Background and Aims: extrahepatic organ failure (EHOF) including the onset time, number, type, and sequence on the prognosis of acute-onchronic liver failure (ACLF) patients remains unknown. This study aimed to identify the association between the characteristics of EHOF and the prognosis of ACLF patients. Methods: ACLF subjects enrolled at six hospitals in China were included in the analysis. The risk of mortality based on the characteristics of EHOF was evaluated. Survival of study groups was compared by Kaplan-Meier analysis and log-rank tests. Results: A total of 736 patients with ACLF were included. EHOF was observed in 402 patients (54.6%), of which 295 (73.4%) developed single EHOF (SEHOF) and 107 (26.6%) developed multiple EHOF (MEHOF). The most commonly observed EHOF was coagulation failure (47.0%), The impact of the characteristics of followed by renal (13.0%), brain (4.9%), respiratory (4.3%), and circulatory (2.3%) failure. Survival analysis found that MEHOF or SEHOF patients with brain failure had a worse prognosis. However, no significant outcome was found in the analysis of the effect of onset time and sequence of failed organs on prognosis. Patients were further divided into three risk subgroups by the EHOF characteristics. Kaplan-Meier analysis showed that risk stratification resulted in the differentiation of patients with different risks of mortality both in the training and validation cohorts. Conclusions: The mortality of ACLF patients was determined by the number and type, but not the onset time and sequence of EHOF. Risk stratification applicable to clinical practice was established.

Objective:To investigate the clinical characteristics and risk factors for the progression of acute-on-chronic liver failure(ACLF)associated with hepatitis B in elderly patients.Methods:A total of 168 elderly patients with hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)at Tianjin Third Central Hospital who met the diagnostic criteria of the Asian Pacific Association for the Study of the Liver(APASL)-ACLF were enrolled, 176 non-elderly HBV-ACLF patients served as the control group during the same period, and their baseline and progression data were recorded.At the same time, the elderly group was divided into the progressive subgroup and the non-progressive subgroup based on the diagnostic criteria of the European Society for the Study of the Liver(EASL)-ACLF, and their baseline and progression data were recorded.Independent risk factors for HBV-ACLF progression in the elderly were analyzed using multivariate Cox proportional risk model regression.Results:Compared with non-elderly patients with HBV-ACLF, elderly patients were more likely to progress to meet the EASL-ACLF diagnostic criteria and have higher mortality.Multivariate Cox proportional risk model regression analysis showed that baseline arterial lactic acid levels( HR=1.77, 95% CI: 1.36-2.30, P<0.01), secondary nosocomial infections( HR=13.90, 95% CI: 3.73-51.87, P<0.01), rates of change in maximum total bilirubin( HR=1.08, 95% CI: 1.01-1.15, P=0.04), rates of change in maximum MELD( HR=4.06, 95% CI: 1.53-10.77, P=0.01)and rates of change in maximum CLIF-SOFA( HR=12.74, 95% CI: 2.46-66.08, P<0.01)were independent risk factors for progression of HBV-ACLF in elderly patients. Conclusions:Compared with non-elderly patients, elderly patients with HBV-ACLF have more advanced disease and higher mortality.Therefore, risk factors should be identified as soon as possible and treatment plans should be formulated as soon as possible to further reduce the mortality.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is difficult to treat and carries a high risk of short-term mortality. This study aimed to explore the effect of artificial liver support system (ALSS) on the survival of HBV-ACLF patients and to investigate which HBV-ACLF patients may benefit from ALSS treatment. We enrolled 132 patients hospitalized for HBV-ACLF according to the criteria of the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) from 425 ACLF patients who were determined to at least meet the Asian Pacific Association for the Study of the Liver criteria and followed up for 90 days. Overall 132 eligible patients were divided into two groups: standard medical treatment (SMT) group, which included 54 patients who underwent SMT alone, and ALSS group, which included 78 patients who underwent ALSS treatment plus SMT. The proportion of HBV-ACLF grade 1, 2, and 3 was 57.69%, 37.18%, and 5.13% in the ALSS group and 51.85%, 35.19%, and 12.96% in the SMT group, respectively. Bacterial infection was present in 43.6% of patients in the ALSS group and in 55.6% of patients in the SMT group. The mortality rates in the ALSS group at 28 and 90 days were significantly lower than those in the SMT group (23.08% vs. 48.15% and 33.33% vs. 57.41%, P < 0.05). ALSS was an independent factor related to both the 28- and 90-day survival of HBV-ACLF patients. Particularly, a higher cumulative survival rate in either patients with HBV-ACLF grade 1 or those with HBV-ACLF with bacterial infection was observed in the ALSS group. Moreover, ALSS had an independent influence on mortality. Based on the COSSH-ACLF criteria, ALSS could better improve the short-term survival of HBV-ACLF patients than SMT alone, especially in those with HBV-ACLF grade 1 or HBV-ACLF with infection.

