Kjell Skaug

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 μg/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. (HEPATOLOGY 2004;40: 1260–1265.)

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-α 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.

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. (HEPATOLOGY 2004;39:74–80.)

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. J. Med. Virol. 53:69–75, 1997.

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.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 r < r 0.001). It was also higher among smokers compared to non-smokers (2.0% versus 0.2%, P r < r 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.

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.

Hepatitis C Virus (HCV) RNA among Anti-HCV-Positive Blood Donors and Their Recipients

Seven of 24 blood donors positive in Orthos first‐generation antibody to hepatitis C virus (anti‐HCV) test (EIA‐1) were also positive in Orthos 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 Willebrands 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 Waldenstroems hypergammaglobulinemia was EIA‐2 negative but HCV‐PCR positive. All the EIA‐2‐positive sera showed reactivity in Orthos 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.

Hepatitis B virus‐infected peripheral blood progenitor cell harvests in liquid nitrogen freezer containing non‐infectious products

In 1995 Tedder and coworkers 1 reported five cases of HBV infections in patients receiving bone marrow stored in a HBV-contaminated liquid nitrogen freezer. The freezer was contaminated by leakage of HBV-containing material suspended in the liquid nitrogen , and intact bags were probably contaminated on the outer surface. The authors recommended mandatory virus testing before storage of cell suspension in the freezer and storage of products in double bags in the gas phase of nitrogen. In 1997, another publication showed potential microbial contamination of bags from a contaminated liquid nitrogen freezer. 2

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.