Prognosis In Acute-on-chronic Liver Failure Patients Research Articles

Impact of Onset Time, Number, Type, and Sequence of Extrahepatic Organ Failure on Prognosis of Acute-on-chronic Liver Failure.

The impact of the characteristics of extrahepatic organ failure (EHOF) including the onset time, number, type, and sequence on the prognosis of acute-on-chronic liver failure (ACLF) patients remains unknown. This study aimed to identify the association between the characteristics of EHOF and the prognosis of ACLF patients. 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. 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%), 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. 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.

Plasma S100A8 and S100A9 Are Strong Prognostic Factors for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure.

The rapidly evolving organ failure and high short-run mortality of acute-on-chronic liver failure (ACLF) are inseparable from the role of systemic inflammatory response. S100A8 and S100A9 are associated with the excessive cytokine storm and play a decisive part within the process of inflammation. We aimed to clarify the role of them in predicting prognosis of hepatitis B virus-related ACLF (HBV-ACLF). S100A8 and S100A9 levels were analyzed in plasma of 187 transplant-free HBV-ACLF patients, 28 healthy controls and 40 chronic hepatitis B (CHB) patients. S100A8 and S100A9 mRNAs were checked in liver samples from 32 HBV-ACLF patients with liver transplantation, 19 patients undergoing surgery for hepatic hemangioma and 10 CHB patients with needle biopsy. The plasma levels of the S100A8 and S100A9 were higher in HBV-ACLF patients than in CHB patients (S100A8 : P < 0.001 and S100A9 : P < 0.001) and healthy controls (S100A8 : P < 0.001 and S100A9 : P < 0.001), and similar results were obtained for mRNA expression. Moreover, both proteins were related to ACLF grade, different types of organ failure, and infection, and they correlated with other prognostic scoring systems. S100A8 and S100A9 can dependently predict 28/90-day mortality (28-day: S100A8: hazard ratio (HR): 1.027; 95% confidence interval (CI): 1.007-1.048; P=0.026, S100A9 : HR: 1.009; 95% CI: 1.001-1.017; P=0.007, 90-day: S100A8 : HR: 1.023; 95% CI: 1.011-1.035; P=0.004, S100A9 : HR: 1.008; 95% CI: 1.004-1.012; and P < 0.001). Among all of the scoring systems, the combined scoring model (S100A8 and S100A9 jointly with the Chronic Liver Failure-Consortium Organ Failure score (CLIF-C OFs)) displayed the highest area under the receiver operating curve (0.923 (95% CI, 0.887-0.961)) in the prediction of 90-day mortality. S100A8 and S100A9 are promising biomarkers for the analysis of risk stratification and prognosis in ACLF patients. In addition, combining them with the CLIF-C OFs may better predict the prognosis of ACLF.

Assessment Value of Short-Term Prognosis of Six Predictive Models for Patients with Acute-on-Chronic Liver Failure Treated with Artificial Liver Support System

To apply 6 predictive models on acute-on-chronic liver failure (ACLF) patients treated with artificial liver support system (ALSS), and to compare their assessment values for the short-term prognosis of patients. A total of 258 ACLF patients who underwent ALSS therapy between January 2018 and December 2019 were selected from the ALSS clinical database established by West China Hospital, Sichuan University, and their clinical data and 90-day prognosis information were collected. Cox proportional hazards model was used to estimate the association between the six predictive models, including Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH ACLF), European Association for the Study of the Liver--Chronic Liver Failure-Consortium (CLIF-C) ACLF, CLIF-C Organ Failure (OF), Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) ACLF, Model for End-Stage Liver Disease (MELD) and Simplified MELD (sMELD), and 90-day mortality, which included death or receiving liver transplantation. The area under the receiver operating characteristic (ROC) curve ( AUC), Harrell's C-index and Brier scores were calculated and compared to evaluate the predictive power. A total of 258 ACLF patients were enrolled. Of these patients, who had a mean age of (46.2±11.7) years old, 37 (14.3%) patients were female, 202 (78.3%) patients had a diagnosis of liver cirrhosis, and 107 (41.5%) patients died during the 90-day follow-up period. The six predictive models all yielded higher scores for patients who died than those for patients who survived (all P<0.001). The six predictive models were all independent risk factors for the short-term prognosis of ACLF patients treated with ALSS (all adjusted hazard ratio [HR]>1, all P<0.001). The AUC (0.806, 95% confidence interval [CI]: 0.753-0.853) and Harrell's C-index (0.772, 95% CI: 0.727-0.816) of COSSH ACLF were much higher than those of the five other predictive models (all AUCs<0.750, P<0.01; all Harrell's C-indices<0.750, P<0.001). The Brier score of COSSH ACLF was 0.18 (95% CI: 0.15-0.20). The 90-day mortality of patients defined as having low risk, moderate risk, and high risk according to the risk stratification of COSSH ACLF were 22.2%, 56.3%, and 90.2%, respectively. The COSSH ACLF could more accurately predict short-term prognosis in ACLF patients who received ALSS therapy, and could facilitate clinical decision-making.

