Direct‐acting antiviral agents (DAAs) are highly effective and well tolerated in patients with chronic hepatitis C virus infection, including those with compensated cirrhosis. However, fewer data are ...available in patients with more advanced liver disease. Our retrospective, noninterventional, national, multicenter study in patients from the Spanish Hepa‐C registry investigated the effectiveness and safety of interferon‐free DAA regimens in patients with advanced liver disease, including those with decompensated cirrhosis, in routine practice (all currently approved regimens were registered). Patients transplanted during treatment or within 12 weeks of completing treatment were excluded. Among 843 patients with cirrhosis (Child‐Turcotte‐Pugh CTP class A, n = 564; CTP class B/C, n = 175), 90% achieved sustained virologic response 12 weeks after treatment (SVR12). Significant differences in SVR12 and relapse rates were observed between CTP class A and CTP class B/C patients (94% versus 78%, and 4% versus 14%, respectively; both P < 0.001). Serious adverse events (SAEs) were more common in CTP class B/C versus CTP class A patients (50% versus 12%, respectively; P < 0.001). Incident decompensation was the most common serious adverse event (7% overall). Death rate during the study period was 16/843 (2%), significantly higher among CTP class B/C versus CTP class A patients (6.4% versus 0.9%; P < 0.001). Baseline Model for End‐Stage Liver Disease (MELD) score alone (cut‐off 18) was the best predictor of survival. Conclusion: Patients with decompensated cirrhosis receiving DAAs present lower response rates and experience more SAEs. In this setting, a MELD score ≥18 may help clinicians to identify those patients with a higher risk of complications and to individualize treatment decisions. (Hepatology 2017;65:1810‐1822).
Upadacitinib in refractory ulcerative colitis Rodríguez Toboso, Gabriel; Rivera Vaquerizo, Pedro Ángel; Martínez López, María Nieves ...
Revista española de enfermedades digestivas,
11/2022, Letnik:
114, Številka:
11
Journal Article
Recenzirano
Odprti dostop
We report the first clinical-practice case to date of treatment with upadacitinib for ulcerative colitis, prior refractoriness to all therapeutic options, and preventing proctocolectomy as of today ...after treatment for 7 months.
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•A pragmatic algorithm to manage HCV therapy is proposed.•Charlson index (apart from liver function) reveals the global benefit of the treatment.•HepCom index can be used for ...decision-making in the management of patients with HCV.
Patients with advanced liver fibrosis remain at risk of cirrhosis-related outcomes and those with severe comorbidities may not benefit from hepatitis C (HCV) eradication. We aimed to collect data on all-cause mortality and relevant clinical events within the first two years of direct-acting antiviral therapy, whilst determining the prognostic capability of a comorbidity-based model.
This was a prospective non-interventional study, from the beginning of direct-acting antiviral therapy to the event of interest (mortality) or up to two years of follow-up, including 14 Spanish University Hospitals. Patients with HCV infection, irrespective of liver fibrosis stage, who received direct-acting antiviral therapy were used to build an estimation and a validation cohort. Comorbidity was assessed according to Charlson comorbidity and CirCom indexes.
A total of 3.4% (65/1,891) of individuals died within the first year, while 5.4% (102/1,891) died during the study. After adjusting for cirrhosis, platelet count, alanine aminotransferase and sex, the following factors were independently associated with one-year mortality: Charlson index (hazard ratio HR 1.55; 95% CI 1.29–1.86; p = 0.0001), bilirubin (HR 1.39; 95% CI 1.11–1.75; p = 0.004), age (HR 1.06 95% CI 1.02–1.11; p = 0.005), international normalized ratio (HR 3.49; 95% CI 1.36–8.97; p = 0.010), and albumin (HR 0.18; 95% CI 0.09–0.37; p = 0.0001). HepCom score showed a good calibration and discrimination (C-statistics 0.90), and was superior to the other prognostic scores (model for end-stage liver disease 0.81, Child-Pugh 0.72, CirCom 0.68) regarding one- and two-year mortality. HepCom score identified low- (≤5.7 points: 2%–3%) and high-risk (≥25 points: 56%–59%) mortality groups, both in the estimation and validation cohorts. The distribution of clinical events was similar between groups.
