All-cause and liver-related mortality in hepatitis C infected drug users followed for 33 years: a controlled study.

BACKGROUND & AIMS: The course of chronic hepatitis C virus (HCV) in injecting drug users (IDUs) has not been well described. The aim of this study was to compare long-term all-cause and liver-related mortality among anti-HCV positive IDUs with and without persisting HCV infection. METHODS: A retrospective-prospective controlled cohort design was applied. All IDUs admitted to resident drug treatment (1970-1984) and with available stored sera were screened for anti-HCV antibody. Anti-HCV positive individuals were further tested for the presence of HCV RNA. All-cause and liver-related mortality was compared between HCV RNA positive (n=328) and HCV RNA negative individuals (n=195). The observation was accomplished through register linkage to national registers. Mean observation time was 33 years. RESULTS: All-cause mortality rate was 1.85 (95% CI 1.62-2.11) per 100 person-years, male 2.11 (95% CI 1.84-2.46), female 1.39 (95% CI 1.07-1.79). Mortality rates were not influenced by persisting HCV infection. Main causes of death were intoxications (45.0%), suicide (9.1%), and accidents (8.2%). Liver disease was the cause of death in 7.5% of deaths among HCV RNA positive subjects. Five of 13 deaths among male IDUs with persisting HCV infection occurring after the age of 50 years were caused by liver disease. CONCLUSIONS: The all-cause mortality in IDUs is high and with no difference between HCV RNA positive and HCV RNA negative individuals, the first three decades after HCV transmission. However, among IDUs with chronic HCV infection who have survived until 50years of age, HCV infection emerges as the main cause of death.

[Risk factors for hepatitis C among injecting drug users in Oslo]. / Risikofaktorer for hepatitt C-smitte blant sprøytemisbrukere.

BACKGROUND: Hepatitis C virus (HCV) infection is common among injecting drug users. The aims of this study were to assess the prevalence of risk behaviour and its association with HCV infection. MATERIAL AND METHODS: All users of the needle exchange program in Oslo, within a given time period, were eligible for inclusion in this cross-sectional study; 327 chose to participate. The users were asked about type of drug use and risk behaviour for HCV exposure in a structured interview. Sera were drawn and tested for anti HCV (EIA-3) and HCV RNA (in- house PCR). RESULTS: The prevalence of HCV RNA was 51 % and 81 % had anti-HCV. A multivariate analysis revealed positive associations between anti-HCV positive status and age < 20 years at first injection, > 5 years of drug use, age > 34 years, sharing of syringes, injecting drug use while imprisoned, back-loading and use of heroin. One in five users with anti-HCV reported to never have shared syringes. However, sharing of drug paraphernalia other than needles was not associated with anti-HCV. Sharing of needles the last four weeks before the interview was more common among those living with a partner than those who lived alone. INTERPRETATION: Most injecting drug users in Oslo have been exposed to HCV (anti HCV+) and half of them have developed chronic infection (HCV RNA+). HCV was associated with back-loading and sharing of syringes - especially during incarceration. Sharing of injection paraphernalia was not associated with being anti HCV positive.

[Hepatitis C--a health problem also in Norway]. / Hepatitt C--et helseproblem også i Norge.

BACKGROUND: Hepatitis C is a large global health problem; approximately 20 - 30 000 are infected in Norway. Hepatitis C-infection is often chronic and can progress into chronic liver disease, liver cirrhosis and hepatocellular carcinoma. The most important transmission route is through percutaneous exposure to infected blood. The aim of this article is to describe the clinical course, microbiological diagnostic approaches, therapy, prophylaxis and public health aspects of Hepatitis C infection. MATERIAL AND METHODS: The paper is based on results from annual health examinations (conducted since 2001) of persons who abuse drugs intravenously in Oslo, from diagnostic work in a national reference laboratory for Hepatitis C and studies of literature (retrieved from Pubmed). RESULTS AND INTERPRETATION: The prevalence of Hepatitis C varies by country and subgroup of patients. In Norway the prevalence is 0.13 % among new blood donors, 0.7 % among pregnant women, 0.55 % in the general adult population and approximately 70 % among persons who abuse drugs intravenously. Treatment with pegylated interferon and ribavirin induces sustained virological response in 80 % of patients with genotypes 2 and 3 and in 30 - 40 % of those with genotype 1.

Molecular epidemiological studies show that hepatitis A virus is endemic among active homosexual men in Europe.

Large outbreaks of hepatitis A have occurred in Denmark, Germany, the Netherlands, Norway, Spain, Sweden, and the United Kingdom during the period 1997-2005 affecting homosexual men. A collaborative study was undertaken between these countries to determine if the strains involved in these hepatitis A outbreaks were related genetically. The N-terminal region of VP1 and the VP1/P2A region of the strains were sequenced and compared. The majority of the strains found among homosexual men from the different European countries formed a closely related cluster, named MSM1, belonging to genotype IA. Different HAV strains circulated among other risk groups in these countries during the same period, indicating that specific strains were circulating among homosexual men exclusively. Similar strains found among homosexual men from 1997 to 2005 indicate that these HAV strains have been circulating among homosexual men for a long time. The homosexual communities are probably too small within the individual countries to maintain HAV in their population over time, whereas the homosexual communities across Europe are probably sufficiently large to sustain continued circulation of homologous HAV strains for years resulting in an endemic situation among homosexual men.

