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1.
Gastroenterology ; 165(3): 696-716, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37263305

RESUMEN

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , COVID-19 , Humanos , América Latina/epidemiología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/genética , Estudios Prospectivos , COVID-19/complicaciones , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/epidemiología , Insuficiencia Hepática Crónica Agudizada/genética , Inflamación/complicaciones , Pronóstico
2.
J Viral Hepat ; 30(1): 56-63, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36197907

RESUMEN

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Humanos , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , América Latina/epidemiología , Perdida de Seguimiento , Hepacivirus/genética , Organización Mundial de la Salud
3.
Ann Hepatol ; 21: 100298, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33359234

RESUMEN

INTRODUCTION & OBJECTIVES: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. MATERIALS & METHODS: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. RESULTS: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7-47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4-16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9-21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1-14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1-2.0); P = 0.01], and severe COVID-19 (2.6 [2.0-3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. CONCLUSIONS: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. CLINICALTRIALS.GOV: NCT04358380.


Asunto(s)
COVID-19/epidemiología , Hospitalización/estadística & datos numéricos , Hepatopatías/epidemiología , SARS-CoV-2 , Comorbilidad , Femenino , Humanos , América Latina/epidemiología , Hepatopatías/diagnóstico , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo
4.
Ann Hepatol ; 25: 100350, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33864948

RESUMEN

INTRODUCTION AND OBJECTIVES: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PATIENTS: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. RESULTS: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). CONCLUSIONS: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.


Asunto(s)
COVID-19/epidemiología , Hospitalización , Cirrosis Hepática/epidemiología , Índice de Masa Corporal , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Cirrosis Hepática/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2 , América del Sur/epidemiología , Tasa de Supervivencia/tendencias
5.
J Viral Hepat ; 27(12): 1430-1436, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32813904

RESUMEN

Prisoners in most countries have a higher prevalence of HCV than the general population, but their access to treatment is very limited. Our aim was to evaluate a pilot programme using the ECHO model to enhance linkage to care in patients with HCV in 3 Argentinean prisons between October 2018 and January 2020. All inmates were invited to participate, and data were collected through a personal interview. We then estimated HCV prevalence with dried blood spot and performed a logistic regression analysis to identify risk behaviours associated with HCV infection. Finally, HCV management was assessed and monitored through ECHO. Overall, 1141 inmates agreed to participate, representing 39.7% of the total prison population. Anti-HCV prevalence was estimated at 1.58% (CI 0.93; 2.48), being significantly higher in women 2.98% (CI 1.4;5.6) than in men 1.07% (CI 0.5; 2.0); P = .03. Patients with anti-HCV were significantly older than those who tested negative, 42.3 years (CI 37.6;47.1) vs 30.1 years (CI 30.6;31.2), P < .001, respectively. Multiple logistic regression analysis, identified age OR 1.07 (CI 1.03;1.12, P = .001), history of sexually transmitted disease OR 3.08 (CI 0.97;9.82, P = .057) and intravenous drug use OR 12.6 (CI 3.31;48.53, P < .001) as risk factors associated with anti-HCV. Treatment was initiated in all the patients with specialist physician support utilizing ECHO model. In conclusion, our pilot study reported a low prevalence of anti-HCV in the studied population. Incarceration provides an ideal opportunity for testing and treating HCV. ECHO model arises as a useful tool to support assessment and treatment for inmates with chronic HCV.


