Sharma BC, Sharma P, Lunia MK et al. A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol. 2013;108(9):1458-63.1
This study evaluated the efficacy and safety of rifaximin plus lactulose vs. lactulose alone for treatment of overt HE. In this prospective double-blind randomised controlled trial, 120 patients with overt HE were randomised into two groups: (group A lactulose plus rifaximin 1,200 mg/day; n=63) and group B (lactulose (n=57) plus placebo). The primary end point was complete reversal of HE and the secondary end points were mortality and hospital stay.
There was a significant decrease in mortality after treatment with lactulose plus rifaximin vs. lactulose and placebo (23.8% vs. 49.1%, p<0.05). There were significantly more deaths in group B because of sepsis (group A vs. group B: 7:17, p=0.01), whereas there were no differences because of gastrointestinal bleed (group A vs. group B: 4:4, p=non-significant) and hepatorenal syndrome (group A vs. group B: 4:7, p=non-significant). Patients in the lactulose plus rifaximin group had shorter hospital stay (5.8±3.4 vs. 8.2±4.6 days, p=0.001)
Combination of lactulose plus rifaximin is more effective than lactulose alone in the treatment of overt HE.1
Bai M, Yang Z, Qi X et al. l-ornithine-l-aspartate for hepatic encephalopathy in patients with cirrhosis: a meta-analysis of randomized controlled trials. J Gastroenterol Hepatol. 2013;28(5):783-92.2
The purpose of this study was to update the meta-analysis to re-evaluate the safety and efficacy of LOLA on HE in patients with cirrhosis.
Eight randomised controlled trials with 646 patients were included. When comparing placebo/no-intervention control, LOLA was significantly more effective in the improvement of HE in the total (RR: 1.49, 95% confidence interval [CI]: 1.10 to 2.01), overt HE (RR: 1.33, 95% CI: 1.04 to 1.69), and minimal HE patients (RR: 2.25, 95% CI: 1.33 to 3.82). Furthermore, the reduction of fasting ammonia significantly favoured LOLA (post-treatment value, MD: -18.26, 95% CI: -26.96 to -9.56; change, MD: 8.59, 95% CI: 5.22 to 11.96). The tolerance ratio, incidence of adverse events, and mortality were not significantly different between LOLA and the placebo/no-intervention control. LOLA and lactulose demonstrated similar effectiveness in the improvement of HE (RR: 0.88, 95% CI: 0.57 to 1.35).
OLA benefits both overt and minimal HE patients in the improvement of HE by reducing the serum ammonia concentration compared with the placebo/no-intervention control.2
Pérez Hernández JL, Higuera de la Tijera F, Serralde-Zúñiga AE, Abdo Francis JM. Critical analysis of studies evaluating the efficacy of infusion of L-ornithine L-aspartate in clinical hepatic encephalopathy in patients with liver failure. Ann Hepatol. 2011;10 Suppl 2:S66-9.3
Hepatic encephalopathy refers to a complex neuropsychiatric syndrome that is progressive but potentially reversible and may have a significant impact on quality of life, as it is characterized by alterations in cognitive function, behaviour and personality as well as transient neurological symptoms and electroencephalographic abnormalities. The aim of this study was to evaluate scientific evidence for the effectiveness and safety of LOLA infusions for treatment of clinical hepatic encephalopathy in patients with chronic liver disease. Six publications were selected as having met the inclusion criteria. A total of 623 patients were observed in studies published in these publications.
The available scientific evidence supports the adoption of LOLA infusion as a treatment for clinical encephalopathy in patients with liver failure, because it has been shown to improve neuropsychiatric status and decrease serum levels of ammonia with a low incidence of adverse effects (less than 5%).3
Abid S, Jafri W, Mumtaz K et al. Efficacy of L-ornithine-L-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy. J Coll Physicians Surg Pak. 2011;21(11):666-71.4
This randomised placebo controlled study aimed to evaluate the efficacy of LOLA as an adjuvant therapy in cirrhotic patients with HE. Patients with HE were randomised to receive LOLA or placebo medicine as an adjuvant to treatment of HE. Number connection test-A (NCT-A), ammonia level, clinical grade of HE and duration of hospitalisation were assessed.
Improvement in HE was higher (n=40, 66.7%) in LOLA group as compared to the placebo group (n=28, 46.7%, p=0.027). In patients with grade I or less encephalopathy, improvement was seen in 6 (35.3%) and 3 (20%) patients in LOLA and placebo groups respectively (p=0.667). Patients with HE grade II and above showed improvement in 34 (79.1%) and 25 (55.6%) cases in LOLA and placebo group respectively (p=0.019). Duration of hospitalisation was 93.6 ± 25.7 hours and 135.2 ± 103.5 hours in LOLA and placebo groups respectively (p=0.025). No side effects were observed in either group.
In cirrhotic patients with advanced hepatic encephalopathy treatment with LOLA was safe and associated with relatively rapid improvement and shorter hospital stay.4
1. Sharma BC et al. A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol. 2013;108(9):1458-63.
2. Bai M et al. l-ornithine-l-aspartate for hepatic encephalopathy in patients with cirrhosis: a meta-analysis of randomized controlled trials. J Gastroenterol Hepatol. 2013;28(5):783-92.
3. Pérez Hernández JL et al. Critical analysis of studies evaluating the efficacy of infusion of L-ornithine L-aspartate in clinical hepatic encephalopathy in patients with liver failure. Ann Hepatol. 2011;10 Suppl 2:S66-9.
4. Abid S et al. Efficacy of L-ornithine-L-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy. J Coll Physicians Surg Pak. 2011;21(11):666-71.