Study on HBV-related acute-on-chronic liver failure risk factors and novel predictive survival model / 中华肝脏病杂志

Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.

A Case of Cryptococcal Meningitis Mimicking Hepatic Encephalopathy in a Patient with Liver Cirrhosis Caused by Chronic Hepatitis C / 대한소화기학회지

Cryptococcus neoformans, an encapsulated fungus, is an important opportunistic pathogen that can cause meningitis in immunocompromised patients. Since patients with cryptococcemia have high mortality, it is essential to make an early diagnosis and promptly initiate antifungal therapy. However, it is often very difficult to differentiate between cryptococcal meningitis and hepatic encephalopathy in patients with liver cirrhosis, and there is delay in making the diagnosis. Therefore, these patients have a particularly grave prognosis and consequently many patients die before culture results become available. In one study, starting antifungal therapy within 48 hours of the blood culture was associated with improved survival, but patients with liver cirrhosis were significantly less likely to receive antifungal therapy within 48 hours compared to those without liver cirrhosis. Recently, the authors experience a case of a 68-year-old woman with liver cirrhosis who presented with fever and a drowsy mental status. She had a previous history of having been admitted for infection-associated hepatic encephlopathy. Cryptococcal meningitis and cryptococcemia were diagnosed by spinal puncture and culture of cerebrospinal fluid. In spite of adequate treatment, the patient developed multi-system organ failure and eventually expired. Herein, we report a case of cryptococcal meningitis mimicking hepatic encephalopathy in a patient with liver cirrhosis.

Acute Hepatic Encephalopathy Presenting as Cortical Laminar Necrosis: Case Report

We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.

A eritromicina utilizada como tratamento da encefalopatia hepática em portadores de cirrose: estudo prospectivo, randomizado, duplo-cego e controlado / Erythromycin used as treatment of hepatic encephalopathy in patients with cirrhosis: prospective study, randomized, double-blind and controlled

A encefalopatia hepática (EH) é uma complicação da cirrose considerada como sinal de mau prognóstico na doença hepática avançada. As conseqüências da EH não são completamente reversíveis, por isso o tratamento deve ter rápido início de ação e ser altamente eficaz. Atualmente os antibióticos são os medicamentos mais eficazes na EH aguda, porém no tratamento da EH são utilizados apenas os de baixa absorção, que em geral demandam certo tempo para apresentar resultados. Além disso, esses antibióticos não são isentos de efeitos adversos. Análise comparativa da eficácia da eritromicina (ERY), usada pela primeira vez no tratamento da EH em portadores de cirrose. Ensaio clínico prospectivo, randomizado e duplo cego de pacientes adultos portadores de cirrose, internados por EH no período de agosto/2008 a outubro/2010 no Hospital das Clínicas da Faculdade de Medicina de Botucatu - UNESP. Após a admissão, os indivíduos receberam tratamento com ERY 250 mg ou neomicina (NEO) 1 grama. As medicações foram utilizadas por via oral e administradas de 6/6 horas até a alta hospitalar, prescrição de outro antibiótico ou óbito. Todos os pacientes foram avaliados diariamente por meio do índice de encefalopatia hepática (IEH). Foram realizadas dosagens diárias de amônia sérica e proteína C reativa (PCR), bem como exames de bioquímica hepática e renal. A análise estatística foi realizada por meio de testes de comparação entre os grupos (testes t de Student e Mann-Whitney), medidas de distribuição central e análise descritiva. 30 casos de EH foram avaliados (15 tratados com ERY e 15 com NEO). Os grupos foram homogêneos em relação a idade, IEH, grau de EH à admissão hospitalar, escala de coma de Glasgow, escore Meld e classificação de Child-Pugh modificada.(...)

Hepatic encephalopathy (HE) is one of the major complications in patients with hepatic cirrhosis, and is considered a sign of bad prognosis in this setting. The consequences of HE are not totally reversible, thus the treatment must to be effective in a short time to attain HE regression. Actually, antibiotics are the best options in acute HE treatment. However, the antibiotics used in HE are drugs of low absorption, which often spend a long time to obtain its effect. Nevertheless, these antibiotics are not free of adverse effects. Comparative analysis of efficacy of erythromycin (ERY) used by the first time as a treatment of HE. Randomized controlled trial of adult patients with HE and hepatic cirrhosis admitted from August 2008 to October 2010 in the hospital of the Botucatu Medical School - UNESP. After randomization, the patients received either ERY 250 mg or neomycin (NEO) 1 g. The drugs were administered orally q.i.d. until hospital discharge, prescription of another antibiotic or death. All subjects were evaluated diary and the hepatic encephalopathy index (HEI) was calculated every day. Serum ammonia, C reactive protein (CRP) and biochemical profile (hepatic and renal exams) were obtained diary of each patient. Statistical analysis was performed using tests for comparison between the groups (Student t test and Mann-Whitney test), Spearman’s rank correlation, central distribution measures and descriptive analysis. 30 cases of HE were evaluated (15 treated with each drug). In the moment of admission, the groups were homogeneous with respect to age, HEI, HE grade, Glasgow coma scale, Meld score and Child-Pugh modified classification. The subjects that received ERY had a short time of hospitalization (p = 0.032) and a great degree in the alanine aminotransferase (ALT) levels (p = 0.026).(...)

