Validation of prognostic scores predicting mortality in acute liver decompensation or acute-on-chronic liver failure: A Thailand multicenter study.

BACKGROUND & OBJECTIVES: Cirrhosis patients with worsening of the liver function are defined as acute decompensation (AD) and those who develop extrahepatic organ failure are defined as acute-on-chronic liver failure (ACLF). Both AD and ACLF have an extremely poor prognosis. However, information regarding prognostic predictors is still lacking in Asian populations. We aimed to identify prognostic factors for 30-day and 90-day mortality in cirrhosis patients who develop AD with or without ACLF. METHODS: We included 9 tertiary hospitals from Thailand in a retrospective observational study enrolling hospitalized cirrhosis patients with AD. ACLF was diagnosed according to the EASL-CLIF criteria, which defined as AD patients who have kidney failure or a combination of at least two non-kidney organ failure. Outcomes were clinical parameters and prognostic scores associated with mortality evaluated at 30 days and 90 days. RESULTS: Between 2015 and 2020, 602 patients (301 for each group) were included. The 30-day and 90-day mortality rates of ACLF vs. AD were 57.48% vs. 25.50% (p<0.001) and 67.44% vs. 32.78% (p<0.001), respectively. For ACLF patients, logistic regression analysis adjusted for demographic data, and clinical information showed that increasing creatinine was a predictor for 30-day mortality (p = 0.038), while the CLIF-C OF score predicted both 30-day (p = 0.018) and 90-day (p = 0.037) mortalities, achieving the best discriminatory power with AUROCs of 0.705 and 0.709, respectively. For AD patients, none of the parameters was found to be significantly associated with 30-day mortality, while bacterial infection, CLIF-AD score and Child-Turcotte-Pugh score were independent parameters associated with 90-day mortality, with p values of 0.041, 0.024 and 0.024. However, their predictive performance became nonsignificant after adjustment by multivariate regression analysis. CONCLUSIONS: Regarding Thai patients, the CLIF-C OF score was the best predictor for 30-day and 90-day mortalities in ACLF patients, while appropriate prognostic factors for AD patients remained inconclusive.

Physician- and patient-reported barriers to hepatocellular carcinoma surveillance: A nationwide survey.

Hepatocellular carcinoma (HCC) surveillance rates are suboptimal. We aimed to identify HCC surveillance barriers from both physician's and patient's perspectives and assess the effectiveness of physician education using social networks. A nationwide survey with 513 physicians and another single-center survey with 315 HCC-risk patients were conducted. Barriers to suboptimal surveillance were identified using univariate and multivariate logistic regression analysis. We educated 143 physicians by sending brief notes on HCC surveillance guidelines via social networks and re-evaluated their knowledge after 60 days using t test. Surveys showed 458 (86.3%), 254 (47.8%), and 225 (42.4%) physicians recommended surveillance in patients with cirrhosis, at-risk hepatitis B virus, and hepatitis C virus infection, respectively. Only 228 (42.9%) and 241 (38.0%) respondents adhered to recommended surveillance tools and interval, respectively. The main surveillance barriers among physicians were the lack of knowledge and resource limitations. The lack of a doctor's prescription was identified as a major barrier by patient' perspectives (odds ratio 1.4, 95% CI: 1.1-1.8, P = .024). Education via social networks enhanced physicians' knowledge, with pre- and post-education scores for guideline awareness of 63.0% versus 84.3% (P < .001) and for surveillance indication and tools of 40.0% versus 63.0% (P = .001), and 42.0% versus 59.3% (P = .015), respectively. Physicians' knowledge gap is a primary barrier for adherence to HCC surveillance protocols. Brief education via social networks shows effectiveness at increasing physicians' knowledge of HCC surveillance.

Acute-on-chronic liver failure: Epidemiology, prognosis, and outcome of a multicenter study in Thai population.

