Metabolic biomarkers significantly enhance the prediction of HBV-related ACLF occurrence and outcomes.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality in patients with chronic liver disease. Chronic hepatitis B is the main cause of ACLF (HBV-ACLF) in China and other Asian countries. To improve disease management and survival for patients with ACLF, we aimed to discover novel biomarkers to enhance HBV-ACLF diagnosis and prognostication. METHODS: We performed a metabolomics profiling of 1,024 plasma samples collected from patients with HBV-related chronic liver disease with acute exacerbation at hospital admission in a multi-year and multi-center prospective study (367 ACLF and 657 non-ACLF). The samples were randomly separated into equal halves as a discovery set and a validation set. We identified metabolites associated with 90-day mortality in the ACLF group and the progression to ACLF within 28 days in the non-ACLF group (pre-ACLF) using statistical analysis and machine learning. We developed diagnostic algorithms in the discovery set and used these to assess the findings in the validation set. RESULTS: ACLF significantly altered the plasma metabolome, particularly in membrane lipid metabolism, steroid hormones, oxidative stress pathways, and energy metabolism. Numerous metabolites were significantly associated with 90-day mortality in the ACLF group and/or pre-ACLF in the non-ACLF group. We developed algorithms for the prediction of 90-day mortality in patients with ACLF (area under the curve 0.87 and 0.83 for the discovery set and validation set, respectively) and the diagnosis of pre-ACLF (area under the curve 0.94 and 0.88 for the discovery set and validation set, respectively). To translate our discoveries into practical clinical tests, we developed targeted assays using liquid chromatography-mass spectrometry. CONCLUSIONS: Based on novel metabolite biomarkers, we established tests for HBV-related ACLF with higher accuracy than existing methods. CLINICAL TRIAL NUMBER: NCT02457637 and NCT03641872. IMPACT AND IMPLICATIONS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality affecting 25% of patients hospitalized with cirrhosis. Chronic hepatitis B is the main etiology of ACLF in China and other Asian counties. There is currently no effective therapy. Early diagnosis and accurate prognostication are critical for improving clinical outcomes in patients with ACLF. Based on novel metabolite biomarkers, we developed liquid chromatography-mass spectrometry tests with improved accuracy for the early diagnosis and prognostication of HBV-related ACLF. The liquid chromatography-mass spectrometry tests can be implemented in clinical labs and used by physicians to triage patients with HBV-related ACLF to ensure optimized clinical management.

Portal vein thrombosis compromises the performance of MELD and MELD-Na scores in patients with cirrhosis.

BACKGROUND AND AIMS: The accuracy of model for end-stage liver disease (MELD) and MELD with sodium (MELD-Na) scores in reflecting the clinical outcomes of patients with cirrhosis and portal vein thrombosis (PVT) remains unclear. This study aimed to evaluate the performance of scores in predicting 90-day mortality in patients with cirrhosis and PVT. METHODS: Post hoc analysis was performed in two prospective cohorts (NCT02457637 and NCT03641872). The correlation between the MELD/MELD-Na score and 90-day liver transplantation (LT)-free mortality was investigated in patients with cirrhosis with and without PVT. RESULTS: In this study, 2826 patients with cirrhosis were included, and 255 (9.02%) had PVT. The cumulative incidence of 90-day LT-free mortality did not significantly differ between patients with and without PVT (log-rank P = 0.0854). MELD [area under the receiver operating curve (AUROC), 0.649 vs. 0.842; P = 0.0036] and MELD-Na scores (AUROC, 0.691 vs. 0.851; P = 0.0108) were compared in patients with and without PVT, regarding the prediction of 90-day LT-free mortality. In MELD < 15 and MELD-Na < 20 subgroups, patients with PVT had a higher 90-day LT-free mortality than those without PVT (7.91% vs. 2.64%, log-rank P = 0.0011; 7.14% vs. 3.43%, log-rank P = 0.0223), whereas in MELD ≥ 15 and MELD-Na ≥ 20 subgroups, no significant difference was observed between patients with and without PVT. CONCLUSIONS: The performance of MELD and MELD-Na scores in predicting 90-day LT-free mortality of patients with cirrhosis was compromised by PVT. MELD < 15 or MELD-Na < 20 may underestimate the 90-day LT-free mortality in patients with PVT.

