MELD score < 18 rule out 28-day ACLF development among inpatients with hepatitis B-related previous compensated liver disease.

The acute-on-chronic liver failure (ACLF) development is highly dynamic. Currently, no satisfactory algorithm identifies patients with HBV at risk of this complication. The aim of the study was to characterize ACLF development in hospitalized HBV-related patients without previous decompensation and to test the performance of traditional prognostic models in ruling out ACLF development within 28 days on admission we conducted a cohort study. Two multi-center cohorts with hospitalized HBV-related previous compensated patients were analyzed. Performances of MELD, MELD-Na, CLIF-C AD, and CLIF-C ACLF-D in ruling out ACLF development within 28 days were compared and further validated by ROC analyses. In the derivation cohort (n = 892), there were 102 patients developed ACLF within 28 days, with profound systemic inflammatory levels and higher 28-day mortality rate (31.4% vs. 1.0%) than those without ACLF development. The MELD score (cut-off = 18) achieved acceptable missing rate (missed/total ACLF development) at 2.9%. In the validation cohort (n = 1656), the MELD score (<18) was able to rule out ACLF development within 28 days with missing rate at 3.0%. ACLF development within 28 days were both lower than 1% (0.6%, derivation cohort; 0.5%, validation cohort) in patients with MELD < 18. While in patients with MELD ≥ 18, 26.6% (99/372, derivation cohort) and 17.8% (130/732, validation cohort) developed into ACLF within 28 days, respectively. While MELD-Na score cut-off at 20 and CLIF-AD score cut-off at 42 did not have consistent performance in our two cohorts. MELD < 18 was able to safely rule out patients with ACLF development within 28 days in HBV-related patients without previous decompensation, which had a high 28-day mortality.

Tri-typing of hepatitis B-related acute-on-chronic liver failure defined by the World Gastroenterology Organization.

BACKGROUND AND AIM: Tri-typing of acute-on-chronic liver failure (ACLF), as proposed by the World Gastroenterology Organization (WGO), has not been validated in patients infected with hepatitis B virus (HBV). We aim to compare the three types of ACLF patients in clinic characteristics. METHODS: Hospitalized ACLF patients with chronic hepatitis B from five hepatology centers were retrospectively selected and grouped according to the WGO classification. For each group, we investigated laboratory tests, precipitating events, organ failure, and clinical outcome. RESULTS: Compared with type-B (n = 262, compensated cirrhosis) and type-C (n = 129, decompensated cirrhosis) ACLF, type-A patients (n = 195, non-cirrhosis) were associated with a younger age, the highest platelet counts, the highest aminotransferase levels, and the most active HBV replications. HBV reactivation were more predominant in type-A, while bacterial infections in type-B and type-C ACLF cases. Liver failure (97.4%) and coagulation failure (86.7%) were most common in type-A compared with type-B or type-C ACLF patients. Kidney failure was predominantly identified in type-C subjects (41.9%) and was highest (23/38, 60.5%) in grade 1 ACLF patients. Furthermore, type-C ACLF showed the highest 28-day (65.2%) and 90-day (75.3%) mortalities, compared with type-A (48.7% and 54.4%, respectively) and type-B (48.4% and 62.8%, respectively) ACLF cases. Compared with type-A (11.7%) ACLF patients, the increased mortality from 28 to 90 days was higher in type-B (31.6%) and type-C (37.5%). CONCLUSION: Tri-typing of HBV-related ACLF in accordance with the WGO definition was able to distinguish clinical characteristics, including precipitating events, organ failure, and short-term prognosis in ACLF patients.

