RESUMEN
Vanishing bile duct syndrome is a rare acquired condition, characterized by progressive loss of intrahepatic bile ducts leading to ductopenia and cholestasis. It can be associated with infections, ischemia, drug adverse reactions, neoplasms, autoimmune disease, and allograft rejection. Prognosis is variable and depends on the etiology of bile duct injury. We report the case of a 25-year-old female with cholestatic hepatitis and concomitant intakes of hepatotoxic substances, such as garcinia, field horsetail, and ketoprofen. On suspicion of a drug-induced liver injury, the drugs were promptly withdrawn and ursodeoxycholic acid was started with initial clinical and laboratory improvement, and the patient was discharged from the hospital. One month later, she had a new increase in bilirubin levels and canalicular enzymes, requiring a liver biopsy that showed significant loss of intrahepatic bile ducts, which was compatible with vanishing bile duct syndrome. This was confirmed by using cytokeratin 19 on immunohistochemistry. There was subsequent lymph node enlargement in several chains, and relevant weight loss. Histological analysis of a cervical lymph node revealed nodular sclerosis-subtype classic Hodgkin lymphoma. In this setting, vanishing bile duct syndrome was related to Hodgkin lymphoma and a drug-induced liver injury overlap, leading to progressive cholestasis with a worse prognosis. The patient's response to chemotherapy was poor, requiring biological therapy with brentuximab vedotin. It is crucial for physicians to create a broad differential diagnosis in suspected vanishing bile duct syndrome patients, especially to rule out malignancies.
Asunto(s)
Conductos Biliares Intrahepáticos/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/complicaciones , Colestasis Intrahepática/etiología , Enfermedad de Hodgkin/complicaciones , Hígado/patología , Ganglios Linfáticos/patología , Adulto , Alanina Transaminasa/sangre , Antiinflamatorios no Esteroideos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Biopsia , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colagogos y Coleréticos/uso terapéutico , Colestasis Intrahepática/sangre , Colestasis Intrahepática/tratamiento farmacológico , Colestasis Intrahepática/patología , Equisetum/efectos adversos , Femenino , Garcinia/efectos adversos , Gastritis/etiología , Hematemesis/etiología , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Humanos , Cetoprofeno/efectos adversos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
Lysosomal acid lipase deficiency is a poorly diagnosed genetic disorder, leading to accumulation of cholesterol esters and triglycerides in the liver, with progression to chronic liver disease, dyslipidemia, and cardiovascular complications. Lack of awareness on diagnosis of this condition may hamper specific treatment, which consists on enzymatic replacement. It may prevent the progression of liver disease and its complications. We describe the case of a 53-year-old Brazilian man who was referred to our center due to the diagnosis of liver cirrhosis of unknown etiology. He was asymptomatic and had normal body mass index. He had dyslipidemia, and family history of myocardial infarction and stroke. Abdominal imaging tests showed liver cirrhosis features and the presence of intrahepatic calcifications. Initial investigation of the etiology of the liver disease was not elucidated, but liver biopsy showed microgoticular steatosis and cholesterol esters deposits in Kuppfer cells. The dosage of serum lysosomal acid lipase was undetectable and we found the presence of a rare homozygous mutation in the gene associated with the lysosomal acid lipase deficiency, (allele c.386A > G homozygous p.H129R).
