Barriers to HCV Treatment in the Era of Triple Therapy
Barriers to HCV Treatment in the Era of Triple Therapy
Multi-centred, prospective, observational study to analyse the limitations regarding provision of triple therapy in patients with CHC genotype 1.
This study was undertaken in 16 hospitals with different healthcare levels. All patients with CHC referred to the hepatology outpatient clinic between the 1 June and 30 December 2012 were assessed consecutively.
Patients were included in this study if they fulfilled each of the following criteria: (i) clinical history and detailed physical examination; (ii) CHC genotype 1 documented by polymerase chain reaction (PCR); (iii) negativity for the surface HBV antigen, and anti-HIV 1 and 2; (iv) exclusion of other causes of liver disease. The patients with unknown genotype or non-1 genotype were excluded. Hence, this study represents a scenario of standard clinical practice, with a cohort of non-selected patients with CHC genotype 1, in Spain.
We developed a structured questionnaire that was filled-in, by the physician, before the decision to initiate the treatment. The data were collected and coded to preserve anonymity throughout this study, including the analyses (Table 1 and Table 2). The principal variable of this study was the proportion of patients who had the treatment initiated among those patients with no medical contraindications. Data were collected, as well, on the following variables (Table 1 and Table 2): (i) Patient factors: age, gender, location (rural, urban), education level (primary school, secondary school, university or equivalent), alcohol consumption; (ii) Characteristics related to the infection: genotype, viral load (HCV Amplicor, Roche Pharmaceuticals, Basel, Switzerland), genotype of the IL28B (rs12979860, LightMix Kit rs12979860 Roche), liver function tests, grade of fibrosis evaluated using liver biopsy and/or transient elastography and stratification using the Metavir scale. In those patients in whom evaluation of fibrosis was available by both methods, we analysed the results with the most recent determinations; (iii) Factors related to the healthcare environment: The level of the hospital was classified in three groups. The experience of the hepatologist was evaluated from two arbitrary stand-points (number of years of clinical experience and number of prescriptions per year). Final evaluation was whether or not a specialist nurse was available in the liver units.
In assessing contraindications, the following conditions were taken into account: (i) age limit that was at the discretion of the attending physician; (ii) decompensated cirrhosis; (iii) severe psychiatric disorder; (iv) excessive consumption of alcohol or intravenous drug user (IDU); (v) transplant of solid organ and/or haematological; (vi) advanced cardiac insufficiency, or severe coronary disease; (vii) poorly controlled diabetes; (viii) severe obstructive pulmonary disorder; (ix) severe reaction or intolerance to previous antiviral treatment containing interferon and/or ribavirin.
Finally, after completing the questionnaire, two final questions are raised: (i) Do you believe the treatment is indicated? In case of affirmative response to the question but treatment had not been initiated, the follow-up question was; (ii) What is the reason for non-treatment? The reasons were previously established and included: (a) refusal by the patient; (b) mild disease; (c) in expectation of newer treatments; (d) restrictions imposed by the healthcare provider; (e) others. Approval was obtained from the governing body concerning human research CEIC (Comité Ensayos e Investigación Cantabria). This study was conducted within the guidelines of Good Clinical Practice and the recommendations of the Helsinki Declaration.
Descriptive analyses of the qualitative variables included frequencies and, for the quantitative variable, the means and standard deviations (SD). The median and range were used depending on whether the distributions were normal and, if not, the Kolmogorov–Smirnov test was used. Univariate analyses for the qualitative variables were with the χ test. The Student t-test or anova was used if the quantitative variable was normal, or the Mann–Whitney or Kruskal–Wallis test in case the distribution was non-normal. Multivariate analyses were conducted using a logistic regression model that included binary variable (yes/no) for initiating treatment as a dependent variable and the covariates of interest as the independent variables. The covariables of interest for inclusion in the multivariate analyses were selected according to the statistical significance in the univariate analyses and/or according to the clinical relevance (including genotype, hospital type, expertise of the physician, grade of fibrosis, academic level of the host, initial viral load, initial co-morbidities).
The magnitude of the effect was described using odds ratio (OR) and its 95% CI. Continuous quantitative variables such as age were dichotomized using appropriate cut-off points for sensitivity and specificity (optimum cut-off 60 years) to predict the principal variable of this study using typical ROC analyses. Statically significance was set at P < 0.05. All statistical analyses were performed using the SPSS package (version 20).
