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1.
Int J Mol Sci ; 25(2)2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38255857

RESUMEN

Twenty-nine patients with HCV infection (HCV+) and mixed cryoglobulinemia (MC+) were retrospectively selected and matched for age and sex with 31 HCV+ MC- patients. Biomarkers of cholestasis (direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase), HCV-RNA and genotype, and plasma cryoprecipitates were measured before and after virus eradication; liver histology and plasma cells (aggregation and distribution), observed blinded by two pathologists, were analyzed. Sixty participants (mean age: 56.5; range: 35-77, males: 50%) with HCV infection were enrolled. Cholestasis (≥2 pathologically increased cholestasis biomarkers) was significantly higher in the MC group (p = 0.02) and correlated with cryoglobulinemia (OR 6.52; p = 0.02). At liver histological assessment, plasma cells were significantly increased in the MC+ group (p = 0.004) and tended to form aggregates more than the control group (p = 0.05). At multivariate analysis with MC, age, HCV-RNA, HBV diabetes, and cirrhosis, cholestasis was only significantly correlated to MC (OR 8.30; p < 0.05). In 25% patients, MC persisted after virus eradication with new antiviral treatment. Our study identified for the first time an association between MC, cholestasis, and an increased number of intrahepatic plasma cells in chronic hepatitis C (CHC) patients before virus eradication. Future studies are required to understand how MC contributes to liver damage and how its persistence affects the patients' follow-up after antiviral therapies.


Asunto(s)
Colestasis , Crioglobulinemia , Hepatitis C Crónica , Hepatitis C , Masculino , Humanos , Persona de Mediana Edad , Antivirales/uso terapéutico , Estudios de Casos y Controles , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/etiología , Estudios Retrospectivos , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Colestasis/complicaciones , Colestasis/tratamiento farmacológico , Biomarcadores , ARN
2.
Hepatology ; 76(1): 220-232, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34919289

RESUMEN

BACKGROUND AND AIMS: Mixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium-term to long-term period. APPROACH AND RESULTS: Direct-acting antiviral-treated cryoglobulinemic patients, consecutively enrolled in the multicentric Italian Platform for the Study of Viral Hepatitis Therapy cohort, were prospectively evaluated. Cumulative incidence Kaplan-Meier curves were reported for response, clinical deterioration, relapse and relapse-free survival rates. Cox regression analysis evaluated factors associated with different outcomes. A clinical response was reported in at least one follow-up point for 373 of 423 (88%) patients with CV who achieved SVR. Clinical response increased over time with a 76% improvement rate at month 12 after the end of treatment. A full complete response (FCR) was reached by 164 (38.8%) patients in at least one follow-up point. CV clinical response fluctuated, with some deterioration of the initial response in 49.6% of patients (median time of deterioration, 19 months). In patients who achieved FCR and had an available follow-up (137 patients) a relapse was observed in 13% and it was transient in 66.7% of patients. The rate of patients without any deterioration was 58% and 41% at 12 and 24 months, respectively. After achieving SVR, a clinical nonresponse was associated with older age and renal involvement; a clinical deterioration/relapse was associated with high pretreatment rheumatoid factor values, and FCR was inversely associated with age, neuropathy, and high cryocrit levels. CONCLUSION: In patients with CV, HCV eradication may not correspond to a persistent clinical improvement, and clinical response may fluctuate. This implies an attentive approach to post-SVR evaluation through prognostic factors and tailored treatment.


Asunto(s)
Deterioro Clínico , Crioglobulinemia , Hepatitis C Crónica , Vasculitis , Antivirales/uso terapéutico , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/etiología , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Estudios Prospectivos , Recurrencia , Respuesta Virológica Sostenida , Vasculitis/tratamiento farmacológico
3.
J Viral Hepat ; 27(11): 1214-1221, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32593212

RESUMEN

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.


Asunto(s)
Antivirales , Hepacivirus , Hepatitis C Crónica , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/tratamiento farmacológico , Masculino
4.
Hepatology ; 66(6): 1814-1825, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28741307

RESUMEN

We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus-infected patients: policy 1, "universal," treat all patients, regardless of fibrosis stage; policy 2, treat only "prioritized" patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus-infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies' cost-effectiveness. The patients' age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post-sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis. CONCLUSION: Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases when lowering treatment prices in early fibrosis stages. (Hepatology 2017;66:1814-1825).


