Implementing non-invasive markers for liver fibrosis in clinical practice

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Interpreting liver stiffness in the cirrhotic range: What are we measuring?

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Hepatic steatosis in hepatitis C is a storage disease due to HCV interaction with microsomal triglyceride transfer protein (MTP)

Liver steatosis is a frequent histological feature in patients chronically infected with hepatitis C virus (HCV). The relationship between HCV and hepatic steatosis seems to be the result of both epigenetic and genetic factors. In vivo and in vitro studies have shown that HCV can alter intrahepatic lipid metabolism by affecting lipid synthesis, oxidative stress, lipid peroxidation, insulin resistance and the assembly and secretion of VLDL. Many studies suggest that HCV-related steatosis might be the result of a direct interaction between the virus and MTP. It has been demonstrated that MTP is critical for the secretion of HCV particles and that inhibition of its lipid transfer activity reduces HCV production. However, higher degrees of hepatic steatosis were found in chronic hepatitis C patients carrying the T allele of MTP -493G/T polymorphism that seems to be associated with increased MTP transcription. We propose here that liver steatosis in hepatitis C could be a storage disease induced by the effects of the virus and of its proteins on the intracellular lipid machinery and on MTP. Available data support the hypothesis that HCV may modulate MTP expression and activity through a number of mechanisms such as inhibition of its activity and transcriptional control. Initial up regulation could favour propagation of HCV while down regulation in chronic phase could cause impairment of triglyceride secretion and excessive lipid accumulation, with abnormal lipid droplets facilitating the "storage" of virus particles for persistent infection

Fine structure of the male genital systems, spermatophores and unusual sperm cells of saxidromidae (Acari, Actinotrichida)

The early derivative actinedid Saxidromidae, Saxidromus delamarei, Bovidromus roussouwi, and Rhinodromus lootsi perform indirect spermatophore transfer by means of a peculiar mating behaviour. The anatomy and fine structure of the male genital systems are described and are shown to exhibit the organisation considered to be fundamental in Actinotrichida: paired testes with germinal and glandular parts, paired vasa deferentia, unpaired ejaculatory duct, progenital chamber containing genital papillae. The genital system is located ventral of the digestive tract. The testes produce relatively few or even very few aflagellate sperm cells, which represent synspermia consisting of likely four undivided sperm cell equivalents in a common cytoplasm. Whereas S. delamarei produces a rather large stalked spermatophore containing many synspermia, both the other species produce very tiny stalked spermatophores with a spherical head representing only one synspermium. Thus, in these latter species only one synspermium is transferred to the female at atime, but the male can convey several (possibly five or more) spermatophores to the female during the mating session. A scenario is suggested which could describe the evolution of this remarkable mating system and behaviour.Fil: Alberti, Gerd. ERNST MORITZ ARNDT UNIVERSITÄT GREIFSWALD (UG);Fil: Coineau, Yves. Muséum National d'Histoire Naturelle; FranciaFil: Fernández, Néstor Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Pampa. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Théron, Pieter D.. North-West University; Sudáfric

Budget impact analysis of the use of daclatasvir in Italy for the treatment of Hepatitis C Virus (HCV) genotype 3 patients

