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

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

Interferon-free therapy in hepatitis C virus mixed cryoglobulinaemia: a prospective, controlled, clinical and quality of life analysis

Background: Cryoglobulinaemic vasculitis (CV) is a lymphoproliferative disorder related to hepatitis C virus (HCV) infection; anti-viral therapy is the first therapeutic option. CV can be incapacitating, compromising the patients’ quality of life (QoL). In a controlled study, interferon-based therapy was associated with a lower virological response in vasculitic patients than in patients without vasculitis. Limited, uncontrolled data on direct-acting anti-virals are available. Aim: To evaluate safety, clinical efficacy, virological response and the impact of interferon-free treatment on QoL in HCV patients with and without mixed cryoglobulinaemia (MC). Methods: We prospectively studied HCV patients with cryoglobulinaemia (with vasculitis-CV- and without vasculitis-MC-) and without cryoglobulinaemia (controls), treated with direct-acting anti-virals. Hepato-virological parameters, CV clinical response and impact on QoL were assessed. Results: One hundred and eighty-two HCV patients were recruited (85 with CV, 54 with MC and 43 controls). A sustained virological response at 12 weeks (SVR12) was achieved in 166 (91.2%) patients (77/85 CV, 48/54 MC, 41/43 controls). In CV SVR patients, cryocrit levels progressively decreased and clinical response progressively improved, reaching 96.7%, 24 weeks after treatment. QoL, baseline physical and mental component summaries were lower in the CV group compared to the other groups (P < 0.05). Scores improved in all groups, and significantly in CV patients after SVR. Conclusions: No significant differences in SVR rates were recorded between cryoglobulinaemic patients and controls and a high clinical and immunological efficacy was confirmed in CV, supporting the role of interferon-free therapy as the first therapeutic option. Interestingly, CV patients had worse baseline QoL than other HCV-positive groups and interferon-free therapy was effective in significantly increasing QoL, suggesting the important role of direct-acting anti-viral-based therapy in improving CV's individual and social burden

Non-Invasive B-Cell Clonality Markers May Help in the Rational Approach to HCV Svr Cryoglobulinemic Patients with Persisting Manifestations

Background: The mixed cryoglobulinemia syndrome (MCS), a benign lymphoproliferative disorder (LPD), is the most frequent HCV extrahepatic manifestation. DAAs can improve or heal MCS, but persistence or recurrence may be observed even in SVR patients. Rituximab (RTX) is the first-choice therapy in such cases. However, MCS persistence may also be due to causes different from persisting clonal B-cell expansion (eg, the occurrence of irreversible organ/tissue damage). Consequently, the evaluation of B-cell clonal expansion is the key for a correct clinical, prognostic and therapeutic approach. Methods: We prospectively evaluated HCV patients consecutively referred to the MASVE Center, with the following features: Group A: DAA-treated SVR MCS patients with complete clinical response; Group B: DAA-treated SVR MCS patients maintaining symptoms. B-cell clonal expansion was evaluated, after DAA-therapy, by flow cytometry, Free Light Chains ratio (κ/λ) and t(14;18). Results: We evaluated 36 patients: 11 group A and 25 group B (mean FU 25.7 months, range: 36-3). B-cell clonality markers were not observed in group A patients, despite small levels of cryocrit in some cases (30%). At least one clonality marker was detected in 19/25 (76%) patients with persisting symptoms, including five patients with lymphoma, in hematological regression after DAAs. Three patients had systemic symptoms (e.g. itchiness, nocturnal sweating) suggestive of the evolution the LPD. The remaining patients, negative for B-cell clonality, were generally characterized by persisting arthralgia, sicca syndrome, and neuropathy. κ/λ ratio was altered in 74 % of cases, flow cytometry in 24% and t(14;18) in 30%. In 20% of cases more than a marker was detected. Conclusion: Previous studies showed the association between MCS and B-cell clonal expansion. In this study, whereas subjects with a complete clinical response did not have clonality markers, the majority of patients who maintained vasculitis symptoms did. Interestingly, clonality markers were associated with more severe pre-therapy vasculitis, including patients with lymphoma in remission. This suggests the hypothesis of having gone beyond the LPD point of no return and the rationale for RTX treatment. Furthermore, this study suggests that the κ/λ ratio, may be a very useful and easy marker in MCS patients with persisting symptoms, in the light of a more rational clinical and therapeutic approach to these patients