Ascites, Hepatorenal Syndrome and Spontaneous Bacterial Peritonitis in Patients with Portal Hypertension / 대한소화기학회지

Ascites, hepatic encephalopathy and variceal hemorrhage are three major complications of portal hypertension. The diagnostic evaluation of ascites involves an assessment of its etiology by determining the serum-ascites albumin gradient and the exclusion of spontaneous bacterial peritonitis. Ascites is primarily related to an inability to excrete an adequate amount of sodium into urine, leading to a positive sodium balance. Sodium restriction and diuretic therapy are keys of ascites control. But, with the case of refractory ascites, large volume paracentesis and transjugular portosystemic shunts are required. In hepatorenal syndrome, splanchnic vasodilatation with reduction in effective arterial volume causes intense renal vasoconstriction. Splanchnic and/or peripheral vasoconstrictors with albumin infusion, and renal replacement therapy are only bridging therapy. Liver transplantation is the only definitive modality of improving the long term prognosis.

Análisis de las complicaciones más frecuentes de la cirrosis hepática en nuestro medio / Analysis of the complication frequence of the cirrhosis hepatic in means

Conocer las principales causas de cirrosis hepática (CH) en nuestro medio. Analizar la relación entre edad, sexo, etiología y parámetros hematológicos: albúmina (Alb), tiempo de protrombina (PT) y bilirrubina (BT) con las causas de descompensación de la CH. Se evaluó parámetros: clínicos, hematológicos, endoscópicos, ecográficos y en algunos casos histológicos de la base de datos de la consulta de hepatología del Hospital IVSS "Dr. Miguel Pérez Carreño" establecida desde diciembre de 1999. Se utilizó la escala de Child-Pugh en los casos con cirrosis hepática compensada (CHC); la cirrosis hepática descompensada (CHC) se definió por la presencia de algunas de las complicaciones: Ascitis (A), Encefalopatía (E), Hemorragía Digestiva Superior (HDS) y Peritonitis Bacteriana Espontánea (PBE). Se estableció factores pronósticos de descompensación: edad, sexo, Alb, PT, BT. Análisis estadístico: se utilizó medidas de tendencia central, frecuencias absolutas y relativas, medidas de asociación y comparación. Se obtuvo 80 casos de los cuales el 55 por ciento (n=44) perteneció al sexo masculino con un promedio (X) de edad de 53 años, y el 45 por ciento (n=36) restante al femenino con un X de edad de 50 años. La etiología más frecuente de CH fue por alcohol (ETOH) en un 31,3 por ciento (n=25), seguido de infección viral (VHC) en un 17,5 por ciento (n=14). La principal complicación fue la (A) entre los casos con CHD en un 26,25 por ciento (n=21), seguido de la (HDS) con 6,25 por ciento (n=5). Los hallazgos endoscópicos resultantes: varices esofágicas y la gastropatía hipertensiva con 45 y 24 casos respectivamente; mientras que los ecográficos: esplenomegalia en 34 casos, seguido de enfermedad hepática difusa con 32 casos. Hubo un 3,75 por ciento de muertes en 30 meses de seguimiento. La causa más frecuente de CH en nuestro medio es el alcohol siendo la princiapl complicación la ascitis, algunos parámetros hematológicos guarda relación con la misma

Intoxicación por hierbas y su posible relación con encefalopatía hepática: sindrome de Reye / Herbal poisining with possible association whit Reye syndrome

Lactante, masculino de 7 meses de edad que ingresó al Hospital del Niño de La Paz, por presentar un cuadro de deshidratación, acidosis metabólica, antecedente de diarrea aguda y a quien le administraron una infusión casera de múltiples hierbas con propósitos curativos. Evolucionó con datos clínicos de encafalopatía, hepatopatía y crisis convulsivas. Las aminotransferasas estuvieron elevadas al triple y el amonio sérico incrementado al doble de los valores de referencia. La tomografía de cráneo mostró edema cerebral y la biopsia hépática reporto lesiones microvacuolas en hepatocitos compatibles con Síndrome de Reyé. La evolución del cuadro fue lentamente favorable con uso de terapia antiedema cerebral, soluciones parenterales y apoyo nutricio para paciente insuficiente hepático. El diagnóstico final fue: Síndrome de Reyé posiblemente asociado a intoxicación por hierbas.