Asunto(s)
Hepatitis C , Prisioneros , Femenino , Hepacivirus , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C , Humanos , Masculino , Proyectos Piloto , Prevalencia , Prisiones , Factores de Riesgo
6.
Ann Intern Med ; 171(7): 496-504, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31546256

RESUMEN

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is an extensive update of KDIGO's 2008 guideline on HCV infection in CKD. This update reflects the major advances since the introduction of direct-acting antivirals (DAAs) in the management of HCV infection in the CKD population. Methods: The KDIGO work group tasked with developing the HCV and CKD guideline defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence previously summarized by the evidence review team. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to appraise the quality of evidence and rate the strength of the recommendations. Searches of the English-language literature were conducted through May 2017 and were supplemented with targeted searches for studies of DAA treatment and with abstracts from nephrology, hepatology, and transplantation conferences. A review process involving many stakeholders, subject matter experts, and industry and national organizations informed the guideline's final modification. Recommendation: The updated guideline comprises 66 recommendations. This synopsis focuses on 32 key recommendations pertinent to the prevention, diagnosis, treatment, and management of HCV infection in adult CKD populations.


Asunto(s)
Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/terapia , Insuficiencia Renal Crónica/complicaciones , Antivirales/uso terapéutico , Transmisión de Enfermedad Infecciosa/prevención & control , Genotipo , Tasa de Filtración Glomerular , Hepacivirus/genética , Humanos , Trasplante de Riñón , Tamizaje Masivo , Pronóstico , Donantes de Tejidos , Receptores de Trasplantes
7.
Ann Hepatol ; 18(2): 338-344, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31053539

RESUMEN

INTRODUCTION AND AIM: Liver transplantation (LT) for acute liver failure (ALF) still has a high early mortality. We aimed to evaluate changes occurring in recent years and identify risk factors for poor outcomes. MATERIAL AND METHODS: Data were retrospectively obtained from the Argentinean Transplant Registry from two time periods (1998-2005 and 2006-2016). We used survival analysis to evaluate risk of death. RESULTS: A total of 561 patients were listed for LT (69% female, mean age 39.5±16.4 years). Between early and later periods there was a reduction in wait-list mortality from 27% to 19% (p<0.02) and 1-month post-LT survival rates improved from 70% to 82% (p<0.01). Overall, 61% of the patients underwent LT and 22% died on the waiting list. Among those undergoing LT, Cox regression analysis identified prolonged cold ischemia time (HR 1.18 [1.02-1.36] and serum creatinine (HR 1.31 [1.01-1.71]) as independent risk factors of death post-LT. Etiologies of ALF were only available in the later period (N=363) with indeterminate and autoimmune hepatitis accounting for 28% and 26% of the cases, respectively. After adjusting for age, gender, private/public hospital, INR, creatinine and bilirubin, and considering LT as the competing event, indeterminate etiology was significantly associated with death (SHR 1.63 [1.06-2.51] and autoimmune hepatitis presented a trend to improved survival (SHR 0.61 [0.36-1.05]). CONCLUSIONS: Survival of patients with ALF on the waiting list and after LT has significantly improved in recent years. Indeterminate cause and autoimmune hepatitis were the most frequent etiologies of ALF in Argentina and were associated with mortality.


Asunto(s)
Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Listas de Espera , Adulto , Argentina/epidemiología , Técnicas de Apoyo para la Decisión , Femenino , Supervivencia de Injerto , Estado de Salud , Indicadores de Salud , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/mortalidad , Humanos , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/mortalidad , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Obtención de Tejidos y Órganos , Resultado del Tratamiento , Listas de Espera/mortalidad , Adulto Joven
8.
Kidney Int ; 94(4): 663-673, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30243313

RESUMEN

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy and in those with a kidney transplant. Since the publication of the original Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2008, major advances in HCV management, particularly with the advent of direct-acting antiviral therapies, have now made the cure of HCV possible in CKD patients. In addition, diagnostic techniques have evolved to enable the noninvasive diagnosis of liver fibrosis. Therefore, the Work Group undertook a comprehensive review and update of the KDIGO HCV in CKD Guideline. This Executive Summary highlights key aspects of the guideline recommendations.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Trasplante de Riñón , Cirrosis Hepática/diagnóstico , Insuficiencia Renal Crónica/complicaciones , Infección Hospitalaria/prevención & control , Transmisión de Enfermedad Infecciosa/prevención & control , Tasa de Filtración Glomerular , Hepatitis C/complicaciones , Hepatitis C/prevención & control , Hepatitis C/transmisión , Humanos , Cirrosis Hepática/virología , Guías de Práctica Clínica como Asunto , Diálisis Renal , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia
9.
Liver Transpl ; 23(9): 1210-1215, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28590520