Asunto(s)
ADN/genética , Cirrosis Hepática/etiología , Hígado/diagnóstico por imagen , Mutación , Esterol Esterasa/genética , Enfermedad de Wolman/genética , Biopsia , Análisis Mutacional de ADN , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/genética , Masculino , Persona de Mediana Edad , Enfermedades Raras , Esterol Esterasa/metabolismo , Tomografía Computarizada por Rayos X , Enfermedad de Wolman/complicaciones , Enfermedad de Wolman/diagnóstico , Enfermedad de WolmanRESUMEN
INTRODUCTION AND AIM: Studies have shown that two polymorphisms were associated with steatosis and progression of non-alcoholic fatty liver disease (NAFLD) in different populations: the Patatin-like Phospholipase Domain Containing 3 (PNPLA3) and Transmembrane 6 Superfamily Member 2 (TM6SF2). However, the frequency and significance of these polymorphisms in an admixed population, i.e., Brazilian, is unknown. Therefore, we aimed to evaluate them in healthy subjects in comparison to patients with NAFLD. MATERIAL AND METHODS: This was a multicenter cross-sectional study in 248 patients with biopsy-proven NAFLD and in 134 healthy controls from two tertiary centers in Brazil. PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) polymorphisms were evaluated. RESULTS: In controls, the frequencies of PNPLA3 CC and CG+GG were 49.25% and 50.74%, respectively; in NAFLD patients, this was 31.05% and 68.88% (p=0.0044, 95% CI 1.037-2.977). PNPLA3 GG subjects had an increased risk (3.29-fold) of having NAFLD when compared to CC subjects (p=0.0044, 95% CI 1.504-7.225). In patients with nonalcoholic steatohepatitis (NASH), PNPLA3 GG compared to CC was associated with higher AST levels [38.4±25.3 versus 36.7±40.1IU/L, p=0.0395)] and with the presence of liver fibrosis (≥F2 fibrosis, p=0.0272). TM6SF2 polymorphisms were not in Hardy-Weinberg equilibrium in our NAFLD group precluding further analysis. CONCLUSION: We demonstrated for the first time that PNPLA3 CG+GG increase the risk of NAFLD among Brazilian subjects. Moreover, PNPLA3 GG was associated with liver enzyme elevation and fibrosis in NASH patients.
Asunto(s)
ADN/genética , Predisposición Genética a la Enfermedad , Lipasa/genética , Cirrosis Hepática/genética , Hígado/patología , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Biopsia/métodos , Brasil/epidemiología , Estudios de Casos y Controles , Estudios Transversales , Progresión de la Enfermedad , Femenino , Genotipo , Humanos , Incidencia , Lipasa/metabolismo , Hígado/metabolismo , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Factores de Riesgo , Adulto JovenRESUMEN
INTRODUCTION: Bacterial infection is present in up to 30% of hospitalized cirrhotic patients. It can lead, even after its resolution, to organ dysfunction and even acute-on-chronic liver failure (ACLF). It is the precipitating factor of ACLF in one third of the cases and is the main cause of mortality in patients with liver cirrhosis. OBJECTIVES: The aim of this study was to evaluate the prevalence and identify early risk factors for severe ACLF and death in hospitalized patients with liver cirrhosis with bacterial infection. PATIENTS AND METHODS: This was a prospective observational study. Hospitalized patients with liver cirrhosis and bacterial infection were included. Clinical and laboratory data and their evolution to organ dysfunction and death were assessed. A statistical analysis were carried out to identify predictors of severe ACLF and in-hospital mortality. RESULTS: This study included 88 patients. ACLF was observed in 62 (70%) patients, with 48 (55%) grade 2 or higher. Of the 27 deaths (31% of all patients), 26 had severe ACLF (54% mortality) (P<0.0001). The independent risk factors for ACLF of at least 2 and death were baseline serum sodium [odds ratio (OR): 0.874; P=0.01, and OR: 0.9, P=0.04], initial MELD (OR: 1.255, P=0.0001, and OR: 1.162, P=0.005), and a recent invasive procedure (OR: 3.169, P=0.01, and OR: 6.648, P=0.003). CONCLUSION: Lower serum sodium values, higher MELD scores at diagnosis of infection, and a recent history of invasive procedures were independent risk factors for severe ACLF and death in patients with cirrhosis and bacterial infection.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada/diagnóstico , Infecciones Bacterianas/diagnóstico , Técnicas de Apoyo para la Decisión , Hiponatremia/diagnóstico , Cirrosis Hepática/diagnóstico , Admisión del Paciente , Sodio/sangre , Insuficiencia Hepática Crónica Agudizada/sangre , Insuficiencia Hepática Crónica Agudizada/microbiología , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/sangre , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/mortalidad , Biomarcadores/sangre , Brasil/epidemiología , Distribución de Chi-Cuadrado , Progresión de la Enfermedad , Femenino , Mortalidad Hospitalaria , Humanos , Hiponatremia/sangre , Hiponatremia/mortalidad , Pacientes Internos , Cirrosis Hepática/sangre , Cirrosis Hepática/microbiología , Cirrosis Hepática/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto JovenRESUMEN