The HepCom score, a combination of Charlson comorbidity index, age, and liver function (international normalized ratio, albumin, and bilirubin) enables detection of a group at high risk of one- and two-year mortality, and relevant clinical events, after starting direct-acting antiviral therapy.
The prognosis of patients with severe comorbidities may not benefit from HCV viral clearance. An algorithm to decide who will benefit from the treatment is needed to manage the chronic HCV infection better.
Background: Affordable and effective diagnostic and treatment monitoring algorithms are urgently needed to achieve the global elimination of hepatitis C virus (HCV) infection. Methods: A total of 274 ...patients were treated with direct-acting antivirals (DAAs) in the Spanish Hospital of Albacete between 2004 and 2020. This study compared the enzyme-immunoassay technique for HCV core antigen (HCVcAg) with the determination of RNA of HCV (HCV RNA) by polymerase chain reaction (PCR) in monitoring treatment with DAA, setting the lower limit of detection of HCVcAg < 3 fmol/L and RNA < 10 IU/mL. In all cases, the P value of differences associated with the contrast test was less than or equal to 0.05. Results: We evaluated the viral loads of our patients before treatment, during their treatment, and after its completion. The HCV RNA quantification at diagnosis was 2309327 IU/mL. The mean HCVcAg load was 5972 fmol/L. There was a strong correlation between HCVcAg levels and RNA levels with a Spearman rho of 0.832 (P < 0.01). The HCVcAg sensitivity at diagnosis was 99%, but the specificity could not be calculated because there were no true negatives or false positives at this point. Twelve weeks after treatment, in patients with treatment failure, we obtained a mean of 19084 IU/mL for RNA, while for HCVcAg, the mean was 103 fmol/L. At this time point, we also found a strong correlation between HCVcAg levels and HCV RNA levels with a Spearman rho of 0.775 (P < 0.01). Finally, the virological cure was achieved in 99% of our patients. The results for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 99.87%, 86.33%, and 100%, respectively. Conclusions: HCVcAg determination is an excellent alternative to HCV RNA in the assessment of treatment response. This is particularly relevant in lower- and middle-income countries and resource-limited settings where the high cost of labor, equipment, and reagents can prohibit molecular testing.
Abstract
Background
Cobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine ...estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known.
Methods
Changes in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient’s characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses.
Results
The analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR adjusted median difference (±SD) –3.5 ± 1.6 (95% CI –6.6 to –0.3), P = 0.047, and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent adjusted OR 3.233 (95% CI 1.343–7.782), P = 0.009, with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390).
Conclusions
Concomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.
The effectiveness of the hepatitis C virus (HCV) treatment seems to be lower in people who inject drugs (PWID). We analyze the influence of various factors as psychiatric disorders and opioid ...substitution therapy (OST) on the treatment with direct-acting antivirals (DAA) in this collective.
Three hundred thirty-two PWID patients were treated with DAA in 12 Spanish hospitals between 2004 and 2020. They were catalogued in recent and former consumers (if the last consumption was in the last 3 years) and several variables were included, evaluating the effectiveness of the treatment according to the viral load 12 weeks after the end of the treatment with the parameter «sustained viral response» (SVR12).
23.4% were recent consumers and 27.7% were on OST. The 41.5% had any diagnosis of psychiatric disorder. SVR12 was 84.04%, ascending to 96.21% when excluded from the analyses the patients lost to follow-up (12.7%). SVR12 was lower due to an increase in the loss to follow-up in recent consumers and other factors like OST, being in prison the last 5 years, naïve patients, generalized anxiety disorder and benzodiazepine consumption.
The effectiveness of the HCV treatment with DAA in PWID is similar than in general population in patients whit an appropriate follow-up. It is important to maintain a closer follow-up in patients on OST, recent consumers and those with psychiatric disorders.
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