ABSTRACT
BACKGROUND: The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. METHODS: PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). RESULTS: SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. CONCLUSION: The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.
Subject(s)
Glycation End Products, Advanced/metabolism , Liver Cirrhosis/metabolism , Skin/metabolism , Adult , Aged , Fluorescence , Humans , Middle AgedABSTRACT
OBJECTIVES: Several prognostic indices (PIs) have been proposed for Budd-Chiari syndrome (BCS). However, patient characteristics, causal factors, and treatment outcomes have changed since these indices have been elaborated. Validation in a recent patient population and comparison of predictive accuracy between these PIs are needed. METHODS: A database of 96 BCS patients diagnosed between 1995 and 2005 was analyzed. Cox survival models were fitted with time to liver transplantation or death, and time to invasive therapy or death, as end points. The prognostic values of known indices (Child-Pugh score, model for end-stage liver disease (MELD), Clichy, Rotterdam BCS index, New Clichy, and BCS-TIPS (transjugular intrahepatic portosystemic shunt)) at diagnosis were assessed in Cox models using the chi-square test, the Kent and O'Quigley measure of dependence, and unrestricted bootstrapping analysis. Areas under receiver operating characteristic curves (AUROCs) were built for both end points and compared. RESULTS: All prognostic indices, except BCS-TIPS, were significant predictors of transplant-free and invasive therapy-free survival. However, only 31 and 37% of the variance in transplant-free and invasive therapy-free survival, respectively, were explained by the best performing indices. For transplant-free survival, AUROCs were < 0.70. For invasive therapy-free survival, AUROCs were < 0.80. For both end points, BCS-TIPS PI AUROCs were significantly lower than others. CONCLUSIONS: Most PIs are valid for transplant-free survival and invasive therapy-free survival in a population of current BCS patients, and thus can be used for stratification in clinical studies. However, predictive accuracy is insufficient to be used for individual patients.
Subject(s)
Budd-Chiari Syndrome/diagnosis , Budd-Chiari Syndrome/surgery , Cause of Death , Liver Transplantation/mortality , Portasystemic Shunt, Transjugular Intrahepatic/mortality , Adult , Area Under Curve , Budd-Chiari Syndrome/mortality , Chi-Square Distribution , Female , Humans , Liver Function Tests , Liver Transplantation/methods , Male , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/methods , Postoperative Complications/mortality , Predictive Value of Tests , Prognosis , Proportional Hazards Models , Registries , Retrospective Studies , Risk Factors , Severity of Illness Index , Survival Analysis , Time Factors , Treatment Outcome , Vascular Patency/physiologyABSTRACT
Our purpose was to determine in HCV-infected patients whether T-lymphocyte sub-populations were modified before and during interferon-alpha and ribavirin treatment, and whether this correlated with virological response. Twenty-two naive patients were given IFN-alpha 3 Million Units three times per week for 24 or 48 weeks and ribavirin. Sustained virological response corresponded to undetectable serum HCV RNA at treatment completion and 6 months later. Total blood lymphocyte counts and CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD4(+)HLA-DR(+), and CD3(+)CD8(+)HLA-DR(+) lymphocyte subsets evaluated before, during, and after treatment were compared to values from 37 healthy subjects. At inclusion, patients and controls had similar total lymphocyte counts. CD3(+)CD4(+) counts and percentages were significantly higher in HCV patients. HLA-DR expression was also increased in CD4(+) (p < 0.0001) and CD8(+) T-cells (p = 0.0008) as compared with controls. During treatment, all lymphocyte subset counts and percentage decreased except the CD3(+)CD4(+) T-cell percentage which increased. Moreover, after 1 month of treatment, virological responders exhibited higher CD4(+) counts than nonresponders (p = 0.025), whereas they did not differ at inclusion or during the 2nd to 6th months of treatment. After treatment completion, all populations returned to baseline values. These results suggest that CD3(+)CD4(+) T-lymphocyte percentage increase under treatment could be related to IFN immunomodulation and associated with virological response.
