Cytokines in hepatitis C-infected patients with or without opioid maintenance therapy.

OBJECTIVE: Both chronic hepatitis C virus (HCV) infection and opioids cause altered blood levels of cytokines. Previous studies have investigated levels of selected groups of cytokines in patients on opioid maintenance treatment. Little is known about the levels of multiple cytokines in patients with chronic HCV infection on opioid maintenance treatment. Our aim was to investigate the cytokine profile in patients with active HCV infection with and without opioid maintenance treatment. METHODS: We conducted a cross-sectional study in an out-patients population included upon referral for antiviral hepatitis C infection treatment. The level of 27 cytokines was measured in serum using multiplex technology. Patients were interviewed using a modified version of the European addiction severity index. Data pertaining to weight, height, current medication, smoking habits, allergies, previous medical history and ongoing withdrawal symptoms were collected. Non-parametric testing was used to investigate differences in levels of cytokines between the two groups. A 3-model hierarchical regression analysis was used to analyse associations between cytokines and confounding variables. RESULTS: Out of 120 included patients, 53 were on opioid maintenance treatment. Median duration of opioid treatment was 68.4 months. There were no demographical differences between the two groups other than age. IL-1ß was lower and eotaxin-1 higher in the group on opioid maintenance treatment than in the non-opioid group. No other inter-group differences in the remaining cytokine levels were found. CONCLUSION: In HCV infection patients, the impact of chronic opioid administration on peripheral circulating cytokine level is minimal.

Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway.

Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5-10%) at baseline in direct-acting antiviral agents (DAA) treatment-naïve genotype (GT) 3a patients when studied by the population-sequencing method (cut-off 20%). This RAS may impair HCV DAA treatment response, since it possesses a high fold in vitro resistance to daclatasvir (DCV) and velpatasvir (VEL) in GT 3. We investigated the effect of baseline Y93H in patients with GT 3a infection on treatment outcome, with or without resistance-based DAA-treatment during 2014-2017. Patients/Methods: Treatment in the intervention group (n = 130) was tailored to baseline resistance-findings by population-sequencing method. Detection of baseline Y93H above 20% prompted a prolonged treatment duration of NS5A-inhibitor and sofosbuvir (SOF) and/or addition of ribavirin (RBV). Patients without baseline Y93H in the intervention group and all patients in the control group (n = 78) received recommended standard DAA-treatment. Results: A higher sustained virologic response rate (SVR) in the intervention group was shown compared to the control group at 95.4% (124/130) and 88.5% (69/78), respectively (p = .06). All five patients with baseline Y93H in the intervention group achieved SVR with personalised treatment based on results from resistance testing; either with the addition of RBV or prolonged treatment duration (24w). In the control group, 2/4 patients with Y93H at baseline treated with ledipasvir/SOF/RBV or DCV/SOF without RBV, failed treatment. Conclusion: The results from this real-life study are in accordance with the findings of the randomised controlled trials in 2015 and the EASL-guidelines of 2016, thus, baseline Y93H impacts on DCV and VEL treatment outcome.

Clinical outcomes in a prospective study of community-acquired hepatitis C virus infection in Northern Norway.

OBJECTIVE: Knowledge on the natural course of the morbidity of unselected community-acquired hepatitis C virus (HCV) infection is limited. The aim of our study was to characterize the clinical outcomes of both hepatic and extrahepatic morbidity in patients infected with HCV in a community-based setting in Northern Norway. MATERIAL AND METHODS: This prospective cohort study included 1010 HCV-positive patients diagnosed by recombinant immunoblot assay (RIBA), between 1 January 1990 and 1 January 2000. Questionnaires were sent to those physicians in Northern Norway who had requested the RIBA tests during the relevant period. Data were collected from medical records in the period between 1 January 2004 and 30 June 2006. Access to confidential information was obtained from the Norwegian Directorate of Health. RESULTS: Median age at follow-up was 39 and 41 years in females and males, respectively. In patients with positive HCV RNA status following results were found: Alanine aminotransferase was elevated in 27.4%, decompensated liver disease in 2.9% and hepatocellular carcinoma in 0.4%. Median observation period from estimated acquisition of the disease to follow-up in these patients was 26 years. Depression was reported in 10.7% of chronic infected subjects. Renal failure caused by membranoproliferative glomerulonephritis occurred in 0.2%. CONCLUSIONS: In an unselected HCV-RNA positive population severe liver disease developed in a sub-group of patients. These observations suggest that chronic HCV disease in relatively young subjects may cause a substantial burden on the health system in the future.