Relationship Between Platelet to White Blood Cell Ratio and 30-Day Prognosis of Patients with Acute-on-Chronic Liver Failure

Background: Acute-on-chronic liver failure (ACLF) is always associated with thrombocytopenia or leukocytosis. Therefor the platelet to white blood cell ratio (PWR) in ACLF patients is always reduced. Objectives: Here, we assessed the relationship between PWR and prognosis in ACLF patients. Methods: A retrospective cohort of 415 patients, including 100 patients that were diagnosed of chronic hepatitis B, 104 patients suffered of HBV-related liver cirrhosis and 211 patients suffered of HBV-related ACLF, was investigated. Univariate and multivariate COX models were used to investigate the relationship between PWR and 30-day survival in patients with ACLF. Factors affecting PWR in ACLF patients were also analysed using logistic regression analysis. Results: At baseline, the platelet count in patients with HBV-related ACLF was significantly lower than that in patients with CHB and patients suffered of HBV-related cirrhosis. The PWR value was much higher in the survivors of ACLF than in ACLF patients who died. PWR, age, total bilirubine, prothrombin activity, and aspartate transaminase were independent predictors of the 30-day survival rate of ACLF patients. We also found that ascites and infection were independent factors related to the decrease of PWR in ACLF patients. Conclusions: The PWR value was significant declined in ACLF patients. And it was independent risk factors for the survival rate of those patients.

Metabolomic profiles of breath odor compounds for prognostic prediction in patients with acute-on-chronic liver failure: A pilot study.

The aim of this study was to use a metabonomics approach to identify potential biomarkers of exhaled breath condensate (EBC) for predicting the prognosis of acute-on-chronic liver failure (ACLF). Using liquid chromatography mass spectrometry, EBC metabolites of ACLF patients surviving without liver transplantation (n=57) and those with worse outcomes (n=45), and controls (n=15) were profiled from a specialized liver disease center in Beijing. The metabolites were used to identify candidate biomarkers, and the predicted performance of potential biomarkers was tested. Forty-one metabolites, involving glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, and amino acid metabolism, as candidate biomarkers for discriminating the different outcomes of ACLF were selected. A prognostic model was constructed by a panel of four metabolites including phosphatidylinositol [20:4(5Z,8Z,11Z,14Z)/13:0], phosphatidyl ethanolamine (12:0/22:0), L-metanephrine and ethylbenzene, which could predict the worse prognosis in ACLF patients with sensitivity (84.4%) and specificity (89.5%) (area under the receiver operating characteristic curve [AUC]=0.859, 95% confidence interval [CI]=0.787-0.931). Compared with Model for End-Stage Liver Disease (MELD) score (AUC=0.639, 95% CI=0.526-0.753) and MELD-sodium (MELD-Na) score (AUC=0.692, 95% CI=0.582-0.803), EBC-associated metabolite signature model could better predict worse outcomes in patients with ACLF (p<0.05). Using the MELD-Na score and EBC metabolite signatures, a decision tree model was built for predicting the prognosis of ACLF identified on logistic regression analyses (AUC=0.906, 95% CI=0.846-0.965). EBC metabolic signatures show promise as potential biomarkers for predicting worse prognosis of ACLF.

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

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. 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. 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 90days was higher in type-B (31.6%) and type-C (37.5%). 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.

