UNASSIGNED: Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients.
UNASSIGNED: Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT.
UNASSIGNED: In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated.
UNASSIGNED: COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT.
UNASSIGNED: This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).

UNASSIGNED: Pre-acute-on-chronic liver failure (ACLF) is a distinct intermediate stage between acute decompensation (AD) and ACLF. However, identifying patients with pre-ACLF and predicting progression from AD to ACLF is difficult. This study aimed to identify pre-ACLF within 28 days, and to develop and validate a prediction model for ACLF in patients with HBV-related decompensated cirrhosis.
UNASSIGNED: In total, 1,736 patients with HBV-related cirrhosis and AD were enrolled from 2 large-scale, multicenter, prospective cohorts. ACLF occurrence within 28 days, readmission, and 3-month and 1-year outcomes were collected.
UNASSIGNED: Among 970 patients with AD without ACLF in the derivation cohort, the 94 (9.6%) patients with pre-ACLF had the highest 3-month and 1-year LT-free mortality (61.6% and 70.9%, respectively), which was comparable to those with ACLF at enrollment (57.1% and 67.1%); the 251 (25.9%) patients with unstable decompensated cirrhosis had mortality rates of 22.4% and 32.1%, respectively; while the 507 (57.9%) patients with stable decompensated cirrhosis had the best outcomes (1-year mortality rate of 2.6%). Through Cox proportional hazard regression, specific precipitants, including hepatitis B flare with HBV reactivation, spontaneous hepatitis B flare with high viral load, superimposed infection on HBV, and bacterial infection, were identified to be significantly associated with ACLF occurrence in the derivation cohort. A model that incorporated precipitants, indicators of systemic inflammation and organ injuries reached a high C-index of 0.90 and 0.86 in derivation and validation cohorts, respectively. The optimal cut-off value (0.22) differentiated high-risk and low-risk patients, with a negative predictive value of 0.95.
UNASSIGNED: Three distinct clinical courses of patients with AD are validated in the HBV-etiology population. The precipitants significantly impact on AD-ACLF transition. A model developed by the precipitant-systemic inflammation-organ injury framework could be a useful tool for predicting ACLF occurrence.
UNASSIGNED: NCT02457637 and NCT03641872.
UNASSIGNED: It was previously shown that patients with decompensated cirrhosis could be stratified into 3 groups based on their short-term clinical prognoses. Herein, we showed that this stratification applies to patients who develop cirrhosis as a result of hepatitis B virus infection. We also developed a precipitant-based model (i.e. a model that incorporated information about the exact cause of decompensation) that could predict the likelihood of these patients developing a very severe liver disease called acute-on-chronic liver failure (or ACLF).

UNASSIGNED: The forecast accuracy of the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) and Asian Pacific Association for the Study of the Liver (APASL) acute-on-chronic liver failure (ACLF) criteria in assessing long-term outcomes after liver transplantation (LT) is still unclear, especially when the staging of the two standards is inconsistent.
UNASSIGNED: A retrospective cohort (NCT05036031) including 565 patients from January 2015 to June 2021 was conducted. The 28 and 90 days, 1- and 3-years overall survival (OS) after LT were compared between different grades.
UNASSIGNED: Total of 162 (28.7%) and 230 (40.7%) patients met the ACLF standards. In the EASL-CLIF criteria, the 3-year OS rates were 83·0%, 80·3%, and 69·8% for ACLF1-3, respectively. In the APASL criteria, the 3-year OS rates were 85·7% for APASL ACLF Research Consortium (AARC)-1, similar to ACLF-1. The 3-year OS rates were 84·5% for AARC-2, which were slightly better than ACLF-2. Regarding AARC-3, the 3-year OS rate was 5·8% higher than ACLF-3. For patients who met neither set of criteria for ACLF, the 3-year OS rates were 89·8%. The multivariate analysis showed that alanine aminotransferase >100 U/L, respiration failure, and cerebral failure were independent risk factors for post-LT death.
UNASSIGNED: This study provides the first large-scale long-term follow-up data in Asia. Both criteria showed favorable distinguishing ability for post-LT survival. Patients with ACLF had a higher post-LT mortality risk, and ACLF-3 and AARC-3 correlated with significantly greater mortality.
UNASSIGNED: National Natural Science Foundation of China and Science and Technology Commission of Shanghai Municipality.

UNASSIGNED: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19).
UNASSIGNED: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n = 17), severe (n = 40) and critical groups (n = 43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve.
UNASSIGNED: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 μg/L vs. 501.90 μg/L, p < 0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p = 0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP.
UNASSIGNED: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.
UNASSIGNED: El objetivo de este estudio fue evaluar si la hiperferritinemia podría ser un factor predictivo de la mortalidad en pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19).
UNASSIGNED: Se incluyó un total de 100 pacientes hospitalizados con COVID-19 en la unidad de cuidados intensivos (UCI), clasificándose como grupos moderado (n = 17), grave (n = 40) y crítico (n = 43). Se recopiló la información clínica y de laboratorio, comparándose los niveles de ferritina entre los diferentes grupos. Se evaluó la asociación entre ferritina y mortalidad mediante un análisis de regresión logística. Además, se evaluó la eficacia del valor predictivo utilizando la curva ROC (receiver operating characteristic).
UNASSIGNED: La cantidad de ferritina fue significativamente superior en el grupo de pacientes críticos en comparación con el grupo de pacientes graves. La media de concentración de ferritina fue cerca de 3 veces superior en el grupo de muerte que en el grupo de supervivientes (1.722,25 μg/L vs. 501,90 μg/L, p < 0,01). La concentración de ferritina guardó una correlación positiva con otras citoquinas inflamatorias tales como interleucina (IL)-8, IL-10, proteína C reactiva (PRC) y factor de necrosis tumoral (TNF)-α. El análisis de regresión logística demostró que la ferritina era un factor predictivo independiente de la mortalidad intrahospitalaria. En especial, el grupo de ferritina alta estuvo asociado a una mayor incidencia de la mortalidad, con un valor de odds ratio ajustado de 104,97 [intervalo de confianza (IC) del 95% 2,63-4.185,89; p = 0,013]. Además, el valor de ferritina tuvo una ventaja de capacidad discriminativa en el área bajo la curva ROC (AUC) de 0,822 (IC 95% 0,737-0,907] superior al de procalcitonina y PRC.
UNASSIGNED: El valor de ferritina medido durante el ingreso puede servir de factor independiente para prevenir la mortalidad intrahospitalaria en los pacientes de COVID-19 en la UCI.