A Novel SAVE Score to Stratify Decompensation Risk in Compensated Advanced Chronic Liver Disease (CHESS2102): An International Multicenter Cohort Study.

INTRODUCTION: In patients with compensated advanced chronic liver disease (cACLD), the invasive measurement of hepatic venous pressure gradient is the best predictor of hepatic decompensation. This study aimed at developing an alternative risk prediction model to provide a decompensation risk assessment in cACLD. METHODS: Patients with cACLD were retrospectively included from 9 international centers within the Portal Hypertension Alliance in China (CHESS) network. Baseline variables from a Japanese cohort of 197 patients with cACLD were examined and fitted a Cox hazard regression model to develop a specific score for predicting hepatic decompensation. The novel score was validated in an external cohort (n = 770) from 5 centers in China, Singapore, Korea, and Egypt, and was further assessed for the ability of predicting clinically significant portal hypertension in a hepatic venous pressure gradient cohort (n = 285). RESULTS: In the derivation cohort, independent predictors of hepatic decompensation were identified including Stiffness of liver, Albumin, Varices, and platElets and fitted to develop the novel score, termed "SAVE" score. This score performed significantly better (all P < 0.05) than other assessed methods with a time-dependent receiver operating characteristic curve of 0.89 (95% confidence interval [CI]: 0.83-0.94) and 0.83 (95% CI: 0.73-0.92) in the derivation and validation cohorts, respectively. The decompensation risk was best stratified by the cutoff values at -6 and -4.5. The 5-year cumulative incidences of decompensation were 0%, 24.9%, and 69.0% in the low-risk, middle-risk, and high-risk groups, respectively ( P < 0.001). The SAVE score also accurately predicted clinically significant portal hypertension (AUC, 0.85 95% CI: 0.80-0.90). DISCUSSION: The SAVE score can be readily incorporated into clinical practice to accurately predict the individual risk of hepatic decompensation in cACLD.

Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients.

BACKGROUND AND AIMS: Anti-tuberculosis drugs remain as an important cause of drug-induced liver injury (DILI) worldwide. Adverse drug reactions reduce the effectiveness of treatment. We aimed to determine the incidence and risk factors associated with anti-tuberculosis DILI (ATDILI). METHODS: Using established criteria and causality assessment methods, risk factors for ATDILI were identified in a contemporary cohort and validated in another cohort prospectively. Independent determinants of ATDILI were identified using Cox regression analysis. RESULTS: In the derivation cohort (n = 3155), 170 (5.4%) developed ATDILI of which 27 (15.9%) developed jaundice; 9(5.3%) developed acute liver failure (ALF) and 3 died. Among HBsAg positive patients, 11/27 (40.7%) of ATDILI developed after 3 months of starting treatment. In addition, of 218 (6.9%) who developed raised alanine transferase (ALT) levels ≥3 times upper limit normal, 193 (88.5%) resolved and 25 (11.4%) progressed to DILI. Age (HR = 1.014, 95% CI: 1.005-1.023), baseline ALT (HR = 1.014, 95% CI: 1.003-1.024), haemoglobin (HR = 1.011, 95% CI: 1.002-1.020) and HBsAg positivity (HR = 1.516, 95% CI: 1.004-2.290) were independent risk factors for DILI. In the second cohort (n = 1497) of which 85 (5.7%) developed ATDILI. Age (HR = 1.029, 95% CI: 1.003-1.056), baseline AST (HR = 1.036, 95% CI: 1.010-1.062), previous TB treatment (HR = 3.894, 95% CI: 1.304-11.625) and active drinking (HR = 3.624, 95% CI: 1.147-11.454) were risk factors for developing jaundice. CONCLUSION: Elevation of ALT of ≥3 × ULN during anti-TB treatment resolves in the vast majority without developing serious consequences. In two cohorts involving 4652 patients, incidence of ALF and death because of ATDILI are low. Age, baseline ALT, haemoglobin and HBsAg positivity are risk factors for the development of DILI and these inform monitoring and management of these patients.

