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INTRODUCTION AND OBJECTIVES: Autoimmune liver diseases (AILDs) are rare and require precise evaluation, which is often challenging for medical providers. Chatbots are innovative solutions to assist healthcare professionals in clinical management. In our study, ten liver specialists systematically evaluated four chatbots to determine their utility as clinical decision support tools in the field of AILDs. MATERIALS AND METHODS: We constructed a 56-question questionnaire focusing on AILD evaluation, diagnosis, and management of Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Primary Sclerosing Cholangitis (PSC). Four chatbots -ChatGPT 3.5, Claude, Microsoft Copilot, and Google Bard- were presented with the questions in their free tiers in December 2023. Responses underwent critical evaluation by ten liver specialists using a standardized 1 to 10 Likert scale. The analysis included mean scores, the number of highest-rated replies, and the identification of common shortcomings in chatbots performance. RESULTS: Among the assessed chatbots, specialists rated Claude highest with a mean score of 7.37 (SD = 1.91), followed by ChatGPT (7.17, SD = 1.89), Microsoft Copilot (6.63, SD = 2.10), and Google Bard (6.52, SD = 2.27). Claude also excelled with 27 best-rated replies, outperforming ChatGPT (20), while Microsoft Copilot and Google Bard lagged with only 6 and 9, respectively. Common deficiencies included listing details over specific advice, limited dosing options, inaccuracies for pregnant patients, insufficient recent data, over-reliance on CT and MRI imaging, and inadequate discussion regarding off-label use and fibrates in PBC treatment. Notably, internet access for Microsoft Copilot and Google Bard did not enhance precision compared to pre-trained models. CONCLUSIONS: Chatbots hold promise in AILD support, but our study underscores key areas for improvement. Refinement is needed in providing specific advice, accuracy, and focused up-to-date information. Addressing these shortcomings is essential for enhancing the utility of chatbots in AILD management, guiding future development, and ensuring their effectiveness as clinical decision-support tools.
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This review aims to gather and disseminate updated information regarding hepatitis A virus (HAV) in Latin America (LA) in the last 11 years, including seroprevalence, post-vaccination studies, virus detection in aqueous matrices and food samples, and outbreak reports. Only 24 seroprevalence studies were published between 2012 and 2023 with 55%-100% reported prevalences of anti-HAV IgG. Among the 25 LA countries, only eight of them have introduced HAV vaccines into their immunisation programs. Outbreaks of hepatitis A occurred between 2017-2019, mainly affecting men who have sex with men in Argentina, Brazil and Chile, probably as a consequence of the abrupt decline of young adults' immunity. This could be due to that young adult have never been infected in childhood (due to socio-health improvements) and are above the cut-off ages to be included when the vaccination programs were introduced. Although scarce, studies focused on environmental and food HAV surveillance have shown viral presence in these samples. Surface waters presented HAV detections between 1.2% and 86.7%, and untreated wastewaters between 2.8% and 70.9%. Genotypes found in all cases were IA and IC. The only wastewater-based epidemiology study showed to be a useful tool as a complement of traditional epidemiological surveillance. Only four LA countries have looked for HAV in food samples, with genome detection rates between 9% and 33%. Latin American HAV circulation scenario is changing. In countries where socioeconomic and sanitary conditions have not improved, the virus persists with high endemicity and the access to the vaccine should be re-evaluated by local governments. In countries where access to clean water, better sanitary conditions and HAV immunisation programs have been implemented, the number of cases among young adults seems to be increasing, alerting health authorities.
