The role of chemokines in chronic hepatitis C virus (HCV) infection is not fully understood. The present study aimed to characterize the baseline serum concentrations and the initial β-chemokine response to treatment with interferon-α and ribavirin with respect to the final clinical outcome of virological response to treatment. Serum concentrations of alanine aminotransferase (ALT) and of the CC subfamily chemokines [macrophage inflammatory protein (MIP)-1α, MIP-1β, monocyte chemoattractant protein (MCP)-1 and the regulated on activation, normal T expressed and secreted (RANTES) chemokine] were measured in patients with chronic HCV infection and in healthy individuals. Necroinflammation and fibrosis were scored in liver biopsies. Treatment outcomes were classified as with or without a sustained virological response after a full-course treatment according to the genotypes. The main treatment group consisted of 72 patients with chronic hepatitis C, whereas 24-h blood samples were available for 42 patients. Increased baseline levels of all CC chemokines were found in the two responder groups compared to the healthy controls, although significant levels were reached only for MIP-1α and MCP-1. No correlation was observed between chemokine levels and serum ALT levels, any histological necroinflammatory parameters, or the fibrosis grade. After 24 h of treatment, increases in MIP-1α, MIP-1β and RANTES levels were exclusively observed in the group with sustained virological response. MCP-1 was also significantly increased after 24 h in both responder groups, although no differences were observed between the two responder groups. In conclusion, an early MIP-1α, MIP-1β, and RANTES response may predict a sustained response to virological treatment.

Knowledge of the natural course and especially the total and cause-specific mortality of community-acquired chronic HCV infection is limited. The aims of our study were to determine the total and cause-specific mortality in patients infected with chronic hepatitis C in a community-based setting in northern Norway. This prospective cohort study included 1010 HCV-positive patients diagnosed with recombinant immunoblot assay between 1 January 1990 and 1 January 2000, with a median observation time from diagnosis to follow-up of 7 years. Data were collected from medical records in the period between 1 January 2004 and 30 June 2006. Time and cause of death were ascertained from the Norwegian Causes of Death Register. Age-adjusted death rates and standardised mortality ratios (SMRs) were compared with those of the general Norwegian population. In total, 122 deaths were recorded. The Kaplan-Meier estimate of survival was 88% at 14 years. The SMR in the cohort relative to the general population was 6.66. Most of the excess deaths in both genders were because of liver-related causes, those associated with a drug-using lifestyle and suicide. The statistically significant increase in SMRs ranged from 4.2 for death by cancer in women to 64.6 for liver disease in women. There was no statistically significant increase in SMRs from cardiovascular disease in either gender or from cancer in men. In conclusion, our study shows that the death rate in patients infected with hepatitis C is 6.66 times higher than in the general Norwegian population.

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 ¼ 130) was tailored to baseline resistancefindings 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 ¼ 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 ¼ .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.

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.