D0472 - Response-Guided Ascites Mobilization in Patients of Acute on Chronic Liver Failure (ACLF) With Acute Kidney Injury Treated With Slow Albumin, Furosemide and Vasoconstrictor Therapy (SAFI+T) versus Standard Treatment

Introduction: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcome. Severely deranged systemic hemodynamic and decreased effective arterial blood volume contributes to tissue damage and organ failure. Response guided therapy with albumin, vasoconstrictors and furosemide may help overcome effective hypovolemia improve diuresis and impact survival.

Methods: In observation cohort, 56 patients with ACLF (CANONIC criteria) complicated with AKI ( S.Cr ³ 1.5, >50% increased S.cr from baseline), ascites (≥ Grade II) were enrolled. 30 patients (GROUP I) received response guided(Urine sodium >80mmol/day) slow albumin-furosemide infusion ±  terlipressin (SAFI±T), while 26 patients (GROUP II) received standard medical therapy. 28-day survival, ascites mobilization (nil or grade 1), reversal of AKI and adverse events were noted. Laboratory evidences for improvement in various pathophysiological alterations; endotoxemia, cytokine storm, neutrophil dysfunction and secondary infections, following SAFI±T were evaluated.

Results: Alcohol and sepsis were the commonest etiologies for chronic and acute insult respectively. Ascites was completely mobilized in 18/30 (60%) patients in Group I (SAFI±T) and 7/26 (26.9%) in Group II (p< 0.05). At 28 days the survival analysis showed, Group I 23/30 (76.4%) and Group II 14/26 (53.8%) (P=< 0.05). There was a lower incidence of hospital acquired infection in Group I of 6.7% vs 38.4% in Group II (p=0.05) and the same was reflected in serum endotoxin and pro-inflammatory cytokine levels; IL-6 and IL-1b showed significant reduction in Group I. Serum endotoxin and TNF-a level increased in Group II despite SMT while it showed significant fall in SAFI+T arm post treatment. Renal artery resistive index was significantly lower after SAFI(T) therapy (0.84 to 0.72) (p< 0.05) as similar trend emulated in UNa level.

Discussion: Patients with ACLF treated with SAFI+T protocol had higher natriuresis, enhanced urine output, complete ascites removal, and improved renal function with a faster mean duration of treatment and better 28-day survival. An in-hospital infection rate was lower. Ascites mobilization was associated with improvement in gut permeability, endotoxemia, pro-inflammatory cytokines, and NETosis in the SAFI+T cohort, showing an association between ascites mobilization and improved pathophysiologic dysfunctions.