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Vacunas contra la Hepatitis A , Virus de la Hepatitis A , Hepatitis A , Hepatitis A/epidemiología , Hepatitis A/virología , Hepatitis A/prevención & control , Humanos , América Latina/epidemiología , Estudios Seroepidemiológicos , Virus de la Hepatitis A/inmunología , Virus de la Hepatitis A/genética , Virus de la Hepatitis A/aislamiento & purificación , Vacunas contra la Hepatitis A/administración & dosificación , Vacunas contra la Hepatitis A/inmunología , Brotes de Enfermedades , Anticuerpos de Hepatitis A/sangre , GenotipoRESUMEN
BACKGROUND: Until 2005, when a single dose of vaccine was implemented in one-year-old children, the Hepatitis A virus (HAV) was responsible for approximately 90% of acute hepatitis cases in the paediatric population in Argentina. However, despite vaccination success, sporadic outbreaks of HAV still occur among adults. This study aimed to assess the seroepidemiology of HAV in Argentina, analysing IgG and IgM antibodies against HAV in a large population, both vaccinated and unvaccinated. METHODS: The study included 16,982 patients attending a hospital from 2001 to 2023. The cohort was divided into two groups: 16,638 individuals who were not reached by the vaccination program implemented in 2005 and 344 children who were covered by the universal vaccination. RESULTS: Anti-HAV IgG was detected in 56.7% of cases. The rate was significantly higher in individuals born after 2005 (77.7%) compared to those born before (56.3%), p < 0.001. The age groups 19-40 and 41-60 years showed the anti-HAV IgG lowest rates. On the other hand, 100/3956 cases (2.5%) with suspected acute hepatitis were positive for Anti-HAVIgM. Notably, none of these were born after the mandatory vaccine rollout. CONCLUSIONS: The study of this large cohort contributes to the understanding of the seroepidemiology of HAV. Although the implementation of the vaccine achieved its main goal, the age segment between 19 and 60 years does not reach the estimated threshold to achieve herd immunity. These findings reveal the importance of targeting vaccination campaigns, provide essential insights for public health planning, and guide future immunisation strategies against HAV in Argentina.
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Anticuerpos de Hepatitis A , Vacunas contra la Hepatitis A , Hepatitis A , Inmunoglobulina G , Inmunoglobulina M , Humanos , Argentina/epidemiología , Estudios Seroepidemiológicos , Hepatitis A/epidemiología , Hepatitis A/prevención & control , Adulto , Masculino , Femenino , Persona de Mediana Edad , Adulto Joven , Anticuerpos de Hepatitis A/sangre , Niño , Vacunas contra la Hepatitis A/administración & dosificación , Vacunas contra la Hepatitis A/inmunología , Adolescente , Preescolar , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lactante , Vacunación/estadística & datos numéricos , Virus de la Hepatitis A/inmunología , Anciano , Programas de InmunizaciónRESUMEN
INTRODUCTION AND OBJECTIVES: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. PATIENTS AND METHODS: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. CONCLUSIONS: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Pronóstico , Estudios Prospectivos , Quimioembolización Terapéutica/efectos adversos , Estadificación de Neoplasias , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins may reduce HCC incidence. Its antitumor activities may be mediated by disrupting several hepatocarcinogenic pathways. To evaluate in vivo and in vitro the antiproliferative and antiangiogenic action of atorvastatin (AT) in the development of HCC as well as its mechanisms of action. In vivo model: hexachlorobenzene (HCB) was used to promote the development of HCC in Balb/C nude mice. Number of hepatic tumor, liver cell proliferation parameters (proliferating cell nuclear antigen, PCNA), angiogenesis, and VEGF levels were analyzed. In vitro model: Hep-G2 and Ea-hy926 cells were used to evaluate the effect of different doses of AT on HCB induced cell proliferation, migration, and vasculogenesis and to analyze proliferative parameters. In vivo: AT prevented liver growth and tumor development and inhibited PCNA, TGF-ß1, and pERK levels increase. AT prevented skin blood vessel formation. In vitro, AT prevented cell proliferation and migration as well as tubular formation in the endothelial cell line by inhibiting the MAPK ERK pathway. We were able to demonstrate the potential AT antiproliferative and antiangiogenic effects in an HCC model and the involvement of TGF-ß1 and pERK pathways.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Atorvastatina/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología , Ratones Desnudos , Hexaclorobenceno/farmacología , Células Hep G2 , Transducción de Señal , Proliferación Celular , Línea Celular Tumoral , Movimiento CelularRESUMEN
Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury. We analyzed 23 cases from the Latin American DILI Network (LATINDILI) and the Spanish DILI Registry. Causality was assessed with the RUCAM and RECAM scale. Of the 23 DILI cases included in our series, 96% patients were women, and the mean age of the whole cohort was 61 years. The median time of drug exposure was 175 days (interquartile range [IQR] 96-760), with 11 patients who were prescribed nitrofurantoin for more than six months. Hepatocellular damage was the most frequent pattern of liver injury (83%), and nearly half of the patients had an asymptomatic presentation (52%). Neither death nor liver transplantation was documented in this series. Overall, 65% of the patients (n = 15) presented with positive autoantibody titres. The median time to resolution was 81 days (IQR 57-141), and 15 patients (83%) recovered within six months. Five patients (22%) developed nitrofurantoin-induced autoimmune-like hepatitis (NI-AILH), of whom two were characterized by a persistent increase in transaminases that required immunosuppressive treatment to achieve normalization of liver enzymes. Clinicians who prescribe nitrofurantoin should be aware that patients who had taken nitrofurantoin for a long term may be at risk of developing nitrofurantoin-induced autoimmune-like hepatitis.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatitis Autoinmune , Humanos , Femenino , Persona de Mediana Edad , Masculino , Nitrofurantoína/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Estudios de Seguimiento , Estudios Prospectivos , Sistema de RegistrosRESUMEN
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.
