstruktiv lungesykdom.

BACKGROUND: We have studied how patients with obstructive lung disease are treated in Norwegian hospitals and whether the treatment is in accordance with international guidelines. MATERIAL AND METHODS: During 76 days from 1 April 1997 we registered all 176 patients (110 women) admitted for obstructive lung disease in two hospital catchment areas in western Norway. The medical treatment given the first three hours after admission was recorded by the doctors on call. RESULTS: 106 patients (60%) were above 65 years of age; 21 (12%) below 35.31% of the patients had a mild form of the disease, 42% a moderate, 21% a severe, and 6% a life-threatening condition. Almost all patients with moderate and severe disease were treated with beta 2 agonists on admission. Among the patients with moderate disease, 25% did not receive glucocorticoids during the first three hours in hospital. The proportion of patients treated with theophylline was lower among those with mild disease than among those with moderate disease (15% and 65% respectively). INTERPRETATION: Guidelines are followed to a high degree in patients with severe or life threatening obstructive lung disease, but only party in those with mild or moderate disease.

[Hepatitis C virus among pregnant women in Norway--occurrence of antibodies and pregnancy outcome]. / Hepatitt C-virus blant gravide kvinner i Norge--forekomst av antistoffer og svangerskapsutfall.

BACKGROUND: Transmission of hepatitis C virus from mother to child is well documented. The prevalence of antibodies against hepatitis C virus among pregnant women in Norway is however, not known. The aim of this study was to estimate the maternal prevalence of antibodies against hepatitis C virus and to study the association between presence of antibodies and fetal death. MATERIAL AND METHODS: From a study of 35,940 pregnant women, a random sample of 970 women and all women with fetal death after 16 weeks of gestation (n = 283), were tested for antibodies against hepatitis C virus. RESULTS: 7 out of 970 women in the random sample (0.7%; 0.2-1.3%, 95% confidence interval) had antibodies against hepatitis C virus. The same prevalence (0.7%, 2 out of 283) was found among women with fetal death. INTERPRETATION: The prevalence of antibodies against hepatitis C virus among Norwegian women was unexpectedly high. Further research is necessary to understand the causes and implications of this observation.

[Surveillance of hepatitis A by molecular epidemiologic studies]. / Overvåking av hepatitt A ved molekylaerepidemiologiske undersøkelser.

Hepatitis A virus was studied by molecular epidemiology in connection with an outbreak of hepatitis A associated with intravenous drug users (IVDU) in Norway. Hepatitis A virus was characterised by sequencing 114 of 1,242 notified cases of hepatitis A from January 1995 to July 1998. One hepatitis A variant (IVDU variant I) was detected among IVDU during an outbreak of hepatitis A, as well as among 19 out of 49 cases with no apparent association to this outbreak. During the autumn of 1997, a new variant (IVDU variant II) was detected in the IVDU communities. Genotyping of virus from imported cases associated with travel to endemic regions, revealed that they were distinct from the two other IVDU variants. Hepatitis A has disseminated among IVDU over years; this indicates that hepatitis A is endemic in these communities. At the turn of the year 1997/98, there was a smaller outbreak of hepatitis A among homosexual men in Oslo, distinguished by genotyping from the outbreaks in the IVDU communities. By molecular epidemiology we have been able to identify individual outbreaks of hepatitis A and distinguish them from the IVDU outbreak.

The spectrum of hepatobiliary disease in primary hypogammaglobulinaemia.

OBJECTIVE: To study the prevalence of hepatobiliary disease in a clinically and immunologically well-characterized group of 88 adult Norwegian patients with primary hypogammaglobulinaemia. SUBJECTS: Eighty-eight patients with primary hypogammaglobulinaemia were followed and signs and symptoms of liver disease were recorded. The patients were examined clinically and radiologically on a regular basis with liver biopsies performed when indicated. All patients were tested for hepatitis C virus (HCV) RNA, hepatitis G virus (HGV) RNA and hepatitis B virus (HBsAg). RESULTS: Twenty-one patients were HCV RNA-positive, all having signs of chronic liver disease. Only four patients were HGV RNA-positive, of whom two were also HCV RNA-positive. Amongst the 67 HCV RNA-negative patients, 26 had signs of chronic liver disease, including two who were HGV RNA-positive. HCV RNA-negative patients with liver disease had received intravenous immune globulin substitution more frequently, had a longer history of any form of immune globulin substitution and had a greater incidence of common variable immunodeficiency than patients without signs of liver disease. In most cases (21 of 26 patients) the liver disease was relatively mild. Three patients had granulomatous liver disease, with a relatively aggressive course in all three. CONCLUSION: Hepatobiliary disease is a frequent complication in primary hypogammaglobulinaemia. Liver disease in HCV RNA-negative patients usually has a mild course. HGV does not seem to be a major cause of chronic liver disease in these patients.