Asunto(s)
Antivirales/economía , Política de Salud/economía , Hepatitis C/tratamiento farmacológico , Modelos Económicos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Análisis Costo-Beneficio , Hepatitis C/economía , Humanos , Persona de Mediana Edad , Adulto Joven
5.
Liver Int ; 38(12): 2190-2198, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29900654

RESUMEN

BACKGROUND & AIMS: Advances in direct-acting antiviral treatment of HCV have reinvigorated public health initiatives aimed at identifying affected individuals. We evaluated the possible impact of only diagnosed and linked-to-care individuals on overall HCV burden estimates and identified a possible strategy to achieve the WHO targets by 2030. METHODS: Using a modelling approach grounded in Italian real-life data of diagnosed and treated patients, different linkage-to-care scenarios were built to evaluate potential strategies in achieving the HCV elimination goals. RESULTS: Under the 40% linked-to-care scenario, viraemic burden would decline (60%); however, eligible patients to treat will be depleted by 2025. Increased case finding through a targeted screening strategy in 1948-1978 birth cohorts could supplement the pool of diagnosed patients by finding 75% of F0-F3 cases. Under the 60% linked-to-care scenario, viraemic infections would decline by 70% by 2030 but the patients eligible for treatment will run out by 2028. If treatment is to be maintained, a screening strategy focusing on 1958-1978 birth cohorts could capture 55% of F0-F3 individuals. Under the 80% linked-to-care scenario, screening limited in 1968-1978 birth cohorts could sustain treatment at levels required to achieve the HCV elimination goals. CONCLUSION: In Italy, which is an HCV endemic country, the eligible pool of patients to treat will run out between 2025 and 2028. To maintain the treatment rate and achieve the HCV elimination goals, increased case finding in targeted, high prevalence groups is required.


Asunto(s)
Causas de Muerte , Erradicación de la Enfermedad/tendencias , Hepatitis C/epidemiología , Mortalidad/tendencias , Viremia/epidemiología , Antivirales/uso terapéutico , Carcinoma Hepatocelular/mortalidad , Costo de Enfermedad , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Humanos , Italia/epidemiología , Cirrosis Hepática/mortalidad , Neoplasias Hepáticas/mortalidad , Cadenas de Markov , Respuesta Virológica Sostenida , Viremia/diagnóstico , Viremia/tratamiento farmacológico , Organización Mundial de la Salud
6.
Liver Int ; 36(1): 49-58, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26104535

RESUMEN

BACKGROUND & AIMS: The addition of protease inhibitors, boceprevir (BOC) or telaprevir (TRV), to peg-interferon and ribavirin (PR) increases the incidence of anaemia in patients with chronic hepatitis C virus (HCV) infection. Although genetic variants in inosine triphosphatase (ITPA) gene have been linked to the haemolytic anaemia induced by PR, the mechanism sustaining severe anaemia during triple therapy is still unknown. This study aims to elucidate the molecular mechanisms underlying anaemia in chronic HCV patients with combined therapy. METHODS: We studied 59 patients with chronic HCV genotype-1: 29 treated with TRV/PR and 30 with BOC/PR. We evaluated biochemical and haematological parameters, red cell index at baseline, 4, 12, 16 and 24 weeks of treatment; in a subgroup, we performed functional studies: osmotic fragility, red cell membrane protein separation, mass spectrometry analysis, quantification of erythroid microparticles release. IL28B and ITPA polymorphisms were also evaluated. RESULTS: We found early acute normochromic normocytic haemolytic anaemia (4-8 weeks) followed by a late macrocytic hypo-regenerative anaemia with inappropriate low reticulocyte count (12-24 weeks). Studies on red cells revealed: (i) presence of spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in red cell membrane protein composition; (iv) reduced membrane-cytoskeleton stability; (v) increased release of erythroid microparticles. ITPA polymorphisms impacted only the early phase of anaemia. CONCLUSIONS: The bimodal pattern of anaemia in chronic HCV patients on triple therapy might be because of acquired spherocytic-like anaemia in the early phase, followed by hyporegenerative anaemia, most likely related to the combined effects of PR and TRV or BOC on erythropoiesis.


