Patient-reported outcomes 12 months after hepatitis C treatment with direct-acting antivirals: Results from the PROP UP study.

BACKGROUND & AIMS: The long-term impact of hepatitis C virus (HCV) therapy with all-oral direct-acting antivirals (DAAs) on patient-reported outcomes (PROs) has not been well-described. We characterized changes in PROs from pre-treatment to 12 months post-treatment in a real-world cohort. METHODS: PROP UP was a multi-centre observational cohort study of 1601 patients treated with DAAs at 11 US gastroenterology/hepatology practices from 2015 to 2017. PROs were evaluated pre-treatment (T1) and 12 months post-treatment (T5). A minimally important change (MIC) threshold was prespecified as >5% change in PRO scores from T1 to T5. Multivariable analyses identified predictors of change. RESULTS: Three-quarters of patients were 55 or older; 45% were female, 60% were white, 33% were black, nearly half had cirrhosis. The most commonly-prescribed DAA regimens were sofosbuvir-based (83%) and grazoprevir/elbasvir (11%). Study retention was >95%. On average, small improvements were observed at 3 months post-treatment in all PROs and sustained at 12 months post-treatment among patients with sustained virologic response (SVR). Clinically meaningful improvements were achieved in fatigue (mean change score: -3.7 [-4.2, -3.1]), sleep (mean change score: -3.1 [-3.7, -2.5]), abdominal pain (mean change score: -2.6 [-3.3, -1.9]) and functional well-being (mean change score: -7.0 [-6.0, -8.0]). Symptom improvements were generally not sustained with no SVR (n = 52). Patients with cirrhosis and MELD ≥12 had the greatest improvements in functional well-being (-12.9 [-17.6, -8.1]). CONCLUSIONS: The improvements in patient-reported outcomes reported by patients who achieved SVR following HCV DAA therapy were durable at 12 months post-treatment.

Medication Non-adherence in a Prospective, Multi-center Cohort Treated with Hepatitis C Direct-Acting Antivirals.

BACKGROUND: The prevalence and risk factors for non-adherence to direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) in clinical practice settings are under-studied. OBJECTIVES: (1) To quantify DAA non-adherence in the total cohort and among subgroups with and without mental health conditions, alcohol use, and substance use, and (2) to investigate patient- and treatment-level risk factor non-adherence. DESIGN: Prospective, observational cohort study. PARTICIPANTS: A total of 1562 patients receiving DAAs between January 2016 and October 2017 at 11 US medical centers including academic and community practices. MAIN MEASURES: Self-reported medication non-adherence, defined as any missed doses in the past 7 days, surveyed early (T2: at 4 ± 2 weeks) and late in treatment (T3: 2-3 weeks prior to end of treatment). Non-adherence to post-treatment follow-up visits was defined as absence of lab results after DAA therapy completion. KEY RESULTS: Of 1447 patients, 162 (11%) reported non-adherence at T2 or T3. Medical records indicated 262 (17%) of the 1562 participants had not returned for post-treatment visits. At baseline, 37% of patients reported mental health conditions, 15% reported alcohol use, and 23% reported using substances in the previous year. Baseline characteristics associated with DAA non-adherence included alcohol use (OR 1.96), younger age (< 35 years vs. > 55 years: OR 3.40), non-white race (OR > 2.26), and DAA treatment cohort, but not substance use or mental health condition. Non-adherence to follow-up exhibited association with younger age and a higher baseline overall symptom burden. Among 1287 patients with evaluable sustained virologic response (SVR) data, 53 patients (4%) did not achieve SVR. The bivariate correlation between adherence and SVR was negligible (r = 0.01). CONCLUSIONS: DAA non-adherence was low and SVR rates were high. Mental health conditions, substance use, and alcohol use should not disqualify patients from DAA therapy. Patients with alcohol use disorder before DAA therapy initiation may benefit from targeted on-treatment support.

Patient-reported symptoms during and after direct-acting antiviral therapies for chronic hepatitis C: The PROP UP study.

BACKGROUND & AIMS: A comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients with HCV treated with commonly prescribed DAAs. METHODS: PROP UP is a US multicenter observational study of 1,601 patients with HCV treated with DAAs in 2016-2017. PRO data were collected at baseline (T1), early on-treatment (T2), late on-treatment (T3) and 3-months post-treatment (T4). PRO mean change scores were calculated from baseline and a minimally important change (MIC) threshold was set at 5%. Regression analyses investigated patient and treatment characteristics independently associated with PRO changes on-treatment and post-treatment. RESULTS: Of 1,564 patients, 55% were male, 39% non-white, 47% had cirrhosis. Sofosbuvir/ledipasvir was prescribed to 63%, sofosbuvir/velpatasvir to 21%, grazoprevir/elbasvir to 11%, and paritaprevir/ombitasvir/ritonavir + dasabuvir to 5%. During DAA therapy, mean PRO scores improved slightly in the overall cohort, but did not reach the 5% MIC threshold. Between 21-53% of patients experienced >5% improved PROs while 23-36% experienced >5% worse symptoms. Of 1,410 patients with evaluable sustained virologic response (SVR) data, 95% achieved SVR. Among those with SVR, all mean PRO scores improved, with the 5% MIC threshold met for fatigue, sleep disturbance, and functioning well-being. Regression analyses identified subgroups, defined by age 35-55, baseline mental health issues and a higher number of health comorbidities as predictors of PRO improvements. CONCLUSIONS: In real-world clinical practices, we observed heterogeneous patient experiences during and after DAA treatment. Symptom improvements were more pronounced in younger patients, those with baseline mental health issues and multiple comorbidities. LAY SUMMARY: Patients who received direct-acting antiviral medications for hepatitis C at several liver centers in the US did not generally experience significant changes in baseline symptoms during treatment. We observed a full range of patient experiences with some patients experiencing substantial symptom improvements, yet others experiencing less improvements and some even experiencing a worsening of symptoms. The 1,346 patients who were cured of hepatitis C experienced improvements in fatigue, sleep disturbance, and functional well-being, and trends for improved pain and depression; whereas the 64 who were not cured experienced minimal improvements. Clinicaltrial.gov: NCT02601820.