Infection is a common cause of death in patients with advanced cirrhosis. We aimed to develop a predictive model in Child-Turcotte-Pugh (CTP) class C cirrhotics hospitalized with infection for optimizing treatment and improving outcomes. Clinical information was retrospectively abstracted from 244 patients at Tianjin Third Central Hospital, China (cohort 1). Factors associated with mortality were determined using logistic regression. The model for predicting 90-day mortality was then constructed by decision tree analysis. The model was further validated in 91 patients at Mayo Clinic, Rochester, MN (cohort 2) and 82 patients at Seoul St. Mary's Hospital, Korea (cohort 3). The predictive performance of the model was compared with that of the CTP, model for end-stage liver disease (MELD), MELD-Na, Chronic Liver Failure-Sequential Organ Failure Assessment, and the North American consortium for the Study of End-stage Liver Disease (NACSELD) models. The 3-month mortality was 58%, 58%, and 54% in cohort 1, 2, and 3, respectively. In cohort 1, respiratory failure, renal failure, international normalized ratio, total bilirubin, and neutrophil percentage were determinants of 3-month mortality, with odds ratios of 16.6, 3.3, 2.0, 1.1, and 1.03, respectively (P<.05). These parameters were incorporated into the decision tree model, yielding area under receiver operating characteristic (AUROC) of 0.804. The model had excellent reproducibility in the U.S. (AUROC 0.808) and Korea cohort (AUROC 0.809). The proposed model has the highest AUROC and best Youden index of 0.488 and greatest overall correctness of 75%, compared with other models evaluated. The proposed model reliably predicts survival of advanced cirrhotics with infection in both Asian and U.S. populations.

AimTo compare the prognosis between the patients with progression into acute-on-chronic liver failure (ACLF) from acute deterioration of pre-existing chronic liver disease and patients without this progression, and to determine predictors of this disease progression.MethodsWe retrospectively analyzed clinical data from 285 patients admitted with acute worsening of pre-existing chronic liver disease within 4weeks characterized by total bilirubin (TBIL) of 51M/L or more and prothrombin activity (PTA) of more than 40% but less than 70%, which did not meet the Asia-Pacific Association for the Study of the Liver criteria for ACLF. Patient survival was estimated by Kaplan-Meier analysis and subsequently compared by log-rank test. Independent predictors of disease progression were determined using univariate analysis and multivariate Cox regression analysis.ResultsThe 90-day survival rates significantly worsened in patients with progression into ACLF compared with those without this progression. Baseline TBIL, baseline Model for End-Stage Liver Disease (MELD) score, and the maximum changing rates of PTA level and Child-Turcotte-Pugh (CTP) score were independently associated with progression into ACLF in patients with acute deterioration of pre-existing chronic liver disease.ConclusionPatients with acute worsening of pre-existing chronic liver disease characterized by TBIL of 51M/L or more and PTA of more than 40% but less than 70% should receive aggressive prediction and prevention of ACLF development. Baseline TBIL, baseline MELD score, and the maximum changing rates of PTA level and CTP score may early predict the progression into ACLF.

In clinical practice, establishing a subsequent optimum treatment for chronic hepatitis B patients with a history of multiple NAs treatment failures, including a suboptimal response to a final therapy with combined ETV and ADV, is a complicated but crucial challenge. This study investigated the efficacy and safety of a tenofovir rescue regimen in these patients. A total of six eligible patients were enrolled and were switched to a tenofovir rescue regimen. At baseline, the genotypes and genotypic mutations of the reverse transcriptase and surface gene were determined by ultra‐deep pyrosequencing, and further clonal analyses of the reverse transcriptase domain were performed to identify multidrug‐resistant HBV strains. In addition, HBV DNA levels, serology, and biochemistry parameters were monitored at baseline and every 3 months, and abdominal ultrasonography was performed at baseline and every 6 months. All patients were confirmed to harbor LAM‐related resistant HBV strains. After switching to the tenofovir rescue treatment, all patients had an undetectable level of HBV DNA within 6 months and achieved normalization of the ALT level within 9 months. These virological and biochemical responses persisted until the end of the observation period. None of the patients developed clinical deterioration or any adverse events related to the tenofovir therapy during the median 16.5‐month follow‐up. In conclusion, the tenofovir rescue regimen can be employed confidently as a highly effective and safe treatment choice following a suboptimal response to ETV plus ADV therapy for a subset of chronic hepatitis B patients with a history of multiple unsuccessful antiviral treatments. J. Med. Virol. 87:1013–1021, 2015. © 2015 Wiley Periodicals, Inc.

Background and aim: It has been shown that mean platelet volume (MPV) can be used as a prognostic biomarker in some chronic diseases. The aim of the present study is to investigate the possible association between MPV and clinical outcome and prognosis in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) within 4 weeks.Methods: This study included 64 patients with HBV-ACLF, 19 chronic hepatitis B (CHB) patients, 27 patients with hepatitis B-related cirrhosis (CR, Child-Pugh A/B), 51 healthy subjects (healthy controls [HC]). The complete blood counts and biochemical examination of blood were obtained after 12 h of fasting. In the ACLF group, the relationships between the prognosis and the MPV were analyzed.Results: At baseline, a statistically significant increase in MPV was shown in patients with ACLF (median 9.5, range 7.1-14.1) compared with HC (8.0, 7.2-11.9, P < 0.001), CR (8.4, 5.9-11.1, P < 0.001) and CHB (8.3, 7.3-12.0, P < 0.001). The MPV value was positively correlated with model of end-stage liver disease (MELD) score and international normalized ratio (INR). The MPV level was significantly increased in nonsurvivors than survivors. High MPV level showed a significantly lower survival rate (P = 0.001). Multivariate logistic regression analysis showed that only MPV level was independent factor predicting poor short-term outcomes.Conclusion: MPV values at presentation were higher among nonsurvivors than survivors, and this parameter was well correlated with liver function parameters and may be used as a predictor for 4-week mortality rate in patients with HBV-ACLF. (C) 2014 Elsevier Masson SAS. All rights reserved.