Noninvasive models for predicting poor prognosis of chronic HBV infection patients precipitating acute HEV infection

Hepatitis E virus (HEV) infection contributes to a considerable proportion of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B virus (HBV) infection. This study aimed to predict the prognosis of chronic HBV infection patients precipitating acute HEV infection. A total of 193 patients were enrolled in this study. The performances of three chronic liver disease prognostic models (CTP score, MELD score, and CLIF-C ADs) were analyzed for predicting the development of ACLF following HEV superimposing chronic HBV infection. Subsequently, the performances of five ACLF prognostic assessment models (CTP score, MELD score, CLIF-C ACLFs, CLIF-C OFs, and COSSH-ACLFs) were analyzed for predicting the outcome of those ACLF patients. Of 193 chronic HBV infection patients precipitating acute HEV infection, 13 patients were diagnosed ACLF on admission, 54 patients developed to ACLF after admission, and 126 patients had non-ACLF during the stay in hospital. For predicting the development of ACLF, CTP score yielded a significantly higher AUROC compared with MELD score and CLIF-C ADs (0.92, 0.88, and 0.86, respectively; all p < 0.05). For predicting the poor prognosis of ACLF patients, the COSSH-ACLFs yielded a significantly higher AUROC compared with CLIF-C ACLFs, CLIF-C OFs, MELD score, and CTP score (0.89, 0.83, 0.81, 0.67, and 0.58, respectively; all p < 0.05). In conclusion, the stepwise application of CTP score and COSSH-ACLFs can predict the prognosis of chronic HBV infection patients precipitating acute HEV infection.

Prediction value of antithrombin III activity in the prognosis of patients with acute-on-chronic liver failure

Objective To analyze the relationship between antithrombin Ⅲ(AT-Ⅲ) activity and survival, bleeding and thrombosis complications in patients with acute-on-chronic liver failure (ACLF), and to explore the prediction value of AT-Ⅲ activity in the prognosis of ACLF patients. Methods The clinical data of 130 hospitalized patients with ACLF were retrospectively collected in Wuxi No.5 People′s Hospital from January 1, 2013 to April 1, 2019. The liver function, international normalized ratio (INR), and 90-day survival rate were detected. The AT-Ⅲ activity values at admission, week two, week four, and week eight of hospitalization were recorded, and the occurrences of fecal occult blood and femoral vein thrombosis were also recorded. The measurement data were compared by t test, analysis of variance, or rank sum test, and the categorical data were compared by chi-square test. The risk factors affecting the survival of ACLF patients were analyzed by Cox regression. The survival analysis was performed using the Kaplan-Meier method. Results At the end of 90-day follow-up of 130 patients, 56 patients died, 20 patients (15.38%) were fecal occult blood positive and 15 (11.54%) had femoral vein thrombosis. The baseline AT-Ⅲ activity in the death group was lower than that in the survival group ((17.89±13.68)% vs (36.03±11.96)%), and the difference was statistically significant (t=-8.045, P 0.05). The Cox regression analysis suggested INR (odds ratio (OR)=1.364, 95% confidence interval (CI) 1.078-1.726, P=0.010) and AT-Ⅲ activity (OR=0.930, 95%CI 0.906-0.954, P<0.01) were the independent factors affecting the survival of patients with ACLF. The area under the receiver operator characteristic curve of the AT-Ⅲ activity for predicting 90-day survival outcome of the patient was 0.706 (95%CI 0.773-0.952, P<0.01), and the cut-off value was 25%. Patients with AT-Ⅲ activity ≥ 25% had a higher survival rate than those with AT-Ⅲ activity <25% (χ2=58.20, P<0.01). Conclusions AT-Ⅲ activity is associated with fecal occult blood positive and femoral vein thrombosis in ACLF patients. The AT-Ⅲ activity is an independent influencing factor for predicting the prognosis of ACLF patients. Patients with AT-Ⅲ activity less than 25% have the higher mortality rate. Key words: Antithrombin Ⅲ, activity; Liver failure, acute-on-chronic; Prognosis; Forecasting

Acute-on-Chronic Liver Failure: Getting Ready for Prime Time?

ACLF is a clinically relevant syndrome that is epidemic worldwide and requires a dedicated multinational approach focused on prognostication and management; investigations are underway worldwide to prepare ACLF for prime time. (Hepatology 2018; 00:000-000).