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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 SaludRESUMEN
INTRODUCTION AND OBJECTIVES: The Choosing Wisely (CW) initiative aims to improve daily practice supported by evidence concerning unnecessary medical tests, procedures, and treatments. This philosophy is essential in managing viral hepatitis (VH), which primary care physicians increasingly carry out. It is also essential to achieving disease elimination. Thus, the aim of our study was to propose evidence-based CW recommendations in VH. MATERIALS AND METHODS: The Brazilian Society of Hepatology (SBH) formed a panel of experts in VH who selected evidence-based CW recommendations, which were subsequently scrutinized and ranked by all members of SBH using a web-based approach. RESULTS: Five recommendations were chosen in order of importance: 1) do not order anti-HCV testing after achieving sustained virological response; 2) do not request serial HCV viral load to evaluate HCV progression, 3) do not add ribavirin to direct-acting antivirals in non-cirrhotic, naïve HCV patients; 4) do not screen for hepatocellular carcinoma in HCV patients with none to moderate fibrosis (≤ F2); 5) do not request anti-HBs after HBV vaccination, except for children born to HBV-infected mothers, hemodialysis patients, healthcare professionals, people who have had sexual contact with chronic HBV carriers, HIV-positive persons and immunocompromised individuals (hematopoietic stem-cell transplant recipients or persons receiving chemotherapy). CONCLUSIONS: CW recommendations may help general practitioners adopt a more rational and cost-effective approach in managing patients with VH in Brazil and Latin America, leading to lesser waste or harm to patients.
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Gastroenterología , Hepatitis C Crónica , Hepatitis Viral Humana , Neoplasias Hepáticas , Niño , Humanos , Antivirales/efectos adversos , Brasil , América Latina , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis Viral Humana/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions (RAS). However, the consequence of resistance selection during new direct-acting antiviral drug (DAA) treatment is not necessarily the therapeutic failure. In fact, DAA treatment has shown a high rate (> 95%) of sustained virological response even when high baseline RAS prevalence has been reported. In the context of RAS emergence and high rates of sustained viral response, the clinical relevance of variants harboring RAS is still controversial. Therefore, in order to summarize the data available in international guidelines, we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.
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Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Hexachlorobenzene (HCB) is an endocrine disruptor and a liver tumor promoter. Deregulation of thyroid hormone (TH) homeostasis may play a significant role in early neoplastic transformation. The aim of this study was to evaluate the relation between TH metabolism and the regulation of cell growth in an in vivo and in vitro model. We examined the role of transforming growth factor-ß1 (TGF-ß1) on TH deiodinase expression and hepatocyte proliferation. An initiation (DEN)/promotion (HCB) tumor model from rat liver and HepG2 cells were used. We evaluated PCNA, p21, p27, SMAD2/3, TGF-ß1, deiodinase 1 (D1), D3, protein expression levels; D1 and D3 mRNA expression; TH and TGF-ß1, D1, D3, and GST-P protein levels in focal/non-focal areas. In vivo, HCB decreased triiodothyronine (T3) and D1 mRNA levels and increased thyroxine (T4) and D3 mRNA levels in liver from DEN+HCB vs. DEN group. HCB increased protein levels from D3, TGF-ß1, and PCNA and decreased D1 in focal-areas. In vitro, HCB increased PCNA, pSMAD 2/3, and TGF-ß1 protein levels and mRNA expression and decreased p21 and p27 protein levels. Exogenous T3 treatment prevent HCB induced molecular alterations related to hepatocyte proliferation whereas T4 did not have any effect. These effects were prevented by using a TGF-ß1 receptor II inhibitor. Results suggest that alteration of TH homeostasis, through D1 function, play a key role in hepatocyte proliferation and that TGF-ß1-SMAD pathway is involved in this process confirming their role in early neoplastic transformation in HCC.
