RESUMEN
BACKGROUND AND STUDY AIMS: Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices. METHODS: 83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn's disease or the Mayo Endoscopic Score (MES) for ulcerative colitis. RESULTS: In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (â¼0.96). CONCLUSIONS: FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy.
Asunto(s)
Biomarcadores , Proteína C-Reactiva , Enfermedad de Crohn , Heces , Interleucina-6 , Complejo de Antígeno L1 de Leucocito , Proteína Amiloide A Sérica , Índice de Severidad de la Enfermedad , Humanos , Proteína Amiloide A Sérica/análisis , Proteína Amiloide A Sérica/metabolismo , Complejo de Antígeno L1 de Leucocito/análisis , Interleucina-6/sangre , Heces/química , Femenino , Masculino , Adulto , Biomarcadores/sangre , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/sangre , Enfermedad de Crohn/metabolismo , Persona de Mediana Edad , Colitis Ulcerosa/sangre , Colitis Ulcerosa/diagnóstico , Colonoscopía , Adulto Joven , Curva ROC , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/metabolismoRESUMEN
BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) prevalence inchronic kidney disease (CKD) patients is significantly higher than in the general population. This study evaluated the efficacy and safety of combined ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with renal impairment. PATIENTS AND METHODS: Our study included 829 patients with normal kidney functions (group 1) and 829 patients with CKD (group 2),which were subdivided into patients not requiring dialysis (group 2a) and those on hemodialysis (group2b). Patients received regimens of ombitasvir/paritaprevir/ritonavir with or without ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 weeks. Clinical and laboratory assessment was done before treatment, and patients were followed up for12 weeks after treatment. RESULTS: The sustained virological response (SVR) at week 12 was significantly higher in group 1 than in the other three groups/subgroups, being 94.2% vs 90.2%, 90%, and 90.7%, respectively. The regimen with the highest SVR was ombitasvir/paritaprevir/ritonavir with ribavirin. The most common adverse event was anemia, which was more common in group 2. CONCLUSION: Ombitasvir/paritaprevir/ritonavir-based therapy in chronic HCV patients with CKD is highly effective, with minimal side effects despite ribavirin-induced anemia.
Asunto(s)
Hepatitis C Crónica , Compuestos Macrocíclicos , Insuficiencia Renal Crónica , Humanos , Ritonavir/efectos adversos , Ribavirina/efectos adversos , Antivirales/efectos adversos , Hepacivirus , Valina/uso terapéutico , Compuestos Macrocíclicos/uso terapéutico , Compuestos Macrocíclicos/efectos adversos , Quimioterapia Combinada , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/tratamiento farmacológico , Anilidas/efectos adversos , Carbamatos/efectos adversos , Genotipo , Resultado del TratamientoRESUMEN
BACKGROUND: Nonstructural protein 5A (NS5A) is an important regimen for the treatment of chronic hepatitis C virus (HCV) genotype-4 infected patients. Retreatments for NS5A virologic failure are limited. The aim of this study is to provide real-life data regarding the effectiveness and safety of retreatment with different regimens after NS5A regimen virologic failure in GT4 patients. PATIENTS AND METHODS: A total of 524 HCV patients (mean age 48 ± 11 years, 71% males), with virologic failure to sofosbuvir+daclatasvir, n = 450 and sofosbuvir/ledipasvir, n = 74 were included in this study. Patients were retreated with sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin, n = 278 and sofosbuvir + simeprevir + daclatasvir + ribavirin, n = 246. Response was evaluated 12 weeks after the end of treatment (SVR12). RESULTS: Overall, SVR12 was 95.2% [95% confidence interval (CI) 93.3%-97.1%]. In sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir + simeprevir + daclatasvir + ribavirin, SVR12s were 94.9% (95% CI 92.5%-97.4%) and 95.5% (95% CI 92.8%-98%), respectively. In liver cirrhosis patients, SVR12s were 96.4% (95% CI 90.7%-100%) and 98% (95% CI 94.9%-100%), respectively. Relapse in the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin was n = 14 patients, and n = 11 patients in sofosbuvir + simeprevir + daclatasvir + ribavirin. Three patients developed hepatic encephalopathy, haematemesis, lower limb oedema, and one patient died in the SOF + OBV/PTV/RTV + RIB. In the sofosbuvir + simeprevir + daclatasvir + ribavirin, three patients developed hepatocellular carcinoma and one patient died. No treatment discontinuation due to anaemia. CONCLUSION: Salvage treatment for NS5A-treatment failure is effective and well tolerated in genotype-4 patients, in both noncirrhotic and compensated cirrhotic groups.
