Ammonia is associated with liver-related complications and predicts mortality in acute-on-chronic liver failure patients

Abstract The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients

Asia–Pacific association for study of liver guidelines on management of ascites in liver disease

The development of ascites is a landmark event in the natural history of cirrhosis. This guidance statement by the Asia–Pacific Association for Study of Liver (APASL) provides an evidence-based approach to managing ascites and its complications in patients with chronic liver disease. These guidelines extensively review the differential diagnosis, diagnostic evaluation, and management of ascites, hyponatremia, hepatic hydrothorax and hepatorenal syndrome (HRS) in patients with cirrhosis and acute-on-chronic liver failure (ACLF). A panel of international experts was invited to formulate the guidelines. The opinions of the experts were collected using two sets of Delphi questionnaires. Then, an online meeting of all the experts was held to discuss the evidence and formulate the final recommendations by consensus. The guidelines were developed using the GRADE system for analysing the level of evidence and strength of recommendation (Table 1). All authors have gone through the guidance document and endorse the same.In this document, we have also covered the grey areas which have been underexplored in previous guidelines and some of the issues which are relatively peculiar to the Asia–Pacific region. Given the high burden of tuberculosis in some of the countries of the Asia–Pacific region, mixed ascites is not uncommon in these patients with liver disease. We discuss the diagnostic approach to mixed ascites and the role of ascitic fluid adenosine deaminase (ADA) and other tests for tuberculosis. In addition, many countries in the Asia–Pacific region are low-middle-income countries, and financial constraints are an essential barrier to liver transplants and other costly therapies like albumin. Hence, we have discussed the role of low-dose albumin in the prevention of paracentesis-induced circulatory dysfunction (PICD) after large-volume paracentesis (LVP) and the prevention of acute kidney injury (AKI) in patients with spontaneous bacterial peritonitis (SBP). We have also reviewed the current evidence of outpatient albumin in managing patients with ascites and have made practical recommendations. We also highlight the timing of albumin infusion concerning LVP. To decrease adverse events and improve patient compliance with diuretic therapy, the guidelines emphasize initiating low-dose diuretics and gradually increasing the dose to the maximum tolerable dose. Non-alcoholic fatty liver disease (NAFLD), also referred to as Metabolic associated fatty liver disease (MAFLD) by some societies has become a significant cause of chronic liver disease worldwide [1]. Many patients with NAFLD/MAFLD related cirrhosis are on angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) when they present to a hepatologist or gastroenterologist with ascites. For the first time, we provide guidance statements regarding the use of these drugs in patients with cirrhosis and ascites. For refractory ascites, we have now defined renal dysfunction following the International Club of Ascites (ICA) recommendations on AKI. Lastly, we have highlighted the gaps in our knowledge and have provided directions for future research

Development of Predisposition,Injury,Response,Organ failure model for predicting acute kidney injury in acute on chronic liver failure.

Background and Aim There is limited data on predictors of acute kidney injury(AKI) in ACLF. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting AKI in a multi-centric cohort of 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 ACLF patients (n=997) Results Factors significant for P component were serum creatinine[(≥2mg/dl)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(/dL,OR 1) versus (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) versus (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(/LOR-1)versus (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) versus (≥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 AKI 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 \u3c 0.001) in both the derivation and validation cohorts. Conclusions The PIRO model identifies and stratifies ACLF patients at risk of developing AKI. It reliably predicts mortality in these patients, underscoring the prognostic significance of AKI in patients with ACLF