El hepatocarcinoma (HCC) es un tumor hepático primario. El hexaclorobenceno (HCB) es un disruptor endocrino y un promotor de tumores hepáticos. La desregulación de la homeostasis de las hormonas tiroideas (HT) puede ser un proceso importante para la transformación neoplásica temprana. Nuestro objetivo fue evaluar la relación entre el metabolismo de las HT y la regulación de la proliferación celular. Se utilizó un modelo tumoral de iniciación (DEN)/promoción (HCB) de hígado de rata (in vivo) (DEN/HCB) y células HepG2 (in vitro). Evaluamos los niveles de PCNA, p21, p27, SMAD2/3, TGF-ß1, D1, D3, ARNm de D1 y D3, HT y los niveles de TGF-ß1, D1, D3 y GST-P en áreas focales/no focales. In vivo, HCB disminuyó los niveles de T3 y ARNm de la D1 y aumentó los niveles de T4 y ARNm de D3 del grupo DEN + HCB frente al grupo DEN. El HCB aumentó los niveles de D3, TGF-ß1 y PCNA y disminuyó el D1 en las áreas focales. In vitro, HCB aumentó los niveles de PCNA, pSMAD 2/3 y TGF-ß1 y la expresión de ARNm mientras que disminuyó los niveles de p21 y p27. El tratamiento con T3 exógeno previno las alteraciones moleculares relacionadas con la proliferación hepatocitaria. Estos efectos se evitaron utilizando un inhibidor del receptor II de TGF-ß1. Los resultados sugieren que la alteración de la homeostasis de HT, a través de la D1 y la vía TGF-ß1-SMAD, juega un papel clave en la proliferación celular y en las transformaciones neoplásicas tempranas en el HCC.
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Carcinoma Hepatocelular , Yoduro Peroxidasa , Neoplasias Hepáticas , Factor de Crecimiento Transformador beta1 , Animales , Proliferación Celular , Yoduro Peroxidasa/genética , RatasRESUMEN
Abstract Hepatocellular carcinoma (HCC) is the most common primary liver tumor. Hexachlorobenzene (HCB) is an endocrine disruptor and a liver tumor promoter. Deregulation of thyroid hormone (TH) homeostasis may play a significant role in early neoplastic transformation. The aim of this study was to evaluate the relation between TH metabolism and the regulation of cell growth in an in vivo and in vitro model. We examined the role of transforming growth factor-β1 (TGF-β1) on TH deiodinase expression and hepatocyte proliferation. An initiation (DEN)/promotion (HCB) tumor model from rat liver and HepG2 cells were used. We evaluated PCNA, p21, p27, SMAD2/3, TGF-β1, deiodinase 1 (D1), D3, protein expression levels; D1 and D3 mRNA expression; TH and TGF-β1, D1, D3, and GST-P protein levels in focal/non-focal areas. In vivo, HCB decreased triiodothyronine (T3) and D1 mRNA levels and increased thyroxine (T4) and D3 mRNA levels in liver from DEN+HCB vs. DEN group. HCB increased protein levels from D3, TGF-β1, and PCNA and decreased D1 in focal-areas. In vitro, HCB increased PCNA, pSMAD 2/3, and TGF-β1 protein levels and mRNA expression and decreased p21 and p27 protein levels. Exogenous T3 treatment prevent HCB induced molecular alterations related to hepatocyte proliferation whereas T4 did not have any effect. These effects were prevented by using a TGF-β1 receptor II inhibitor. Results suggest that alteration of TH homeostasis, through D1 function, play a key role in hepatocyte proliferation and that TGF-β1-SMAD pathway is involved in this process confirming their role in early neoplastic transformation in HCC.
Resumen El hepatocarcinoma (HCC) es un tumor hepático primario. El hexaclorobenceno (HCB) es un disruptor endocrino y un promotor de tumores hepáticos. La desregulación de la homeostasis de las hormonas tiroideas (HT) puede ser un proceso importante para la transformación neoplásica temprana. Nuestro objetivo fue evaluar la relación entre el metabolismo de las HT y la regulación de la prolifera ción celular. Se utilizó un modelo tumoral de iniciación (DEN)/promoción (HCB) de hígado de rata (in vivo) (DEN/ HCB) y células HepG2 (in vitro). Evaluamos los niveles de PCNA, p21, p27, SMAD2/3, TGF-β1, D1, D3, ARNm de D1 y D3, HT y los niveles de TGF-β1, D1, D3 y GST-P en áreas focales/no focales. In vivo, HCB disminuyó los niveles de T3 y ARNm de la D1 y aumentó los niveles de T4 y ARNm de D3 del grupo DEN + HCB frente al grupo DEN. El HCB aumentó los niveles de D3, TGF-β1 y PCNA y disminuyó el D1 en las áreas focales. In vitro, HCB aumentó los niveles de PCNA, pSMAD 2/3 y TGF-β1 y la expresión de ARNm mientras que disminuyó los niveles de p21 y p27. El tratamiento con T3 exógeno previno las alteraciones moleculares relacionadas con la proliferación hepatocitaria. Estos efectos se evitaron utilizando un inhibidor del receptor II de TGF-β1. Los resultados sugieren que la alteración de la homeostasis de HT, a través de la D1 y la vía TGF-β1-SMAD, juega un papel clave en la proliferación celular y en las transformaciones neoplásicas tempranas en el HCC.