Asunto(s)
Anemia , Eritropoyesis/efectos de los fármacos , Hepatitis C Crónica , Oligopéptidos , Prolina/análogos & derivados , Adulto , Anciano , Anemia/sangre , Anemia/inducido químicamente , Anemia/diagnóstico , Anemia/genética , Anemia/fisiopatología , Antivirales/administración & dosificación , Antivirales/efectos adversos , Monitoreo de Drogas/métodos , Quimioterapia Combinada , Índices de Eritrocitos , Membrana Eritrocítica , Femenino , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Polimorfismo de Nucleótido Simple , Prolina/administración & dosificación , Prolina/efectos adversos , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/efectos adversos , Pirofosfatasas/genética , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Resultado del Tratamiento
7.
Gut ; 64(2): 322-31, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24815676

RESUMEN

OBJECTIVE: Reliable tools to predict long-term outcome among patients with well compensated advanced liver disease due to chronic HCV infection are lacking. DESIGN: Risk scores for mortality and for cirrhosis-related complications were constructed with Cox regression analysis in a derivation cohort and evaluated in a validation cohort, both including patients with chronic HCV infection and advanced fibrosis. RESULTS: In the derivation cohort, 100/405 patients died during a median 8.1 (IQR 5.7-11.1) years of follow-up. Multivariate Cox analyses showed age (HR=1.06, 95% CI 1.04 to 1.09, p<0.001), male sex (HR=1.91, 95% CI 1.10 to 3.29, p=0.021), platelet count (HR=0.91, 95% CI 0.87 to 0.95, p<0.001) and log10 aspartate aminotransferase/alanine aminotransferase ratio (HR=1.30, 95% CI 1.12 to 1.51, p=0.001) were independently associated with mortality (C statistic=0.78, 95% CI 0.72 to 0.83). In the validation cohort, 58/296 patients with cirrhosis died during a median of 6.6 (IQR 4.4-9.0) years. Among patients with estimated 5-year mortality risks <5%, 5-10% and >10%, the observed 5-year mortality rates in the derivation cohort and validation cohort were 0.9% (95% CI 0.0 to 2.7) and 2.6% (95% CI 0.0 to 6.1), 8.1% (95% CI 1.8 to 14.4) and 8.0% (95% CI 1.3 to 14.7), 21.8% (95% CI 13.2 to 30.4) and 20.9% (95% CI 13.6 to 28.1), respectively (C statistic in validation cohort = 0.76, 95% CI 0.69 to 0.83). The risk score for cirrhosis-related complications also incorporated HCV genotype (C statistic = 0.80, 95% CI 0.76 to 0.83 in the derivation cohort; and 0.74, 95% CI 0.68 to 0.79 in the validation cohort). CONCLUSIONS: Prognosis of patients with chronic HCV infection and compensated advanced liver disease can be accurately assessed with risk scores including readily available objective clinical parameters.


Asunto(s)
Hepatitis C Crónica/complicaciones , Cirrosis Hepática/virología , Modelos Estadísticos , Adulto , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/mortalidad , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Pronóstico , Reproducibilidad de los Resultados , Medición de Riesgo/métodos
8.
Dig Liver Dis ; 56(9): 1522-1528, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38281869