A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: Results from a large US multi-center observational study.

BACKGROUND: Symptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables. METHODS AND FINDINGS: PROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016-2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0-15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20-50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40-50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not. CONCLUSIONS: This large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication. TRIAL REGISTRATION: (Clinicaltrial.gov: NCT02601820).

Sensibilidad y especificidad de indicadores antropométricos de adiposidad y distribución de grasa en niños y adolescentes Venezolanos / Sensitivity and specificity of anthropometric indicators of adiposity and fat distribution in Venezuelan children and adolescents / Sensibilidade e especificidade de indicadores antropométricos de adiposidade e distribuição de gordura em crianças e adolescentes Venezuelanos

Se exploró la sensibilidad y especificidad del índice de masa corporal (IMC) y de los índices cintura/talla (C/T), conicidad (C) y circunferencia de cintura (CCint), como identificadores de sobrepeso y de distribución de grasa, respectivamente. Se evaluaron 382 niños y adolescentes venezolanos entre 7 y 17 años. Para el IMC se utilizó como regla de oro el área grasa (AG); para C/T, C y CCint se empleó como regla de oro el cociente subescapular/tríceps (S/T). Se aplicó regresión logística, que sustenta el análisis de curvas ROC, para determinar la sensibilidad y especificidad de los índices. El IMC resultó un buen estimador para clasificar el sobrepeso en los cuatro grupos de edad (7-9, 10-12, 13-15 y 16-17 años) con sensibilidad y especificidad de 0,86 y 0,92; 0,89 y 0,90; 1,00 y 1,00; y 0,86 y 0,92 respectivamente, y con áreas bajo la curva ROC >0,85 (p<0,000). Los indicadores de distribución no presentaron valores de sensibilidad y especificidad satisfactorios, excepto para conicidad en el grupo de 7-9 años (0,86 y 0,68), con área bajo la curva de 0,76 (p<0,000). El IMC se comporta como buen estimador de la adiposidad, pero los indicadores de distribución de grasa son menos específicos. Es importante impulsar estudios para explorar la sensibilidad y especificidad de estos indicadores en muestras mayores y distintas edades, a fin de aproximarse al establecimiento de valores óptimos para la identificación de factores de riesgo de sobrepeso y obesidad a edades tempranas, y distribución centrípeta.

The sensitivity and specificity of the body-mass index (BMI) and of the waist-to-height ratio (W/H), conicity index (CI) and waist circumference (WCirc) as indicators of overweight and fat distribution identifiers, respectively, were explored. Venezuelan children and adolescents 7-17 years of age (N= 382) were evaluated. The fat area was used as the golden rule for the BMI, while the subscapular/triceps index was used for W/H, CI and WCirc. Logistic regression, which sustains the analysis of ROC curves, was used to determine the sensitivity and specificity of the indices. The BMI turned out to be a good estimator to classify overweight in the four age-groups (7-9, 10-12, 13-15 and 16-17 years old) with sensitivity and specificity values of 0.86 and 0.92, 0.89 and 0,90, 1.00 and 1.00, and 0.86 and 0.92, respectively, and with areas under the ROC curve <0.85 (p<0.000). The distribution indicators did not show satisfactory sensitivity and specificity values, except for conicity in the 7-9 years group (0.86 and 0.68), with an area under the ROC curve of 0.76 (p<0.000). The BMI behaves as a good adiposity indicator, but the fat distribution indicators are less specific. Studies to explore the sensitivity and specificity of these indicators in larger samples and different ages are needed in order to approximate optimal values for overweight and obesity risk factor identification at early ages and centripetal distribution.

Explorou-se a sensibilidade e especificidade do índice de massa corporal (IMC) e dos índices cintura/tamanho (C/T), conicidade (C) e circunferência de cintura (CCint), como identificadores de sobrepeso e de distribuição de gordura, respectivamente. Avaliaram-se 382 crianças e adolescentes venezuelanos entre 7 e 17 anos. Para o IMC se utilizou como regra de ouro a área gordurosa (AG); para C/T, C e CCint se empregou como regra de ouro o quociente subescapular/tríceps (S/T). Aplicou-se regressão logística, que sustenta a análise de curvas ROC, para determinar a sensibilidade e especificidade dos índices. O IMC resultou um bom estimador para classificar o sobrepeso nos quatro grupos de idade (7-9, 10-12, 13-15 e 16-17 anos) com sensibilidade e especificidade de 0,86 e 0,92; 0,89 e 0,90; 1,00 e 1,00; e 0,86 e 0,92 respectivamente, e com áreas sob a curva ROC >0,85 (p<0,000). Os indicadores de distribuição não apresentaram valores de sensibilidade e especificidade satisfatórios, exceto para conicidade no grupo de 7-9 anos (0,86 e 0,68), com área sob a curva de 0,76 (p<0,000). O IMC se comporta como bom estimador da adiposidade, mas os indicadores de distribuição de gordura são menos específicos. É importante impulsar estudos para explorar a sensibilidade e especificidade destes indicadores em amostras maiores e distintas idades, a fim de aproximar-se ao estabelecimento de valores ótimos para a identificação de fatores de risco de sobrepeso e obesidade a idades prematuras, e distribuição centrípeta.