Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy

Abstract

Background The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE. Methods We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60 minutes post‐load ammonia levels. Combined evaluation of baseline hyperammonemia (>78 mcg/dL) and impaired OGC (Δ >32 mcg/dL) defined low‐, intermediate‐ and high‐risk groups. Patients were censored at HE, liver transplantation and death or 6 years of follow‐up. Results The 28.3% (56/198) of the main cohort suffered from HE during the follow‐up. In the competing risk analysis, both intermediate‐ (subhazard ratio (sHR) 2.01 (95% CI 1.00‐4.14); P = .048) and high‐risk groups (sHR 4.67 (95% CI 2.19‐9.98); P = .0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high‐risk group was two and four times greater than the intermediate‐ and low‐risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P = .035). The most common precipitant factor was diuretics in the high‐risk group, while infections and electrolyte imbalance predominated in the rest of patients. Conclusion Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision‐making process for the adequate management of HE.

Minimal hepatic encephalopathy is associated with a higher risk of overt hepatic encephalopathy and poorer survival

“…and ours are not easily comparable given that except for PHES different testing strategies were used to define MHE. Moreover, our current study cannot answer whether the predictive ability of a combination of PHES and S‐ANT1 is better for predicting OHE episodes than a combination of PHES and, for example, an oral glutamine challenge or even genetic risk scores [31, 32]. Additionally, we acknowledge that results in S‐ANT1 were only available for a subset of the cohort; therefore, our findings need validation in future prospective studies.…”

Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy

“…[173][174][175] Importantly, a response to intervention that is associated with a reduction in ammonia concentrations is associated with good outcomes, 41,176 while the reverse is true if ammonia increases further. 49,177 This observation is supported by studies of various interventions such as lactulose, rifaximin or extracorporeal albumin dialysis where reduction in ammonia was indeed associated with improvement in the severity of HE. 31,178,179 In a prospective study, an ammonia cutoff of 80 lmol/L was shown to be associated with a high risk of death, irrespective of the severity of HE.…”

North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension

“…3,4,97,98,[172][173][174] Notably, most studies excluded patients with a history of recurrent overt HE. Patient factors for the development of post-TIPS overt HE includes prior HE, advanced liver dysfunction (CTP class C, MELD score >18), 4,97,98,175,176 older age, 166 increased creatinine level, 166 hyponatremia, and sarcopenia. 177,178 Question 2.…”

“…174 Few studies have determined the role of oral glutamine challenge in prognostication for overt HE after TIPS. [175][176][177] Cognitive testing by and large worsens after TIPS, which can contribute to further worsening of health-related quality of life. 162,178 In patients being considered for elective TIPS, a diagnosis of covert HE should guide discussion of the pros and cons of TIPS creation with patients, family members, and clinical teams.…”