RESUMO
The increased risk of cardiovascular disease (CVD) conferred by hepatitis C virus (HCV) is especially relevant after liver transplantation (LT), but its mechanism is still not well defined. This study aimed to evaluate the influence of HCV eradication in inflammatory and endothelial activation markers after LT. We evaluated inflammatory (TNF-alfa, IL-6, IL-8, and MCP-1) and endothelial activation (E-selectin, ICAM-1, VCAM-1, and MMP-9) markers before and after eradication in 45 LT recipients with HCV infection (LT+/HCV+) and 44 non-transplanted HCV-infected patients (LT-/HCV+). We also considered an additional group of 40 LT recipients without HCV infection (LT+/HCV-). LT+/HCV+ patients presented a higher endothelial activation status before eradication compared with LT+/HCV- patients. However, levels of E-selectin, ICAM-1, VCAM-1, and MMP-9 were comparable between LT+/HCV+ and LT-/HCV+ patients before eradication. HCV eradication decreased ICAM-1 (5466.55 pg/ml vs. 3354.88 pg/ml, P < 0.001) and VCAM-1 (10456.52 pg/ml vs. 6658.85 pg/ml, P < 0.001) levels in LT+/HCV+ and LT-/HCV+ patients. Remarkably, HCV eradication restored levels of endothelial activation markers of LT+/HCV+ patients compared with that of LT+/HCV- patients. HCV plays a major role in endothelial dysfunction after LT. Furthermore, HCV eradication restores endothelial activation despite the exposure to immunosuppressive therapy.
Assuntos
Hepatite C Crônica , Hepatite C , Transplante de Fígado , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , HumanosRESUMO
BACKGROUND: Autoimmune hepatitis (AIH) is a chronic liver disease able to progress to acute liver failure, cirrhosis, and liver cancer. A significant proportion of patients fail to first-line therapy or develop severe toxicity. AIMS: To assess safety and effectiveness of tacrolimus as a second-line therapy in AIH patients. METHODS: Multicentric retrospective study of AIH patients treated with tacrolimus for at least 3 months as a second-line therapy. Effectiveness was defined as complete normalization of transaminases and IgG. RESULTS: A total of 23 AIH patients were included in the final analysis. In 13% of patients tacrolimus was initiated because of toxicity to previous first-line treatments and the rest were switched because of previous non-efficacy. Tacrolimus was effective in 18 patients (78%; 95%CI: 55.20-91.92%). The median time receiving tacrolimus was 16 months (IQR 20). There was a sustained response with a significant improvement in all liver enzymes and IgG on last follow-up. Only one patient discontinued tacrolimus at the third month because of severe neuropathy, and ototoxicity. Responders were significantly older at diagnosis of AIH (41 ± 13 vs. 27 ± 10 years old; p = 0.0496). CONCLUSION: Tacrolimus is effective and well tolerated as a second-line therapy in patients with AIH.
Assuntos
Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Doença Crônica , Feminino , Humanos , Imunoglobulina G/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
INTRODUCTION: the presence of donor-specific antibodies (DSA) is thought to affect survival of the allograft and patient after liver transplantation (LT). However, their significance is not well understood. PATIENTS AND METHODS: a prospective study was performed of 32 adult patients who underwent LT in 2011 to analyze the existence of DSA, associated risk factors and medium-term impact. Immunological determinations were performed immediately before LT and at three, six, 12 months and five years after LT. RESULTS: eight patients (24.2 %) presented pre-formed DSA. However, titers were negative in all patients five years after LT and there were no associated events. Eight out of 24 patients (33.3 %) developed de novo DSA. After five years, only two remained positive; both were class II with high mean fluorescence intensity (MFI) values at diagnosis (over 15,000). No association was found between the development of DSA and the risk of rejection, graft loss or death. However, an increase in liver stiffness values was observed in patients with persistent DSA, and focal sinusoidal deposition of C4d and moderate liver fibrosis were reported. CONCLUSION: the incidence of DSA is high after LT. In addition, the persistence of de novo DSA could be associated with silent liver fibrosis with a potential impact on graft outcomes.