Background and Aim: Acute-on-chronic liver failure (ACLF) leads to multi-organ failure related to high mortality rates. This study aimed to gather epidemiological data and validate a scoring system to predict mortality in ACLF. Methods: This retrospective cohort study collected data from multicenter tertiary care hospitals in Thailand. A total of 638 hospitalized patients (acute decompensated liver disease [ADLD], 292 patients; ACLF, 346 patients) from January 2019 to June 2020 were enrolled in this study. We compared the mortality rate at days 30 and 90 between patients with ADLD and ACLF. Areas under the receiver operating characteristic (AUROC) curves of chronic liver failure-sequential organ failure assessment (CLIF-SOFA) and other existing scoring systems were compared among patients with ACLF. Results: The incidence of patients with ACLF was 54%. The main cause of chronic liver disease was alcohol (38%), with sepsis (50%) as the most common precipitating factor. ACLF with coagulopathy (AUROC 0.58, 95% confidence interval [CI]: 0.52-0.64), metabolic acidosis (AUROC 0.58, 95% CI: 0.52-0.64), and high aspartate aminotransferase (AST) (AUROC 0.59, 95% CI: 0.53-0.66) were associated with high 30-day mortality. The 30-day mortality rate of patients with acute decompensation and patients with ACLF was 46 and 58%, respectively. Respiratory system (P = 0.001) failure was the major end result in ACLF and constituted a significant factor to predict mortality. The AUROC of CLIF-SOFA score was superior to that of the other predicted score (AUROC 0.64, 95% CI: 0.585-0.704). Conclusion: Patients with ACLF with more organ failure and high CLIF-SOFA score were associated with high short-term mortality. Future studies should include an ACLF prospective registry to confirm these finding.

Impact of compensated cirrhosis on survival in patients with acute-on-chronic liver failure.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is considered a main prognostic event in patients with chronic liver disease (CLD). We analyzed the 28-day and 90-day mortality in ACLF patients with or without underlying cirrhosis enrolled in the ACLF Research Consortium (AARC) database. METHODS: A total of 1,621 patients were prospectively enrolled and 637 (39.3%) of these patients had cirrhosis. Baseline characteristics, complications and mortality were compared between patients with and without cirrhosis. RESULTS: Alcohol consumption was more common in cirrhosis than non-cirrhosis (66.4% vs. 44.2%, p < 0.0001), while non-alcoholic fatty liver disease/cryptogenic CLD (10.9% vs 5.8%, p < 0.0001) and chronic HBV reactivation (18.8% vs 11.8%, p < 0.0001) were more common in non-cirrhosis. Only 0.8% of patients underwent liver transplantation. Overall, 28-day and 90-day mortality rates were 39.3% and 49.9%, respectively. Patients with cirrhosis had a greater chance of survival compared to those without cirrhosis both at 28-day (HR = 0.48; 95% CI 0.36-0.63, p < 0.0001) and 90-day (HR = 0.56; 95% CI 0.43-0.72, p < 0.0001), respectively. In alcohol CLD, non-cirrhosis patients had a higher 28-day (49.9% vs. 23.6%, p < 0.001) and 90-day (58.4% vs. 35.2%, p < 0.001) mortality rate than cirrhosis patients. ACLF patients with cirrhosis had longer mean survival than non-cirrhosis patients (25.5 vs. 18.8 days at 28-day and 65.2 vs. 41.2 days at 90-day). Exaggerated systemic inflammation might be the reason why non-cirrhosis patients had a poorer prognosis than those with cirrhosis after ACLF had occurred. CONCLUSIONS: The 28-day and 90-day mortality rates of ACLF patients without cirrhosis were significantly higher than those with cirrhosis in alcoholic CLD. The presence of cirrhosis and its stage should be evaluated at baseline to guide for management. Thai Clinical Trials Registry, TCTR20191226002.

Acute liver failure and death predictors in patients with dengue-induced severe hepatitis.

