Clinical study of serum human-βeta-defensin-1 level for evaluating short-term prognosis in patients with acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of serum human-βeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.

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.

Falla hepática aguda sobre crónica (ACLF), síndrome subdiagnosticado con alta mortalidad / Acute-on-chronic liver failure (ACLF), an underdiagnosed syndrome with high mortality

Acute on chronic liver failure is an increasingly recognized syndrome characterized by acute decompensation of chronic liver disease associated with organ failure and high short-term mortality. ACLF is frequent, affecting between 24 and 40% of patients admitted for complications of cirrhosis. Sepsis, active alcoholism, and relapse of chronic viral hepatitis are the most frequent precipitating factors. However, in up to 40%­50% of the cases of ACLF have no identifiable trigger. The stage of severity of Acute on chronic liver failure is very important because it allows us to stratify patients according to their prognosis, evaluate therapeutic response, determine transplant urgency, deciding intensive care unit admission, and also have a basis on which to decide therapeutic futility. (AU)

Frecuencia, perfil clínico y mortalidad de la insuficiencia hepática crónica reagudizada en un hospital público de Lima - Perú / Frequency, clinical profile and mortality of acute-on-chronic liver failure in a public hospital of Lima - Peru

Introducción: Una condición de alta mortalidad a corto plazo en el cirrótico es la Insuficiencia hepática crónica reagudizada (ACLF por sus siglas en inglés), caracterizada por la falla de órgano(s) y precedida habitualmente por una descompensación aguda (DA). Objetivo: Determinar la frecuencia, el perfil clínico y la mortalidad en los cirróticos hospitalizados con ACLF. Materiales y métodos: Estudio analítico observacional realizado de julio 2016 a junio 2017. Se estableció la condición de ACLF según los criterios del estudio CANONIC. Resultados: Se reclutaron 118 pacientes cirróticos, 34 (28,8%) de los cuales presentaron ACLF, con grado 1: 14 (41%), grado 2: 16 (47%) y grado 3: 4 (12%) pacientes. La edad promedio fue 61,5 años; siendo la etiología más frecuente el alcoholismo en 18 pacientes (53%) y la mayoría no tenían historia previa de DA (64,7%). Los factores precipitantes más frecuentes fueron: la hemorragia digestiva (41%) y las infecciones (29,4%). Los grupos con y sin ACLF tuvieron una diferencia estadísticamente significativa en el puntaje Child-Turcotte-Pugh (CTP) (11,4 ± 1,8 vs 8,69 ± 2,04; p<0,0001), puntaje MELD (26,4 ± 8,1 vs 14,4 ± 4,6; p<0,0001), leucocitos (11 809,7 ± 6906,3/mm3 vs 8434,01 ± 5434,9/mm3; p: 0,006) y mortalidad a 28 días (76,5% vs 21,4%; p<0,0001), con un riesgo relativo (RR) de 3,5. Conclusiones: La frecuencia de ACLF fue 28,8%, similar a la del estudio CANONIC (30,9%). El principal factor precipitante fue la hemorragia digestiva. Los puntajes CTP, MELD y leucocitos fueron más altos en el grupo con ACLF, observándose una mortalidad a 28 días de 76,5% (3,5 veces mayor que en los pacientes sin ACLF).

Introduction: A condition of high short-term mortality in the cirrhotic patient is Acute-on-Chronic Liver Failure (ACLF), characterized by organ failure (s) and usually preceded by acute decompensation (AD). Objective: To determine the frequency, clinical profile, and mortality in cirrhotic patients hospitalized with ACLF. Materials and methods: This is an observational analytical study conducted from July 2016 to June 2017. We established the ACLF condition through the criteria of the CANONIC study. Results: The study population was 118 patients, of whom 34 (28.8%) presented ACLF, 14 (41%) were Grade 1, 16 (47%) Grade 2 and 4 (11.9%) Grade 3. The average age was 61.5 years old, alcoholism being the most frequent etiology with 18 patients (53%) and mostly without episodes of AD (64.7%). The most frequent precipitating factors were: Digestive hemorrhage (41%) and infections (29.4%). The groups with and without ACLF were statistically significant in the Child-Turcot- Pugh score (CTP) (11.4 ± 1.8 vs. 8.69 ± 2.04; p < 0.0001), MELD score (26.4 ± 8.1 vs. 14.4 ± 4.6; p < 0.0001), leukocytes (11,809.7 +/- 6,906.3 per mm3 vs. 8,434.01 ± 5,434.9 per mm3; p: 0.006) and 28-day mortality (76.5% vs. 21.4%, p < 0.0001), with a relative risk (RR) of 3.5. Conclusions: The frecuency of ACLF was 28.8%, similar to that of the CANONIC study (30.9%). The digestive hemorrhage being the main precipitating factor. The CTP, MELD and leukocyte scores were highest in this group. Mortality in patients with ACLF was 3.5 times more frequent than in patients without ACLF.