RESUMEN

The development of consortia has been useful for exploring challenging scenarios and uncharted territories in liver disease treatments. Several consortia already developed in the United States and Europe have become key factors in patient care decision-making processes and medical education, and they have also impacted policy makers' decisions. In Latin America, the situation is different. As a result of a combination of different factors, our region has not been able to develop networking advantages in research and education in liver diseases. Thus far, most of the initial experiences focused on the development of collaborative groups established to investigate a particular topic, which were dissolved once the questions were answered. It is the aim of this review to describe those difficulties we confront in developing multicenter liver consortia in Latin America, to identify those challenges we face, and also to describe the opportunities we have for improvement. Liver Transplantation 23 1210-1215 2017 AASLD.


Asunto(s)
Toma de Decisiones Clínicas/métodos , Atención a la Salud/organización & administración , Hepatopatías/terapia , Mejoramiento de la Calidad/organización & administración , Integración de Sistemas , Investigación Biomédica/organización & administración , Atención a la Salud/métodos , Educación Médica/organización & administración , Conocimientos, Actitudes y Práctica en Salud , Humanos , Colaboración Intersectorial , América Latina , Hepatopatías/diagnóstico , Educación del Paciente como Asunto , Calidad de la Atención de Salud
10.
J Med Virol ; 89(9): 1590-1596, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28370222

RESUMEN

Information about the use of ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r/DSV ± RBV) in real-clinical practice in Latin America is scarce. We aimed to confirm safety and effectiveness of OBV/PTV/r/DSV ± RBV therapy in real-world setting. We analyzed a cohort of patients with genotype 1 infection treated with OBV/PTV/r/DSV ± RBV. Data on demographics, clinical features, safety, and virological response were retrospectively collected from 21 centers in Latin America. A total of 96 patients received OBV/PTV/r/DSV, associated with RBV in 68% of the cases. Most were genotype 1b (80%), 56 (58%) had cirrhosis, and 45 (47%) failed prior HCV treatment. Adverse events occurred in 62% of patients. The most common adverse events were pruritus (21%), hyperbilirubinemia (17%), and asthenia (17%). Five patients discontinued therapy prematurely due to hepatic decompensation, three of them were Child-Pugh B at baseline and one patient died due to multi-organ failure. Follow up HCV-RNA 12 weeks after completion of therapy was evaluated in all the patients and sustained virologic response rate was 97%. No virologic breakthrough was detected. Our study confirms that OBV/PTV/r/DSV treatment is highly effective in patients with chronic HCV without cirrhosis or with Child-Pugh A cirrhosis in non-European populations. Adverse events were often mild and rarely led to treatment discontinuation except for patients with Child-Pugh B cirrhosis or with previous history of hepatic decompensation. These results can support the development of public strategies to expand the access of OBV/PTV/r + DSV and other DAAs combinations in order to reduce the burden of HCV infection in our region.


Asunto(s)
Antivirales/efectos adversos , Antivirales/uso terapéutico , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Hepatitis C Crónica/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/virología , Humanos , América Latina , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
12.
Liver Transpl ; 20(4): 483-9, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24425668

