Circulating protein biomarkers in systemic sclerosis related pulmonary arterial hypertension: a review of published data

Pulmonary arterial hypertension (PAH) develops in 7-12% of patients with systemic sclerosis (SSc) and is associated with a 3 year survival of 52%. Early detection by screening is therefore recommended for all patients with SSc. Historically, screening has been performed using echocardiography and measurement of gas transfer. More recently the DETECT protocol, using a combination of biomarkers (including N-terminal pro-brain natriuretic peptide) and clinical parameters, has been developed. The optimal method of screening for PAH with high sensitivity and specificity is, however, not clear. Protein expression differences between different SSc disease phenotypes have been reported, and include alterations in concentration of NT-proBNP, endoglin, soluble vascular endothelial growth factor receptor 1, placenta growth factor, growth differentiation factor-15, vascular endothelial growth factor alpha, resistin-like molecule beta, and soluble thrombomodulin. This review summarizes the current knowledge of these protein changes in patients with SSc and PAH

Expert opinion on managing chronic HCV in patients with mixed cryoglobulinaemia vasculitis

International audienceMixed cryoglobulinaemia vasculitis (CryoVas) is a small-vessel systemic vasculitis caused by deposition of mixed cryoglobulins and is characterized by a wide range of clinical symptoms. HCV is the primary cause of CryoVas, which is associated with significant morbidity and mortality. The mortality rate among patients with HCV-associated CryoVas is 3× that of the general population, with a 63% 10-year survival rate. First-line treatment for CryoVas is anti-HCV therapy because viral clearance is associated with clinical improvement. The introduction of highly effective, interferon-free, direct-acting antiviral regimens provides additional treatment options for these patients. Here, we review recent studies investigating the effect of antiviral therapy on HCV-associated CryoVas and provide expert opinion for health-care professionals managing these patients

Quantifying hope: an EU perspective of rare disease therapeutic space and market dynamics

Rare diseases, affecting millions globally, pose a significant healthcare burden despite impacting a small population. While approximately 70% of all rare diseases are genetic and often begin in childhood, diagnosis remains slow and only 5% have approved treatments. The UN emphasizes improved access to primary care (diagnostic and potentially therapeutic) for these patients and their families. Next-generation sequencing (NGS) offers hope for earlier and more accurate diagnoses, potentially leading to preventative measures and targeted therapies. In here, we explore the therapeutic landscape for rare diseases, analyzing drugs in development and those already approved by the European Medicines Agency (EMA). We differentiate between orphan drugs with market exclusivity and repurposed existing drugs, both crucial for patients. By analyzing market size, segmentation, and publicly available data, this comprehensive study aims to pave the way for improved understanding of the treatment landscape and a wider knowledge accessibility for rare disease patients

Direct medical costs associated with the extrahepatic manifestations of hepatitis C infection in Europe

Hepatitis C virus (HCV) infection is a systemic disease associated with both hepatic and extrahepatic manifestations. The burden associated with the hepatic manifestation of HCV infection has been well documented in Europe, although that of HCV extrahepatic manifestations remains unknown. In this study, we estimated the annual direct medical costs associated with HCV extrahepatic manifestations in five European countries. A previously validated economic model was used to estimate the annual direct medical cost associated with HCV extrahepatic manifestations. Global excess prevalence of extrahepatic manifestations in HCV patients relative to that in non-HCV patients was obtained from a recent meta-analysis. Per-patient per-year inpatient, outpatient and medication costs to treat each extrahepatic manifestation were from the literature, national databases or expert opinion if unavailable otherwise. All costs were adjusted to 2016 euros (€). The overall direct medical costs associated with HCV extrahepatic manifestations were calculated by multiplying the total per-patient per-year costs of each by the respective excess prevalence rates and then by the size of the HCV-infected population in each country. Treatment impact with direct-acting antivirals (DAAs) was explored using HCV extrahepatic manifestations excess prevalence rates among cured patients compared to untreated HCV patients, as sourced from a meta-analysis. The total annual direct medical cost associated with HCV extrahepatic manifestations was estimated to be 2.17 billion euro (€), with a per-HCV-patient cost ranging from €899 to €1647 annually. DAA treatment was projected to result in cost savings of €316 million per year. We find that the annual economic burden of extrahepatic manifestations is significant and may be partly mitigated by treatment with DAAs

Meta-analyses of FibroTest diagnostic value in chronic liver disease

<p>Abstract</p> <p>Background</p> <p>FibroTest (FT) is a biomarker of liver fibrosis initially validated in patients with chronic hepatitis C (CHC).</p> <p>The aim was to test two hypotheses, one, that the FT diagnostic value was similar in the three other frequent fibrotic diseases: chronic hepatitis B (CHB), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD); and the other, that the FT diagnostic value was similar for intermediate and extreme fibrosis stages.</p> <p>Methods</p> <p>The main end points were the FT area under the ROC curves (AUROCs) for the diagnosis of bridging fibrosis (F2F3F4 vs. F0F1), standardized for the spectrum of fibrosis stages, and the comparison of FT AUROCs between adjacent stages. Two meta-analyses were performed: one combining all the published studies (random model), and one of an integrated data base combining individual data. Sensitivity analysis integrated the independency of authors, lenght of biopsy, prospective design, respect of procedures, comorbidities, and duration between biopsy and serum sampling.</p> <p>Results</p> <p>A total of 30 studies were included which pooled 6,378 subjects with both FT and biopsy (3,501 HCV, 1,457 HBV, 267 NAFLD, 429 ALD, and 724 mixed). Individual data were analyzed in 3,282 patients. The mean standardized AUROC was 0.84 (95% CI, 0.83–0.86), without differences between causes of liver disease: HCV 0.85 (0.82–0.87), HBV 0.80 (0.77–0.84), NAFLD 0.84 (0.76–0.92), ALD 0.86 (0.80–0.92), mixed 0.85 (0.80–0.93). The AUROC for the diagnosis of the intermediate adjacent stages F2 vs. F1 (0.66; 0.63–0.68, n = 2,055) did not differ from that of the extreme stages F3 vs. F4 (0.69; 0.65–0.72, n = 817) or F1 vs. F0 (0.62; 0.59–0.65, n = 1788).</p> <p>Conclusion</p> <p>FibroTest is an effective alternative to biopsy in patients with chronic hepatitis C and B, ALD and NAFLD. The FT diagnostic value is similar for the diagnosis of intermediate and extreme fibrosis stages.</p