Función renal en los pacientes con hepatopatía por virus C. Influencia en el tratamiento

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 20-06-2017La relación entre la infección crónica por el virus de la hepatitis C (VHC) y el riñón es recíproca. Una infección por VHC de una mano aumenta el riesgo de insuficiencia renal con un mayor riesgo de morbilidad y mortalidad, por otro lado, la insuficiencia renal, especialmente en la etapa 4-5, aumenta el riesgo de la incidencia de VHC (en diálisis) y del deterioro hepático. En la presente tesis hemos estudiado esta relación desde diversos puntos de vista. Se ha estudiado la relación ente el VHC y la ERC, realizando los análisis de cuatro poblaciones distintas. En un primer lugar 6334 pacientes en los que se determinó la serología frente al virus C de la Hepatitis en laboratorio de la Fundación Jiménez Díaz. En 3832 pacientes se analizó la función renal mediante el filtrado glomerular estimada por la fórmula MDRD4, para ver el grado de función renal. En 383 pacientes con hepatitis C de la Unidad de Hepatología antes de recibir terapia antiviral entre abril de 2014 Y octubre de 2015 hemos analizado la tasa estimada de filtración glomerular calculada por la fórmula de Levey, el índice de fibrosis de elastografía transitoria (FibroScan) y el genotipo del virus antes y después del tratamiento. Y en 157 pacientes con un FGe basal entre 60 y 90 ml/min se ha analizado la función renal después del tratamiento viendo las diferencias entre diversos tratamientos. Hemos observado que los pacientes VHC positivo tienen valores de cinética del hierro (hierro, ferritina e Índice de saturación de transferrina) superiores a los negativos y los valores de transaminasas han sido superiores en los pacientes VHC positivos, con valores de plaquetas más bajos. La prevalencia de enfermedad renal crónica en los pacientes VHC es superior a los pacientes con HVC negativo, y los genotipos más prevalentes en la población estudiada fueron el 1b, 1a y 3. En los pacientes con filtrados inferiores a 45 ml/min tienen una menor carga viral. Después del tratamiento antiviral se observa un leve deterioro de la función renal con un aumento de la creatinina sérica y descenso del filtrado glomerular. Así el 50% de los pacientes presenta un deterioro de la función renal tras el tratamiento, y los pacientes con mayor edad y carga viral son los que más empeora la función renal, este descenso es mayor en los tratados con sofosbuvir.The relationship between the chronic infection by the hepatitis C virus (HCV) and the kidney is reciprocal. A HCV infection heightens the risk of renal insufficiency, as well as that of morbidity and mortality. On the other hand, renal insufficiency, especially on stages 4 to 5, heightens the risk of HCV incidence (in dialysis) and hepatic deterioration. Therefore, in this thesis project this relationship has been studied from different viewpoints. The relationship between HCV and chronic kidney disease (CKD) has also been studied, taking analysis from four different populations. Firstly, there are 6334 patients in which the serology was determined against the hepatitis C virus in a laboratory of the Fundación Jiménez Díaz. In 3882 patients, the kidney functioning was analyzed via glomerular filtering estimated by the MDRD4 formula, in order to see the order of kidney functioning. In 383 patients with hepatitis C from the hepatology unit, before receiving antiviral treatment between April 2014 and October 2015, the glomerular filtering rate was analyzed, being calculated by the Leyey formula, the rate of transient elastography fibrosis (FibroScan) and the virus genotype before and after the treatment. In 157 patients with a base estimated glomerular filtration rate between 60 and 90 ml/min, after receiving treatment the kidney functioning was analyzed, being able to spot the differences between the different treatments. It has been noted that the HCV positive patients have iron kinetic values (iron, ferritin and transferrin saturation index) superior to the negative ones, and the transaminases values have been higher in the HCV positive patients, with platelets values being lower. The prevalence of the chronic kidney disease in HCV positive patients is superior to those that are HCV negative, and the most common genotypes in the studied population were 1b, 1a and 3. In patients with filtering rates inferior to 45 ml/min, the viral load was lower. After antiviral treatment, a mild deterioration in kidney functioning was observed, with serum creatinine increased and a descent in glomerular filtering. Therefore, 50% of the patients have a deterioration of kidney functioning after treatment. The patients in which the kidney functioning decreases the most are those of higher age and viral load. This descent is higher in those treated with sofosbuvir

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb-V and dialysis in Spanish clinical practice - Vie-KinD study

Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r ± DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015.Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records.Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan®, 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient´s decision.These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials

Transarterial chemoembolisation in intermediate-stage hepatocellular carcinoma. Survey on clinical practice in hospitals in the Madrid Region

Background. Transarterial chemoembolisation (TACE), having demonstrated survival benefits, is the treatment of choice in intermediate-stage hepatocellular carcinoma, although there is great heterogeneity in its clinical application.Material and methods. A survey was sent to the Madrid Regional hospitals to assess applicability, indications and treatment protocols. The assessment was made overall and according to the type of hospital (groups A vs. B and C).Results. Seventeen out of 22 hospitals responded (8/8 group A, 9/ 14 group B-C). All do/indicate transarterial chemoembolisation, 13/17 at their own facilities. Eight of the 17 hospitals have multidisciplinary groups (5/8 A, 3/9 B-C). Nine hospitals perform > 20 procedures/year (7 group A), and 6 from group B-C request/perform < 10/year. It is performed on an “on-demand” basis in 12/17. In 5 hospitals, all the procedures use drug-eluting beads loaded with doxorubicin. The average number of procedures per patient is 2. The mean time from diagnosis of hepatocellular carcinoma to transarterial chemoembolisation is ≤ 2 months in 16 hospitals. In 11/17 hospitals, response is assessed by computed tomography. Radiological response is measured without specific criteria in 12/17 and the other five hospitals (4 group A) assessed using standardised criteria.Conclusion. Uniformity among the Madrid Regional hospitals was found in the indication and treatment regimen. The use of DEB-TACE has become the preferred form of TACE in clinical practice. The differentiating factors for the more specialised hospitals are a larger volume of procedures, decision-making by multidisciplinary committees and assessment of radiological response more likely to be standardised

Real-world evidence of the effectiveness of ombitasvir-paritaprevir/r ± dasabuvir ± ribavirin in patients monoinfected with chronic hepatitis C or coinfected with human immunodeficiency virus-1 in Spain

Aim: We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r ± DSV ± RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain. Material and methods: Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r ± DSV ± RBV at 61 Spanish sites within the initial implementation year of the first government-driven "National HCV plan." Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded. Results: Overall, 2,408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8-97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of -2.2% (90% CI, -4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r ± DSV ± RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r ± DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin. Conclusions: Our results confirm that OBV/PTV/r ± DSV ± RBV is effective and generally well tolerated in a representative sample of the HCV monoinfected and HCV/HIV coinfected population in Spain within the experience of a national strategic plan to tackle HCV