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  1. Verma N, Choudhury A, Singh V, Duseja A, Al-Mahtab M, Devarbhavi H, et al.
    Liver Int, 2023 Feb;43(2):442-451.
    PMID: 35797245 DOI: 10.1111/liv.15361
    BACKGROUND AND AIMS: We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute-on-chronic liver failure (ACLF).

    METHODS: We recruited ACLF patients between 2009 and 2020 from APASL-ACLF Research Consortium (AARC). Their clinical data, investigations and organ involvement were serially noted for 90-days and utilized for AI modelling. Data were split randomly into train and validation sets. Multiple AI models, MELD and AARC-Model, were created/optimized on train set. Outcome prediction abilities were evaluated on validation sets through area under the curve (AUC), accuracy, sensitivity, specificity and class precision.

    RESULTS: Among 2481 ACLF patients, 1501 in train set and 980 in validation set, the extreme gradient boost-cross-validated model (XGB-CV) demonstrated the highest AUC in train (0.999), validation (0.907) and overall sets (0.976) for predicting 30-day outcomes. The AUC and accuracy of the XGB-CV model (%Δ) were 7.0% and 6.9% higher than the standard day-7 AARC model (p AARC-AI model was developed and validated twice with optimal performance for 30-day predictions.

    CONCLUSIONS: The performance of the AARC-AI model exceeds the standard models for outcome predictions in ACLF. An AI-based decision tree can reliably undertake severity-based stratification of patients for timely interventions.

  2. Verma N, Dhiman RK, Choudhury A, Taneja S, Duseja A, Singh V, et al.
    Hepatol Int, 2021 Aug;15(4):970-982.
    PMID: 34275111 DOI: 10.1007/s12072-021-10221-7
    BACKGROUND: We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence.

    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 AARC score (≥ 9) and ammonia levels (≥ 85 μmol/L) (p ACLF patients.

    CONCLUSIONS: HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.

  3. Sharma S, Agarwal S, Saraya A, Choudhury AK, Saigal S, Soin AS, et al.
    Hepatol Int, 2023 Aug;17(4):989-999.
    PMID: 36790652 DOI: 10.1007/s12072-023-10482-4
    BACKGROUND AND AIMS: Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment.

    METHODS: Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks.

    RESULTS: Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p AARC score > 6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF.

  4. Choudhury A, Vijayaraghavan R, Maiwall R, Kumar M, Duan Z, Yu C, et al.
    Hepatol Int, 2021 Oct 04.
    PMID: 34608586 DOI: 10.1007/s12072-021-10206-6
    BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT).

    METHODS: Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant.

    RESULTS: The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. 'Emergent LT' should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.

  5. Kumar A, Arora A, Choudhury A, Arora V, Rela M, Jothimani DK, et al.
    Am J Gastroenterol, 2024 Jul 17.
    PMID: 39016385 DOI: 10.14309/ajg.0000000000002951
    BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied.

    METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered.

    RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts.

    CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

  6. Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al.
    Hepatol Int, 2019 11;13(6):826-828.
    PMID: 31595462 DOI: 10.1007/s12072-019-09980-1
    The article Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update, written by [Shiv Sarin], was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 06, 2019 without open access.
  7. Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al.
    Hepatol Int, 2019 Jul;13(4):353-390.
    PMID: 31172417 DOI: 10.1007/s12072-019-09946-3
    The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.
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