BACKGROUND: Hepatitis C Virus (HCV) infection represents a global health problem, leading to chronic cirrhosis, hepatocellular carcinoma (HCC), hepatic decompensation and liver transplant. The aim of the study was the evaluation of the impact on the budget of the Italian National Health Service (INHS) of the use of Daclatasvir (DCV) for the treatment of HCV genotype 3 in patients with advanced fibrosis.METHODS: An analytical decision model with a five year time horizon was implemented. Two scenarios were considered: a. 100% of market share for Interferon (INF-α)+Ribavirin (RBV)+Sofosbuvir (SOF) for 12 weeks; b. SOF+DCV+RBV for 24 weeks with annual market shares of 50% in 2015 and 2016, 55% in 2017 and 2018, 60% in 2019, and INF-α+RBV+SOF for 12 weeks with the remaining market shares. Every annual cycle a percentage of patients equal to the effectiveness of the antiviral treatment reach a sustained virologic response and during the first year of treatment patients may experience treatment related adverse events. The costs considered (2015) are those of the antiviral therapy, and direct medical costs for health state and adverse events management. Univariate and multivariate sensitivity analyses were performed.RESULTS: DCV would lead to an increase of the costs for the INHS (year 1 +21.31 millions, year 2 +21.35 millions, year 3 + 23.37 millions, year 4 + 23.26 millions and year 5 +16.37 millions). The sensitivity analysis confirmed the robustness of the results.CONCLUSIONS: The use of DCV is likely to have a short term impact on the INHS budget increasing resources use compared to the sole use of INF-α+RBV+SOF. However, a trend of reduction of the costs increase is observed due to the management of health states and adverse events which may lead to the possibility to reduce costs in the long term

Treatment and outcome of metastatic parathyroid carcinoma: A systematic review and pooled analysis of published cases

Parathyroid carcinoma (PC) is an extremely rare malignant tumor with an incidence of about 6 new cases per 10 million inhabitants per year. While several papers have been published on treatments and outcomes of PC patients with loco-regional disease, little is known about the prognosis, treatment strategies, and prognostic factors of patients with distant metastasis

optimizing patient referral and center capacity in the management of chronic hepatitis c lessons from the italian experience

Abstract Aims In 2017 the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) revised the criteria for access to therapy for patients with chronic hepatitis C as part of a three-year plan to eradicate HCV. We conducted a Delphi study to determine strategies to identify and treat patients with HCV and to develop through a shared pathway, a model to manage patient referral and optimize prescription center capacity with the overall aim of increasing access to therapy. Methods The process took place in two phases – Phase I (January 2017), before the criteria for treatment of HCV were revised and Phase II (May 2017) when AIFA developed a framework for the eradication of HCV infection in Italy. Two questionnaires were devised with Q1 administered in Phase I and Q2 in Phase II. Results Q1 was sent to 823 hepatitis specialists working in 235 Italian HCV centers authorized to prescribe direct-acting antiviral drugs (DAAs). Overall, 167 centers (71%) participated with a good geographical representativeness (North 69%, Centre 74%; South and islands 70%). 548 prescribers (68.8%) provided responses to Q1 and 443 (80%) specialists who responded to Q1 completed Q2. Over 70% considered that to meet the new therapy targets local/regional networks need to be consolidated and reinforced with GPs providing the 'missing link' in current regional networks. Adherence to therapy was considered important by 75% of clinicians with reduction in follow-up intervals/length considered important by 65% – to free up staff/resources to manage increasing numbers of new patients. About 80% of respondents stated that medical personnel were principally involved in follow-up with follow-up having a significant impact on center capacity. Conclusion Enhancing patient referral, the need for an increased role of GPs, increasing center capacity in particular medical personnel in outpatient centers and greater liaison between Hub centers and healthcare professionals currently managing high-risk groups as yet untreated, were factors that need to be streamlined in order to meet treatment targets for eradication of HCV

position paper per un programma di eliminazione della epatite c nella popolazione a rischio dei consumatori di sostanze e dei detenuti

The data recently published in scientific literature identify in substance abuse the most important risk factor for the transmission of HCV. Another population at risk is represented by detainees, mainly because most of them have a history of substance use. Treatment of the population at risk (substance users and detainees) must become a priority for health systems both to ensure fairness of access to care and to achieve the public health goal of eliminating HCV. The programs to take charge should be multi-disciplinary, flexible, tailored, evidence-based, disseminated homogeneously throughout the national territory, and supported by procedures and guidelines including harm reduction actions, as suggested by the WHO

Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

Background:Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods: Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log 10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results: We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion: LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients

Therapeutic Value and Innovation of a Drug and Criteria for Evaluation: A Multidisciplinary Experience in the Veneto Region

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