Raised intracranial pressure in hepatic encephalopathy.

Intracranial hypertension secondary to cerebral edema is the cause of death in 50%-80% of patients with fulminant hepatic failure (FHF). This is rarely seen in chronic hepatic failure. The genesis of cerebral edema in FHF is poorly understood. The grade of encephalopathy and coagulopathy are the most important predictors of outcome in FHF. However, it is important to emphasize that intracranial pressure (ICP) may not reflect clinical course. Decerebrate posturing may be seen with ICP recording of 16 mmHg, while a quarter of the patients may have brain damage without clinical signs of raised ICP. ICP monitoring is therefore vital. The gold standard for ICP monitoring is the intraventricular method. Non-invasive methods like computerized tomography scan and magnetic resonance imaging have poor correlation with ICP. Other methods like transcranial Doppler and jugular venous oximetry measurement of brain metabolites need evaluation. The main indications for ICP monitoring in FHF are (a) patients in grade III or IV encephalopathy and (b) patients undergoing liver transplantation. Generally, patients with an ICP >40 mmHg with cerebral perfusion pressure <50 mmHg for over 2 hours are poor subjects for liver transplant.

Management of agitation and convulsions in hepatic encephalopathy.

Hepatic encephalopathy represents a reversible decrease in neurological function caused by liver disease. Overall incidence of seizures in hepatic encephalopathy varies between 2% and 33%. Non-convulsive status epilepticus may be particularly common in these patients. Psychiatric disturbances manifest as agitation, personality change, delusions, etc. Aims of seizure management include treatment of basic disease, correction of precipitant factors, imaging of head, and choice of a pharmacologically safe agent. It is important to consider non-convulsive status epilepticus and rule it out by an EEG. Absolute data for safety profile of drugs in liver disease is still not clear, as changes of pharmacokinetics make choice of drugs difficult. Free drug concentrations may be higher, making plasma concentration monitoring essential in such circumstances. A single seizure may not require therapy. However when started, antiepileptic drugs are usually discontinued early. Drugs with sedative effects are best avoided because of a risk of precipitating coma. Phenytoin and gabapentin are relatively preferred drugs; however, monitoring of drug levels is desirable. Management of agitation includes physical restraint and medication. Benzodiazepines are best avoided. Haloperidol is a safer choice in the presence of liver disease. Overall management of neuropsychiatric state aims at management of underlying pathology, the resolution of which leads to improvement in the clinical symptomatology.

Complicações agudas das doenças hepáticas crônicas / Acute complications of chronic liver diseases

As doenças hepáticas crônicas, em fases avançadas, cursam com graves complicações, responsáveis pela maioria das indicações de internações hospitalares e causas de morte dos pacientes. Neste capítulo, são discutidas as principais complicações das doenças hepáticas crônicas, que são a encefalopatia hepática, a peritonite bacteriana espontânea e a síndrome hepatorrenal. São apresentados os aspectos importantes, na prática médica, dessas três condições clínicas, com ênfase na abordagem diagnóstica e terapêutica

Análisis de supervivencia en pacientes cirróticos / Analysis of the survival rate in cirrhotic patients

Antecedentes: La cirrosis hepática (CH) es una enfermedad crónica y progresiva, que favorece la presencia de algunas complicaciones idependientes de su causa y que disminuyen la supervivencia de los pacientes. Objetivos: Determinar la frecuencia, la causa, los principales factores de descompensación y analizar las curvas de supervivencia en CH en una población de Durango, México. Métodos: Se incluyeron pacientes de uno u otro sexo con diagnóstico de cirrosis hepática del Hospital General del IMSS de Durango, Méx. Se determinó su causa factores de descompensación y grado de hipertensión portal (HTP). Se realizó un seguimiento de 39 meses, registrándose las complicaciones y causas de muerte. Análisis estadístico: Prueba exacta de Fischer, ANOVA de Friedman, chicuadrada de Mantel-Haenzsel y curvas de Kaplan-Meier. Resultados: Se estudiaron 50 pacientes, 30 del sexo femenino y 20 del masculino, edad promedio de 54.3 años (32-74). La causa más frecuente fue la alcohólica (42 por ciento) en 19 hombres y dos mujeres. El 86 por ciento tenían descompensación por ascitis; hemorragia por várices 38 por ciento, encefalopatía 36 por ciento e ictericia 32 por ciento. El 52 por ciento tenía HTP III y 60 por ciento clase B de Child-Pugh. Conclusiones: La supervivencia en el grupo descompensado fue de 62 por ciento y en el grupo total de 73 por ciento y falleció 20 por ciento. Existió relación entre el grado de HTP y la clase funcional de Chil-Pugh (p< 0.05); a menor reserva hepática, mayor probabilidad de hemorragia (p < 0.05) y encefalopatía (p < 0.01); el mayor grado de HTP se relacionó como hemorragia, encefalopatía y muerte (p< 0.05), y no se encontró relación entre la causa y la presencia de complicaciones.