Asunto(s)
Hepatitis C Crónica , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Retratamiento , Ribavirina/efectos adversos , Sofosbuvir/efectos adversos , Respuesta Virológica SostenidaRESUMEN
Aim: Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment. Methods: Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point. Results: We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis. Conclusion: SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/uso terapéutico , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Carbamatos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pirrolidinas , Retratamiento , Resultado del Tratamiento , Valina/análogos & derivadosRESUMEN
Hepatitis C virus (HCV) treatment is aiming to cure and prevent the development, progression of fibrosis, and related complications. Interferon-based therapy was claimed to reduce or even reverse fibrosis. Although direct-acting agents have a better cure rate, we still lack the knowledge of their effect on fibrosis regression. We aim to assess fibrosis regression in direct-acting agents compared with interferon-based treatment regimens in the treatment of chronic HCV patients. The 204 chronic HCV patients were divided into 3 groups; group 1(N = 68) received Peg-IFN and ribavirin, group 2 (N = 69) received sofosbuvir and ribavirin, and group 3 (N = 67) received Peg-IFN, ribavirin, and sofosbuvir. Fibrosis assessment was performed by transient elastography (TE), APRI and FIB 4, in the pretreatment and at least 3 months after end of treatment. Of these, 66.2% of the patients did not show significant fibrosis changes, 6.4% fibrosis progressed, and 27.5% of fibrosis regressed (P < 0.0001) by TE. Similar results were detected in the different treatment regimens with no statistically significant difference between the regimens. Fibrosis regression was detected in 43.3% of cirrhotic patients who achieved sustained virological response (SVR) and only in 27.4% with significant fibrosis. Significant improvement of posttreatment aspartate transaminase, alanine transaminase, and alpha fetoprotein as well as APRI and FIB 4 scores were detected. Fibrosis regression (TE, APRI and FIB 4) was detected with direct-acting agents and interferon-based therapy. Treated patients with significant fibrosis will benefit of fibrosis regression irrespective to their treatment response, whereas fibrosis regression was associated with SVR in cirrhotic patients.
Asunto(s)
Antivirales/farmacología , Fibrosis/tratamiento farmacológico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/farmacología , Ribavirina/farmacología , Sofosbuvir/farmacología , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIMS: The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources. METHODS: Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included. RESULTS: For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5â¯kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24â¯weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%. CONCLUSION: Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed. LAY SUMMARY: We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Adulto , Anciano , Medicamentos Genéricos/uso terapéutico , Egipto , Femenino , Recursos en Salud , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Hepatitis C virus (HCV) is a major public health problem being the most common cause of chronic liver disease in Egypt. HCV-induced decompensated liver cirrhosis patients have a median survival of 2 years even with currently used new treatments. Silymarin is the most commonly used herbal product in chronic liver disease for its anti-inflammatory, antiviral, antioxidant, and antifibrotic effects. The aim of this study was to assess the effects of silymarin in high dose on the clinical and biochemical status of chronic HCV-associated decompensated liver cirrhosis. The study was conducted on 62 chronic HCV-decompensated cirrhotic patients. Patients were randomized according to treatment plans: group A, included 31 patients who received silymarin in dose of 1,050 mg/day, and group B, included 31 patients who received silymarin in dose of 420 mg/day. Patients were subjected to baseline history taking, laboratory evaluation, abdominal ultrasound, Child scoring, and quality-of-life (QoL) questionnaire. Follow-up was done every 2 weeks for 12 weeks. Silymarin in high dose had an effect on reducing alanine transaminase, aspartate aminotransferase levels (P ≤ 0.01), as well as improving albumin (P = 0.04), bilirubin (P = 0.02), and international normalized ratio (P = 0.03), thus resulted in improvement in Child score (P = 0.048), however, regular silymarin regimen (420 mg/day) failed to achieve the previous biochemical changes. High-dose regimen of silymarin also had a positive impact on improving QoL. No serious adverse events were reported. Silymarin in high dose is a good choice for improvement of liver biochemical profile and QoL in chronic HCV cirrhotic patients.
