L-Ornithine l-Aspartate in Acute Overt Hepatic Encephalopathy

Abstract

Background and Aim: High quality data on efficacy of l-ornithine l-aspartate (LOLA) in cirrhotics with acute overt hepatic encephalopathy (HE) is missing. We aimed to evaluate the efficacy of intravenous LOLA in reversal of acute overt HE in cirrhotics. This prospective double-blind randomized placebo controlled trial was conducted at Gastroenterology department of two tertiary care institutes in India. Methods: Three hundred and seventy cirrhotics 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 to 5 days. Serum concentration of tumor necrosis factor α, interleukin 1β, interleukin 6, interleukin10, hemogram, liver, renal function tests were performed at day 0 and 5. Primary outcome was mental state grade at day 5 of treatment. Results: After 5 days of treatment there was no significant difference in mental state grade between LOLA and placebo groups. However the mean time taken for recovery was 1.92 ± 0.93 days in LOLA group and 2.45 ± 1.06 days in placebo group, P = 0.002 (95% CI −0.852 to −0.202). Venous ammonia at day 5 and length of hospital stay 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 with acute overt HE, intravenous LOLA decreases venous ammonia, decrease the time of recovery and shortens the length of hospital stay (Table 1).Table 1Results From a Linear Regression Analysis on Venous Ammonia and Interleukins at Day 5 Adjusted for Baseline and Center.LOLA (mean ± SD)Placebo (mean ± SD)Adjusted difference (95% confidence interval)aLOLA–placebo. #: Number of patients tested.P-valueAmmonia (μg/dL) # (L = 81, P = 81)40.3 ± 33.860.7 ± 35.120.9 (10.4–31.3)0.0001Interleukin 1β (pg/ml) # (L = 85, P = 78)3.1 ± 19.52.4 ± 5.30.9 (−0.4 to 2.3)0.15Interleukin6 (pg/ml) # (L = 83, P = 79)37.8 ± 46.545.8 ± 54.43.3 (−8.8 to 15.4)0.59Interleukin10 (pg/ml) # (L = 84, P = 79)12.5 ± 32.019.1 ± 21.46.7 (−0.2 to 12.7)0.06TNF alpha (pg/ml) # (L = 84, P = 78)11.33 ± 50.07.97 ± 13.1−1.30 (−8.67 to 6.1)0.73a LOLA–placebo.#: Number of patients tested. Open table in a new tab The authors have none to declare.