L-Ornithine L-Aspartate In Acute Overt Hepatic Encephalopathy

Abstract

Introduction: Good quality data on effectiveness of L-Ornithine L-Aspartate (LOLA) in cirrhotic patients with acute overt hepatic encephalopathy (HE) is absent. We aimed to evaluate efficacy of intravenous LOLA in reversal of acute overt HE in cirrhotic patients. Methods: A prospective double-blind, randomized placebo controlled trial was conducted at Gastroenterology department of two tertiary care institutes in India. Three hundred and seventy cirrhotic patients with acute overt HE were screened. After exclusion, 196 (52.97%) patients were randomized to receive either intravenous infusions of LOLA (n=98), 30 grams daily or Placebo (n=98) for 5 days. Standard of care treatment (including Lactulose) was given in both groups. Fasting venous ammonia levels were estimated daily from 0-5 days. Serum concentration of, Interleukin 1β, Interleukin 6, Interleukin 10, Tumor Necrosis Factor α, Hemogram, liver, renal function tests were performed at day 0 and 5. Primary outcome was mental state grade at day 5 of treatment. Results: On completion of 5 days of treatment, 75.5% patients in LOLA group and 74.5% patients in placebo group had resolution of overt HE. Mean time taken for recovery was 1.92±0.93 days in LOLA group & 2.45±1.06 days in placebo group, p=0.002 (95% CI -0.852 to - 0.202). Length of hospital stay and Venous ammonia at day 5 were significantly lower in LOLA group. No significant change was seen in Interleukins and Tumor Necrosis Factor α in both the groups. Conclusion: In patients suffering from acute overt HE, intravenous LOLA decreases the time of recovery from HE, shortens the length of hospital stay and decreases the venous ammonia.Table: Table. Results from a linear regression analysis on venous ammonia and interleukins at day 5 adjusted for baseline and center.Figure: Percentage of patients with resolution of Hepatic encephalopathy from day 1 to day 5.