L‐ornithine L‐aspartate in bouts of overt hepatic encephalopathy

Abstract

In patients with bouts of OHE, intravenous LOLA (as an add-on therapy to lactulose and ceftriaxone) significantly improves the grade of OHE over days 1-4, but not on day 5, and decreases venous ammonia, time of recovery, and length of hospital stay. (Hepatology 2017).

Solving doubts about L‐ornithine L‐aspartate for overt hepatic encephalopathy: Whom and how to treat

“…Notably, some precipitating factors for OHE, including oxidative stress and inflammation, are not covered by the usual treatments. In fact, LOLA did not reduce proinflammatory cytokines compared to placebo in this study (in contrast to the reduction of ammonia plasma levels) . Consequently, this drug could be suboptimal in some scenarios where inflammation is the main driver for the bout of OHE, which makes necessary to identify the main trigger before selecting and initiating the therapy.…”

“…The article by Sidhu et al is an example of a good approach to the problem: it takes into account the daily dynamics of HE over 5 days, which represents a reasonable time interval to assess the treatment. Further, the outcome of OHE may depend on its severity, so categorizing the OHE grade not only provides information about the clinical status but might also help in the selection of the most appropriate therapy .…”

“…Further, the outcome of OHE may depend on its severity, so categorizing the OHE grade not only provides information about the clinical status but might also help in the selection of the most appropriate therapy . Of note, Sidhu et al assessed the global effect of L‐ornithine L‐aspartate (LOLA), taking into account the OHE grade. LOLA was found more effective in lower (particularly grade 2) than higher (3/4) OHE grades in comparison with placebo, confirming previous results .…”

“…Currently, the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver guidelines indicate that intravenous LOLA can be used as an alternative or additional agent to treat patients nonresponsive to conventional therapy . Sidhu et al considered as basal treatment the association of LOLA with nonabsorbable disaccharides plus ceftriaxone. This can provide a reasonable baseline treatment in a study evaluating a metabolic drug, such as LOLA, because this kind of treatment does not interact with LOLA and can homogenize bouts of OHE that might require mainly disaccharides (e.g., OHE precipitated by constipation) or antibiotics (e.g., OHE precipitated by infection).…”

“…In the era of personalized medicine, known drugs for OHE must be adapted and selective therapies developed, taking into account the severity of the bout and the main triggers. Despite its limits, the study performed by Sidhu et al clarifies the role of LOLA to treat a bout of OHE, especially in patients with relevant hyperammonemia, regarding the adequate dose (30 g) and length of the therapy (up to 4 days), as well as the target population (low HE grades) and the concomitant treatment (at least, lactulose). In addition, this study provides new opportunities for treatment and suggests further studies with an add‐on design to improve the speed of recovery for bouts of OHE.…”