METHODS: A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP). The test solutions pre-treatment were made orally once daily for 7 consecutive days, and 1 h after the last test solutions administration (on Day 7th), the rats were treated with vehicle or APAP. Blood were collected from those treated rats for biochemical analyses, which were then euthanized to collect their liver for endogenous antioxidant enzymes determination and histopathological examination. The extract was also subjected to in vitro anti-inflammatory investigation and, HPLC and GCMS analyses.
RESULTS: Pre-treatment of rats (Group 2) with 10% DMSO failed to attenuate the toxic effect of APAP on the liver as seen under the microscopic examination. This observation was supported by the significant (p
METHODS: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted.
RESULTS: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p
METHODS: Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-R2, relative prediction errors, and odds ratios.
RESULTS: Thirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p 12 had the lowest 30-day survival (5.7%).
CONCLUSIONS: APASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score > 12 may be used as a futility criterion in APASL-ACLF patients.
PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997).
RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P