Asunto(s)
Hepatopatías/tratamiento farmacológico , Silimarina/administración & dosificación , Silimarina/uso terapéutico , Albúminas/metabolismo , Bilirrubina/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Hemoglobinas/metabolismo , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Silimarina/efectos adversos , Silimarina/farmacología , Encuestas y CuestionariosRESUMEN
BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) and HCV-genotype-4 (GT4) has become very effective, it remains very expensive, and affordable options are needed, especially in limited resource countries. The aim of this study was to assess the efficacy and safety of the combination of ravidasvir (an NS5A inhibitor) and sofosbuvir to treat patients with chronic HCV-GT4 infection. METHODS: A total of 300 patients with HCV-GT4 infection were recruited in three groups: treatment-naïve patients with or without compensated Child-A cirrhosis (Group 1); interferon-experienced patients without cirrhosis (Group 2); and interferon-experienced patients with cirrhosis (Group 3). Groups 1 and 2 received ravidasvir 200â¯mg QD plus sofosbuvir 400â¯mg QD for 12 weeks and were randomized 1:1 to treatment with or without weight-based ribavirin. Group 3 patients received ravidasvir plus sofosbuvir with ribavirin and were randomized 1:1 to a treatment duration of 12â¯weeks or 16â¯weeks. The primary endpoint was sustained virologic response at 12â¯weeks post-treatment (SVR12). RESULTS: A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated. CONCLUSIONS: Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02371408. LAY SUMMARY: This study evaluated efficacy and safety of the new oral hepatitis C drug ravidasvir in combination with the approved oral drug sofosbuvir in 298 patients infected with hepatitis C type 4. Our results showed that treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high response rate in patients with and without cirrhosis.
RESUMEN
BACKGROUND AND AIM: In tropical regions, Hepatitis C virus (HCV) - Schistosomiasis coinfection remains one of the health problems. With the new era of HCV treatment and the variety of methods of assessment of liver fibrosis so we aimed to evaluate the effectiveness of FibroScan for staging hepatic fibrosis in HCV-Schistosomiasis coinfected patients. METHODOLOGY: Three groups of patients were enrolled. Group 1: chronic HCV with out antischistosomal antibody (122 patients), Group 2: chronic HCV with positive antischistosomal antibodies and without periportal tract thickening (122 patients), Group 3: chronic HCV with positive antischistosomal antibodies and ultrasonographic picture of periportal tract thickening (108 patients). Routine laboratory workup, serum Antischistosomal antibody, and Schistosomal antigen in serum were performed. Ultrasound guided liver biopsy with histopathological examination; abdominal ultrasound and fibroscan examination were done for all patients. RESULTS: The agreement between results of liver biopsy and results of fibroscan in the staging of fibrosis was the best in group 1 (55.7%), Although the agreement was higher among those with no periportal tract thickening (70.7%) and the disagreement was higher among those with positive schistosomal serology (66.5%), yet this relation was not statistically significant. Multivariate logistic regression analysis showed that disagreement is significantly associated with older age, higher BMI (≥30), and increase in anti Schistosomal antibody titer. CONCLUSION: Fibroscan is a reliable, non-invasive tool for staging hepatic fibrosis among HCV-schistosomiasis co-infected patients with no effect of the induced periportal tract thickening on the readings. Only higher antischistosomal antibody titres may cause disagreement between liver biopsy and fibroscan.