RESUMEN

There is significant geographic variation in the etiologies and prognoses of acute liver failure (ALF). The aims of the present study were to determine the causes and short-term outcomes of ALF in Argentina, to evaluate the performance of prognostic criteria, and to identify clinical prognostic factors of death. We performed a retrospective analysis of 154 adult patients with ALF who were admitted to 6 liver transplantation (LT) programs between June 2005 and December 2011. The most frequent causes of ALF were viral hepatitis B (46 patients or 30%), autoimmune hepatitis (AIH; 40 patients or 26%), and indeterminate causes (40 patients or 26%). No acetaminophen (ACM) overdose was reported. One hundred and twenty one patients (78%) were included on the waiting list, and LT was performed for 83 patients (54%). Overall survival rate is now corected to 73%. Multivariate logistic regression identified 2 independent variables associated with adverse outcomes on admission: a Model for End-Stage Liver Disease (MELD) score ≥ 29 and an encephalopathy grade ≥ 3. In a direct comparison using a receiving operating characteristic curve analysis, the MELD score [C statistic = 0.830, 95% confidence interval (CI) = 0.73-0.93] had better prognostic accuracy for predicting outcomes than the Clichy criteria (C statistic = 0.719, 95% CI = 0.58-0.85) or the King's College criteria (C statistic = 0.631, 95% CI = 0.49-0.77). In conclusion, hepatitis B and AIH were the most frequent causes of fulminant hepatic failure in our series, and no cases of ACM overdosing were identified. A MELD score ≥ 29 and an encephalopathy grade ≥ 3 at admission were associated with death. The MELD score at admission showed the highest prognostic accuracy.


Asunto(s)
Fallo Hepático Agudo/etiología , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Adulto , Argentina , Femenino , Hepatitis B/cirugía , Hepatitis Autoinmune/cirugía , Humanos , Fallo Hepático Agudo/diagnóstico , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Curva ROC , Estudios Retrospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
13.
Ann Hepatol ; 13(3): 327-36, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24756007

RESUMEN

BACKGROUND AND AIMS: Entecavir (ETV) is effective and safe in patients with chronic hepatitis B in the short term, but its long term efficacy and safety has not been established. MATERIAL AND METHODS: We evaluated HBV DNA clearance, HBeAg/antiHBe and HBsAg/antiHBs seroconversion rates in HBeAg-positive and negative NUC naïve HBV patients treated with ETV for more than 6 months, and predictors of response. RESULTS: A hundred and sixty nine consecutive patients were treated with ETV for a median of 181 weeks. 61% were HBeAg positive, 23% were cirrhotics, and mean HBV-DNA levels were 6,88 ± 1,74 log10 IU/mL. Overall, 156 (92%) patients became HBV DNA undetectable, 92 (88%) HBeAg positive and 64 (98%) HBeAg negative patients. Seventy four (71%) patients cleared HBeAg after a median of 48 weeks of treatment, 23 (14%) patients cleared HBsAg (19 HBeAg positive and 4 HBeAg negative, p 0.025) after a median of 96 weeks of treatment, and 22 (13%) patients developed protective titers of anti-HBs. At the end of the study, 35 (20%) patients had discontinued therapy: 33 HBeAg positive and 2 HBeAg negative; 9 of them (26%) developed virological relapse after a median of 48 weeks of stopping treatment. None of the patients had primary non response and one patient developed breakthrough. Two patients developed HCC, three underwent liver transplantation and 3 deaths were attributable to liver-related events. No serious adverse events were reported. CONCLUSION: Long term ETV treatment showed high virological response rates, and a favorable safety profile for NUC-naive HBeAg-positive and negative patients treated in clinical practice.


Asunto(s)
Antivirales/uso terapéutico , ADN Viral/sangre , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Carga Viral , Adulto , Anciano , Estudios de Cohortes , Femenino , Guanina/uso terapéutico , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/inmunología , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/cirugía , Trasplante de Hígado , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
14.
J Hepatol ; 59(1): 31-7, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23454058