RESUMEN

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a severe complication of advanced liver disease. A significant number of ACLF patients have not clear precipitating factors. The aim of the study was to investigate the role of alterations in porto-hepatic hemodynamics, especially non-forward portal flow (NFPF), in ACLF and liver-related mortality. METHODS: 233 cirrhotic patients were included in the study with a median follow-up of 24 months. Color-Doppler ultrasound was used to assess portal vein patency, flow direction and significant porto-systemic collaterals (>8 mm). Patients with active cancer, both at baseline and during follow-up and severe non liver-related comorbidities were excluded. ACLF and liver-related mortality were recorded during follow-up. RESULTS: Fifty-six patients (24%) developed ACLF; 24 (10,3%) had baseline NFPF. In survival analysis, NFPF, but not portal vein thrombosis, was independently associated with ACLF development (HR 2.85 95% C.I. [1.49-5.42], p = 0.001) and liver-related mortality (HR 2.24 95% C.I. [1.16-4.28], p = 0.015), even after adjustment for liver disease severity scores, age and etiology of liver disease. CONCLUSION: NFPF is independently associated with ACLF development and liver-related mortality, regardless of etiology, severity disease scores and portal vein thrombosis. Although there is no specific measure to reverse NFPF, patients with NFPF should receive prompt intensive management and urgent prioritization for liver transplantation. CLINICAL TRIAL NUMBER: 2730 CESC.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Hemodinámica , Cirrosis Hepática , Vena Porta , Humanos , Insuficiencia Hepática Crónica Agudizada/fisiopatología , Insuficiencia Hepática Crónica Agudizada/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Vena Porta/fisiopatología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/fisiopatología , Anciano , Ultrasonografía Doppler en Color , Adulto , Análisis de Supervivencia
9.
United European Gastroenterol J ; 12(3): 352-363, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38032175

RESUMEN

BACKGROUND & AIMS: Sustained virological response (SVR) by direct-acting antivirals (DAAs) may reverse the hypercoagulable state of HCV cirrhosis and the portal vein thrombosis (PVT) risk. We evaluated the incidence and predictive factors of de novo, non-tumoral PVT in patients with cirrhosis after HCV eradication. METHODS: Patients with HCV-related cirrhosis, consecutively enrolled in the multi-center ongoing PITER cohort, who achieved the SVR using DAAs, were prospectively evaluated. Kaplan-Meier and competing risk regression analyses were performed. RESULTS: During a median time of 38.3 months (IQR: 25.1-48.7 months) after the end of treatment (EOT), among 1609 SVR patients, 32 (2.0%) developed de novo PVT. A platelet count ≤120,000/µL, albumin levels ≤3.5 mg/dL, bilirubin >1.1 mg/dL, a previous liver decompensation, ALBI, Baveno, FIB-4, and RESIST scores were significantly different (p < 0.001), among patients who developed PVT versus those who did not. Considering death and liver transplantation as competing risk events, esophageal varices (subHR: 10.40; CI 95% 4.33-24.99) and pre-treatment ALBI grade ≥2 (subHR: 4.32; CI 95% 1.36-13.74) were independent predictors of PVT. After HCV eradication, a significant variation in PLT count, albumin, and bilirubin (p < 0.001) versus pre-treatment values was observed in patients who did not develop PVT, whereas no significant differences were observed in those who developed PVT (p > 0.05). After the EOT, esophageal varices and ALBI grade ≥2, remained associated with de novo PVT (subHR: 9.32; CI 95% 3.16-27.53 and subHR: 5.50; CI 95% 1.67-18.13, respectively). CONCLUSIONS: In patients with HCV-related cirrhosis, a more advanced liver disease and significant portal hypertension are independently associated with the de novo PVT risk after SVR.


Asunto(s)
Várices Esofágicas y Gástricas , Hepatitis C Crónica , Trombosis de la Vena , Humanos , Antivirales/uso terapéutico , Vena Porta , Várices Esofágicas y Gástricas/complicaciones , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Medición de Riesgo , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Albúminas/uso terapéutico , Bilirrubina
10.
Int J Infect Dis ; 146: 107115, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38801968

RESUMEN

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.


Asunto(s)
Hepatitis D Crónica , Virus de la Hepatitis Delta , Humanos , Femenino , Masculino , Italia/epidemiología , Hepatitis D Crónica/epidemiología , Adulto , Persona de Mediana Edad , Estudios Transversales , Virus de la Hepatitis Delta/inmunología , Virus de la Hepatitis Delta/genética , Estudios de Cohortes , Cirrosis Hepática/epidemiología , Cirrosis Hepática/virología , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Comorbilidad , Anciano , Antígenos de Superficie de la Hepatitis B/sangre , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/virología , Interferones/uso terapéutico , Antivirales/uso terapéutico
11.
Hepatology ; 56(5): 1641-50, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22610885