Metabolic associated fatty liver disease increases coronavirus disease 2019 disease severity in nondiabetic patients.

BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) has attracted increasing worldwide attention. While diabetes is known to aggravate COVID-19 severity, it is not known whether nondiabetic patients with metabolic dysfunction are also more prone to more severe disease. The association of metabolic associated fatty liver disease (MAFLD) with COVID-19 severity in nondiabetic patients was investigated here. METHODS: The study cohort comprised 65 patients with (i.e. cases) and 65 patients without MAFLD (i.e. controls). Each case was randomly matched with one control by sex (1:1) and age (±5 years). The association between the presence of MAFLD (as exposure) and COVID-19 severity (as the outcome) was assessed by binary logistic regression analysis. RESULTS: In nondiabetic patients with COVID-19, the presence of MAFLD was associated with a four-fold increased risk of severe COVID-19; the risk increased with increasing numbers of metabolic risk factors. The association with COVID-19 severity persisted after adjusting for age, sex, and coexisting morbid conditions. CONCLUSION: Health-care professionals caring for nondiabetic patients with COVID-19 should be cognizant of the increased likelihood of severe COVID-19 in patients with MAFLD.

Fatal outcome in a liver transplant recipient with COVID-19.

Liver injury is common in patients with COVID-19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID-19 in a patient who underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID-19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.

Pro-adrenomedullin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival.

Background and aim: Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failures, and high short-term mortality rates. In present study, we explored whether Pro-adrenomedullin (Pro-ADM), a biomarker of sepsis, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients.Methods: 332 consecutive patients with AD of cirrhosis were prospectively enrolled. Pro-ADM was measured for all patients at baseline. Cox regression analysis was used to evaluate the impact of pro-ADM on short-term survival and developing ACLF during hospital stay.Results: Serum pro-ADM levels were significantly high in non-survivors (p < .001) and showed significant correlation with ALT (r = 0.181, p = .001), INR (r = 0.144, p = .009), TB (r = 0.368, p < .001), Creatinine (r = 0.145, p = .004), MELD score (r = 0.334, p = <.001) and CLI-C OF score (r = 0.375, p= <.001). Serum pro-ADM at admission was shown to be a predictor of 28-day mortality independently of MELD and CLIF-C OF scores. Prognostic models incorporating pro-ADM achieved high C index for predicting 28-day mortality in AD patients of cirrhosis. Moreover, baseline pro-ADM was found to be predictive of ACLF development during hospital stay.Conclusions: Serum pro-ADM levels correlate with multiorgan failure and are independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF.

Characteristics of systemic inflammation in hepatitis B-precipitated ACLF: Differentiate it from No-ACLF.

BACKGROUND & AIMS: Patients with severe exacerbation of chronic hepatitis B (SE-CHB) are at risk of developing acute-on-chronic liver failure (ACLF). Systemic inflammation (SI) is a major driver of ACLF. The aim of this study was to identify characteristics of SI in hepatitis B-precipitated-ACLF (HB-ACLF), which may be distinct from No-ACLF patients with SE-CHB. METHODS: Two cohorts of patients with SE-CHB were enrolled in two tertiary hospitals. The associations between circulating leucocyte counts/subsets and ACLF progression and prognoses were analysed in Cohort A. Cytokine measurements, leucocyte phenotyping and whole blood transcriptomic analyses were performed using peripheral blood samples obtained from patients in Cohort B. RESULTS: Circulating leucocyte counts were higher in the HB-ACLF patients than in the No-ACLF patients (P < .001). Peripheral neutrophilic leucocytosis and monocytosis were associated with lymphopenia. The neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) were correlated with risk of death in patients with SE-CHB. NLR independently predicted progression to ACLF in patients without ACLF at enrolment and short-term mortality in ACLF patients. Plasma IL-6, IL-10, G-CSF and GM-CSF levels were higher in ACLF patients (P < .05). Blood transcriptome analyses showed that genes associated with cell migration and mobility and responses to wounding and bacteria were expressed at higher levels while genes involved in lymphocyte-mediated immunity were expressed at lower levels in HB-ACLF patients than in No-ACLF patients. CONCLUSIONS: Systemic inflammation in HB-ACLF was characterized by an excessive innate immune response, which was associated with disease progression and mortality.