Asunto(s)
Diagnóstico por Imagen de Elasticidad/normas , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Esquistosomiasis/complicaciones , Adulto , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Esquistosomiasis/patologíaRESUMEN
Background: Detection of circulating DNA can be applied for the diagnosis of many malignant neoplasms, including the hepatocellular carcinoma (HCC). The molecular pathogenesis of HCC is complex, involving different genetic and epigenetic alterations, chromosomal aberrations, gene mutations and altered molecular pathways. RASSF1A is a well-established tumor suppressor gene which suffers frequent inactivation due to promoter hypermethylation of CPG islands in multiple tumors including HCC, resulting in the reduction or loss of gene expression. Objective: To examine the role of circulating RASSF1A as a non-invasive diagnostic marker for HCC. Participant and Methods: A total of 45 HCC patients with a background of HCV infection, 40 cases of HCV infection without tumours and 40 apparently healthy controls were subjected to full history taking, clinical examination, routine laboratory investigations, assessment of serum AFP and detection of circulating hypermethylated RASSF1A gene by methylation-sensitive restriction enzyme digestion and real-time PCR. Results: The level of hypermethylated RASSF1A was significantly elevated in the HCC group as compared to the HCV and control groups (p=0.001 for both). Copy number in serum was associated with increased tumor size (p value <0.001). On the other hand, no significant correlation was observed between RASSF1A and AFP (p=0.5). Using ROC curve analysis, the best cut-off for circulating serum RASSF1A to differentiate the HCC group was 8 copies/µl. Conclusion: The presence of hypermethylated RASSF1A in serum may be a useful and informative biomarker for HCC diagnosis and might be introduced as a screening method for populations at risk of HCC development.
RESUMEN
BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) accounts for a sizable proportion of chronic liver disease cases and represents the most common indication for liver transplantation. Precise diagnosis of hepatic fibrosis stage is considered a funnel-neck in proper management and follow-up of HCV-infected patients. Given the possible complications of liver biopsy, a non-invasive method for assessing hepatic fibrosis is needed. This study aimed to evaluate the diagnostic accuracy of APRI and hyaluronic acid as non-invasive diagnostic assessment tools for post HCV liver fibrosis. PATIENTS AND METHODS: Systematic literature searching identified studies performed on Egyptian territory to evaluate APRI and hyaluronic acid as non-invasive tests of fibrosis and using liver biopsy as the reference standard. Meta-analysis was performed for areas with an adequate number of publications. Validation of meta- analysis on APRI was done on a subset of 150 treatment-naïve post-hepatitis C patients. RESULTS: Both APRI and hyaluronic acid have superior predictive power for hepatic cirrhosis (F4) than for significant fibrosis (F2-F3). The pooled estimate for sensitivities and specificities of APRI and hyaluronic acid to diagnose F4 were (84% and 82%) and (83% and 89%) respectively. In the subgroup of treatment naïve post-hepatitis C patients, APRI had higher diagnostic performance to diagnose liver cirrhosis with 93.8% sensitivity and 72.4% specificity (AUC; 0.908, 95%CI; 0.851-0.965, p-value; <0.001) compared to its accuracy to diagnose significant hepatic fibrosis with 65.1% sensitivity and 77.8% (AUC; 0.685, 95% CI; 0.59-0.78, p-value; 0.001). CONCLUSION: APRI score and hyaluronic acid levels are simple and reliable non-invasive markers to detect advanced fibrosis among post-hepatitis C patients.
Asunto(s)
Aspartato Aminotransferasas/sangre , Hepatitis C Crónica/complicaciones , Ácido Hialurónico/sangre , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Recuento de Plaquetas , Biopsia , Humanos , Hígado/patología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Valor Predictivo de las Pruebas , Curva ROCRESUMEN
Inosine triphosphatase (ITPA) gene variants can protect against ribavirin (RBV)-induced anemia in patients treated for chronic hepatitis C. The aim of this study was to determine the relationship between genetic variants of ITPA polymorphism, anemia, RBV dose reduction, and treatment response in hepatitis C virus (HCV)-infected patients. This study was conducted on 97 Egyptian chronic HCV patients who were scheduled for pegylated-interferon (PEG-INF) /RBV therapy. ITPA genotypes rs1127354 were determined by Real Time PCR melting curve analysis. Effects of ITPA polymorphism on hemoglobin (Hb) levels, RBV dose reduction and treatment response were analyzed. The homozygous wild genotype (CC) was associated with Hb reduction at week 4 (P = 0.004). The minor allele protected against Hb reduction. No association with sustained virological response was observed (P = 0.492). Female gender; lower baseline Hb and higher baseline WBC were associated with week 4 anemia (P = 0.04; P = 0.023; 0.033, respectively). The ITPA gene polymorphism rs1127354 heterozygous genotype (CA) may influence Hb levels and protect against hemolytic anemia during RBV-containing regimens for HCV. However, such findings were not significantly related to treatment outcomes. Patients with wild ITPA genotype (CC) experienced a more Hb drop and RBV dose reductions more frequently.