Síndrome de falla orgánica múltiple en el curso de la insuficiencia hepática fulminante / Multiple systems organ failures in fulminant hepatic failure

Background: in fulminant hepatic failure, different organs systems become involved and a multiple systems organic failure may ensue. Aim: to perform a retrospective analysis of patients with fulminant hepatic failure admitted to UC Hospital Intensive Care Unit. Patients and methods: the charts of 14 patients (8 male) were analyzed. Multiple systems organic failure was defined as the presence of 2 or more organic dysfunctions. The evolution and mortality of these patients was analyzed. Results: patients` ages ranged from 30 to 74 years. The etiology of hepatic failure was B hepatitis in 4, non A non B hepatitis in 5, acute fatty liver of pregnancy in 3 and use of halothane and HIN in 2. ICU stay ranged from 1 to 44 days and 2 patients survived (one with drug induced liver failure and 1 with acute fatty liver of pregnancy). Mean prothrombin time was 19 ñ 9.5 per cent , total bilirrubin as 24 ñ 8.9 mg/dl and 12 patients reached grade IV encephalopathy. Mean admission APACHE II score was 21.5 ñ 6. Twelve patients developed multiple systems organic failure, that appeared 1.5 days or was already present at ICU admission; it lasted a mean of 2.5 days and all these 12 patients died. Neurologic involvement occured in 13 patients, renal in 10, cardiovascular in 9, respiratory in 5 and hematological involvement in 1. Conclusions: multiple systems organic failure is frequent in fulminant hepatic failure and is associated with a high mortality

Análisis clínico laboratorial de la encefalopatía hepática / Clinical and laboratorial study of hepatic encephalopathy

La encefalopatía es un síndrome neuropsiquíatrico que se presenta en algunos enfermos, con insuficiencia hepática, son características las alteraciones del estado menatl, las alateraciones neurológicas de datos de laboratorio características, pero no especificos. Al comienzo de la enfermedad los rasgos clínicos y mecanismos de encelaopatía varian. Nos propusimos analizar las carácteristicas de esta enfermedad, para determinar la frecuencia de causas praticipantes, al etiología de base, características clínicas y la evolución del estado mental mediante el Test de Pugh, y la evolución del estado mental mediante el test Reitan Trailmaking

Encefalopatía hepática

Mental deterioration in patients with fulminant hepatitis is a poor prognosis sign. Patients in stages III or IV with stupor or coma have cerebral edema. The increase in cerebral fluid eventually leads to endocraneal hypertension. Brain edema is not the cause of encephalopathy, only when the structures are displaced or intracraneal pressure increases, pupilary abnormalities, abnormal caloric reflexes and myoclonic seizures appears. Significant elevation of intracraneal pressure can be asymptomatic leading to temporal lobe herniation and death. Liver transplantation has changed the prognosis, and subdural and epidural monitoring has been developed in order to evaluate this problem optimally. Monitoring of cerebral perfusion pressure (mean arterial pressure - endocraneal pressure) to assess brain flow is essential. Values of less than 40mmHg imply cerebral ischemia. In patients with cirrhosis encephalopathy has several stages, and sleep disturbances can present very early. Asterixis is a sensible but not specific sign and the classic "faetor hepaticus" is not frequent. Most of the time a precipitating factor can be identified: gastrointestinal bleeding, sedatives, iuremia, infections, constipation, high protein intake and hypokalemia, chronic porto-systemic encephalopathy is mainly related to spontaneous porto-systemic collaterals or surgically created shunts. The most important pathogenetic factors are: ammonia, glutamate, increase cerebral serotonine, increase GABA tone and recently the presence of endogenous benzodiazepines. New therapeutic modalities included the administration of flumazenil, vegetable protein, lactulose and sodium benzoate...