RESUMEN

UNLABELLED: Vitamin D deficiency seems to predict the unsuccessful achievement of sustained viral response (SVR) after antiviral treatment in hepatitis C virus (HCV) difficult-to-treat genotypes. Vitamin D binding protein (GC) gene polymorphisms are known to influence vitamin D levels. This study was performed to assess whether the interaction between basal circulating vitamin D and the GC polymorphism plays a role in influencing the rate of antiviral responses in patients affected by chronic hepatitis C. In all, 206 HCV patients treated with a combination therapy of pegylated (PEG)-interferon plus ribavirin were retrospectively evaluated. GC rs7041 G>T, GC rs4588 C>A, and IL-28B rs12979860 C>T polymorphisms were genotyped. Frequencies of GC rs7041 G>T and rs4588 C>A polymorphisms were: G/G = 64 (31.1%), G/T = 100 (48.5%), T/T = 42 (20.4%) and C/C = 108 (52.4%), C/A = 84 (40.8%), A/A = 14 (6.8%). Patients were divided into those carrying ≥3 major alleles (wildtype [WT]+: G-C/G-C, G-C/T-C, G-C/G-A, N = 100) and the remaining (WT-: G-C/T-A, T-A/T-C, T-A/T-A, T-C/T-C, N = 106). Four groups were identified: vitamin D ≤20 ng/mL and WT-, vitamin D ≤20 and WT+, vitamin D >20 and WT-, vitamin D >20 and WT+. In difficult-to-treat HCV genotypes the proportion of patients achieving SVR significantly increased with a linear trend from the first to the last group: 6/25 (24.0%), 9/24 (37.5%), 12/29 (41.4%), 19/29 (65.5%) (P = 0.003). At multivariate analysis, having basal vitamin D >20 ng/mL plus the carriage of GC WT+ was found to be an independent predictor of SVR (odds ratio 4.52, P = 0.015). CONCLUSION: In difficult-to-treat HCV genotypes, simultaneous pretreatment normal serum vitamin D levels and the carriage of GC-globulin WT isoform strongly predicts the achievement of SVR after PEG-interferon plus ribavirin antiviral therapy.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Proteína de Unión a Vitamina D/genética , Vitamina D/sangre , Adolescente , Adulto , Anciano , Alelos , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/sangre , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Interferones , Interleucinas/genética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Polietilenglicoles/uso terapéutico , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Ribavirina/uso terapéutico , Resultado del Tratamiento , Adulto Joven
12.
Intern Emerg Med ; 18(5): 1397-1404, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37212944

RESUMEN

Chronic anaemia in advanced liver disease is a frequent finding. The aim was to explore the clinical impact of spur cell anaemia, a rare entity typically associated with end-stage of the disease. One-hundred and nineteen patients (73.9% males) with liver cirrhosis of any etiology were included. Patients with bone marrow diseases, nutrients deficiencies and hepatocellular carcinoma were excluded. In all patients, a blood sample was collected to check for the presence of spur cells on blood smear. A complete blood biochemical panel was recorded together with Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) score. For each patients, clinically relevant events, such as acute-on-chronic liver failure (ACLF) and 1 year liver-related mortality, were registered. Patients were then grouped according to the percentage of spur cells at smear (> 5%, 1-5%, < 1%). Severe anaemia was defined as haemoglobin levels lower than 8 g/dL. 9.2% of subjects had > 5% spur cells, only 2 had evidence of haemolysis. In patients with > 5% spur cells, haemoglobin and albumin were lower compared with the other sub-group, while MELD score, CP score, International Normalized Ratio, ferritin, creatinine and unconjugated bilirubin were higher. Patients with more spur cells were more decompensated and developed more frequently ACLF. ACLF and liver-related mortality were significantly and independently associated with the presence of > 5% spur cells but not with baseline severe anaemia. Cirrhotic patients have a fairly high prevalence of spur cells, not always associated with severe haemolytic anaemia. The presence of spur red cells is per se associated with a worse prognosis and, therefore, should be always evaluated to prioritize patients for intensive management and eventually liver transplantation.