UNASSIGNED: Chronic HCV infection is an important cause of hepatocellular carcinoma (HCC) and liver failure in the US but limited data are available in China. We compared the incidence of clinical outcomes among adults with chronic HCV infection in the US and China and examined factors associated with outcomes.
UNASSIGNED: A parallel prospective study of 2 cohorts of patients with HCV RNA+ recruited in 1 site in the US (UMHS) and 3 sites (PUHSC) in China between September 2011 and July 2015 was carried out. Composite liver outcomes (liver-related deaths, HCC, liver transplantation or liver decompensation), were analysed using competing-risk Cox proportional hazards model to determine incidence and associated factors.
UNASSIGNED: A total of 795 UMHS and 854 PUHSC patients were followed for a median of 3.06 and 3.99 years, respectively. At enrolment, a significantly higher percentage of UMHS patients had cirrhosis (45.4% vs. 16.2%). The 5-year cumulative incidence of composite liver outcomes was significantly higher in UMHS than in PUHSC patients (25.3% vs. 6.6%, p <0.0001). Stratification by stage of liver disease at enrolment showed this difference persisted only in the subgroup without cirrhosis due to higher aspartate aminotransferase to platelet ratio index (APRI) in the UMHS cohort. A total of 493 UMHS and 502 PUHSC patients received HCV treatment, and sustained virologic response (SVR) was achieved in 88.0% UMHS and 86.8% PUHSC treated-patients. SVR as time-dependent variable was associated with 80% lower risk of composite liver outcomes among patients with decompensated cirrhosis but not the overall cohorts.
UNASSIGNED: When accounting for disease severity at entry, the incidence of composite liver outcomes was similar in patients with HCV in the US and China. Achievement of SVR had the greatest short-term impact on patients with decompensated cirrhosis.
UNASSIGNED: Patients with chronic hepatitis C virus infection were recruited from centres in the United States and China. During follow-up, a higher percentage of the American patients had clinical outcomes: liver failure, liver cancer, liver transplant or liver-related deaths than the Chinese patients, mainly because more American patients had cirrhosis at enrolment. Older age and more advanced liver disease were associated with higher incidence of outcomes overall and viral clearance after hepatitis C treatment was associated with a lower incidence of outcomes in patients with advanced cirrhosis. Our findings highlight the importance of improving diagnosis and treatment of hepatitis C before advanced liver disease develops.

BACKGROUND: Warfarin is the most commonly used antithrombotic drug. Single nucleotide polymorphisms (SNPs) of CYP2C9, CYP4F2, VKORC1 1173 and VKORC1-1639 influence warfarin maintenance dosage. We aimed to determine the impact of SNPs of these genes on mean daily warfarin dosage (MDWD) in Han-Chinese patients.
METHODS: Strict literature inclusion criteria were established, and literature searching was performed on PubMed, Embase and Cochrane Library for English articles and CNKI, CBM and Wanfang database for Chinese articles before September 2, 2014. Revman 5.3 was used to analyze the relationship between gene SNPs and MDWD in Han-Chinese subjects.
RESULTS: We included 33 studies researching the impact of gene SNPs on MDWD in Han-Chinese subjects. CYP2C9 *3/*3, *1/*3 and *3 carriers needed a 72% (95% confidence interval [CI]: 62.0%-81.0%), 28% (22.0%-33.0%) and 26% (21.0%-32.0%) lower MDWD, respectively, than CYP2C9 *1/*1 carriers. CYP4F2 TT, CT and T carriers required a 18% (7.0%-30.0%), 7% (7.0%-7.0%) and 11% (7.0%-14.0%) higher MDWD, respectively, than CYP4F2 CC carriers. VKORC1 1173 CC, CT and C carriers required a 98% (78.0%-118.0%), 49% (37.0%-62.0%) and 56% (44.0%-67.0%) higher MDWD, respectively, than VKORC1 1173 TT carriers. VKORC1-1639 GG, GA and G carriers needed a 101% (53.0%-149.0%), 40% (36.0%-45.0%) and 38% (35.0%-42.0%) higher MDWD, respectively, than VKORC1-1639 AA carriers.
CONCLUSIONS: This meta-analysis is the first to report the relationship between genotypes and MDWD among Han-Chinese patients. The results showed that SNPs of CYP2C9, CYP4F2, VKORC1 1173 and VKORC1-1639 significantly influenced the MDWD in Han-Chinese patients.