Assuntos
Transplante de Fígado , Adulto , Rejeição de Enxerto/epidemiologia , Antígenos HLA , Humanos , Isoanticorpos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
INTRODUCTION: liver enzyme elevation has been reported in SARS-CoV-2 disease (COVID-19) in heterogeneous cohorts, mainly from China. Comprehensive reports from other countries are needed. In this study, we dissect the pattern, evolution, and predictive value of such abnormalities in a cohort from Madrid, Spain. METHODS: a retrospective study with a prospective 14-day follow-up of 373 patients with confirmed COVID-19 in five Madrid hospitals, including 50 outpatients. A COVID-19 severe course was defined as the need for mechanical ventilation. RESULTS: a total of 33.1 % of hospitalized patients showed baseline AST elevation and 28.5 % showed ALT elevation, compared with 12 % and 8 % of outpatients (p ≤ 0.001). Baseline AST, ALT and GGT levels correlated with LDH and C-reactive protein (CRP) levels (r ≤ 0.598, p < 0.005). AST elevation was associated with other severity markers such as male sex, lymphopenia, and pneumonia on X-Ray (p < 0.05 for all). ALP and bilirubin levels were rarely increased. Patients with elevated baseline AST showed a progressive normalization of this enzyme and an increase in ALT and GGT levels. Patients with normal baseline AST showed a flattened evolution pattern with levels within the range. Patients with a severe course of COVID-19 more frequently showed elevated baseline AST than those with a milder evolution (54.2 % vs. 25.4 %, p < 0.001). Age, AST and CRP were independent risk factors for a severe course of COVID-19. CONCLUSION: mild liver enzyme elevation is associated with COVID-19 severity. Baseline AST is an independent predictor of severe COVID-19 course, and tends to normalize over time. ALT and GGT show a late elevation.
Assuntos
COVID-19 , Hepatopatias , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND AND AIM: Assessment of the severity of liver disease following infection with hepatitis C virus (HCV) is important in treatment selection and prognosis. As invasive liver biopsy procedures are regarded as the reference method to assess the stage of fibrosis, it is important to identify patient characteristics that are predictive of liver fibrosis severity. The aim of the study was to describe the distribution of liver severity scores, clinical characteristics, and physicians' assessment of fibrosis among HCV patients in five European countries. METHODS: This cross-sectional study retrospectively reviewed the medical records of patients who were chronically infected with HCV in 2006. Patients managed for HCV at any of 60 sites in France, Germany, Italy, Spain, and the UK were included. Data collected included patient demographics and clinical characteristics. A combination of univariate and multivariate regression analyses were used to identify predictors of fibrosis severity and factors associated with undergoing biopsy. RESULTS: Four thousand five hundred and ninety-four chronically infected HCV patients were included in this analysis. Management approaches differed between countries, with variations in biopsy use (59.3-18.4%) and preferred fibrosis scoring systems. Where histology results were available, 43.4%, 23.8%, and 32.9% had mild, moderate, and severe fibrosis, respectively. Factors associated with undergoing a biopsy included male gender and co-infection with hepatitis B virus. Chronic alcoholism, a lower first platelet count, and older age were predictors of increased liver fibrosis severity. CONCLUSIONS: These data suggest that there are major differences in how specialists manage their HCV patients across five major European countries.
Assuntos
Hepatite C Crônica/patologia , Fígado/patologia , Adulto , Alcoolismo , Biópsia/estatística & dados numéricos , Coinfecção , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Fibrose , Previsões , Hepatite , Hepatite C Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Observacionais como Assunto , Contagem de Plaquetas , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Budd-Chiari syndrome (BCS) is characterized by an obstruction of hepatic venous outflow from small hepatic veins to inferior vena cava, caused by acute thrombosis or its fibrous sequellae. An underlying myeloproliferative neoplasm is present in 50% of cases. Clinical manifestations are widely variable, from asymptomatic to fulminant episodes. Long-term complications range from cirrhosis to hepatocellular carcinoma. Behçet's disease (BD) is a rare recurrent inflammatory multisystemic disorder characterized by recurrent skin-mucosa lesions and systemic involvement. Vascular involvement is observed in up to 40% of the patients with BD, and it is one of the major causes of mortality and morbidity. BCS is a rare complication of BD with a frequency of < 5% among patients with vascular involvement. Immunosuppressive treatment is the cornerstone for the management of vascular involvement in BD, while anticoagulant therapy has been an issue of debate. Transjugular intrahepatic portosystemic shunt (TIPS) in severe cases of BCS-of all causes- improves survival. However, there is scarce evidence about the role of TIPS in the setting of BCS in BD. We present a case of a vascular Behçet's disease associated with chronic Budd-Chiari syndrome with progression of thrombosis despite adequate anticoagulant and immunosuppressive treatment, successfully managed with TIPS.
