5 research outputs found
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Differential induction of P-glycoprotein and MRP by rifamycins in T lymphocytes from HIV-1/tuberculosis co-infected patients
Real-world outcomes in patients with chronic hepatitis C: primary results of the PROBE study.
BackgroundThis large prospective multicentre cohort study aimed to improve knowledge of therapy for chronic hepatitis C (CHC) in real clinical practice.MethodsA diverse population of adults with CHC including patients with comorbid conditions, laboratory abnormalities and demographic features [comorbidities or special populations (CSP)] who were under-represented or excluded from peginterferon registration studies was treated with peginterferon -2a (40 kDa) or -2b (12 kDa) plus ribavirin at the investigator's discretion.ResultsDuring the study, 5399 treatment-naive patients [2527 (46.8%) with CSP] received peginterferon -2a (n=3513, 65.1%) or peginterferon -2b (n=1886, 34.9%). The sustained virological response rate was 56.6% (3057/5399) overall, 59.7% (1716/2872) in patients without CSP and 53.1% (1341/2527) in patients with CSP. Significant predictors of sustained virological response included hepatitis C virus genotype 2 or 3 infection, absence of cirrhosis, hepatitis C virus RNA500 000 IU/ml, alanine transaminase quotient >3x the upper limit of normal, age 65 years, BMI<25 kg/m(2), at least 80% of the planned exposure to peginterferon and ribavirin and prescription of peginterferon -2a.ConclusionThe results provide detailed information on the outcome of therapy for CHC in a diverse Italian population that included a large number of patients with CSP and provides an insight into the generalizability of the results obtained in the more restricted setting of randomized registration trials
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Role of lymphocyte multidrug resistance protein 1 in HIV infection: expression, function, and consequences of inhibition
PEG-interferon and ribavirin in HCV-related cirrhotic patients with profound thrombocytopenia.
Background and Aim: In cirrhotic patients with HCV infection
and severe thrombocytopenia (<80,000 cell/mL), therapy with Peg-
Interferon (Peg-IFN) and ribavirin is deferred due to safety concerns
related to hematological complications.
Methods: 555 consecutive cirrhotic patients, na\uefve to therapy, were
enrolled prospectively in an observational study of therapy with
either Peg-IFN alpha-2a or alpha-2b and ribavirin in Italy (the
PROBE study). Incidence and severity of thrombocytopenia and
neutropenia during treatment were the main endpoints of this
study; sustained virological response (SVR) constituted a secondary
outcome.
Results: HCV genotype 1 was most prevalent (52%). At baseline,
110 patients (20%) presented with PLT levels <80,000/mL (group
A), 333 (60%) with levels between 81,000 and 139,000/mL (group
B), and 112 (20%) with levels 65140,000/mL. Dose reductions of
Peg-IFN were more frequent in Group A (33%) than in Group B
(19%), or Group C (12%). Dose reductions of ribavirin were noted
in 24%, 23%, and 21% of Groups A, B and C, respectively. Overall,
44.3% of patients developed neutropenia (absolute neutrophil count
<1,000/mL). Incidence of neutropenia was higher in Groups A and
B (55.5% and 44.1%, respectively) than in Group C patients (33.9%).
After starting treatment, platelet count dropped in all patients.
The mean relative decrease in platelet count was similar among
the three groups of patients. Nadir values of platelet counts over
treatment were graded 75,000 and 50,000/mL in 29.1%, 37.5%,
and 8.9% of Group A, B, and C, respectively. Values were between
49,000 and 20,00/ml in 54.5%, 20.4% and 1.8% in the three groups,
respectively. Overall, 213 patients attained an SVR (38%). SVR rates
were 30%, 40.5%, and 45.5% in Groups A, B, and C, respectively
(Cochran-Armitage trend test, P = 0.02). No patients complained of
severe hemorrhagic or infective events during therapy.
Conclusion: This investigation confronts the assumption of
thrombocytopenia being a limiting factor to antiviral therapy
in patients with HCV-related, compensated cirrhosis and severe
thrombocytopenia. In this setting, the study reveals the safety
of treatment, and documents that measurement of platelets
counts before therapy provides clinically relevant information on
treatment outcome, as SVR rates independently and inversely
related to the degree of thrombocytopenia
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Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors
We tested the effects of chloroquine (CQ) on glycosylation of HIV particles and in combination with protease inhibitors (PIs) on HIV replication and on P-glycoprotein (P-gp)/multidrug resistance protein-1 (MRP1)