Elevated D-dimer is associated with increased 28-day mortality in acute-on-chronic liver failure in China: a retrospective study.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by profound disrupted coagulation and fibrinolysis. Fibrinolytic marker D-dimer is increased in critically ill patients with cirrhosis which is associated with poorer prognosis. We aim to determine the potential association of D-dimer with the 28-day mortality in ACLF patients. METHODS: In a single center retrospective study performed in China, we collected data of 115 patients with ACLF from October 1, 2012 to December 31, 2016. We investigated correlations between D-dimer and other laboratory tests and prognostic scores. The relationship between D-dimer and 28-day mortality was explored by smoothing plot with an adjustment for potential confounders. Logistic regression analyses with crude and adjusted models were performed to explore the association of D-dimer with 28-day mortality in ACLF patients. RESULTS: In ACLF patients, D-dimer at admission was correlated with all prognostic scores (MELD-Na: r = 0.385, P < 0.001; CLIF-C ADs: r = 0.443, P < 0.001; CLIF-C ACLFs: r = 0.375, P < 0.001). A nonlinear relation between D-dimer and 28-day mortality was found with a turning point at 6.5 mg/L FEU. D-dimer level was independently associated with 28-day mortality with an adjusted odds ratio of [1.4 (1.0-1.9), P = 0.030] as continuous variable and [10.3 (1.3, 81.5), P = 0.028] as a classified variable with the cut-off of 6.5 mg/L FEU. An elevated D-dimer within the following 10 days also tended to be associated with higher risk of 28-day mortality [OR: 27.5 (0.9, 814.9), P = 0.055]. CONCLUSIONS: Elevated D-dimer levels was associated with increased risk of 28-day mortality in patients with ACLF in China.

[Long-term prognosis and quality of life of survivors with hepatitis B virus-related acute-on-chronic liver failure].

OBJECTIVE: To explore the long-term prognosis and health-related quality of life of patients surviving hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: The clinical data were collected from patients with HBV-ACLF, who were hospitalized in our department between November, 2011 and October, 2016 and survived for more than 90 days. The patients were followed for occurrence of newly diagnosed cirrhosis, decompensation events, hepatocellular carcinoma and death. The quality of life of the patients was evaluated using SF-36 score, and the patients with chronic hepatitis B (CHB) and cirrhosis treated during the same period served as controls. RESULTS: A total of 223 ACLF survivors were included in this study. According to the presence of cirrhosis on admission, the enrolled patients were divided into chronic hepatitis B-related ACLF (CHB-ACLF) group (n=130) and liver cirrhosis ACLF (CIR-ACLF) group (n=93). The 12-, 24- and 50-month survival rates in CHB-ACLF group were 97%, 95.7% and 93.9%, respectively, significantly higher than the rates in CIR-ACLF group (91%, 86% and 74%, respectively; P=0.007). In patients with CHB-ACLF, the 12-, 24- and 36-month progression rates of cirrhosis were 37.9%, 58.4% and 68.7% respectively. Multivariate Cox regression identified the peak value of serum creatinine (HR=1.015, P=0.026) and INR (HR=2.032, P=0.006) within 28 days as independent risk factors and serum sodium at baseline (HR=0.84, P=0.035) as an independent protective factor of occurrence of cirrhosis. The score of mental health on SF-36 in ACLF group was significantly lower than the national norms, and the scores for general health and body pain of ACLF patients were significantly higher than those in patients with CHB or cirrhosis. CONCLUSION: The long-term prognosis of ACLF survivors with and without cirrhosis can be different. Acute attacks are associated with an increased rate of cirrhosis progression in CHB patients who recovered from ACLF, possibly in relation with the severity of extra-hepatic organ injuries. The physical and social functions of long-term survivors of ACLF do not significantly decline, but their psychological status can be affected.

Improving survival of acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis.

The mortality of acute-on-chronic liver failure (ACLF) patients complicated with invasive pulmonary aspergillosis (IPA) was extremely high. We aimed to explore prognostic value of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) lung score and to establish an optimal voriconazole regimen for ACLF patients complicated with IPA. We retrospectively screened hospitalized ACLF patients in our hospital from July 2011 to April 2016, from which 20 probable IPA cases were diagnosed. Along with onsets of IPA, deteriorated diseases severity, especially lung conditions were found in those 20 ACLF patients. It was found that IPA patients with CLIF-SOFA lung score <2 had better 28-day survival than those with lung score >1 (11/13 vs 0/7, p < 0.001). Based on plasma voriconazole concentration measurement, an optimal voriconazole regimen (loading doses: 0.2 g twice daily; maintenance doses, 0.1 g once daily) was established, which resulted in rational trough plasma drug concentrations (1-5 µg/mL), good clinical outcomes (90-day survival rate of 6/8) and no observed adverse events. In conclusion, CLIF-SOFA lung score >1 was able to identify ACLF patients complicated with IPA encountering much higher 28-day mortality. An optimal voriconazole regimen was safe and effective in our ACLF patients complicated with IPA.