Interleukin-23 levels in serum and dendritic cells and its relationship with prognosis of acute-on-chronic liver failure patients with chronic hepatitis B

Objective To study interleukin-23 (IL-23) levels in serum and dendritic cells of acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B (CHB) and to explore its relationship with the prognosis. Methods Peripheral blood mononuclear cells and serum were collected from 40 ACLF patients with CHB (including survival group 27 cases and non-survival group 13 cases) and 26 healthy controls. Monocytes were induced to immature dendritic cell in vitro and TNF-α was added to induce dendritic cell maturation. IL-23 mRNA of dendritic cells was detected by real time polymerase chain reaction (PCR), and serum IL-23 level was measured by enzyme-linked immuno sorbent assay (ELISA). Differences among the parameters with normal distribution were compared using t test, those with non-normal distribution were compared using non-parametric Mann-Whitney U-test, and the relationship between two variables was assessed by Spearman′s rank correlation. Results International normalized rate (INR) and model for end-stage liver disense (MELD) scores in non-survival group of ACLF were higher than those in survival group (INR: 2.32 vs 1.64, U=69.00, P=0.002 2; MELD: 36 vs 30, U=64.50, P=0.001 4). However, there were no significant differences between two groups at gender, age, alanin aminotransferase (ALT), aspartate aminotrans ferase (AST), bilirubin, creatinine, hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and serum IL-23. IL-23 mRNA level in dendritic cells at baseline in non-survival group of ACLF was significantly higher than that in survival group (76 vs 43, U=71.50, P=0.002 8). After treatment, serum IL-23 was significantly declined in survival group ([160±75] ng/L vs [91±49] ng/L, t=4.012, P=0.000 2), but not in non-survival group. Significant positive correlation was observed between IL-23 mRNA level in dendritic cells and MELD score at baseline (r=0.7198, P<0.01). Conclusions Persistent high serum IL-23 level suggests poor prognosis in ACLF patients with CHB. IL-23 mRNA expression in dendritic cells has good consistency with MELD score and the patients with high IL-23 mRNA expression has poor outcome. Key words: Hepatitis B virus; Dendritic cells; Liver failure; Interleukin-23

Lymphocyte-monocyte ratio at admission predicts possible outcomes in patients with acute-on-chronic liver failure.

The lymphocyte-monocyte ratio (LMR) in the peripheral blood is suggested to be a potential biomarker for predicting the clinical outcomes of several diseases. We aimed to evaluate the relative efficiency of LMR for predicting 3-month mortality in patients with acute-on-chronic liver failure (AoCLF). In this study, 74 chronic hepatitis B patients, 90 AoCLF patients, and 70 healthy controls were followed up for 4 months. The primary endpoint was 3-month in-hospital mortality. Hematological and virological parameters as well as liver biochemistry were determined using blood samples ordered upon admission. A panel of clinical and biochemical variables were analyzed for potential associations with outcomes using Cox proportional hazards and multiple regression models. A significantly lower LMR was detected in AoCLF patients than in healthy controls and chronic hepatitis B groups (both P=0.001). The LMR inversely correlated with model for end-stage liver disease scores, and a lower LMR was associated with increased 3-month mortality. Multivariate analysis suggested that both LMR and model for end-stage liver disease scores were independent predictors of 3-month mortality (P<0.01). A low LMR measured at admission is predictive of a poor prognosis in AoCLF patients.

Immune dysfunction in cirrhosis: Distinct cytokines phenotypes according to cirrhosis severity