Assuntos
Síndrome de Behçet , Síndrome de Budd-Chiari , Derivação Portossistêmica Transjugular Intra-Hepática , Síndrome de Behçet/complicações , Síndrome de Budd-Chiari/etiologia , Síndrome de Budd-Chiari/cirurgia , Veias Hepáticas , Humanos , Veia Cava InferiorRESUMO
OBJECTIVES: To assess survival and predictive factors of mortality after an episode of spontaneous bacterial peritonitis (SBP) in cirrhotic patients and to analyze the diagnostic and therapeutic measures used. METHODS: We retrospectively reviewed the medical records of 158 consecutive episodes of SBP treated between January 2003 and December 2005. Survival was studied by Kaplan-Meier curves, compared by the log-rank test. Independent predictive factors of mortality were obtained by a Cox regression model, while independent predictive factors of in-hospital mortality were obtained by logistic regression analysis. RESULTS: A total of 80.4% of the SBP episodes occurred in men and the mean age was 61.23 +/- 12.49 years. The most frequent etiology of cirrhosis was viral (51.3%), followed by alcoholic (39.9%). The distribution of Child-Pugh classification was 5.7% (A), 63.3% (B) and 31% (C). Overall 3-year survival in the sample was 43.3%. Four variables were identified as independent predictive factors of in-hospital and 3-month mortality: renal impairment, hepatic encephalopathy, diagnosis of hepatocellular carcinoma (HCC) and mean arterial pressure (MAP) < 75 mmHg. At the end of the monitoring period, the results of the analysis were as follows: diagnosis of HCC, MAP < 75 mmHg, and age > 65 years. Microbiological detection was achieved in 21% of the episodes. The most frequent microorganisms detected were Escherichia coli in ascitic fluid and Staphylococcus aureus in blood cultures. CONCLUSIONS: SBP has a poor short- and long-term prognosis in cirrhotic patients. Independent predictive factors of short-term survival are renal impairment, hepatic encephalopathy, MAP < 75 mmHg, and the presence of HCC.
Assuntos
Cirrose Hepática/mortalidade , Peritonite/epidemiologia , Idoso , Carcinoma Hepatocelular/mortalidade , Causas de Morte , Comorbidade , Infecções por Escherichia coli/epidemiologia , Feminino , Hepatite Viral Humana/epidemiologia , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática Alcoólica/mortalidade , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Infecções Estafilocócicas/epidemiologiaRESUMO
Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events (i.e., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.
Assuntos
Amônia/metabolismo , Resistência a Medicamentos , Encefalopatia Hepática/tratamento farmacológico , Hiperamonemia/sangue , Hipotireoidismo/metabolismo , Cirrose Hepática Alcoólica/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Alcoolismo/complicações , Amônia/sangue , Antitireóideos/uso terapêutico , Encéfalo/diagnóstico por imagem , Carbimazol/uso terapêutico , Diagnóstico Diferencial , Distúrbios do Sono por Sonolência Excessiva/sangue , Distúrbios do Sono por Sonolência Excessiva/diagnóstico por imagem , Distúrbios do Sono por Sonolência Excessiva/etiologia , Disartria/sangue , Disartria/diagnóstico por imagem , Disartria/etiologia , Eletroencefalografia , Embolização Terapêutica , Feminino , Bócio Nodular/sangue , Bócio Nodular/complicações , Bócio Nodular/tratamento farmacológico , Bócio Nodular/metabolismo , Encefalopatia Hepática/sangue , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/metabolismo , Humanos , Hiperamonemia/complicações , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Cirrose Hepática Alcoólica/sangue , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Veia Porta/anormalidades , Veia Porta/diagnóstico por imagem , Derivação Portossistêmica Transjugular Intra-Hepática , Propranolol/uso terapêutico , Veias Renais/anormalidades , Veias Renais/diagnóstico por imagem , Tireotropina/sangue , Tiroxina/uso terapêutico , Tomografia Computadorizada por Raios X , Malformações Vasculares/sangue , Malformações Vasculares/complicações , Malformações Vasculares/terapiaAssuntos
Hemodinâmica , Fígado/irrigação sanguínea , Fígado/patologia , Biópsia/métodos , Pressão Sanguínea , Humanos , Veias JugularesRESUMO
BACKGROUND: Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. METHODS: This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. RESULTS: Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cut-off for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. CONCLUSIONS: Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.