Falla hepática aguda sobre crónica (ACLF) ¿qué es, que sabemos y hacia dónde vamos? / Acute-on-chronic liver failure (ACLF) ¿what is it, what do we know about it and where are we going?

Acute on chronic liver failure (ACLF) is an increasingly recognized syndrome worldwide, in which there is great interest from different scientific societies and an increasing number of publications. It is defined as a syndrome of cirrhotic patients, characterized by the presence of acute decompensation, organ failure and high mortality rate in the short term. ACLF can be reversed using standard therapy in only 16-50% of patients, thus a prompt transfer to liver transplant center can make a difference in the survival chances of the patient.

La falla hepática aguda sobre crónica (ACLF, por su sigla en inglés) es un síndrome cada vez más reconocido a nivel mundial, que genera gran interés por parte de las distintas sociedades científicas y sobre el cual existe un número creciente de publicaciones. Se define como un síndrome de pacientes cirróticos, que se caracteriza por la presencia de una descompensación aguda, falla orgánica y elevada mortalidad a corto plazo. La reversibilidad de este síndrome con las medidas estándar es solo entre 16-50%, por lo que la derivación a un centro con disponibilidad de trasplante hepático puede hacer la diferencia en la sobrevida del paciente.

Static and dynamic prognostic factors for hepatitis-B-related acute-on-chronic liver failure

BACKGROUND/AIMS: Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. METHODS: Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. RESULTS: A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (> or =28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (> or =grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). CONCLUSIONS: Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.

Prognostic value of Gc-globulin in Chinese patients with acute-on-chronic Hepatitis B liver failure

To determine dynamic Gc-globulin level change in Acute-on-Chronic Hepatitis B Liver Failure [ACHBLF] patients, and evaluate the prognostic value of Gc-globulin. An analytical study. The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China, from January 2010 to December 2012. A total of 54 consecutive Chinese ACHBLF patients and 30 healthy volunteers as controls were recruited from 2010 to 2012. The patients were divided into improved group and aggravated group. Gc-globulin levels were determined in both groups and mean values compared with significance at p < 0.05. Cut-off value was also determined. The Gc-globulin level was significantly decreased in ACHBLF patients [p < 0.001]. Gc-globulin levels were significantly higher in improved patients than in aggravated patients, and a 215 mg/L cut-off value carried the best prognostic information. On longitudinal observations, Gc-globulin gradually elevated in improved groups. However, in aggravated groups, the Gc-globulin levels were always below normal levels and no significant change was observed before or after the treatment [p > 0.05]. Gc-globulin monitoring offers a rapid and accurate method to estimate treatment outcomes on admission and an effective temporal indicator of curative effects in ACHBLF patients at an optimal cut-off value of 215 mg/L

Falla hepática aguda sobre crónica / Acute-on chronic liver failure

The decompensation of liver cirrhosis secondary to an identifiable injury (mainly infections among the potential causes) associated to failure of one or more organs (particularly the kidney). Proinflammatory citokines are involved in pathophysiology, produced as a consequence of the injury that triggers the condition. Mortality factors are the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA); Model-For-End-Stage-Liver Disease (MELD); number of organs affected, and presence of leukocytosis. No specific treatment has been described yet that might have an impact on the mortality rates, therefore emphasis should made on prevention and/or diagnosis for early treatment of injuries (pneumonia and Spontaneous Bacterial Peritonitis-SBP among others) in order to prevent synthesis of cytokines that have a role in its pathophysiology.

La falla hepática aguda sobre crónica corresponde a una situación de alta mortalidad, pero potencialmente reversible. Conceptualmente corresponde a la descompensación de la cirrosis hepática secundaria a un daño cuya etiología es muchas veces identificable (destacando las infecciones entre las posibles causas) asociada a la falla de uno o más órganos (especialmente el riñón). En su patogenia actúan en forma importante citoquinas proinflamatorias que se generan como consecuencia del daño que gatilla el cuadro. Son factores pronósticos de mortalidad el Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA); Model-For-End-Stage-Liver Disease (MELD); número de órganos disfuncionantes y existencia de leucocitosis. Aún no se ha descrito ningún tratamiento específico que impacte en la mortalidad del cuadro, por lo que se debe enfatizar en prevenir y/o diagnosticar para tratar precozmente las causas de daño (neumonía y peritonitis bacteriana espontánea- PBE entre otros) y así evitar la síntesis de citoquinas que participan en su patogenia.