RESUMEN

BACKGROUND & AIMS: To examine the antiviral activity of boceprevir, a hepatitis C virus (HCV) protease inhibitor, in HCV genotype (G) 2/3-infected patients. METHODS: We assessed boceprevir and telaprevir activity against an HCV G2 and G3 isolates enzyme panel, in replicon, and in phenotypic cell-based assays. Additionally, a phase I study evaluated the antiviral activity of boceprevir monotherapy (200mg BID, 400mg BID, or 400mg TID) vs. placebo for 14 days in HCV G2/3 treatment-naive patients. RESULTS: Boceprevir and telaprevir similarly inhibited G1 and G2 NS3/4A enzymes and replication in G1 and G2 replicon and cell-based assays. However, telaprevir demonstrated lower potency than boceprevir against HCV G3a enzyme (Ki=75 nM vs. 17 nM), in the G3a replicon assay (EC50=953 nM vs. 159 nM), and against HCV G3a NS3 isolates (IC50=3312 nM vs. 803 nM) in the cell-based assay. In HCV G2/3-infected patients, boceprevir (400 mg TID) resulted in a maximum mean decrease in HCV RNA of -1.60 log vs. -0.21 log with placebo. CONCLUSIONS: In vitro, boceprevir is more active than telaprevir against the HCV G3 NS3/4A enzyme in cell-based and biochemical assays and against G3 isolates in replicon assays. In HCV G2/3-infected treatment-naive patients, decreases in HCV RNA levels with boceprevir (400 mg TID) were comparable to those observed with the same dose in HCV treatment-experienced G1-infected patients.


Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Prolina/análogos & derivados , Adulto , Antivirales/administración & dosificación , Antivirales/farmacocinética , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/enzimología , Humanos , Cinética , Masculino , Persona de Mediana Edad , Oligopéptidos/uso terapéutico , Prolina/administración & dosificación , Prolina/farmacocinética , Prolina/uso terapéutico , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/farmacocinética , Inhibidores de Proteasas/uso terapéutico , ARN Viral/sangre , Replicón/efectos de los fármacos , Carga Viral/efectos de los fármacos , Proteínas no Estructurales Virales/antagonistas & inhibidores
15.
Clin Transplant ; 27(4): E469-77, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23758407

RESUMEN

Post-transplant lymphoproliferative disorder (PTLD) is a major and potentially life-threatening complication after solid-organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (± 14) yr with a mean time of 39.7 (± 35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second-line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post-PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post-PTLD mortality included lactate dehydrogenase ≥ 250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long-term survival is possible.


Asunto(s)
Rechazo de Injerto/etiología , Inmunosupresores/uso terapéutico , Fallo Hepático/cirugía , Trasplante de Hígado/efectos adversos , Trastornos Linfoproliferativos/etiología , Complicaciones Posoperatorias , Adulto , Anciano , Femenino , Estudios de Seguimiento , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/mortalidad , Humanos , Trasplante de Hígado/mortalidad , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , América del Sur , Tasa de Supervivencia , Factores de Tiempo , Adulto Joven
17.
Ann Pharmacother ; 45(7-8): e43, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21672886