Chronic anaemia is a frequent finding in liver cirrhosis and spur cell anaemia has been shown to be an uncommon non-immune haemolytic disease typically related to advanced-liver disease. In our study, spur cell anaemia (spur cells >5%) was found in almost 10% of outpatient cirrhotics and was significantly related to more decompensated disease, higher incidence of ACLF and 1 year liver-related mortality. More importantly, the vast majority of patients with high percentage of spur cells did not have severe anaemia. Therefore, spur cells should be searched for in patients with advanced liver disease by a simple blood smear evaluation, even in the absence of significant anaemia, because of relevant prognostic impact and in order to prioritize patients to intensive management and possibly liver transplantation.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Anemia , Enfermedad Hepática en Estado Terminal , Masculino , Humanos , Femenino , Insuficiencia Hepática Crónica Agudizada/complicaciones , Enfermedad Hepática en Estado Terminal/complicaciones , Índice de Severidad de la Enfermedad , Cirrosis Hepática/complicaciones , Pronóstico , Anemia/complicaciones
13.
PLoS One ; 18(2): e0281813, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36795664

RESUMEN

BACKGROUND AND PURPOSE: Bacterial infections represent a major cause of morbidity and mortality in cirrhotic patients. Our aim was to assess the incidence of bacterial infections, in particular due to multidrug-resistant organisms (MDROs) before and after the introduction of the antimicrobial stewardship program, "Stewardship Antimicrobial in VErona" (SAVE). In addition, we also analysed the liver complications and the crude mortality during the whole follow up. METHODS: We analysed 229 cirrhotic subjects without previous hospitalization for infections enrolled at the University Verona Hospital from 2017 to 2019 and followed up until December 2021 (mean follow-up 42.7 months). RESULTS: 101 infections were recorded and 31.7% were recurrent. The most frequent were sepsis (24.7%), pneumonia (19.8%), spontaneous bacterial peritonitis (17.8%). 14.9% of infections were sustained by MDROs. Liver complications occurred more frequently in infected patients, and in case of MDROs infections with a significantly higher MELD and Child-Pugh score. In Cox regression analysis, mortality was associated with age, diabetes and bacterial infections episodes (OR 3.30, CI 95%: (1.63-6.70). Despite an increase in total infections over the past three years, a decrease in the incidence rate in MDROs infections was documented concurrently with the introduction of SAVE (IRD 28.6; 95% CI: 4.6-52.5, p = 0.02). CONCLUSIONS: Our study confirms the burden of bacterial infections in cirrhotic patients, especially MDROs, and the strong interconnection with liver complications. The introduction of SAVE decreased MDROs infections. Cirrhotic patients require a closer clinical surveillance to identify colonized patients and avoid the horizontal spread of MDROs in this setting.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Infecciones Bacterianas , Humanos , Estudios de Cohortes , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Enterococcus , Bacterias Gramnegativas , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple , Antibacterianos/uso terapéutico , Antibacterianos/farmacología
14.
Hepatol Commun ; 7(11)2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37870985

RESUMEN

BACKGROUND: Vaccine hesitancy and lack of access remain major issues in disseminating COVID-19 vaccination to liver patients globally. Factors predicting poor response to vaccination and risk of breakthrough infection are important data to target booster vaccine programs. The primary aim of the current study was to measure humoral responses to 2 doses of COVID-19 vaccine. Secondary aims included the determination of factors predicting breakthrough infection. METHODS: COVID-19 vaccination and Biomarkers in cirrhosis And post-Liver Transplantation is a prospective, multicenter, observational case-control study. Participants were recruited at 4-10 weeks following first and second vaccine doses in cirrhosis [n = 325; 94% messenger RNA (mRNA) and 6% viral vaccine], autoimmune liver disease (AILD) (n = 120; 77% mRNA and 23% viral vaccine), post-liver transplant (LT) (n = 146; 96% mRNA and 3% viral vaccine), and healthy controls (n = 51; 72% mRNA, 24% viral and 4% heterologous combination). Serological end points were measured, and data regarding breakthrough SARS-CoV-2 infection were collected. RESULTS: After adjusting by age, sex, and time of sample collection, anti-Spike IgG levels were the lowest in post-LT patients compared to cirrhosis (p < 0.0001), AILD (p < 0.0001), and control (p = 0.002). Factors predicting reduced responses included older age, Child-Turcotte-Pugh B/C, and elevated IL-6 in cirrhosis; non-mRNA vaccine in AILD; and coronary artery disease, use of mycophenolate and dysregulated B-call activating factor, and lymphotoxin-α levels in LT. Incident infection occurred in 6.6%, 10.6%, 7.4%, and 15.6% of cirrhosis, AILD, post-LT, and control, respectively. The only independent factor predicting infection in cirrhosis was low albumin level. CONCLUSIONS: LT patients present the lowest response to the SARS-CoV-2 vaccine. In cirrhosis, the reduced response is associated with older age, stage of liver disease and systemic inflammation, and breakthrough infection with low albumin level.


