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.
Humans ; Acute-On-Chronic Liver Failure/diagnosis* ; Prognosis ; Liver Cirrhosis ; C-Reactive Protein/analysis* ; ROC Curve ; Defensins ; Retrospective Studies

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.
Humans ; Hepatitis B virus ; Hepatic Encephalopathy/complications* ; Acute-On-Chronic Liver Failure/diagnosis* ; End Stage Liver Disease/complications* ; Severity of Illness Index ; Risk Factors ; ROC Curve ; Prognosis ; Retrospective Studies

Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and also have organ failure(s) are at high risk of short-term death. These patients have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now considered as a new syndrome that it is distinct from "mere" AD not only because of the presence of organ failure(s) and high short-term mortality but also because of younger age, higher prevalence of alcoholic etiology of cirrhosis, higher prevalence of some precipitants (such as bacterial infections, active alcoholism), and more intense systemic inflammatory response. ACLF is a new syndrome also because severe sepsis or severe alcoholic hepatitis do not account for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown" origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of "unknown origin" are subcategories of the syndrome.
Acute-On-Chronic Liver Failure/complications/mortality/*pathology ; Age Factors ; Cytokines/metabolism ; Hepatitis, Alcoholic/complications ; Humans ; Liver Cirrhosis/*complications/diagnosis ; Sepsis/complications ; Severity of Illness Index ; Survival Rate

OBJECTIVETo compare the acute kidney injury classification systems of RIFLE,AKIN,KDIGO and conventional criteria for determining prognosis of acute-on-chronic liver failure (ACLF) patients.

METHODSPatients with ACLF admitted to our hospital between July 2008 and March 2014 were enrolled in the study. The incidence, stages, and outcomes of acute kidney injury were determined according to the RIFLE, AKIN,KDIGO and conventional criteria.ROC curves were generated to compare the predictive ability for 30-day mortality of the four systems.Chi-square test and Fisher's exact test were used for statistical analyses, as well.

RESULTSAll four classification systems detected acute kidney injury among the patients in the study population (n =358), but the detection rates were not consistent (expressed as % of total): KDIGO criteria: 45.0%, AKIN: 38.8%, rIFLE: 35.5%, conventional criterion: 20.4%. The KDIGO and AKIN criteria showed higher sensitivity (72%), especially to early kidney injury, but the conventional criterion showed higher specificity (92%). The AUC for 30-day mortality was highest for the conventional criteria (0.75), followed by AKIN (0.72), rIFLE (0.70) and KDIGO (0.69) (all, P less than 0.05). In-hospital mortality increased with severity of AKI in a stepwise manner.

CONCLUSIONAmong the four common evaluation systems for acute kidney injury, the conventional criteria has the highest specificity for predicting short-term prognosis of patients with ACLF, while the AKIN and KDIGO criteria have the highest sensitivity for the presence of acute kidney injury, especially at the early stage.

Acute Kidney Injury ; classification ; diagnosis ; Acute-On-Chronic Liver Failure ; diagnosis ; Hospital Mortality ; Humans ; Incidence ; Prognosis ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Antiviral Agents ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Nucleosides ; therapeutic use ; Nucleotides ; therapeutic use ; Prognosis

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.
Acute-On-Chronic Liver Failure/*diagnosis/drug therapy/etiology ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/therapeutic use ; Cyclophosphamide/therapeutic use ; DNA, Viral/analysis ; Doxorubicin/therapeutic use ; Female ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/drug therapy ; Hospitalization ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prednisone/therapeutic use ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Vincristine/therapeutic use ; Young Adult

OBJECTIVETo investigate the short-term prognostic value of the indocyanine green clearance test when used in combination with the model for end-stage liver disease (MELD) scoring system to assess patients with hepatitis B virus acute-on-chronic liver failure (HBV-ACLF).

METHODSClinical data of 105 patients diagnosed with HBV-ACLF were retrospectively analyzed. The indocyanine green retention rate at 15 minutes (ICGR15), clinical data within 24 h after diagnosis, Child-Turcotte-Pugh (CTP) classification, MELD score, MELD combined with sodium concentration (MELD-Na) score, and King's Hospital (KCH) criteria data were collected for analysis. Measurement data were assessed by t-test and count data by the chi-square test. Short-term predictive accuracy for patients with HBV-ACLF was compared between different models using the area under the receiver operating characteristic (ROC) curve (AUC).