Characterization and genetic variability of Hepatitis A virus genotype IIIA.

Molecular epidemiological studies of hepatitis A outbreaks in Norway showed the emergence of Hepatitis A virus (HAV) genotype IIIA in association with parenteral transmission among haemophiliacs and intravenous drug users. The complete genomic sequence of one of these outbreak isolates, NOR-21, was determined. This is the first complete genomic sequence of HAV genotype IIIA. Phylogenetic analysis showed that genotype IIIA/NOR-21 was genetically distinct from the other human and simian genotypes. Phylogenetic analysis of the nucleotide sequences clearly distinguished the different HAV genotypes, regardless of the genomic region used for analysis, whereas the amino acid sequences showed a more vague distinction between human HAV genotypes I and II. In particular, the inferred phylogeny based on the capsid proteins showed that the human HAV strains were related more closely to each other than to the simian strains. The greatest variability and clearest distinction between genotypes were observed for the polymerase gene. The outbreak isolates of HAV genotype IIIA in this study showed greater nucleotide variability than is generally seen in outbreaks of genotype I. This high nucleotide variability, which may be characteristic of this HAV genotype, the mode of transmission in this outbreak or parallel introductions, is discussed.

Reliability of the Amplicor internal control to disclose false-negative Chlamydia trachomatis PCR results.

Four possibly false-negative samples were detected when 514 male urine specimens were tested in the Amplicor Chlamydia trachomatis assay. In three of the four samples, the inhibition could be reduced by removal of urine supernatant. Under partially inhibitory conditions, after spiking with 50 C. trachomatis elementary bodies/ml specimen, a selective inhibition of the C. trachomatis target amplification and a preferential internal control amplification was observed. We conclude that a positive internal control signal might be misleading in inhibitory specimens with low amount of C. trachomatis.

Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study.

The aim of this study was to determine the efficacy of 14 weeks of treatment in patients infected with hepatitis C virus (HCV) genotype 2 or 3 who achieve early virological response (EVR). In a noncontrolled multicenter trial, 122 treatment-naive patients received 1.5 mug/kg pegylated interferon alfa-2b subcutaneously once weekly and 800 to 1,400 mg/d ribavirin based on body weight. Treatment was stopped at week 14 in patients with EVR, defined as undetectable HCV RNA at weeks 4 and 8. Patients without EVR were assigned to 24 weeks of treatment. The primary end point was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after end of treatment. Among the 122 patients, 95 (78%) had EVR and received 14 weeks of treatment. The remaining 27 (22%) were treated for 24 weeks. SVR was obtained in 85 (90%) of 95 patients in the 14-week treatment group and 15 of (56%) 27 in the 24-week treatment group. Altogether, SVR was obtained in 100 of 122 patients (82%; 95% CI, 75%-89%). SVR after 14 weeks of treatment was achieved more frequently among genotype 3a patients with low viral load compared with high viral load (98% vs. 79%; P = .019). Logistic regression analysis showed that absence of bridging fibrosis/cirrhosis was the only independent predictor of SVR. In conclusion, patients with genotype 2 or 3 and EVR obtained a high SVR after 14 weeks of treatment. The results need to be confirmed in a randomized, controlled study before this treatment approach can be recommended, particularly for patients with genotype 3 and high viral load or severe fibrosis.

Health-related quality of life in active injecting drug users with and without chronic hepatitis C virus infection.

This study assessed the effect of chronic hepatitis C virus (HCV) infection on the health-related quality of life (HRQOL) of injecting drug users, comparing the HRQOL of injecting drug users with and without chronic HCV infection. The study included 199 injecting drug users of more than 18 years of age who participated in a needle exchange program. Blood samples were tested for the presence of HCV RNA in serum with a polymerase chain reaction method. HRQOL was measured using the questionnaire SF-36, measuring HRQOL over the last 4 wk. The HCV RNA test was positive in 102 (51%) and negative in 97 (49%) subjects. The HRQOL scores of actively injecting drug users were markedly reduced compared to the population norm. However, we did not find poorer HRQOL in injecting drug users with chronic HCV infection than in injecting drug users without HCV infection. HCV RNA positive injecting drug users who were aware of the infection had lower HRQOL scores than those unaware of the infection in 4 of the 8 SF-36 dimensions (general health, physical functioning, physical role, and vitality). HCV RNA negative subjects, who believed they were infected, scored worse in one dimension (general health) compared to those who did not believe they were infected. In conclusion, chronic HCV infection per se did not negatively affect the HRQOL of active injecting drug users. Those who thought they were infected had a lower HRQOL scores than those who believed they were not infected.