Background/objectivesCirrhosis associated immune dysfunction has been proposed to switch from a pro-inflammatory phenotype in stable cirrhosis to an immunodeficient one in patients with decompensated cirrhosis and acute-on-chronic liver failure. The aim of the present study was to compare serum cytokine levels between healthy patients, stable cirrhosis, and decompensated cirrhotic patients with and without development of acute-on-chronic liver failure (ACLF); and to explore whether any of the measured cytokines is associated with cirrhosis severity and prognosis in ACLF patients. MethodsPatients were enrolled from October 2013 to May 2014 in two hospitals located in Buenos Aires. Cirrhotic patients with an acute decompensating event were enrolled accordingly to the development of ACLF defined by the CANONIC study group. There were two control groups: healthy subjects (n=14) and stable cirrhotic patients (n=14). Demographic, clinical and biochemical data were obtained. Seventeen cytokines were measured using Bio-Plex Pro Human Cytokine 17-plex Assay. ResultsOf the 49 decompensated cirrhotic patients enrolled, 18 (36.7%) developed ACLF. Leukocyte count, MELD score at admission, Clif-SOFA at admission and day 7 were significantly higher in the ACLF group (p=0.046, p<0.001, p<0.001, p<0.001 respectively) as well as short-term mortality (p<0.001) compared to stable and decompensated cirrhotic patients. In comparison with healthy controls, stable cirrhotic and decompensated cirrhotic patients showed increased levels of pro-inflammatory and anti-inflammatory cytokines: IL-6, IL-7, IL-8, IL-10, IL 12, and TNF-α. Decompensated cirrhotic patients with the development of ACLF showed a significant decrease of IL-7, IL-10, IL-12, TNF-α, MCP-1 and IFN-γ, but a sustained response of IL-6 and IL-8. When evaluating cirrhosis severity, IL-6 and IL-8 correlated positively with MELD score, whereas only IL-6 correlated positively with Clif-SOFA score at day 7; IL-2 correlated negatively with Clif-SOFA at admission. In comparison with all scores, leukocyte count showed positive correlation and IFN-γ negative correlation with disease severity. When evaluating survival, only MELD and Clif-SOFA scores had a significant association with mortality. ConclusionsPro-inflammatory cytokines and chemo-attractant elements are increased in cirrhosis in comparison with healthy subjects, and display higher values concomitantly with cirrhosis progression. However, in acute-on-chronic liver failure an opposite cytokine pattern that can be resumed as a combination of immune paresis and excessive inflammatory response was observed. Several pro-inflammatory cytokines (IL-2, IL-6, IL-8 and IFN-γ) showed correlation with disease severity; their utility as prognostic biomarkers needs to be further studied.

Usefulness of serum thyroid-stimulation hormone (TSH) as a prognostic indicator for acute-on-chronic liver failure

Background and rationale for the study. To investigate thyroid function in patients with acute-on-chronic liver failure (ACLF) caused by hepatitis B virus infection and to determine whether thyroid hormone levels can be used as prognostic markers for assessing severity and prognosis of ACLF patients. We enrolled 75 patients with ACLF and70 patients with chronic hepatitis B (CHB).Continual serum samples were collected during hospitalization from the ACLF patients. The serum thyroid hormone levels (triiodothyronine [T3], thyroxine [T4], free (F)-T3, FT4, and thyroid stimulation hormone [TSH]) were measured by chemiluminescence. The Model for End-stage Liver Disease (MELD) score was used to assess severity.Results. ACLF patients showed significantly (p < 0.001) lower values of serum T3, T4, FT3/FT4 and TSH than CHB patients. The T3, T4, and TSH levels in ACLF patients were negatively correlated with the MELD score (T3: r = -0.495, p < 0.001; T4: r = -0.281, p < 0.001; TSH: r = -0.498, p < 0.001), suggesting that serum thyroid hormone levels reflect disease severity. At 1 year, 31 patients died. The T3 (p = 0.016), T4 (p = 0.008), and TSH (p = 0.003) levels in non-survivors were significantly lower than in survivors. The serum TSH level was a significant factor for predicting mortality in ACLF patients (optimal cutoff value = 0.38 IU/mL). The cumulative survival rate was decreased significantly when the serum TSH level was < 0.38 IU/mL (39.2%, p < 0.001).Conclusion. Serum TSH level may be a useful indicator for assessing severity and prognosis in ACLF patients.

Logistic regression analysis of prognostic factors in 106 acute-on-chronic liver failure patients with hepatic encephalopathy