RESULTSThe mortality rate for all patients was 45.71%. Comparison of the survivors versus the non-survivors showed that age, total bilirubin, albumin, cholinesterase, creatinine, international normalized ratio, and incidence positive rate of relative complications (hepatorenal syndrome, hepatic encephalopathy) were significantly different between the two groups (all, P less than 0.05). The ICGR15 was found to be positively correlated with MELD score (r = 0.205, P less than 0.05). The MELD-ICGR15 model constructed by logistic regression analysis was: Logit(P) = 0.193 * MELD + 0.130 * ICGR15 - 11.256. The AUC was 0.880 and the cut-off was -0.706, with 89.6% sensitivity and 75.4% specificity. The AUC of the MELD-ICGR15 model was significantly higher than that of the ICGR15 (0.820), MELD score (0.779), MELD-Na score (0.761), KCH criteria (0.680), and CTP classification (0.631) (all, P less than 0.05).

CONCLUSIONICGR15, MELD score, and MELD-Na score had higher predictive values for HBV-ACLF than did CTP classification or KCH criteria. Furthermore, the MELD-ICGR15 model was better than any single parameter model for predicting the short-term prognosis of patients with HBV-ACLF.

Acute-On-Chronic Liver Failure ; diagnosis ; virology ; Adult ; Aged ; End Stage Liver Disease ; Female ; Hepatitis B ; complications ; Humans ; Indocyanine Green ; Male ; Middle Aged ; Predictive Value of Tests ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Young Adult

Acute-On-Chronic Liver Failure ; diagnosis ; Humans

OBJECTIVETo investigate the role ofCD4+CD25+ T regulatory (Treg) cells, T helper (Th)17cells and interleukin (IL)-6 in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and determine their value as prognostic markers.

METHODSThe Chinese National Knowledge Infrastructure (CNKI), WanFang, Chinese Scientific Journals (VIP), PubMed, Embase and Web of Science databases were searched for English language case-control studies on the relationship between regulatory T lymphocytes and ACLF.The quality of included studies was assessed using the Newcastle-Ottawa scale. The meta-analysis was designed according to the PICOS approach recommended by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. RevMan software, version 5.1, was used to perform the meta-analysis.

RESULTSNine case-cohort studies were selected for inclusion in the metaanalysis.The results of the meta-analyses showed that the level of CD4+CD25+ Treg cells was not significantly different between patients with HBV-related ACLF and patients with chronic hepatitis B (CHB) (mean difference (MD)=0.59, 95% confidence interval (CI)-1.68, 2.85, P=0.61) nor between patients with HBVrelated ACLF and healthy controls (MD=1.12, 95% CI:-1.42, 3.66, P=0.39). Thus, it appears that ACLF patients do not have a higher level of CD4+CD25+ Treg cells than CHB patients or healthy controls. However, the ACLF patients did appear to have a significantly higher level of Th17 cells than both the CHB patients (MD=1.73, 95% CI:0.21, 3.26, P=0.03) and the healthy controls (MD=1.62, 95% CI:(0.52, 2.72, P=0.004). In addition, the ACLF patients also had significantly higher level than both the CHB patients (MD=11.69, 95%CI:1.98, 21.40, P=0.02) and the healthy controls (MD=13.17, 95% CI:1.38, 24.95, P=0.03).

CONCLUSIONCD4+CD25+ Treg cells may be an important protective factor in the progression and prognosis of HBV-related ACLF, while Thl7 cells and IL-6 may be risk factors for further progression and worsened prognosis.

Acute-On-Chronic Liver Failure ; diagnosis ; immunology ; CD8-Positive T-Lymphocytes ; Case-Control Studies ; Disease Progression ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; Humans ; Interleukin-6 ; immunology ; Prognosis ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology

The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.
Acute Disease ; Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Cholestasis/epidemiology/etiology ; Demography ; Hepatitis A/complications/*diagnosis/mortality ; Humans ; Kidney Failure, Chronic/epidemiology/etiology ; Liver Transplantation ; Middle Aged ; Morbidity ; Republic of Korea ; Retrospective Studies ; Tertiary Care Centers ; Young Adult