Treatment with interferon-alpha2a alone or interferon-alpha2a plus ribavirin in patients with chronic hepatitis C previously treated with interferon-alpha2a. CONSTRUCT Group.

BACKGROUND: Preliminary results from combination therapy with interferon-alpha and ribavirin (IFN/Rib) in patients with chronic hepatitis C have been promising, with up to 50% sustained hepatitis C virus (HCV) RNA response. The aim of this study was to investigate whether a sustained HCV RNA response could be obtained with combination therapy in patients who were non-responders or relapsers after IFN treatment. METHODS: In a multicenter study we randomized 53 HCV RNA-positive patients into 2 treatment groups. They all had biopsy-confirmed chronic hepatitis C, and all were recruited from a previous IFN study: 26 were previous non-responders and 27 responders with relapse. Group A received interferon-alpha2a, 4.5 MIU thrice weekly for 6 months, and group B received ribavirin, 1000-1200 mg/day, in combination with the same dose of interferon-alpha2a for 6 months. Median Knodell index was 5.0 in both groups. Genotype 1 was found in 24 (45%), type 2 in 3 (6%), and type 3 in 26 (49%). RESULTS: Sustained clearance of HCV viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53 patients (23%): 6 of 27 in the IFN group (22%) and 6 of 26 (23%) in the IFN/Rib group (NS). Nine of 27 (33%) former responders with relapse, compared with 3 of 26 (12%) non-responders, obtained a sustained HCV RNA response (P = 0.054). In previous relapse patients sustained loss of viremia was more frequent in genotype 3 (50%) than in genotype 1 (11%) patients (P = 0.022). CONCLUSIONS: In a group of previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained clearance of viremia when retreated either with IFN-alpha2a alone or with a combination of IFN-alpha2a and ribavirin for 6 months. Previous relapse patients with HCV genotype 3 obtained sustained loss of viremia significantly more often (50%) than type-patients (11%). Previous IFN responders with relapse responded better than previous non-responders.

[HTLV examination of Norwegian blood donors]. / HTLV-undersøkelse av norske blodgivere.

Approximately one third of the Norwegian blood donor population has been tested for infection with human T-lymphotropic virus type I and II (HTLV-I/II). This study was initiated to provide an indication as to whether or not the Norwegian transfusion service should screen the entire donor population for HTLV I/II. No HTLV-I infections were found among the blood donors. One new donor was confirmed HTLV-II positive. This individual had previously used drugs intravenously. HTLV-I/II infection can be regarded as a marker for risk behaviour, and testing can be of significance in the quality assurance of the transfusion service. We recommend that the entire blood donor population be tested for HTLV-I/II infections, and thereafter only new donors. The benefit of this scheme should be evaluated in the future.

Long-term outcome of chronic hepatitis C virus infection in primary hypogammaglobulinaemia.

The clinical course of HCV infection in patients with primary hypogammaglobulinaemia appears to be more severe than in immunocompetent patients. We studied the long-term course of chronic HCV infection in 20 Norwegian hypogammaglobulinaemia patients with a 13-15 year known history of HCV infection. Twelve of 20 patients developed cirrhosis during the observation period (1984-1999), and the remaining eight also had chronic liver disease verified by liver biopsy in the majority of the cases. Eleven of the 20 patients are dead. Two died following liver transplantation for HCV cirrhosis. Five died due to terminal liver failure without receiving a liver allograft. Two patients died from other causes, but with advanced liver disease contributing to the outcome, while two deaths were unrelated to the HCV infection. Among patients with common variable immunodeficiency (CVI), five out of six are dead. Two patients cleared the hepatitis C virus 3 years following interferon monotherapy, while three patients achieved a sustained response to combination therapy with interferon and ribavirin. Viral load did not seem to have a major impact on disease progression. Our results emphasize the severity of hepatitis C virus infection in patients with hypogammaglobulinaemia. Patients with CVI appear to have the poorest prognosis.

[Hospital admissions due to obstructive lung diseases and pneumonia in two hospital districts]. / Innleggelser for obstruktiv lungesykdom og pneumoni i to sykehusområder.

Admission rates for specific diseases in a defined district can be used as a coarse estimate of the need for health services. Such registration has not previously been conducted in the hospital districts of Bergen and Haugesund. We recorded all patients 16 years and older admitted to three hospitals for obstructive lung disease or pneumonia in the two hospital districts of Bergen and Haugesund in April to June 1997. A total of 438 patients were included in both districts, 246 with obstructive lung disease and 192 with pneumonia. The admission rate for obstructive lung disease was 359 per 100,000 inhabitants per year, for pneumonia 280 per 100,000 inhabitants per year. Median age was between 71 and 75 years for men and women for both diseases. 13% of patients with obstructive lung disease were readmitted to the hospital within 30 days. Obstructive lung disease and pneumonia are common causes of hospital admission, especially among older persons. The admission rates for both diseases combined were 639 per 100,000 adults per year in the hospital districts of Bergen and Haugesund.

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.

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.