Prevalences of viremic hepatitis C and viremic hepatitis B in pregnant women in Northern Norway.

BACKGROUND/AIMS: No data exist for current infections of hepatitis C and hepatitis B virus in pregnant women in Northern Norway. The aim of this study was to determine the prevalences of viremic hepatitis C and hepatitis B of pregnant women in Northern Norway. A cross-sectional, multi-center study with participation of all hospitals and delivery rooms in this region was performed. METHODOLOGY: All pregnant women who consecutively underwent ultrasound screening in 17th - 19th weeks of pregnancy during the period between October 2003 and October 2004 were invited to participate in the study. On the day of ultrasonography venous blood samples were collected for analysis of serum for antibody to hepatitis C virus, hepatitis C virus ribonucleicacid, recombinant immunoblot assay, hepatitis B surface antigen, antibody to hepatitis B surface antigen and antibody to hepatitis B core antigen. RESULTS: Out of 4087 eligible pregnant women 1668 (41%) were included in the study. The prevalences of viremic hepatitis C (hepatitis C virus ribonucleicacid positive) and viremic hepatitis B (hepatitis B surface antigen positive) were 0.2% (95% CI 0.0 - 0.5) and 0.1% (95% CI 0.0 - 0.3) respectively. CONCLUSIONS: The prevalences of viremic hepatitis C and hepatitis B in pregnancy in Northern Norway were low.

"Test, score and scope": a selection strategy for safe reduction of upper gastrointestinal endoscopies in young dyspeptic patients referred from primary care.

OBJECTIVE: To test the ability of pre-endoscopic clinical evaluation to predict clinically relevant findings of upper gastrointestinal endoscopy. MATERIAL AND METHODS: Patients (341) who had been referred to upper gastrointestinal endoscopy for further evaluation of dyspeptic symptoms were included in this prospective, single-blinded study. Prior to endoscopy, the patients underwent a standardized clinical evaluation consisting of 1) a symptom questionnaire, 2) serological testing for Helicobacter pylori antibody and 3) determination of blood hemoglobin. Based upon this evaluation, patients were assigned to one of three defined risk groups. Group A comprised patients with known risk factors for diseases that would require further therapeutic or diagnostic management. Patients in groups B and C had no such risk factors. Patients in group C had heartburn or regurgitation as a predominant symptom, whereas patients in group B did not. The prevalence of clinically relevant findings upon upper endoscopy was then compared for these three groups. RESULTS: The prevalence of clinically relevant endoscopic findings in risk groups A, B and C were 20.1, 2.4 and 1.6%, respectively (p<0.01 for both A versus B and A versus C). Furthermore, 89% of those with clinically relevant endoscopic findings belonged to group A, which comprised a total of 45% of the patients studied. In groups B and C, the prevalence of disease was similar to the area-specific prevalence in the general population without dyspeptic symptoms. CONCLUSIONS: By using a simple standardized questionnaire, H. pylori serology and a hemoglobin reading in the evaluation of dyspeptic patients under 45 years of age, the need for endoscopy can be reduced by 55%.

[Hepatitis C in Northern Norway--an 8-year material]. / Hepatitt C i nord-Norge--et åtteårsmateriale.

BACKGROUND: In 1992 a screening and medical follow-up programme of patients with hepatitis C was established in northern Norway. We report the data from the eight-year observation period. MATERIAL AND METHODS: Patients with positive recombinant immunoblot assay (RIBA) confirmation tests of hepatitis C from the counties of Nordland, Troms and Finnmark were referred from primary care. RESULTS: At the end of 1999, 1,132 RIBA positive hepatitis C patients were registered, giving an estimated prevalence of 0.24%. 236 patients were included in the follow-up study. 75% were between 17 and 39 years of age. Drug abuse was the mode of transmission in 67%. Mean age by the time of transmission was 23 years (range 12-63 years). 103 patients were treated; 136 patients did not fulfill the criteria for treatment. At the time of inclusion, 76% had no clinical symptoms. 36% treated with monotherapy and 47% treated with combination therapy had no detectable virus six months after end of treatment. INTERPRETATION: Hepatitis C infection is a disease among young people; intravenous drug abuse is the most frequent mode of transmission. The initial phase of the disease has few symptoms. A hepatitis C programme run by public health authorities is highly recommended.