Objective To analyze the prognostic factors in acute-on-chronic liver failure ( ACLF) patients with hepatic encephalopathy ( HE) and to explore the risk factors for prognosis. Methods A retrospective analysis was performed on106 ACLF patients with HE who were hospitalized in our hospital from January 2010 to July 2013. The patients were divided into improved group and deteriorated group. The univariate indicators including age, sex, laboratory indicators [total bilirubin ( TBil) , albumin ( Alb) , alanine aminotransferase ( ALT) , aspartate amino-transferase ( AST) , and prothrombin time activity ( PTA) ], the stage of HE, complications [persistent hyponatremia, digestive tract bleeding, hepatorenal syndrome ( HRS) , ascites, infection, and spontaneous bacterial peritonitis ( SBP) ], and plasma exchange were analyzed by chi-square test or t-test. Indicators with statistical significance were subsequently analyzed by binary logistic regression. Results Univariate analysis showed that ALT ( P = 0. 009) , PTA ( P = 0. 043) , the stage of HE ( P = 0. 000) , and HRS ( P = 0. 003) were significantly different between the two groups, whereas differences in age, sex, TBil, Alb, AST, persistent hyponatremia, digestive tract bleeding, ascites, infection, SBP, and plasma exchange were not statistically significant ( P >0. 05) . Binary logistic regression demonstrated that PTA ( b =-0. 097, P =0. 025, OR =0. 908) , HRS ( b =2. 279, P =0. 007, OR =9. 764) , and the stage of HE ( b = 1. 873, P = 0. 000, OR = 6. 510) were prognostic factors in ACLF patients with HE. Conclusion The stage of HE, HRS, and PTA are independent influential factors for the prognosis in ACLF patients with HE. Reduced PTA, advanced HE stage, and the presence of HRS indicate worse prognosis.

A novel integrated Model for End‐Stage Liver Disease model predicts short‐term prognosis of hepatitis B virus‐related acute‐on‐chronic liver failure patients

A considerable proportion of chronic hepatitis B (CHB) or hepatitis B virus (HBV)-related cirrhotic patients develop acute-on-chronic liver failure (ACLF) with high short-term mortality. It remains difficult to accurately predict short-term prognosis in ACLF patients. The aim of the study is to develop a new prognostic model by assessing new objective variables. A total of 432 HBV-ACLF patients were recruited into a retrospective observational cohort study including one training and validation cohort. Cox proportional hazard analysis was performed in the training cohort to develop the prognostic model. The performance of the new model was tested in the validation cohort by a receiver-operator curve (ROC). During follow up, 241 deaths were reported, with a high 3-month mortality of 48.4%. On multivariate analysis, age, hepatic encephalopathy (HE) and Model for End-Stage Liver Disease (MELD) score were found to be significantly associated with 3-month mortality. The integrated MELD (iMELD) model had a higher area under the ROC than the original MELD, Sequential Organ Failure Assessment (SOFA), Chronic Liver Failure-SOFA and Child-Turcotte-Pugh score (0.853 vs 0.743 vs 0.726 vs 0.764 vs 0.592) in predicting 3-month mortality. In the validation sample of 212 patients, iMELD remained better than the other models. HBV-ACLF patients are characterized by high short-term mortality, but steady long-term survival. A modified MELD model by incorporating age and HE score has better predictive value of 3-month mortality than other conventional models.

The Curative Effect of ALSS on 1-month Mortality in AoCLF Patients after 72 to 120 Hours

Hepatitis B virus (HBV)-related acute-on-chronic liver failure (AoCLF) is associated with a high mortality rate. An artificial liver support system (ALSS) creates a better environment for the self-regeneration of retained hepatocytes. AIM AND PATIENTS: We investigated the curative effect of ALSS on 1-month mortality at 72-120 h post-ALSS in 289 AoCLF patients. Of the 289 patients, 117 who survived for at least 1 month post-ALSS comprised the survival group; the remaining cases who died within 1 month served as controls. The improvements in laboratory data and clinical syndromes at 72-120 h post-ALSS were compared with those at 24 h. Total bilirubin, international normalized ratio, and creatinine levels, and encephalopathy were significantly improved at 24 h post-ALSS in both the groups (p<0.05); however, these variables showed deterioration at 72-120 h; a rebound occurred in the nonsurvivors (p>0.05). The improvements in these variables in the nonsurvivors were considerably smaller than those in the survivors (p<0.05), particularly at 72-120 h. One-month mortality was more accurately predicted by the logistic regression model at 72-120 h than at 24 h. The prognosis of AoCLF patients was highly dependent on the improvement in encephalopathy, total bilirubin, international normalized ratio, and creatinine levels at 72-120 h post-ALSS. These variables are useful, therefore, as disease severity indexes to determine organ allocation priorities for liver transplant.