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Animales , Ratas , Carcinoma Hepatocelular , Factor de Crecimiento Transformador beta1 , Yoduro Peroxidasa/genética , Neoplasias Hepáticas , Proliferación CelularRESUMEN
Abstract 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.
Resumen El manejo clínico de la infección por el virus la hepatitis C (HCV) presenta 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 nece sario 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.
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Humanos , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Hepacivirus , Cirrosis HepáticaRESUMEN
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.
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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/tendenciasRESUMEN
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.
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Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis HepáticaRESUMEN
Nimesulide is a non-steroidal anti-inflammatory drug still marketed in many countries. We aim to analyze the clinical phenotype, outcome, and histological features of nimesulide-induced liver injury (nimesulide-DILI). We analyzed 57 cases recruited from the Spanish and Latin American DILI registries. Causality was assessed by the RUCAM scale. Mean age of the whole case series was 59 years (86% women) with a median time to onset of 40 days. A total of 46 patients (81%) were jaundiced. Nimesulide-DILI pattern was hepatocellular in 38 (67%), mixed in 12 (21%), and cholestatic in 7 (12%) cases. Transaminases were elevated with a mean of nearly 20-fold the upper limit of normality (ULN), while alkaline phosphatase showed a twofold mean elevation above ULN. Total bilirubin showed a mean elevation of 13-fold the ULN. Liver histology was obtained in 14 cases (25%), most of them with a hepatocellular pattern. Median time to recovery was 60 days. Overall, 12 patients (21%) developed acute liver failure (ALF), five (8.8%) died, three underwent liver transplantation (5.3%), and the remaining four resolved. Latency was ≤ 15 days in 12 patients (21%) and one patient developed ALF within 7 days from treatment initiation. Increased total bilirubin and aspartate transaminase levels were independently associated with the development of ALF. In summary, nimesulide-DILI affects mainly women and presents typically with a hepatocellular pattern. It is associated with ALF and death in a high proportion of patients. Shorter (≤ 15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity, making its risk/benefit ratio clearly unfavorable.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Fallo Hepático Agudo/inducido químicamente , Sulfonamidas/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios no Esteroideos/administración & dosificación , Bilirrubina/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Niño , Colestasis/inducido químicamente , Colestasis/epidemiología , Estudios de Cohortes , Femenino , Humanos , Ictericia/inducido químicamente , Ictericia/epidemiología , América Latina/epidemiología , Fallo Hepático Agudo/epidemiología , Masculino , Persona de Mediana Edad , Sistema de Registros , Factores de Riesgo , España/epidemiología , Sulfonamidas/administración & dosificación , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTIONS AND OBJECTIVES: The introduction of direct-acting antiviral (DAA) agents promises to change dramatically the management of hepatitis C in kidney transplant recipients, a patient group where the treatment of hepatitis C is historically challenging. The purpose of the current study was to assess (in a 'real-life' setting) the safety and efficacy of all-oral, interferon-free, direct-acting antiviral agents in kidney transplant recipients with HCV. MATERIAL AND METHODS: We performed a single-arm, multi-center study in a cohort (n = 95) of kidney transplant recipients who underwent antiviral therapy with DAAs. The primary end-point was sustained virologic response (SVR) (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended; SVR12). We recorded data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. RESULTS: Various regimens were adopted at the discretion of the treating physician: elbasvir/grazoprevir (n = 11), paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens ± ribavirin (n = 23), and sofosbuvir-based regimens ± ribavirin (n = 61). The SVR12 rate was 93.7% (89/95) (95% CI, 88%; 98%), according to intention-to-treat analysis; three patients without viral response (n = 3) were found. Ribavirin was administered in 8 (8.4%) allograft recipients. The frequency of drop-outs was 4.2% (4/95) (95% CI, 0.2%; 8.2%); these were related to arthralgia/myalgia (n = 2), fatigue (n = 1), and lowered estimated glomerular filtration rate (eGFR) (n = 1). There were no differences with regard to serum creatinine and eGFR before and after antiviral therapy and during follow-up in the whole cohort. The patient who interrupted antiviral treatment due to raised serum creatinine was on sofosbuvir/daclatasvir regimen; one of the four drop-outs obtained SVR. CONCLUSIONS: All-oral, interferon-free therapy with DAAs for chronic HCV after kidney transplantation was effective and well-tolerated in a 'real-life' clinical setting. Identical results have been observed in patients with intact kidneys or advanced chronic kidney disease. Careful evaluation of kidney function over follow-up in kidney transplant recipients who received DAAs regimens is recommended. Clinical trials aimed to assess whether sustained viral response translates into improved patient/graft survival are under way.
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Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Trasplante de Riñón , Respuesta Virológica Sostenida , 2-Naftilamina/uso terapéutico , Administración Oral , Adulto , Anciano , Anilidas/uso terapéutico , Benzofuranos , Estudios de Cohortes , Creatinina/sangre , Ciclopropanos/uso terapéutico , Combinación de Medicamentos , Femenino , Tasa de Filtración Glomerular , Hepatitis C/complicaciones , Hepatitis C/patología , Humanos , Imidazoles , Lactamas Macrocíclicas/uso terapéutico , Masculino , Persona de Mediana Edad , Prolina/análogos & derivados , Prolina/uso terapéutico , Quinoxalinas , Ribavirina/uso terapéutico , Ritonavir/uso terapéutico , Sofosbuvir/uso terapéutico , Sulfonamidas/uso terapéutico , Uracilo/análogos & derivados , Uracilo/uso terapéutico , Valina/uso terapéuticoRESUMEN
Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.
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Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Diagnóstico Diferencial , Humanos , América Latina , Guías de Práctica Clínica como Asunto , Sistema de Registros , Factores de RiesgoRESUMEN
Introduction. Blood-borne infections are a major cause of harm in individuals on haemodialysis (HD). In particular, knowledge about hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) status in HD patients is a major concern, since these infections may cause comorbidities in this setting. There is a paucity of data regarding this issue in Argentina.Hypothesis/Gap Statement. The epidemiological surveillance of HBV, HCV, and HIV is a fundamental tool for planning and implementing health strategies in order to prevent and control viral transmission of these viral agents.Aim. To determine the seroprevalence of HBV, HCV and HIV infections in HD patients in Buenos Aires, Argentina.Methodology. Seven hundred and forty-eight HD patients were included in a retrospective cross-sectional study. Serological assays were performed to determine HBV, HCV and HIV status. HBV HBsAg and anti-HBc IgG were analysed using AxSYM (samples before 2010) or the Architect Abbott system (samples since 2010), anti-HCV IgG testing was performed using the anti-HCV enzyme immunoassay AxSYM HCV V3.0 and ARCHITECT anti-HCV, while HIV was tested for using AxSYM HIV 1/2 gO and ARCHITECT HIV Ag/Ab Combination. HCV genotyping was carried out by phylogenetic analysis of the NS5B partial gene.Results. Infection with one of the viruses was detected in 31.1â% of patients [HBV in 82 (11.0â%), HCV in 179 (23.9â%) and HIV in 6 (0.8â%)]. Thirty-two (4.3â%) patients had 2 virus markers [27 (3.6â%) with HCV/HBV, 4 (0.5â%) with HCV/HIV and 1 (0.13â%) with HBV/HIV]. Finally, a single patient (0.13â%) presented all three markers. Time on dialysis was correlated with HCV but not with HBV infection. The HCV subtype distribution in HD patients was inverted with respect to that observed in the general population (HCV-1a 73.2â% and HCV-1b 26.8â% in HD vs HCV-1a 26.5â% and HCV-1b 73.5â% in the general population, P <0.001).Conclusion. Despite the implementation of universal precautionary biosafety standards for dialysis, infection with HBV and HCV continues to occur at very high rates in HD patients. The results emphasize the need to carry out proactive tasks for early diagnosis and treatment of infected individuals and to vaccinate those with non-protective antiHBs antibodies in order to reduce morbidity and mortality in HD patients.