Asunto(s)
Anemia Hemolítica/inducido químicamente , Antivirales/efectos adversos , Hepatitis C Crónica/tratamiento farmacológico , Polimorfismo de Nucleótido Simple , Pirofosfatasas/genética , Ribavirina/efectos adversos , Adulto , Alelos , Antivirales/uso terapéutico , Quimioterapia Combinada , Egipto/epidemiología , Femenino , Variación Genética , Genotipo , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/etnología , Humanos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Resultado del TratamientoAsunto(s)
Simeprevir , Sofosbuvir , Antivirales , Quimioterapia Combinada , Egipto , Genotipo , Hepacivirus , Hepatitis C Crónica , Humanos , Ribavirina , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non-invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir-based treatment regimen. METHODS: This is a retrospective study including 337 chronic HCV Egyptian patients with genotype 4 mainly. They were treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded as well as FIB-4 and APRI were calculated at baseline and SVR12. RESULTS: There was a significant improvement of platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores at SVR12. Liver stiffness measurements were significantly lower in SVR12 (14.8 ± 10.7 vs 11.8 ± 8.8 kPa, P = 0.000). About 77% of responders and 81.1% of cirrhotic patients showed improvement in liver stiffness measurements at SVR12.Univariate and multivariate regression analysis showed that failure to achieve improvement in liver stiffness measurements were significantly associated with relapsers and low baseline liver stiffness measurement. CONCLUSION: Sofosbuvir-based treatment resulted in a clinically significant improvement in parameters of liver fibrosis.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/patología , Hígado/patología , Sofosbuvir/administración & dosificación , Adulto , Diagnóstico por Imagen de Elasticidad , Femenino , Fibrosis , Humanos , Interferones , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy. METHODS: This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12 weeks course of daily combination of sofosbuvir (400 mg) and simeprevir (150 mg). Patients were closely monitored for treatment safety and efficacy. RESULTS: Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%). CONCLUSION: Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Simeprevir/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Quimioterapia Combinada , Egipto/epidemiología , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Índice de Severidad de la Enfermedad , Respuesta Virológica Sostenida , Insuficiencia del Tratamiento , Carga ViralRESUMEN
INTRODUCTION: Vitamin D binding protein (VDBP) is a potential modulator of immune response and is associated with clinical progression of many diseases. Our aim was to assess influence of baseline 25-hydroxyvitamin D levels and VDBP single nucleotide polymorphisms (SNPs), rs4588 (C > A) and rs7041 (G > T), on baseline clinical parameters and response to interferon based therapy in chronic hepatitis C patients in Egypt. METHODOLOGY: Genotyping was performed by RFLP (Restriction Fragment Length Polymorphism) in 112 treatment naïve hepatitis C patients and 50 healthy controls. Vitamin D levels were assessed by ELISA. HCV RNA quantification was performed by PCR to assess therapy outcome. RESULTS: Patients with VDBP WT+ diplotype (3 or 4 VDBP major alleles) had higher viral response rates at weeks 12, 48, and 72 (p = 0.046, 0.034 and 0.029, respectively) and lower base line viral load (p = 0.016). Multivariate logistic regression identified VDBP WT+ diplotype as an independent predictor of sustained viral response (SVR; p = 0.014, RR = 4.716, 95% CI = 1.371 - 16.609). Interestingly, WT- diplotype (less than 3 VDBP major alleles) was associated with significant liver fibrosis (p = 0.045). CONCLUSIONS: VDBP WT+ diplotype is associated with lower baseline viral load and better therapy outcome in HCV treatment naïve patients. The rs4588 genotype is associated with SVR in the Egyptian population.
RESUMEN
AIM: To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS: A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction. RESULTS: Chronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group. CONCLUSION: Elevated Tregs cells in chronic HCV patients dampen both CD4+ and CD8+ autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response.