Asunto(s)
COVID-19 , Trasplante de Hígado , Vacunas Virales , Humanos , Albúminas , Infección Irruptiva , Estudios de Casos y Controles , COVID-19/prevención & control , Vacunas contra la COVID-19 , Cirrosis Hepática , Trasplante de Hígado/efectos adversos , Estudios Prospectivos , ARN Mensajero , SARS-CoV-2 , Vacunación
15.
Hepatology ; 53(4): 1118-26, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21480318

RESUMEN

UNLABELLED: The widely accepted interleukin-28B (IL-28B) rs12979860 C/T polymorphism and the more recently proposed vitamin D serum concentration are two novel predictors of the response to antiviral treatment in chronic hepatitis C virus (HCV) infection. This study aimed to verify whether the IL-28B rs12979860 C/T polymorphism and pretreatment serum vitamin D levels have independent or complementary roles in predicting the rates of sustained viral response (SVR). The present study included 211 consecutive, treatment-naïve chronic HCV patients who had their pretreatment serum 25-OH vitamin D level and IL-28B rs12979860 C/T genotype determined. Overall, SVR was achieved by 134/211 (63.5%) patients and by 47/110 (42.7%) patients infected with difficult-to-treat HCV genotypes. On multivariate analysis, SVR was predicted by the HCV genotype, the IL-28B rs12979860 C/T polymorphism, and gamma-glutamyl transpeptidase, HCV RNA, cholesterol, and 25-OH vitamin D serum levels, with an area under the receiver operating characteristic (ROC) curve of 0.827. When difficult-to-treat HCV genotypes were analyzed separately, the SVR was predicted by the IL-28B rs12979860 C/T polymorphism, viral load, and serum vitamin D level, with an area under the ROC curve of 0.836. Moreover, by categorizing these latter patients into four groups-C/C homozygotes with vitamin D levels >20 ng/mL (group A) or ≤20 ng/mL (group B) and C/T heterozygotes or T/T homozygotes with vitamin D levels >20 ng/mL (group C) or ≤20 ng/mL (group D)-a significant linear trend was observed, with SVR rates in the following descending order: group A, 18/21 (85.7%); group B, 6/11 (54.5%); group C, 14/38 (36.8%); and group D, 9/40 (22.5%) (P < 0.0001). CONCLUSION: Vitamin D serum levels are complementary to the IL-28B rs12979860 C/T polymorphism in enhancing the correct prediction of the SVR in treatment-naïve chronic hepatitis C.


Asunto(s)
Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Interleucinas/genética , Deficiencia de Vitamina D/genética , Adolescente , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Hepatitis C Crónica/complicaciones , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Interferones , Masculino , Persona de Mediana Edad , Polietilenglicoles/uso terapéutico , Polimorfismo Genético , Proteínas Recombinantes , Ribavirina/uso terapéutico , Carga Viral , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico
16.
J Dig Dis ; 23(5-6): 324-330, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35700113