Risk stratification of decompensated cirrhosis patients by Chronic Liver Failure Consortium scores: Classification and regression tree analysis.

AIM: Decompensated cirrhosis patients have greatly variable prognosis. The aim of the study was to carry out a risk stratification for those patients by Chronic Liver Failure (CLIF) Consortium scores. METHODS: The performance of CLIF Consortium acute-on-chronic liver failure scores (CLIF-C ACLFs) and CLIF Consortium Acute Decompensation scores (CLIF-C ADs) were validated in 209 patients with ACLF and 1245 patients without ACLF at admission from the Ningbo Cohort. A classification and regression tree (CRT) analysis by CLIF-C ACLFs/CLIF-C ADs was carried out to stratify death risk among patients. RESULTS: The CLIF-C ACLFs and CLIF-C ADs showed higher predictive accuracy than Model for End-stage Liver Disease (MELD) scores, MELD plus serum sodium (MELD-Na) scores, and Child-Turcotte-Pugh classification (CP) at main time points (28, 90, 180, and 365 days), determined by area under the receiver-operating characteristic curve and concordance index in ACLF and no-ACLF patients at admission. The CRT analysis categorized ACLF patients into two groups (advanced and early ACLF), and no-ACLF patients into three groups (high-, medium-, and low-risk AD) according to risk of death. However, early ACLF and high-risk AD patients had comparable mortality at the main time points. The CRT model had a higher area under the receiver-operating characteristic curve than MELDs, MELD-Nas, and CPs in predicting prognosis in all patients. CONCLUSIONS: The CLIF-C ACLF and CLIF-C AD are better prognostic scores than MELD, MELD-Na, and CP in predicting mortality of ACLF and no-ACLF patients. A combined use of CLIF- Sequential Organ Failure Assessment, CLIF-C ACLFs, and CLIF-C ADs could identify cirrhosis patients at high death risk and assist clinical decisions for management.

Evaluation of Absolute Serum Creatinine Changes in Staging of Cirrhosis-Induced Acute Renal Injury and its Association with Long-term Outcomes.

BACKGROUND/AIMS: To assess the prognostic accuracy of absolute serum creatinine (sCr) changes ('Delta-sCr') on the long-term outcomes in cirrhotic patients, and evaluate the performance of the 'Delta-sCr' approach to stage acute kidney injury (AKI), compared with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. METHODS: We conducted a retrospective analysis of 333 hospitalized patients. We classified AKI stages using two methods: 1) KDIGO AKI criteria; 2) 'Delta-sCr' system, defined by the difference between the baseline and the peak sCr value during the hospitalization. The end point was the hazard of 1-year death. RESULTS: The prevalence of AKI in cirrhotic patients was 18.01% by the KDIGO criteria, and 25.22% by the 'Delta-sCr' system. On multivariable Cox hazard analysis, both of the two methods were independent predictive factors of death ('Delta-sCr' system: OR=2.911, p<0.001), (KDIGO criteria: OR=2.065, p<0.001). However, the 'Delta-sCr' system provided a modest improvement in classification over the KDIGO criteria with a net reclassification improvement (NRI) of 28.7% (p<0.001) and integrated discrimination improvement (IDI) of 7.5% (p=0.03). And the predictive value of the 'Delta-sCr' system could be significantly improved (p=0.006), when combined with age and MELD score. CONCLUSION: The Delta-sCr is associated with the 1-year mortality. And the 'Delta-sCr' system may optimize the discrimination of risk prediction.

Acute-on-chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults.

