Mortality from hepatitis B virus (HBV)–related acute‐on‐chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with ...mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV‐related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV‐related ACLF were enrolled in this open‐label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow–derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%‐84.8%) versus 55.6% (95% confidence interval 42.3%‐68.9%) for the SMT group (P = 0.03). There were no infusion‐related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5‐24 of follow‐up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow–derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End‐Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). Conclusion: Peripheral infusion of allogeneic bone marrow–derived MSCs is safe and convenient for patients with HBV‐related ACLF and significantly increases the 24‐week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209–219).
Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe and life-threatening complication, characterised by multi-organ failure and high short-term mortality. However, there ...is limited information on the impact of various comorbidities on HBV-ACLF in a large population. This study aimed to investigate the relationship between comorbidities, complications and mortality. In this retrospective observational study, we identified 2166 cases of HBV-ACLF hospitalised from January 2010 to March 2018. Demographic data from the patients, medical history, treatment, laboratory indices, comorbidities and complications were collected. The mortality rate in our study group was 47.37%. Type 2 diabetes mellitus was the most common comorbidity, followed by alcoholic liver disease. Spontaneous bacterial peritonitis, pneumonia and hepatic encephalopathy (HE) were common in these patients. Diabetes mellitus and hyperthyroidism are risk factors for death within 90 days, together with gastrointestinal bleeding and HE at admission, HE and hepatorenal syndrome during hospitalisation. Knowledge of risk factors can help identify HBV-ACLF patients with a poor prognosis for HBV-ACLF with comorbidities and complications.
Abstract
Background
Thyroid dysfunction has been reported in severe liver diseases. The aim of this study was to analyze the impact of serum thyroid-stimulation hormone (TSH) levels on the prognosis ...of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).
Methods
This retrospective cohort study included 1,862 patients with HBV-related ACLF. Risk factors associated with 30-day and 90-day survival, hazard ratios (HRs), and 95% confidence intervals (CIs) for TSH were estimated using Cox proportional hazards regression. The Area Under the ROC curve (AUROC) analysis was carried out, and the cut-off values were calculated. After grouping by the cut-off value, survival was compared between the groups using the log-rank test. This study data is from the “Survival Cohort Study (SCS)”, which has been registered at ClinicalTrials.gov (NCT03992898).
Results
Multivariate analysis indicated that an elevated TSH level was a highly significant predictor for 30-day survival (HR = 0.743, 95% CI: 0.629–0.878,
P
< 0.001) and 90-day survival (HR = 0.807, 95% CI: 0.717–0.909,
P
< 0.001). The AUROC of TSH level for 30-day and 90-day mortality were 0.655 and 0.620, respectively, with the same best cut-off values of 0.261 µIU/mL. Log-rank test showed that the group with higher TSH level had higher 30-day (78.5%, 95% CI: 76.1%-80.9% vs. 56.9%, 95% CI: 53.4%-60.4%;
P
< 0.001) and 90-day survival rate (61.5%, 95% CI: 58.6%-64.4% vs. 42.8%, 95% CI: 39.3%-46.3%;
P
< 0.001). Similar findings were observed in subgroups analysis. After adjusting for age and other risk factors, the higher level of TSH remained associated with 30-day survival (HR = 0.602, 95% CI: 0.502–0.721,
P
< 0.001) and 90-day survival (HR = 0.704, 95% CI, 0.609–0.814,
P
< 0.001).
Conclusions
Serum TSH level significantly correlate with HBV-related ACLF patients’ survival and may be of value for predicting 30-day and 90-day survival of patients with HBV-related ACLF.
Background/purpose of the study
Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is high. Severe infection is the most important complication that affects the ...outcomes of ACLF patients. Thymosin α1 (Tα1) can improve immune imbalance and this study aimed to investigate the safety and efficacy of Tα1 treatment for HBV-related ACLF.
Methods
From 2017 to 2019, 120 patients with HBV-related ACLF were enrolled in this open-label, randomized, and controlled clinical trial (ClinicalTrial ID: NCT 03082885). The control group (
N
= 58) was treated with standard medical therapy (SMT) only. The experimental group (
N
= 56) was subcutaneously injected with 1.6 mg of Tα1 once a day for the first week and then twice a week from week 2 to week 12.
Results
The 90-day cumulated liver transplantation free survival rate of the Tα1 group was 75.0% (95% confidence interval 63.2–86.8%) versus 53.4% (95% confidence interval 39.7–67.1%) for the SMT group (
p
= 0.030). No significant difference was found in the survival using competitive risk analysis. The incidences of new infection and hepatic encephalopathy in the Tα1 group were much lower than those in the SMT group (32.1% vs 58.6%,
p
= 0.005; 8.9% vs 24.1%,
p
= 0.029, respectively). Mortality from severe infection in the SMT group was higher than in the Tα1 group (24.1% vs 8.9%,
p
= 0.029).
Conclusion
Tα1 is safe for patients with HBV-related ACLF and significantly improves the 90-day liver transplantation-free survival rate. There may be a subgroup which may benefit from Tα1 therapy by the mechanism of preventing infection.
