Predictors of early treatment discontinuation and severe anemia in a Brazilian cohort of hepatitis C patients treated with first-generation protease inhibitors

Abstract

The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin ≤8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.

Predictors of adverse drug reactions associated with ribavirin in direct‐acting antiviral therapies for chronic hepatitis C

“…SVR was high (98.1%), with no significant differences between groups, in agreement with other Brazilian studies that found an SVR of 91.6‐95% . International studies also showed high rates of response to treatment, ranging from 78.6‐90%, depending on the treatment regimen used …”

“…[24][25][26][27] SVR was high (98.1%), with no significant differences between groups, in agreement with other Brazilian studies that found an SVR of 91.6-95%. 13,28,29 International studies also showed high rates of response to treatment, ranging from 78.6-90%, depending on the treatment regimen used. 14,22,[30][31][32] The most recent Brazilian protocol recommends use of ribavirin for patients with cirrhosis, with a lower chance of SVR (genotype 3, men, aged >40 years), or by medical decision, with consideration of previous intolerance.…”

Hepatitis C in Brazil: lessons learned with boceprevir and telaprevir

“…Corroborating our results, a Brazilian cohort study developed with 203 patients showed high rates (19.2%) of therapy discontinuation owing to AEs. These authors reported that 41% and 37.5% of the BOC or TVR discontinuations, respectively, also occurred due to hematologic events and cutaneous reactions 20 . It was previously described that patients with comorbidities and advanced cirrhosis are more vulnerable to AEs 18 , 21 .…”

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

“…Insofar as IFNL3 (IL28B) influences the responsiveness to PEG‐IFN and RBV, polymorphisms in ITPA gene—the most studied gene in our data mining—influence anaemia induced by RBV and strongly correlated to RBV‐induced haemolytic anaemia (RIHA) . The development of RIHA during anti‐HCV treatment is responsible for treatment discontinuation, dose reduction, and consequently decreased SVR. As such, ITPA represents an indirect but important predictor of effective RBV‐based treatment regimens.…”

“…45 This involves activation of Jak-STAT pathway, the third pathway in our analysis, which in turn stimulates the expression of a myriad of ISG, 48 Insofar as IFNL3 (IL28B) influences the responsiveness to PEG-IFN and RBV, [49][50][51] polymorphisms in ITPA gene-the most studied gene in our data mining-influence anaemia induced by RBV 52 and strongly correlated to RBV-induced haemolytic anaemia (RIHA). 53 The development of RIHA during anti-HCV treatment is responsible for treatment discontinuation, 54 pegylated IFN-α/RBV and DAA was shown to be effective in managing viral resistance and relapse following treatment. 57 The interferon signalling pathway constitutes the first-line defence against viral infections.…”