BACKGROUND: Liver injury in patients with dengue infection is common. Most patients have mild and transient hepatitis. Acute liver failure (ALF) in dengue infection is rare but results in an extremely poor prognosis. AIM: To identify prognostic predictors of ALF and death in patients with dengue-induced severe hepatitis (DISH). METHODS: We retrospectively reviewed 2311 serologically confirmed adolescent and adult dengue patients who were hospitalized during a 12-year study period (between 2007 and 2019) at the university hospital of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients with DISH [n = 134 (5.80%)], defined as a baseline transaminase > 10 times the normal reference cut-off level, and DISH with subsequent ALF as defined by the American Association for the Study of the Liver Diseases 2011 criteria [n = 17 (0.74%)], were included. Predictors of ALF and in-hospital death were identified using logistic regression analysis. RESULTS: Of the 151 dengue-infected patients with severe liver injury or ALF, 51% were female, with a mean age of 27.9 ± 14.5 years. Capillary leakage syndrome (CLS) occurred in 68.2% (n = 103) of DISH and 100% of ALF patients. The mortality rate was low in DISH patients (0.8%) but was remarkably high if ALF developed (58.8%). In univariate analysis, age, sex, hematocrit, white blood count, atypical lymphocyte count, platelet count, international normalized ratio (INR), bilirubin, serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, alkaline phosphatase, albumin, creatinine, Model for End-Stage Liver Disease (MELD) score, presence of liver comorbidity and presence of CLS were identified as potential prognostic parameters for ALF or death. In multivariate analysis, the MELD score remained the only predictor of ALF with an adjusted odds ratio (aOR) of 1.3 [95% confidence interval (CI): 1.1-1.5; P = < 0.001]. An initial MELD score ≥ 15 was associated with ALF from DISH with an area under the receiver operating characteristic (AUROC) of 0.91, 88.2% sensitivity and 87.3% specificity. Regarding mortality prediction, the deterioration of liver function to ALF was the most significant factor related to death in DISH patients (aOR 108.5, 95%CI: 5.5-2145.4, P = 0.002). Other independent factors associated with death included baseline INR (aOR 10.4, 95%CI: 2.6-40.5, P = 0.001). An INR ≥ 1.5 predicted death from DISH with an AUROC of 0.83 (81.8% sensitivity and 86.8% specificity). CONCLUSION: The MELD score is the best predictor of ALF in DISH patients, a complication from dengue that is associated with high mortality. The presence of ALF and the baseline INR level are independent markers of death in DISH patients.

Changes in inflammatory cytokines, antioxidants and liver stiffness after chelation therapy in individuals with chronic lead poisoning.

BACKGROUND: Chronic exposure to lead causes lead to accumulate mainly in the liver. In vivo studies have shown that lead toxicity is related to alterations in the inflammatory response. We aimed to evaluate the association between lead poisoning and liver fibrosis as well as the change in the degree of liver fibrosis, levels of inflammatory mediators and glutathione (GSH) after chelation therapy. METHODS: Workers from a battery factory who were exposed to lead for > 12 months and had a blood lead level (BLL) > 70 µg/dL were enrolled (n = 86) in the study. Participants underwent chelation therapy with intravenous CaNa2EDTA for 2 days followed by treatment with oral D-penicillamine for 90 days. The primary outcome was the change in the degree of liver fibrosis, which was presented as liver stiffness (LS) measured by FibroScan®. Secondary outcomes were the changes in the levels of serum GSH and inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) after chelation therapy. RESULTS: Among the 86 participants, there was a positive correlation between the duration of lead exposure and LS (r = 0.249, p = 0.021). To avoid the confounding effect of obesity-related steatosis, only 70 individuals who had controlled attenuation parameters < 296 dB/m, BMI < 25 kg/m2 and normal waist circumference were included in the interventional analysis. After chelation, the mean LS significantly decreased from 5.4 ± 0.9 to 4.8 ± 1.4 kPa (p = 0.001). Similarly, all of the inflammatory cytokines studied significantly decreased after chelation (p < 0.001); TNF-α decreased from 371.6 ± 211.3 to 215.8 ± 142.7; the levels of IL-1ß decreased from 29.8 ± 1.7 to 25.9 ± 4.3; and the levels of IL-6 decreased from 46.8 ± 10.2 to 35.0 ± 11.9. On the other hand, the mean GSH level increased significantly from 3.3 ± 3.3 to 13.1 ± 3.7 (p < 0.001) after chelation therapy. CONCLUSION: The duration of lead exposure was significantly correlated with the degree of liver fibrosis. Chelation treatment was associated with increased levels of GSH and decreased levels of proinflammatory cytokines and could potentially reduce the degree of LS. TRIAL REGISTRATION: This study was retrospectively registered and approved by the Thai Clinical Trial Registry (TCTR) on 2019-11-07. The TCTR identification number is TCTR20191108001 .