Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV

The World Health Organization foresees the elimination of HCV infection by 2030. In light of this and the curre nt, nearly worldwide, restriction in direct-acting agents (DAA) accessibility due to their high price, we aimed to evaluate the cost-effectiveness of two alternative DAA treatment policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori tized patients and delay treatment of the remaining patients until reaching stage F3. T he model was based on patient’s data from the PITER cohort. We demonstrated that extending HC V treatment of patients in any fibrosis stage improves health outcomes and is cost-effective

Prevalence and clinical relevance of Blastocystis hominis in diverse patient cohorts.

The pathogenicity of Blastocystis hominis is extensively debated in the medical literature. Therefore, we did a prevalence study to investigate the association between the presence of several intestinal parasites and gastrointestinal symptoms in diverse patient cohorts. The study population consisted of 1216 adults, including immunocompromised patients, institutionalized psychiatric or elder subjects, immigrants from developing countries, travellers to developing tropical countries and controls. Several variables for each risk group were considered. Stools specimens, collected in triplicate, were processed by the same technicians. Clinical data about each subject were provided by standardized questionnaires. The presence of gastrointestinal symptoms were related to the presence of any parasite. In addition, on the basis of microbiological results, five subgroups of subjects were evaluated. The results showed a high prevalence of parasites in all the risk groups. Immunocompromised status, recent arrival from developing countries and the presence of behavioural aberrations were significantly related to presence of parasites. B. hominis was the parasite most frequently detected in each studied group. B. hominis showed a significant correlation with gastrointestinal symptoms only when detected in the group including subjects with a severe immunodepression. Immunodepression seems to be a factor of primary importance of the pathogenic role of B. hominis

La giardiasi: una parassitosi di continua attualità. Indagine tra una selezionata popolazione adulta

We studied the prevalence of Giardia intestinalis in five patients risk groups including institutionalised psychiatric of elderly subjects, HIV-positive immunocompromised patients, immigrants from developing countries and travellers to tropical countries. Stool specimens of 1319 subjects were studied. Stools were collected in triplicate from each subject. The presence of bacteria, viruses and parasites was evaluated. A direct smear examination from fresh faecal specimens and after concentration with formalin-ethylacetate was performed for parasite examination. Smears were also stained by a modified acid fast method and then examined for the presence of Cryptosporidium spp. and other coccidia. Cryptosporidium parvum and G. intestinalis were also detected by immunofluorescent assay. Contemporaneously a microbiological investigation was performed with standard culture, biochemical techniques and viral detection. Clinical data about each subject were provided by standardised questionnaires. G. intestinalis was detected in the stools of 41 subjects (3.5%). The immigrants (5.5%), the institutionalised psychiatric patients (5.0%) and HIV immunocompromised patients (4.6%) showed the highest prevalence. By contrast, travellers showed the lowest prevalence (2.5%). G. intestinalis was the pathogen most frequently detected. The cohorts with the presence of more risk factors showed the highest prevalence. The low prevalence of the parasite among travellers demonstrated the significance of health education before travelling and of the most important role of bacterial etiopathogenesis in "traveller's diarrhoea". Epidemiologically, G. intestinalis remains a protozoon of evident importance and is significantly present in Italy

Therapy with immunoglobulin of the HIV infection related idiopathic thrombocytopenia.

The Authors report that in their experience in the therapy of HIV infection related thrombocytopenia with IG at the classic dose of 0.4 gr/Kg/day x 5 days. Moreover they report their experience in a patient with repeated single-dose infusions at low dosage. They treated four patients, who were drug-addicts, with HIV infection thrombocytopenia that didn't exceed 50,000/mm3. Anti-platelets antibodies tested with an indirect method weren't found in any of the patients examined. Among those patients three were of Group III CDC and one of Group IV C1 CDC. Among the first group the best results were obtained in two patients with the immunocompromission of average seriousness but one of these had a rapid decrease in platelets count. In the others where results were low a severe immunocompromission was apparent and probably a severe damaged Reticulo Endothelial System (RES) function. So the AA think that function of RES may be important in the forecast of clinical response. The Authors conclude moreover that good results were obtained with a single-dose infusion at low dosage even if they observed a progressive decrease of response. They propose such a therapy if there isn't an emergency after tested RES functio

[Prevalence of Toxocara spp in public playgrounds in a town of Central Italy]

In this study, the prevalence of Toxocara spp. was evaluated in the soil of 22 public playgrounds of Ancona (Italy). The public playgrounds were selected according to the different areal distribution (centre, low-lying areas centre, hilly areas suburbs) within the urban area of Ancona, central Italy. In six playgrounds there were signs restricting access for dogs; all of them were frequented by children. Parasites were found in the soil samples from 21 out of 22 playgrounds (95.5%). The most prevalent helminth found was Toxocara canis, the common roundworm of dogs. It was detected in the soil samples from 12 (54.5%) playgrounds. This study showed a low frequency of the other parasites. Our data highlight the need for improved knowledge of the relationship between humans and stray animals. Indeed several zooparasites have a role in the etiopathogenesis of common human diseases. The high environmental contamination frequency found underlines the necessity of prompt preventive public health measures, such as control of stray animals, treatment of infected pets and hygiene education of the population to increase awareness of potential zoonotic hazards