RESUMEN

OBJECTIVE: To report a case of severe cholestatic hepatitis caused by thioctic acid in a patient with diabetic peripheral polyneuropathy and mild chronic renal failure. CASE SUMMARY: A 63-year-old man with type 2 diabetes, hypertension, hypothyroidism, and stage 2 chronic renal failure was referred to the outpatient liver clinic with fever, asthenia, nausea, and pruritus. Because of the presence of symptomatic diabetic neuropathy, he began treatment with thioctic acid 600 mg/day. Serum transaminase levels were measured before starting thioctic acid treatment and values were within the normal range. Symptoms progressively worsened and the patient developed a low-grade fever and evidence of increased serum liver enzyme levels 45 days after starting thioctic acid treatment: aspartate aminotransferase (AST) (114 IU/L [reference range <40]), alanine aminotransferase (ALT) (191 IU/L [<35]), alkaline phosphatase (ALP) (562 IU/L [<130]), and γ-glutamyltransferase (GGT) (592 IU/L [<50]). Thioctic acid treatment was discontinued 2 days after admission. Four months after the initial presentation, his AST, ALT, and ALP levels normalized and GGT level had decreased (88 IU/L). As the patient's neuropathic symptoms worsened, thioctic acid therapy was restarted. Two months after restarting therapy, pruritus, nausea, and asthenia reappeared and the patient's liver enzyme levels became clearly abnormal again (AST 100 IU/L, ALT 129 IU/L, ALP 161 IU/L, GGT 180 IU/L). Thioctic acid was stopped, and the patient's liver enzyme levels returned to normal 2 months later. DISCUSSION: Alpha-lipoic acid, also known as thioctic acid, improves metabolic glucose control and peripheral neuropathies associated with diabetes mellitus. Its administration appears to be safe and, as far as we know, there are no reports of liver toxicity associated with its use. Our patient developed acute cholestatic hepatitis after beginning treatment with thioctic acid. Use of the Roussel Uclaf causality assessment scale indicated that the association between thioctic acid treatment and our patient's drug-induced liver injury was highly probable; use of the Maria and Victorino scale indicated that the association was probable. CONCLUSIONS: To our knowledge, this is the first report of probable liver toxicity due to thioctic acid, a proposed "hepatoprotectant."


Asunto(s)
Antioxidantes/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Colestasis Intrahepática/inducido químicamente , Ácido Tióctico/efectos adversos , Antioxidantes/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colestasis Intrahepática/patología , Colestasis Intrahepática/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/complicaciones , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/tratamiento farmacológico , Monitoreo de Drogas , Humanos , Fallo Renal Crónico/complicaciones , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Persona de Mediana Edad , Recurrencia , Índice de Severidad de la Enfermedad , Ácido Tióctico/uso terapéutico , Resultado del Tratamiento
18.
Ann Hepatol ; 10(4): 452-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21911885

RESUMEN

BACKGROUND AND AIMS: Genetic variations in the interleukin 28B (IL28B) gene have been associated with viral response to PEG-interferon-α/ribavirin (PR) therapy in hepatitis C virus (HCV) genotype 1 infected patients from North America, Europe and Asia. The importance of these IL28B variants for Argentine patients remains unknown. MATERIAL AND METHODS: IL28B host genotypes (rs8099917 and rs12979860) were determined in a population of Argentine patients with European ancestry. Results were analyzed looking for their association with sustained virologic response (SVR) to PR therapy and compared with other baseline hosts' biochemical, histological and virological predictors of response. RESULTS: We studied 102 patients, 60% were men, and 40% of them were rs8099917 TT and 18% rs12979860 CC. Mean baseline serum HCV RNA was 1.673.092 IU/mL and mean F score was: 2.10 ± 1.18 (21% cirrhotic). SVR rate was higher in rs8099917 TT genotypes (55%) when compared to GT/GG (25%) (p = 0.002) and in rs1512979860 CC (64%) than in CT/TT (30%) (p = 0.004). The univariate analysis showed that rs8099917 TT (OR 3.7; 95 %CI 1.5-8.7; p = 0.002), rs12979860 CC (OR 4.6; 95%CI 1.5-13.7; p = 0.006), low viral load (OR 4.6; 95% CI 1.7-12.6; p = 0.002) and F0-2 (OR 8.5; 95% CI 2.3-30.6; p = 0.001) were significantly associated with SVR. In the multivariate analysis, rs12979860 CC, rs8099917 TT, viral load < 400.000 IU/mL and F0-2 were associated with SVR rates (p = 0.029, p = 0.012, p = 0.013 and p = 0.004, respectively). CONCLUSION: IL28B host genotypes should be added to baseline predictors of response to PR therapy in Latin American patients with European ancestry.


Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Interleucinas/genética , Polietilenglicoles/uso terapéutico , Polimorfismo de Nucleótido Simple , Ribavirina/uso terapéutico , Adulto , Argentina/epidemiología , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C/diagnóstico , Hepatitis C/etnología , Hepatitis C/genética , Hepatitis C/inmunología , Humanos , Interferón alfa-2 , Interferones , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Población Blanca/genética
19.
Medicina (B Aires) ; 81(2): 252-256, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33906144

RESUMEN

The clinical management of hepatitis C virus (HCV) infection presents several challenges today. WHO's goal is to eliminate it by 2030. It is an ambitious goal and difficult to meet given the barriers to care that arise. This is possible today thanks to the discovery of direct-acting antivirals (DAAs). This treatment achieves a high cure rate and is virtually free of adverse effects. To try to comply with this, in addition to the use of DAAs, it is necessary to reduce the rate of undiagnosed patients and facilitate the access of those diagnosed to care and treatment. For that, it is proposed to carry out a simplified treatment of HCV. This involves reducing controls during and after treatment. This simplification varies according to whether patients have cirrhosis or not. In this way, it seeks to increase significantly the number of patients treated and cured to reduce the burden on public health of this disease.


El manejo clínico de la infección por el virus la hepatitis C (HCV) varios desafíos en la actualidad. El objetivo de la OMS es eliminarlo para el 2030. Es un objetivo ambicioso y muy difícil de cumplir dadas las barreras al cuidado que se presentan. Sin embargo, esto es posible hoy gracias al descubrimiento de los antivirales de acción directa (AAD). Este tratamiento logra una alta tasa de curación y prácticamente está libre de efectos adversos. Para tratar de cumplirlo, además del uso de los AAD, es necesario reducir la tasa de pacientes no diagnosticados y facilitar el acceso de los diagnosticados al cuidado y el tratamiento. Para eso se propone llevar adelante el tratamiento simplificado del HCV. Esto implica reducir los controles durante y después del tratamiento. Esta simplificación varía según los pacientes tengan o no cirrosis. De esta manera se busca aumentar significativamente el número de pacientes tratados y curados para así poder reducir el impacto en la salud pública de esta enfermedad.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática
20.
Ann Hepatol ; 8(4): 390-5, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20009143

RESUMEN

Noncirrhotic portal hypertension (NCPH) represents a relatively infrequent group of conditions that causes portal hypertension in the absence of cirrhosis. An association between NCPH and patients infected with human immunodeficiency virus (HIV) has been reported. Six consecutive patients with HIV infection and NCPH were the subject of this series. Case histories, including medication lists, liver biopsy and laboratory data were reviewed. Age at diagnosis was 43 +/- 3 years (range, 37-47). Liver disease was diagnosed 12 +/- 4 years (range, 8-18) after initiation of antiretroviral therapy (ART). All patients developed esophageal varices, 5 patients presented at least one bleeding episode and 2 required TIPS. Serum liver tests showed a mean total bilirubin of 1.4 +/- .7 mg/dL (range, .5-2.5) and INR was 1.2 +/- .14 (range, 1.0-1.4). CD4 count was 326 +/- 124 cells/mL (range, 198-467) and all patients presented HIV viral load < 75 copes/mL. Didanosine (ddl) was the most common ART drug being used by 4 patients. Portal vein thrombosis was diagnosed in 2 patients. Hepatic portal sclerosis (HPS) alone was observed in 1 patient, nodular regenerative hyperplasia (NRH) alone in 2 patients and combined HPS/NRH in 3 patients. In conclusion, NCPH should be included in the differential diagnosis of HIV-individuals presenting with clinical manifestations of portal hypertension and well preserved liver synthetic function. Prolonged exposure to ART, specially ddl, can play a pathogenic role. Rarely, liver synthetic function is sufficiently severe to warrant liver transplantation.


Asunto(s)
Infecciones por VIH/complicaciones , Hipertensión Portal/complicaciones , Hipertensión Portal/diagnóstico , Hepatopatías/etiología , Adulto , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Didanosina/efectos adversos , Didanosina/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Hipertensión Portal/inducido químicamente , Masculino , Persona de Mediana Edad
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