UNLABELLED: Patients with acute-on-chronic liver failure (ACLF) represent a heterogeneous population. The aim of the study is to identify distinct groups according to the etiologies of precipitating events. A total of 405 ACLF patients were identified from 1,361 patients with cirrhosis with acute decompensation and categorized according to the types of acute insults. Clinical characteristics and prognosis between the hepatic group and extrahepatic group were compared, and the performance of prognostic models was tested in different groups. Two distinct groups (hepatic-ACLF and extrahepatic-ACLF) were identified among the ACLF population. Hepatic-ACLF was precipitated by hepatic insults and had relatively well-compensated cirrhosis with frequent liver and coagulation failure. In contrast, extrahepatic-ACLF was exclusively precipitated by extrahepatic insults, characterized by more severe underlying cirrhosis and high occurrence of extrahepatic organ failures (kidney, cerebral, circulation, and respiratory systems). Both groups had comparably high short-term mortality (28-day transplant-free mortality: 48.3% vs. 50.7%; P = 0.22); however, the extra-hepatic-ACLF group had significantly higher 90-day and 1-year mortality (90-day: 58.9% vs. 68.3%, P = 0.035; 1-year: 63.9% vs. 74.6%, P = 0.019). In hepatic-ACLF group, the integrated Model for End-Stage Liver Disease (iMELD) score had the highest area under the receiver operating characteristic curve (auROC = 0.787) among various prognostic models in predicting 28-day mortality, whereas CLIF-Consortium scores for ACLF patients (CLIF-C-ACLF) had the highest predictive value in the other group (auROC = 0.779). CONCLUSIONS: ACLF precipitated by hepatic insults is distinct from ACLF precipitated by extrahepatic insults in clinical presentation and prognosis. The iMELD score may be a better predictor for hepatic-ACLF short-term prognosis, whereas CLIF-C-ACLF may be better for extrahepatic-ACLF patients.

Associations between hepatitis B virus basal core promoter/pre-core region mutations and the risk of acute-on-chronic liver failure: a meta-analysis.

BACKGROUND: Several studies have suggested a relationship between hepatitis B virus (HBV) basal core promoter/pre-core mutations and HBV-induced acute-on-chronic liver failure (ACLF). Therefore, we evaluated this potential relationship using a meta-analysis. METHODS: Chinese or English studies from 1966 to January 31, 2014 were included in the analysis. A random or fixed-effects model was used to merge the odds ratios (ORs). RESULTS: We identified 31 case-control studies containing a total population of 1995 ACLF and 3822 chronic hepatitis B (CHB) patients. Several mutations were significantly correlated with ACLF: T1753V (1.889, 95 % confidence interval (CI) [1.357-2.631]), A1762T (2.696 [2.265-3.207]), G1764A (3.005 [2.077-4.347]), A1762T/G1764A (2.379 [1.519-3.727]), C1766T (1.849 [1.403-2.437]), T1768A (2.440 [1.405-3.494]), A1846T (3.163 [2.157-4.639]), G1896A (2.181 [1.800-2.642]), G1899A (3.569 [2.906-4.385]) and G1896A/A1762T/G1764A (1.575 [1.172-2.116]). Additionally, HBeAg-negative status was also statistically significant for the progression to ACLF (OR = 2.813, 95 % CI = 2.240-3.533, p < 0.001). However, there was no association between ACLF development and HBV genotype. CONCLUSIONS: The HBV basal core promoter/pre-core mutations T1753V, A1762T, G1764A, C1766T, T1768A, A1846T, G1896A and G1899A, and an HBeAg-negative status correlate with an increased risk of HBV-ACLF.

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.

AIM: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Increased delayed mortality in patients with acute-on-chronic liver failure who have prior decompensation.

BACKGROUND AND AIM: Patients with acute-on-chronic liver failure (ACLF) represent a complex population with differential prognosis. The aim of the study was to categorize ACLF according to the severity of underlying chronic liver diseases. METHODS: A total of 540 ACLF patients were recruited, including 127 with prior decompensated cirrhosis and 413 without prior decompensation (PD) including 193 with underlying chronic hepatitis and 220 with prior compensated cirrhosis. The clinical characteristics and prognosis of subgroups were compared. Cox proportional hazard model and multinominal logistic regression analysis were performed to identify significant prognostic parameters. RESULTS: The 28-day, 3-month and 1-year survival of ACLF patients with or without PD were 58.9% versus 61.4%, 36.2 versus 52.5%, and 29.1% versus 49.6%, respectively. On multinominal logistic regression analysis or time-to-death analysis by Cox proportional hazard model, PD was significantly associated with post-28-day mortality but not within-28-day mortality. On multivariate time-to-death analysis, older age, high international normalized ratio (INR) and serum bilirubin, low levels of serum sodium and platelet count, and presence of hepatic encephalopathy (HE), upper gastrointestinal bleeding, and respiratory or circulation dysfunction were predictors of within-28-day mortality in patients without PD, whereas the risk factors in patients with PD were high INR, creatinine, presence of HE, and respiratory or circulation dysfunction. CONCLUSION: ACLF patients with or without PD had comparable short-term prognosis but differential 1-year mortality. ACLF patients with PD were distinct from those without PD in age, types of acute insults, severity of hepatic damage, and distribution of complications, and the former group was characterized by increased delayed mortality.