Methods
Study Design
Multi-centred, prospective, observational study to analyse the limitations regarding provision of triple therapy in patients with CHC genotype 1.
Patient Selection
This study was undertaken in 16 hospitals with different healthcare levels. All patients with CHC referred to the hepatology outpatient clinic between the 1 June and 30 December 2012 were assessed consecutively.
Inclusion Criteria
Patients were included in this study if they fulfilled each of the following criteria: (i) clinical history and detailed physical examination; (ii) CHC genotype 1 documented by polymerase chain reaction (PCR); (iii) negativity for the surface HBV antigen, and anti-HIV 1 and 2; (iv) exclusion of other causes of liver disease. The patients with unknown genotype or non-1 genotype were excluded. Hence, this study represents a scenario of standard clinical practice, with a cohort of non-selected patients with CHC genotype 1, in Spain.
Description of the Characteristics of Patients, HCV Infection, Attending Physician and Hospital
We developed a structured questionnaire that was filled-in, by the physician, before the decision to initiate the treatment. The data were collected and coded to preserve anonymity throughout this study, including the analyses (Table 1 and Table 2). The principal variable of this study was the proportion of patients who had the treatment initiated among those patients with no medical contraindications. Data were collected, as well, on the following variables (Table 1 and Table 2): (i) Patient factors: age, gender, location (rural, urban), education level (primary school, secondary school, university or equivalent), alcohol consumption; (ii) Characteristics related to the infection: genotype, viral load (HCV Amplicor, Roche Pharmaceuticals, Basel, Switzerland), genotype of the IL28B (rs12979860, LightMix Kit rs12979860 Roche), liver function tests, grade of fibrosis evaluated using liver biopsy and/or transient elastography and stratification using the Metavir scale. In those patients in whom evaluation of fibrosis was available by both methods, we analysed the results with the most recent determinations; (iii) Factors related to the healthcare environment: The level of the hospital was classified in three groups. The experience of the hepatologist was evaluated from two arbitrary stand-points (number of years of clinical experience and number of prescriptions per year). Final evaluation was whether or not a specialist nurse was available in the liver units.
In assessing contraindications, the following conditions were taken into account: (i) age limit that was at the discretion of the attending physician; (ii) decompensated cirrhosis; (iii) severe psychiatric disorder; (iv) excessive consumption of alcohol or intravenous drug user (IDU); (v) transplant of solid organ and/or haematological; (vi) advanced cardiac insufficiency, or severe coronary disease; (vii) poorly controlled diabetes; (viii) severe obstructive pulmonary disorder; (ix) severe reaction or intolerance to previous antiviral treatment containing interferon and/or ribavirin.
Finally, after completing the questionnaire, two final questions are raised: (i) Do you believe the treatment is indicated? In case of affirmative response to the question but treatment had not been initiated, the follow-up question was; (ii) What is the reason for non-treatment? The reasons were previously established and included: (a) refusal by the patient; (b) mild disease; (c) in expectation of newer treatments; (d) restrictions imposed by the healthcare provider; (e) others. Approval was obtained from the governing body concerning human research CEIC (Comité Ensayos e Investigación Cantabria). This study was conducted within the guidelines of Good Clinical Practice and the recommendations of the Helsinki Declaration.
Statistical Analyses
Descriptive analyses of the qualitative variables included frequencies and, for the quantitative variable, the means and standard deviations (SD). The median and range were used depending on whether the distributions were normal and, if not, the Kolmogorov–Smirnov test was used. Univariate analyses for the qualitative variables were with the χ test. The Student t-test or anova was used if the quantitative variable was normal, or the Mann–Whitney or Kruskal–Wallis test in case the distribution was non-normal. Multivariate analyses were conducted using a logistic regression model that included binary variable (yes/no) for initiating treatment as a dependent variable and the covariates of interest as the independent variables. The covariables of interest for inclusion in the multivariate analyses were selected according to the statistical significance in the univariate analyses and/or according to the clinical relevance (including genotype, hospital type, expertise of the physician, grade of fibrosis, academic level of the host, initial viral load, initial co-morbidities).
The magnitude of the effect was described using odds ratio (OR) and its 95% CI. Continuous quantitative variables such as age were dichotomized using appropriate cut-off points for sensitivity and specificity (optimum cut-off 60 years) to predict the principal variable of this study using typical ROC analyses. Statically significance was set at P < 0.05. All statistical analyses were performed using the SPSS package (version 20).
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