RESUMEN
Despite the appearance of new oral antiviral drugs, pegylated interferon (PEG-IFN)/RBV may remain the standard of care therapy for some time, and several viral and host factors are reported to be correlated with therapeutic effects. This study aimed to reveal the independent variables associated with failure of sustained virological response (SVR) to PEG-IFN alpha-2a versus PEG-IFN alpha-2b in treatment of naive chronic hepatitis C virus (HCV) Egyptian patients using both statistical methods and data mining techniques. This retrospective cohort study included 3,235 chronic hepatitis C patients enrolled in a large Egyptian medical center: 1,728 patients had been treated with PEG-IFN alpha-2a plus ribavirin (RBV) and 1,507 patients with PEG-IFN alpha-2b plus RBV between 2007 and 2011. Both multivariate analysis and Reduced Error Pruning Tree (REPTree)-based model were used to reveal the independent variables associated with treatment response. In both treatment types, alpha-fetoprotein (AFP) >10 ng/mL and HCV viremia >600 × 10(3) IU/mL were the independent baseline variables associated with failure of SVR, while male gender, decreased hemoglobin, and thyroid-stimulating hormone were the independent variables associated with good response (P < 0.05). Using REPTree-based model showed that low AFP was the factor of initial split (best predictor) of response for either PEG-IFN alpha-2a or PEG-IFN alpha-2b (cutoff value 8.53, 4.89 ng/mL, AUROC = 0.68 and 0.61, P = 0.05). Serum AFP >10 ng/mL and viral load >600 × 10(3) IU/mL are variables associated with failure of response in both treatment types. REPTree-based model could be used to assess predictors of response.
Asunto(s)
Minería de Datos , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Modelos Estadísticos , Polietilenglicoles/uso terapéutico , Adolescente , Adulto , Egipto , Femenino , Humanos , Inyecciones Subcutáneas , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Adulto JovenRESUMEN
Despite the appearance of the direct acting antiviral drugs, pegylated interferon/ribavirin (PEG-IFN/RBV) still has a place in the standard of care (SOC) therapy for chronic HCV4. Studies were conducted to find an accurate prediction in response to SOC therapy. Pretreatment serum interferon-γ-inducible protein-10 (IP-10) is an independent predictive factor of sustained virological response (SVR) in HCV1-infected patients. To assess whether the pretreatment serum level of IP-10 influences hepatic fibrosis and PEG-IFN/RBV therapy response, a study was conducted on 88 chronic Hepatitis C virus (HCV) patients who received PEG-IFN/RBV. Patients were subjected to a pretreatment routine laboratory evaluation, liver biopsy, and serum IP-10 assessment. They were followed up for 6 months after cessation of therapy (week 72). Patients were classified into 3 groups according to their response; nonresponders, relapsers, or sustained virological responders. The relation of pretreatment IP-10 with fibrosis and response was assessed. The studied groups were matched regarding their demographic data. There was no statistically significant association between the pretreatment IP-10 level and fibrosis (P=0.86) and no relation to response was found at week 12, 24, 48, and 72 (P=0.58, 0.8, 0.47, and 0.43, respectively). Pretreatment IP-10 could not predict either fibrosis or response to PEG-IFN/RIB therapy in chronic HCV Egyptian patients.
Asunto(s)
Antivirales/uso terapéutico , Quimiocina CXCL10/sangre , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adolescente , Adulto , Anciano , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/etiología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
Hepatitis C virus (HCV) infection is the major etiology of chronic liver disease. Polymorphisms in the IL-28B gene region are important in predicting outcome following therapy for chronic hepatitis C virus infection. The aim of this study was to detect the relationship between IL-28B polymorphism and responses to therapy in patients infected with genotype 4. This study included one hundred chronic hepatitis C patients infected with genotype 4, received PEG-IFNα2b plus ribavirin for 24 weeks, as well as, 20 healthy subjects serving as control. Clinical and laboratory parameters, including genetic variation near the IL-28B gene (rs8099917 and rs12979860), were assessed. The results of this study showed significant difference between responders and non-responders as regard SNPs in the interleukin 28B gene at rs8099917 and rs12979860. In rs8099917, TT genotypes had more frequency in responders than GG genotypes. On the other hand, CC genotype in rs12979860 had more frequency in responders than TT genotype. By multiple regression analysis, rs8099917 (TT), total bilirubin, and prothrombin time were independent factors affecting the response to treatment. This results demonstrate that in HCV genotype 4-infected patients, rs12979860 (CC) and rs8099917 (TT) genotypes may identify patients who are likely to respond to treatment. IL-28B SNPs are good predictors of response to combination therapy of HCV.