Association of AST/ALT ratio with 90-day outcomes in patients with acute exacerbation of chronic liver disease: a prospective multicenter cohort study in China.

Background and aim: A high aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is associated with liver injury in liver disease; however, no data exist regarding its relationship with 90-day prognosis in patients with acute exacerbation of chronic liver disease. Methods: In this study, 3,758 participants (955 with advanced fibrosis and 2,803 with cirrhosis) from the CATCH-LIFE cohort in China were included. The relationships between different AST/ALT ratios and the risk of adverse 90-day outcomes (death or liver transplantation) were determined in patients with cirrhosis or hepatitis B virus (HBV)-associated advanced fibrosis, respectively. Results: In the patients with HBV-associated advanced fibrosis, the risk of 90-day adverse outcomes increased with AST/ALT ratio; after adjusting for all confounding factors, the risk of adverse 90-day outcomes was the highest when AST/ALT ratio was more than 1.08 (OR = 6.91 [95% CI = 1.789-26.721], p = 0.005), and the AST/ALT ratio of >1.9 accelerated the development of adverse outcomes. In patients with cirrhosis, an AST/ALT ratio > 1.38 increased the risk of adverse 90-day outcomes in all univariables (OR = 1.551 [95% CI = 1.216-1.983], p < 0.001) and multivariable-adjusted analyses (OR = 1.847 [95% CI = 1.361-2.514], p < 0.001), and an elevated AST/ALT ratio (<2.65) accelerated the incidence of 90-day adverse outcomes. An AST/ALT ratio of >1.38 corresponded with a more than 20% incidence of adverse outcomes in patients with cirrhosis. Conclusion: The AST/ALT ratio is an independent risk factor for adverse 90-day outcomes in patients with cirrhosis and HBV-associated advanced fibrosis. The cutoff values of the AST/ALT ratio could help clinicians monitor the condition of patients when making clinical decisions.

The clinical courses of HBV-related acute-on-chronic liver failure and a multi-state model to predict disease evolution.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a highly dynamic syndrome. The objective of this study was to delineate the clinical course of patients with HBV-ACLF and to develop a model to estimate the temporal evolution of disease severity. METHODS: We enrolled eligible patients from 2 large, multicenter prospective cohorts. The ACLF grade, organ failures, and outcomes were assessed at multiple time points (days 1/4/7/14/21/28). Probabilities for ACLF transitions between these disease states and to death within 28 days were calculated using a multi-state model that used baseline information and updated ACLF status. The model was validated in independent patients. RESULTS: Among all the 445 patients with HBV-ACLF, 76 represented disease progression, 195 had a stable or fluctuating course, 8 with improvement, and the remaining 166 with resolution within 28-day follow-up. New coagulation (63.64%) or renal failure (45.45%) was frequently observed during early progression. Patients with disease progression had a higher incidence of new episodes of ascites [10 (13.16%) vs. 22 (5.96%), p = 0.027] and HE [13(17.11%) vs. 21 (5.69%), p = 0.001], and a significant increase in white blood cell count. The multi-state model represented dynamic areas under the receiver operating characteristic curves ranging from 0.71 to 0.84 for predicting all ACLF states and death at 4, 7, 14, 21, and 28 days post-enrollment and from 0.73 to 0.94 for predicting death alone, performing better than traditional prognostic scores. CONCLUSIONS: HBV-ACLF is a highly dynamic syndrome with reversibility. The multi-state model is a tool to estimate the temporal evolution of disease severity, which may inform clinical decisions on treatment.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.