Abstract Background: Chronic hepatitis B is a major cause of cirrhosis, and the natural history of the disease has several clinical stages that should be thoroughly understood for the implementation of proper treatment. Nonetheless, curing the disease with antiviral treatment remains a challenge. Aims: To describe the clinical course, response to treatment, and poor prognostic factors in 247 hepatitis B virus chronic infection patients treated in a tertiary hospital in Brazil. Methods: This was a retrospective and observational study, by analyzing the medical records of HBV infected patients between January 2000 and January 2015. Results: Most patients were male (67.2%) and 74.1% were HBeAg negative. Approximately 41% had cirrhosis and 8.5% were hepatitis C virus coinfected. The viral load was negative after two years on lamivudine, entecavir and tenofovir in 86%, 90.6%, and 92.9% of the patients, respectively. The five-year resistance rates for lamivudine, adefovir, entecavir, and tenofovir were 57.5%, 51.8%, 1.9%, and 0%, respectively. The overall seroconversion rates were 31.2% for HBeAg and 9.4% for HBsAg. Hepatocellular carcinoma was diagnosed in 9.7% of patients, liver transplantation was performed in 9.7%, and overall mortality was 10.5%. Elevations of serum alanine aminotransferase (p = 0.0059) and viral load (p < 0.0001) were associated with progression to liver cirrhosis. High viral load was associated with progression to hepatocellular carcinoma (p < 0.0001). Significant risk factors associated with death were elevated alanine aminotransferase (p = 0.0039), liver cirrhosis (p < 0.0001), high viral load (p = 0.007), and hepatocellular carcinoma (p = 0.0008). HBeAg positive status was not associated with worse outcomes, and treatment may have been largely responsible. Conclusions: Elevations of viral load and serum alanine aminotransferase may select patients with worse prognosis, especially progression to cirrhosis and hepatocellular carcinoma, which were strongly association with death.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Antivirales/uso terapéutico , Virus de la Hepatitis B/inmunología , Carcinoma Hepatocelular/virología , Hepatitis B Crónica/tratamiento farmacológico , Cirrosis Hepática/virología , Neoplasias Hepáticas/virología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Carcinoma Hepatocelular/mortalidad , Progresión de la Enfermedad , Carga Viral , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/mortalidad , Cirrosis Hepática/mortalidad , Neoplasias Hepáticas/mortalidadRESUMEN
BACKGROUND: Chronic hepatitis B is a major cause of cirrhosis, and the natural history of the disease has several clinical stages that should be thoroughly understood for the implementation of proper treatment. Nonetheless, curing the disease with antiviral treatment remains a challenge. AIMS: To describe the clinical course, response to treatment, and poor prognostic factors in 247 hepatitis B virus chronic infection patients treated in a tertiary hospital in Brazil. METHODS: This was a retrospective and observational study, by analyzing the medical records of HBV infected patients between January 2000 and January 2015. RESULTS: Most patients were male (67.2%) and 74.1% were HBeAg negative. Approximately 41% had cirrhosis and 8.5% were hepatitis C virus coinfected. The viral load was negative after two years on lamivudine, entecavir and tenofovir in 86%, 90.6%, and 92.9% of the patients, respectively. The five-year resistance rates for lamivudine, adefovir, entecavir, and tenofovir were 57.5%, 51.8%, 1.9%, and 0%, respectively. The overall seroconversion rates were 31.2% for HBeAg and 9.4% for HBsAg. Hepatocellular carcinoma was diagnosed in 9.7% of patients, liver transplantation was performed in 9.7%, and overall mortality was 10.5%. Elevations of serum alanine aminotransferase (p=0.0059) and viral load (p<0.0001) were associated with progression to liver cirrhosis. High viral load was associated with progression to hepatocellular carcinoma (p<0.0001). Significant risk factors associated with death were elevated alanine aminotransferase (p=0.0039), liver cirrhosis (p<0.0001), high viral load (p=0.007), and hepatocellular carcinoma (p=0.0008). HBeAg positive status was not associated with worse outcomes, and treatment may have been largely responsible. CONCLUSIONS: Elevations of viral load and serum alanine aminotransferase may select patients with worse prognosis, especially progression to cirrhosis and hepatocellular carcinoma, which were strongly association with death.