Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

To access publisher's full text version of this article click on the hyperlink belowAll-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.UNSW (Sydney, Australia) CanHepC Trainee Program (Canada) National Health and Medical Research Council Australian Government Department of Healt

Impact of the Uridine–Cytidine Kinase Like-1 Protein and IL28B rs12979860 and rs8099917 SNPs on the Development of Hepatocellular Carcinoma in Cirrhotic Chronic Hepatitis C Patients—A Pilot Study

Background and objectives: The hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma (HCC) in the western world. The efficacy of surveillance programs for early detection of HCC is not satisfactory: many tumors are diagnosed at the late, incurable stages. Therefore, there is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine–cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. Materials and Methods: We included 32 HCV cirrhotic patients, 21 (65.6%) of whom had HCC. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry. For IL28B rs12979860 and rs8099917 genotype analysis, the corresponding genomic regions were amplified by polymerase chain reaction (PCR) with appropriate primers. Results: We have found that UCKL-1 expression was significantly increased in HCC (p = 0.003). The presence of rs8099917 TT single-nucleotide polymorphism (SNP) elevated the chances of HCC manifestation more than sevenfold (OR = 7.3, p = 0.0273). The presence of rs12979860 CC SNP also heightened HCC chances more than sevenfold (OR = 7.5, p = 0.0765). Moreover, in the HCC group, a combination of IL28B rs12979860 non-TT and rs8099917 TT genotypes was observed more often, compared with the non-HCC group. Other combinations of IL28B rs12979860 and rs8099917 SNIPs were associated with a reduced risk of HCC development, approximately at the same extent. Conclusions: The presence of IL28B rs8099917 TT and rs12979860 CC SNPs, but not the intensity of UCKL-1 expression, is strongly associated with increased chances of HCC development in HCV-positive cirrhotic patients.This research was funded by Research Council of Lithuania, grant number TAP LU-1/2016

Estimate of vertical transmission of Hepatitis C virus in Pakistan in 2007 and 2012 birth cohorts.

Despite a combination of high Hepatitis C virus (HCV) prevalence, a large adult population and high fertility, no published estimates of the scale and contribution of vertical transmission to HCV incidence in Pakistan exist. The objective of this study was to estimate the number of new HCV infections occurring in Pakistan as a result of vertical transmission. We adapted a published mathematical model based on HCV antibody and viraemia prevalence, fertility rates, risk of HCV vertical transmission and children mortality rates to estimate the number of infections in the 2007 and 2012 birth cohorts nationally and in four subnational regions. We estimated that 19 708 (95% uncertainty interval [UI]: 15 941-23 819) children were vertically infected by HCV in 2007 and 21 676 (95% UI: 17 498-26 126) in 2012. The majority of these cases (72.9% and 72.5% in 2007 and 2012, respectively) occurred in Punjab. We estimated that vertical transmission as a mode of exposure accounted for a quarter of HCV infections among children under 5 years of age (25.2% in 2007 and 24.0% in 2012). CONCLUSION: Our results showed that one in 260 children born in Pakistan in 2007 and 2012 acquired HCV vertically. While currently no interventions during pregnancy and childbirth are recommended to reduce this risk, prevention, testing and treatment strategies should be considered to reduce the burden of vertical HCV infections among young children. Other routes of transmission appear to contribute the majority of HCV infections among children and must also be clarified and urgently addressed

Estimate of vertical transmission of Hepatitis C virus in Pakistan in 2007 and 2012 birth cohorts.

Despite a combination of high Hepatitis C virus (HCV) prevalence, a large adult population and high fertility, no published estimates of the scale and contribution of vertical transmission to HCV incidence in Pakistan exist. The objective of this study was to estimate the number of new HCV infections occurring in Pakistan as a result of vertical transmission. We adapted a published mathematical model based on HCV antibody and viraemia prevalence, fertility rates, risk of HCV vertical transmission and children mortality rates to estimate the number of infections in the 2007 and 2012 birth cohorts nationally and in four subnational regions. We estimated that 19 708 (95% uncertainty interval [UI]: 15 941-23 819) children were vertically infected by HCV in 2007 and 21 676 (95% UI: 17 498-26 126) in 2012. The majority of these cases (72.9% and 72.5% in 2007 and 2012, respectively) occurred in Punjab. We estimated that vertical transmission as a mode of exposure accounted for a quarter of HCV infections among children under 5 years of age (25.2% in 2007 and 24.0% in 2012). CONCLUSION: Our results showed that one in 260 children born in Pakistan in 2007 and 2012 acquired HCV vertically. While currently no interventions during pregnancy and childbirth are recommended to reduce this risk, prevention, testing and treatment strategies should be considered to reduce the burden of vertical HCV infections among young children. Other routes of transmission appear to contribute the majority of HCV infections among children and must also be clarified and urgently addressed

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist