The influence of carvedilol posology timing on clinically significant portal hypertension: insights from elastography measurements.

BACKGROUND AND AIMS: Carvedilol has emerged as the preferred ß-blocker for treating portal hypertension. However, there is still a debate in dosing regimen, with a potential lower bioavailability in once-daily regimens. The aim of this study is to assess the acute effects of carvedilol posology in patients with clinically significant portal hypertension (CSPH), as a surrogate marker of bioavailability. METHODS: In this experimental study, 34 patients with CSPH receiving carvedilol twice daily were asked to suppress the night dose of carvedilol, creating a standardized 24-hour dose interval. Spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) by transient elastography (TE) were performed, with the exact interval between the last carvedilol administration and TE measurements consistently maintained at 24 hours and compared with values prior and under treatment. RESULTS: Thirty-four patients were included, predominantly male (82.9%). SSM after suspending carvedilol for 24 hours [mean, 73.9kPa (SD, 17.0)] was significantly higher ( P < 0.001) than under treatment [mean, 56.3kPa (SD, 13.2)] and was not significantly different ( P = 0.908) from SSM prior to introduction of carvedilol [mean, 74.5kPa (SD, 12.4)]. Differences were also found in stratified analysis for carvedilol dosage, D'Amico classification stages, MELDNa scores, MELD3.0 scores, Child-Pugh class A and CSPH due to alcoholic cirrhosis. LSM after suspension was not significantly different from both under treatment and prior to treatment. CONCLUSION: The differences in SSM after skipping one dose of carvedilol show both the importance of strict adherence to the prescribed dosing regimen to achieve the expected therapeutic benefits and the impact of twice daily prescription in bioavailability throughout the day.

Anticardiolipin Antibody Determination to Guide Q Fever Treatment.

Query (Q) fever is a worldwide infectious disease with acute and chronic manifestations caused by Coxiella burnetii. The clinical manifestations are so variable that the disease is often only diagnosed if systematically considered as a differential diagnosis. Here, we present a case of a 39-year-old man who lived in a countryside house, with cattle and sheep in his field, with acute Q fever hepatitis with the typical granulomatous arrangement in the liver biopsy. The diagnosis was confirmed by polymerase chain reaction (PCR) assay in a serum sample and the presence of phase II antibodies. Anticardiolipin antibody (aCL) determination at diagnosis of acute Q fever and during follow-up was made to persecute early identification and to guide the treatment and prophylaxis of possible complications, such as endocarditis.

Treating Advanced Hepatocellular Carcinoma with Sorafenib: A 10-Year Single Center Experience.

Introduction: Sorafenib was the first therapy used for systemic treatment of unresectable hepatocellular carcinoma (HCC). Multiple prognosis factors associated with sorafenib therapy have been described. Objectives: The aim of this work was to evaluate survival and time to progression (TTP) on HCC patients treated with sorafenib, and check for predictive factors of sorafenib benefit. Materials and Methods: Retrospectively, data from all HCC patients treated with sorafenib in a Liver Unit from 2008 to 2018 were collected and analyzed. Results: Sixty-eight patients were included; 80.9% were male, the median age was 64.5 years, 57.4% had Child-Pugh A cirrhosis and 77.9% were BCLC stage C. Macrovascular invasion (MVI) was present in 25% of the patients and 25% of the subjects had other extrahepatic metastasis. The median survival was 10 months (IQR 6.0-14.8) and median TTP was 5 months (IQR 2.0-7.0). Survival and TTP were similar between Child-Pugh A and B patients: 11.0 months (IQR 6.0-18.0) for Child-Pugh A and 9.0 months (IQR 5.0-14.0) for Child-Pugh B (p = 0.336). In univariate analysis, larger lesion size (LS >5 cm), higher alpha-fetoprotein (AFP >50 ng/mL), and no history of locoregional therapy were statistically associated with mortality (HR 2.17, 95% CI 1.24-3.81; HR 3.49, 95% CI 1.90-6.42; HR 0.54, 95% CI 0.32-0.93, respectively), but only LS and AFP were independent predictive factors, as shown in multivariate analysis (LS: HR 2.08, 95% CI 1.10-3.96; AFP: HR 3.13, 95% CI 1.59-6.16). MVI and LS >5 cm were associated with TTP shorter than 5 months in univariate analysis (MVI: HR 2.80, 95% CI 1.47-5.35; LS: HR 2.1, 95% CI 1.08-4.11), but only MVI was an independent predictive factor of TTP shorter than 5 months (HR 3.42, 95% CI 1.72-6.81). Regarding safety data, 76.5% of patients reported at least one side effect (any grade), and 19.1% presented grade III-IV adverse effects leading to treatment discontinuation. Conclusions: We observed no significant difference in survival or TTP in Child-Pugh A or Child-Pugh B patients treated with sorafenib, as compared to more recent real-life studies. Lower primary LS and AFP were associated with a better outcome, and lower AFP was the main predictor of survival. The reality of systemic treatment for advanced HCC has recently changed and continues to evolve, but sorafenib remains a viable therapeutic option.

Introdução: O sorafenib foi o primeiro fármaco usado em primeira linha na terapêutica sistémica do carcinoma hepatocelular (CHC) em estadio avançado. Têm sido descritos múltiplos factores modificadores de prognóstico associados à sua utilização. Objectivos: Caracterizar um grupo de doentes com CHC que realizaram terapêutica com sorafenib, estudar a sobrevivência e o tempo até progressão (TAP), e avaliar os factores preditores de benefício. Material e Métodos: Estudo retrospectivo com recolha e análise dos dados relativos a todos os doentes com CHC tratados com sorafenib numa Unidade de Hepatologia, entre 2008 e 2018. Resultados: Foram incluídos no estudo sessenta e oito doentes; 80.9% do sexo masculino, com mediana de idades de 64.5 anos, 57.4% tinham cirrose em estadio A de Child-Pugh e 77.9% apresentavam CHC em estadio C do Barcelona Clínic Liver Cancer (BCLC). A invasão macrovascular (IMV) estava presente em 25% dos doentes, e também 25% dos doentes tinha metastização extra-hepática (que não a IMV). A mediana de sobrevivência foi de 10 meses (IQR 6.0-14.8) e a mediana de TAP foi de 5 meses (IQR 2.0­7.0). A sobrevivência e o TAP foram similares nos doentes Child-Pugh A e B: 11.0 meses (IQR 6.0­18.0) para Child-Pugh A e 9.0 meses (IQR 5.0­14.0) para Child-Pugh B (p = 0.336). Na análise univariada, o tamanho da lesão >5 cm (TL), alfa-fetoproteína > 50 ng/mL (AFP) e a ausência de terapêuticas locorregionais prévias (TLP) tiveram relação estatisticamente significativa com a mortalidade (TL: HR 2.17, 95% CI 1.24­3.81; AFP: HR 3.49, 95% CI 1.90­6.42; TLP: HR 0.54, 95% CI 0.32­0.93), mas apenas o TL e AFP foram fatores preditores independentes, como mostrou a análise multivariada (TL: HR 2.08, 95% CI 1.10­3.96; AFP: HR 3.13, 95% CI 1.59­6.16). A IMV e o TL >5 cm estiveram associados com o TAP <5 meses na análise univariada (IMV: HR 2.80, 95% CI 1.47­5.35; TL: HR 2.1, 95% CI 1.08­4.11), mas apenas a IMV foi um fator preditor independente de TAP <5 meses (HR 3.42, 95% CI 1.72­6.81). Relativamente aos dados de segurança, 76.5% dos doentes relataram pelo menos um efeito lateral (qualquer grau), e 19.1% apresentaram efeitos adversos de grau III-IV, que levaram à suspensão do fármaco. Conclusões: Não foi observada diferença significativa na sobrevivência ou no tempo até progressão nos doentes Child-Pugh A ou Child-Pugh B tratados com sorafenib, quando comparado com estudos real-life recentes. Menor TL e AFP estiveram associados a melhor outcome e um valor de AFP baixo mostrou-se o principal preditor de sobrevivência. A realidade da terapêutica sistémica para o CHC avançado alterou-se recentemente e continua em mudança, mas o sorafenib permanece uma alternativa terapêutica viável.

Isolated Intracardiac Metastasis: The First Sign of Hepatocellular Carcinoma.

Metastatic hepatocellular carcinoma (HCC) to the right atrium without invasion of the inferior vena cava is a very rare and difficult diagnosis, especially when the primary tumour is yet to be known. A 68-year-old man with symptoms of heart failure was admitted to the emergency department; his transthoracic echocardiogram showed a mass comprehending almost the totality of the right atrium, obliterating its entrance nearly completely and impeding the normal auricular-ventricular flux, described as a possible auricular myxoma. The patient was promptly transferred to cardiothoracic surgery and submitted to an urgent surgery to completely remove the mass, which was macroscopically described as suspected of malignancy. Further investigation demonstrated a single nodule in the liver with malignant imaging characteristics, and the histology confirmed the diagnosis of metastatic HCC of the right atrium, without metastatic disease elsewhere. He was then submitted to radiofrequency ablation and medicated with sorafenib. The disease progressed slowly but subsequently involved the inferior vena cava and portal vein, culminating in his death 4 years and 3 months after the diagnosis. Although the prognosis for metastatic HCC may be poor, especially with intracavitary heart metastasis, this case shows that an aggressive initial approach with surgical metastasectomy may prolong the median survival of the patients.

A metastização intracardíaca de um carcinoma hepatocelular sem invasão da veia cava inferior é um diagnóstico raro e difícil, especialmente quando o tumor primário não foi ainda diagnosticado. Um homem de 68 anos foi admitido no Serviço de Urgência com sintomas de insuficiência cardíaca aguda. O ecocardiograma transtorácico mostrou uma massa que atingia quase a totalidade da aurícula direita, praticamente obliterando a sua entrada e impedindo o normal fluxo auriculoventricular, descrita como possível mixoma auricular. O doente foi imediatamente transferido para cirurgia cardiotorácica e submetido a cirurgia urgente para resseção da massa que foi macroscopicamente descrita como suspeita de malignidade. A investigação subsequente demonstrou um nódulo isolado hepático com características imagiológicas de malignidade, e a histologia da massa auricular confirmou o diagnóstico de metastização auricular de carcinoma hepatocelular. O doente foi posteriormente submetido a ablação por radiofrequência e medicado com sorafenib, com progressão lenta mas contínua da doença e subsequente atingimento metastático da veia cava inferior e veia porta, que culminou na sua morte quatro anos e três meses após o diagnóstico. Apesar do prognóstico ser reservado para o carcinoma hepatocelular metastático, especialmente na presença de metástases intracardíacas, este caso clínico mostra que uma abordagem inicial mais agressiva com metastasectomia pode prolongar a sobrevida média dos doentes.

Bacterial Infections in Patients with Liver Cirrhosis in an Internal Medicine Department.

BACKGROUND AND AIMS: Liver cirrhosis (LC) is the end stage of multiple processes that lead to hepatic failure and is the 10th most common cause of death in the Western world. Bacterial infections are one of the most important clinical problems in patients with LC, as their underlying immune status is compromised. Approximately 60% of bacterial infections in cirrhotic patients are community acquired (CA) and 40% are nosocomial. The most common infections in cirrhotic patients are spontaneous bacterial peritonitis (SBP) (25%), urinary tract infection (UTI) (20%), pneumonia (15%), bacteremia (12%), and cellulitis (2-11%). The aim of this study was to evaluate the most frequent infections in patients with LC and describe the evolution of the microbiology in these patients. MATERIAL AND METHODS: This is a retrospective analysis of 4 interspersed years (2008, 2010, 2012, and 2014) that included 372 patients. Demographic characteristics were evaluated, including gender, age, type of infection, bacteria resistance profile, antibiotic use, Child-Pugh-Turcotte and Model for End-Stage Liver Disease scores, and mortality rate. RESULTS: The mean age of all patients enrolled in this study was 64.5 ± 12.2 years. Male patients were significantly more prevalent than female ones (72 vs. 28%). In the 4 analyzed years, the following numbers of infections occurred: 71 infections (49% CA and 51% nosocomial) in 2008; 86 infections (60.5% CA and 39.5% nosocomial) in 2010; 99 infections (56.6% CA and 43.4% nosocomial) in 2012; and 116 infections (70.7% CA and 29.3% nosocomial) in 2014. The most frequent infections were UTI (32.5%), respiratory tract infection (29.3%), SBP (26.1%), and cellulitis (6.2%). A microbiological agent was identified in 32.4, 59.3, 53.5, and 61.2% of infections in 2008, 2010, 2012, and 2014, respectively, with a predominance of gram-negative bacilli. In all series, a third-generation cephalosporin was the most frequent antibiotic used empirically. The majority of patients was in stage B (42.7%) of the Child-Pugh-Turcotte score, followed by stage C (39.3%) and stage A (18%). Mortality increased significantly over the years, from 7% in 2008 to 25% in 2014 (p = 0.016). CONCLUSIONS: The present study showed a high prevalence of bacterial infections in patients with LC. A high rate of suspicion is needed for an infectious process in these patients, and an appropriate antibiotic treatment can decrease the morbidity and mortality in cirrhotic patients.

INTRODUÇÃO: A cirrose hepática (CH) é o estágio final de múltiplos processos que conduzem à insuficiência hepática e corresponde à 10a causa de morte mais comum no mundo Ocidental. As infeções bacterianas são uma complicação frequente nos doentes com CH, devido ao seu estado de imunossupressão. Aproximadamente 60% das infeções bacterianas em cirróticos são adquiridas na comunidade (AC) e 40% são nosocomiais. As infeções bacterianas mais comuns em cirróticos são Peritonite Bacteriana Espontânea (PBE) (25%), Infeção do Trato Urinário (ITU) (20%), Pneumonia (15%), Bacteriemia (12%) e Celulite (2-11%). O objetivo deste estudo é avaliar as infeções mais frequentes em doentes com CH e descrever a evolução da microbiologia nos mesmos. MATERIAL E MÉTODOS: Análise retrospetiva de quatro anos intercalados (2008, 2010, 2012 e 2014) que incluiu trezentos e setenta e dois doentes. Características demográficas: género, idade, tipo de infeção, perfil de resistência bacteriana, uso de antibióticos, scores Child-Pugh-Turcotte e Model for End-Stage Liver Disease e taxa de mortalidade. RESULTADOS: A idade média dos doentes incluídos neste estudo foi de 64.5 ± 12.2 anos. Os homens foram, significativamente, mais prevalentes que as mulheres (72 vs. 28%). Nos quatro anos intercalados, ocorreram: 71 infeções (49% AC e 51% nosocomiais) em 2008; 86 infeções (60.5% AC e 39.5% nosocomiais) em 2010; 99 infeções (56.6% AC e 43.4% nosocomiais) em 2012 e 116 infeções (70.7% AC e 29.3% nosocomiais) em 2014. As infeções mais frequentes foram a ITU (32.5%), Infeção do Trato Respiratório (29.3%), PBE (26.1%) e Celulite (6.2%). Identificou-se o agente microbiológico em 32.4, 59.3, 53.5 e 61.2% das infeções em 2008, 2010, 2012 e 2014, respetivamente, com predomínio de bacilos Gram-negativos. Em todas as séries, as cefalosporinas de terceira geração foram o antibiótico mais utilizado empiricamente. A grande maioria dos doentes encontra- se no estadio B (42,7%) do score Child-Pugh-Turcotte, seguido de C (39.3%) e A (18%). A mortalidade aumentou, significativamente, de 7% em 2008 para 25% em 2014 (p = 0.016). CONCLUSÕES: O presente estudo mostrou uma elevada prevalência de infeções bacterianas em doentes com CH. É necessário uma alta suspeita clínica para infeção nestes doentes, pois o tratamento antibiótico precoce e apropriado pode diminuir a morbilidade e a mortalidade.

Successful treatment of chronic hepatitis C in a kidney transplant patient with only 2 weeks of direct-acting antiviral therapy / Eficacia del tiempo de tratamiento ultracorto con terapia antiviral de acción directa para la hepatitis C crónica en un paciente con trasplante de riñón: reporte de un caso

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Light-Chain Deposition Disease with Prominent Hepatic Involvement.

Light-chain deposition disease (LCDD) is a rare monoclonal gammopathy that involves the deposition of light chains (LC) in multiple organs, leading to progressive dysfunction. The kidney is usually the most affected organ and responsible for the initial clinical manifestations. We present the case of a patient with LCDD with prominent liver involvement (marked cholestasis, hepatomegaly and portal hypertension) but with no evidence of coexisting lymphoproliferative disorder. LEARNING POINTS: Light-chain deposition disease (LCDD) is rare, and diagnosis can be challenging, especially in the absence of a coexistent lymphoproliferative disorder. The presence of light chains in blood or urine can be intermittent, and immunohistochemistry results of biopsy can be difficult to interpret. Hence, there is a need for a high level of suspicion in this diagnosis.Although renal involvement is the most classic presentation, LCDD should be suspected when there is multiple organ involvement, as in this case, even when renal manifestations do not dominate the clinical picture.Prognosis depends on the affected organs, and treatment should be started as rapidly as possible to suppress production of the clonal light-chain and halt organ damage.

[Adrenergic beta-agonist intoxication]. / Intoxicação por agonista beta adrenérgico.

The authors describe two clinical cases (father and daughter), observed in the Hospital Urgency with distal tremors, anxiety, palpitations, nausea, headaches and dizziness, two hours after ingestión of cow liver. They also had leucocytosis (with neutrophylia), hypokalemia and hyperglycaemia. After treatment with potassium i.v. and propranolol, the symptoms disappeared. The symptoms recurred at home because the patients didn't take the prescribed medication and persisted for five days, with spontaneous disappearance. The serum of both patients revealed the presence of clenbuterol (65 hg/ml - father and 58 hg/ml - daughter). The animal's liver had a concentration of 1,42 mg/kg. Clenbuterol is a ß-adrenergic agonist with low specificity, with some veterinary indications. However, this substance has been illegally used as a growth's promotor. We intend to alert doctors for this problem, particularly those that work in the Urgency.