Background and Aim
Acute‐on‐chronic liver failure (ACLF) caused by hepatitis B virus (HBV) is a severe disease with high mortality. Immune injury plays an important role during the early stage of the ...disease. Our research aimed to investigate the safety and efficacy of dexamethasone therapy for patients with HBV‐related ACLF.
Methods
A total of 134 inpatients with HBV‐induced ACLF were enrolled from January 2009 to December 2012. All the patients received the standard medicine treatment (SMT), among whom 31 cases underwent additional dexamethasone injection for three times (dexamethasone treatment DMT Group). A total of 35 patients (SMT Group) matched for baseline characters served as controls. Both the groups were followed up for 12 weeks. The survival rates, liver functions, and complications were recorded.
Results
The 12‐week cumulative survival rates were 45.7% (16/35)and 48.4% (15/31) for SMT Group and DMT Group, respectively, and no significant differences were found (P = 0.959). There were no dramatic differences in liver function and model for end‐stage liver disease (MELD) score at 1, 2, 4, 8, and 12 weeks between two groups. There were no significant differences in the incidence of complications (i.e. infection, gastrointestinal bleeding, encephalopathy, hepatorenal syndrome, and ascites) from 1 to 12 weeks between Group SMT and Group DMT. More than 40 ages, MELD score more than 28 and encephalopathy were independent risk factors for the mortality of patients.
Conclusions
Dexamethasone cannot improve liver functions and 12‐week survival rates of patients with HBV‐related ACLF. Age, MELD score, and encephalopathy are independent risk factors.
Background:
Conventional prognostic models do not fully reflect the severity of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to establish an effective and ...convenient nomogram for patients with HBV-related ACLF.
Methods:
A nomogram was developed based on a retrospective cohort of 1,353 patients treated at the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to June 2016. The predictive accuracy and discriminatory ability of the nomogram were determined by a concordance index (C-index) and calibration curve, and were compared with current scoring systems. The results were validated using an independent retrospective cohort of 669 patients consecutively treated at the same institution from July 2016 to March 2018. This study is registered at ClinicalTrials.gov (NCT03992898).
Results:
Multivariable analysis of the derivation cohort found that independent predictors of 90-day survival were age, white blood cell (WBC) count, hemoglobin (Hb), aspartate aminotransferase (AST), total bilirubin (TBil), international normalized ratio, serum creatinine (Cr), alpha fetoprotein (AFP), serum sodium (Na), hepatic encephalopathy (HE), pre-existing chronic liver disease(PreLD), and HBV DNA load. All factors were included in the nomogram. The nomogram calibration curve for the probability of 90-day survival indicated that nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram was 0.790, which was statistically significantly greater than those for the current scoring systems in the derivation cohort (
P
< 0.001). The results were confirmed in the validation cohort.
Conclusions:
The proposed nomogram is more accurate in predicting the 90-day survival of patients with HBV-related ACLF than current commonly used methods.
Objective: Ascites is one of the most frequent complications of cirrhosis. Our study is to investigate the efficacy and safety of the intermittent drainage of ascites for HBV-related cirrhosis ...patients with tense ascites. Material and methods: A total of 2,169 HBV-related, decompensated liver cirrhosis inpatients were screened from January 2009-January 2014. Of them, 112 cases were eligible, among whom 55 patients (treated group) were administered paracentesis with central venous catheter and drained of 1-2 L ascites every 1 or 2 days (PCVC therapy). The remaining 57 patients served as controls (control group). Results: Compared with the baseline, the level of mean arterial pressure (MAP) in the control group markedly declined (82.27 ± 8.36 mm Hg vs. 91.25 ± 10.82 mm Hg, p = 0.000), and the levels of MAP (79.14 ± 10.30 mm Hg vs. 90.53 ± 10.97 mm Hg, p = 0.000) and hemoglobin (99.29 ± 16.78 g/L vs. 107.55 ± 21.80 g/L, p = 0.028) in the treated group dropped significantly. There were no significant differences in the levels of creatinine, sodium, eGFR, incidence of complications , weight loss, improvement rate, urine output and dosage of albumin between the two groups. The hospitalization time of the treated group was longer (21.49 ± 13.34 days vs. 16.56 ± 9.07 days, p = 0.025), and the amount of furosemide used in the treated group was greater than that used in the control group (47.72 ± 18.53 mg vs. 27.99 ± 13.32 mg, p = 0.000). Conclusions: Cirrhosis patients with tense ascites who received PCVC therapy showed decreased levels of Hb and MAP, but did not induce renal dysfunction. The efficacy of PCVC therapy is not superior to diuretic treatment.
Abstract
Using an extended chromomagnetic model, we perform a systematic study of the masses of doubly heavy tetraquarks. We find that the ground states of the doubly heavy tetraquarks are dominated ...by the color-triplet
configuration, which is opposite to that of fully heavy tetraquarks. The combined results suggest that the color-triplet configuration becomes more important when the mass difference between the quarks and antiquarks increases. We find three stable states that lie below the thresholds of two pseudoscalar mesons. They are the
tetraquark,
tetraquark, and
tetraquark.
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