RESUMEN

OBJECTIVES: Hepatitis C virus (HCV) infection is associated with an increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The impact of HCV eradication on the metabolic profile in diabetic patients treated with direct-acting antiviral agents (DAAs) is not well defined. The aim of our study was to evaluate the effects of DAAs on a lipid and glucose profile in a cohort of diabetic patients with different liver fibrotic stages. METHODS: T2DM patients with active HCV infection were consecutively enrolled in this prospective trial. Glycolipidic status was assessed, before starting DAA treatment (T0) and at 12 months after the beginning of treatment (T1). Liver fibrotic stage was assessed by FibroScan. RESULTS: In all, 131 patients were enrolled and all of them achieved a sustained virologic response. At baseline, no significant differences were found in lipid and glucose profiles in subgroup analysis by liver fibrosis, HCV genotype, and cardiovascular risk factors. At T1, total cholesterol and low-density lipoprotein cholesterol, but not triglycerides, significantly increased irrespective of liver fibrotic stage and baseline anthropometric and clinical profiles, while glycated hemoglobin significantly decreased only in F4 patients. CONCLUSIONS: HCV eradication in diabetic patients is associated with a worsening lipid profile that could impact future cardiovascular risk. A careful global monitoring of cardiovascular risk factors in all diabetic patients after HCV eradication is needed.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hepatitis C Crónica , Antivirales/uso terapéutico , Colesterol , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa/farmacología , Glucosa/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Lípidos , Cirrosis Hepática/complicaciones , Estudios Prospectivos , Respuesta Virológica Sostenida
17.
Dig Liver Dis ; 53(12): 1603-1609, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33893040

RESUMEN

BACKGROUND: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. METHODS: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. RESULTS: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. CONCLUSION: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.


Asunto(s)
Hepatitis C Crónica/epidemiología , Migrantes/estadística & datos numéricos , Anciano , Antivirales/uso terapéutico , Coinfección/epidemiología , Comorbilidad , Femenino , Hepacivirus , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad
18.
Hepatol Int ; 14(3): 362-372, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32279177

RESUMEN

BACKGROUND: Liver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated. METHODS: Patients consecutively enrolled in PITER between April 2014 and June 2019 and with at least 12-weeks follow-up following treatment were analysed. Cox regression analysis were used to evaluate HIV coinfection and factors independently associated with liver disease outcomes following viral eradication in DAA treated patients with pre-treatment liver cirrhosis. RESULTS: 93 HIV/HCV coinfected and 1109 HCV monoinfected patients were evaluated during a median follow-up of 26.7 (range 6-44.6) and 24.6 (range 6.8-47.3) months, respectively. No difference in the cumulative HCC incidence and hepatic decompensation was observed between coinfected and monoinfected patients. Age (Hazard Ratio [HR] = 1.08; 95% CI 1.04-1.13), male sex (HR = 2.76; 95% CI 1.28-5.96), lower albumin levels (HR = 3.94; 95% CI 1.81-8.58), genotype 3 (HR = 5.05; 95% CI 1.75-14.57) and serum anti-HBc positivity (HR = 1.99, 95% CI 1.01-3.95) were independently associated with HCC incidence. Older age (HR = 1.03; 95% CI 1.00-1.07), male sex (HR = 2.13; 95% CI 1.06-4.26) and lower albumin levels (HR = 3.75; 95% CI 1.89-7.46) were independently associated with the appearance of a decompensating event after viral eradication. CONCLUSION: Different demographic, clinical and genotype distribution between HIV coinfected vs those monoinfected, was observed in a representative cohort of HCV infected patients in Italy. Once liver cirrhosis is established the disease progression is decreased, but still persists regardless of viral eradication in both coinfected and monoinfected patients. In patients with cirrhosis, HIV coinfection was not associated with a higher probability of liver complications, after viral eradication.


Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular , Infecciones por VIH , Hepatitis C Crónica , Cirrosis Hepática , Neoplasias Hepáticas , Hígado , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/fisiopatología , Carcinoma Hepatocelular/virología , Coinfección , Progresión de la Enfermedad , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Incidencia , Italia/epidemiología , Hígado/fisiopatología , Hígado/virología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/fisiopatología , Cirrosis Hepática/virología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/fisiopatología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Pronóstico , Respuesta Virológica Sostenida
20.
PLoS One ; 12(2): e0172159, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28245248

RESUMEN

BACKGROUND: There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used. AIM: To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study. METHODS: Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org). RESULTS: Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate-to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI. CONCLUSIONS: Based on these results, we can estimate that 30-44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate-to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease.


Asunto(s)
Antivirales/efectos adversos , Antivirales/uso terapéutico , Interacciones Farmacológicas , Hepatitis C Crónica/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hepacivirus , Humanos , Interferones , Italia , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Riesgo
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