“…2Forest plots indicating the pooled effect of LOLA versus placebo/no intervention for improvement of mental state in a all HE patients, b patients with OHE. Trials included: Kircheis et al [8], Stauch et al [9], Chen et al [10], Abid et al [12], Mittal et al [13], Alvares da Silva et al [14], Sidhu et al [15], Ahmad et al [16], Sharma et al [17]Fig. 3Forest plots indicating the pooled effect of LOLA versus placebo/no intervention for improvement of mental state in patients with MHE a irrespective of the drug formulation of LOLA b using the oral formulation.…”
Section: Systematic Reviews and Meta-analyses Of Published Rctsmentioning
This manuscript represents an appraisal of the evidence in support of l-ornithine-l-aspartate (LOLA) for the management and treatment of hepatic encephalopathy (HE) in cirrhosis. Meta-analyses of randomized controlled trials (RCTs) conducted over the last two decades generally reveal evidence of benefit of LOLA in a range of clinical presentations. This included improvement of mental state grade in overt HE (OHE) assessed by West Haven criteria as well as in minimal HE (MHE) assessed by psychometric testing where the oral formulation of LOLA was determined to be particularly effective. However, concerns over study quality were noted in one meta-analysis. Nevertheless, the concomitant lowering of fasting blood ammonia was reported in all RCTs using this endpoint. Network meta-analyses showed that LOLA appears to be comparable (or superior) in efficacy to non-absorbable disaccharides or probiotics. Emerging evidence from single RCTs show efficacy of LOLA for the treatment of post-transjugular intrahepatic portosystemic shunt (TIPSS) HE as well as for secondary HE prophylaxis. These findings provide support for the use of LOLA in the treatment of HE and future trials should focus on the use of LOLA for prophylaxis.
“…2Forest plots indicating the pooled effect of LOLA versus placebo/no intervention for improvement of mental state in a all HE patients, b patients with OHE. Trials included: Kircheis et al [8], Stauch et al [9], Chen et al [10], Abid et al [12], Mittal et al [13], Alvares da Silva et al [14], Sidhu et al [15], Ahmad et al [16], Sharma et al [17]Fig. 3Forest plots indicating the pooled effect of LOLA versus placebo/no intervention for improvement of mental state in patients with MHE a irrespective of the drug formulation of LOLA b using the oral formulation.…”
Section: Systematic Reviews and Meta-analyses Of Published Rctsmentioning
This manuscript represents an appraisal of the evidence in support of l-ornithine-l-aspartate (LOLA) for the management and treatment of hepatic encephalopathy (HE) in cirrhosis. Meta-analyses of randomized controlled trials (RCTs) conducted over the last two decades generally reveal evidence of benefit of LOLA in a range of clinical presentations. This included improvement of mental state grade in overt HE (OHE) assessed by West Haven criteria as well as in minimal HE (MHE) assessed by psychometric testing where the oral formulation of LOLA was determined to be particularly effective. However, concerns over study quality were noted in one meta-analysis. Nevertheless, the concomitant lowering of fasting blood ammonia was reported in all RCTs using this endpoint. Network meta-analyses showed that LOLA appears to be comparable (or superior) in efficacy to non-absorbable disaccharides or probiotics. Emerging evidence from single RCTs show efficacy of LOLA for the treatment of post-transjugular intrahepatic portosystemic shunt (TIPSS) HE as well as for secondary HE prophylaxis. These findings provide support for the use of LOLA in the treatment of HE and future trials should focus on the use of LOLA for prophylaxis.
Hepatic encephalopathy (HE) is part of a spectrum of neurocognitive changes in cirrhosis. HE is divided into two broad categories based on severity, covert (CHE) and overt (CHE). CHE has a significant impact on a patient’s quality of life, driving performances, and has recently been associated with increased hospitalizations and death. Likewise, OHE is associated with increased rates of hospitalizations and mortality, and poor quality of life. Given its significant burden on patients, care takers, and the health care system, it’s imperative for early diagnosis and management. In addition, a focus should also be directed on patient and family member education on the disease progression and adherence to medications. Treatment strategies include the use of non-absorbable disaccharides, antibiotics (i.e. rifaximin), and potentially probiotics. Other therapies currently under further investigation include: L-ornithine-L-aspartate, ornithine phenylacetate, glycerol phenylbutyrate, molecular adsorbent recirculating system, and albumin infusion.
“…However, evidence for its use in mHE is conflicting, with one meta-analysis suggesting a beneficial effect but a randomised control trial suggesting that it had no effect, although the data also suggested that fewer patients progressed to overt HE compared to placebo [30,31]. …”
Minimal hepatic encephalopathy (mHE) is common among patients with cirrhotic liver disease and causes significant morbidity and mortality. It may present as cognitive impairment, behavioural changes and, less frequently, with neurological symptoms which make diagnosis of the disease challenging. A history of falls and accidents may also be suggestive of mHE. Diagnosis primarily relies on at least two positive psychometric tests of which the psychometric hepatic encephalopathy score (PHES) is essential. Alternatively, PHES and an electroencephalogram may be used to establish a diagnosis. Biochemical markers of encephalopathy currently have no role in the diagnosis of mHE. Treatment is not always advocated for a diagnosis of mHE but is dependent on the degree of impairment caused by the symptoms. After treatment of other metabolic abnormalities and co-morbidities associated with cirrhosis, more specific treatment for mHE largely relies on therapies used to lower ammonia levels. Laxatives and rifaximin are commonly used in treatment and work through decreasing ammonia absorption from the gut. Other therapies, such as BCAA, LOLA, L-carnitine and phenylbutyrate, modify responses to ammonia as well as enhancing metabolism and excretion. mHE resulting from spontaneous portosystemic shunts or transhepatic intraportal systemic shunts may require ablation or reduction of the shunt. Early detection and appropriate treatment of mHE is important to prevent significant cognitive impairments and progression to overt HE.
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