Hepatic encephalopathy expands the predictivity of model for end‐stage liver disease in liver transplant setting: Evidence by means of 2 independent cohorts

Abstract

Despite its documented prognostic relevance, hepatic encephalopathy (HE) is not considered in liver transplantation (LT) due to its possible poor objectivity. To override this problem, we aimed to analyze if an objective diagnosis of HE may confer additional mortality risk beyond MELD. Study and validation cohorts of patients with cirrhosis were considered in Italy and Canada, respectively. Patients were considered to be HE+ if an episode of overt HE was documented in a hospitalization. Of the 486 patients enrolled in Italy, 184 (38%) were HE+. During the 6-month follow-up, 77 patients died and 50 underwent transplantation. The 6-month mortality of HE+ versus HE- patients was significantly higher (P < 0.001). Model for End-Stage Liver Disease (MELD; subdistribution hazard ratio [sHR], 1.2; 95% confidence interval [CI], 1.1-1.2; P < 0.001), HE+ (sHR, 3.6; 95% CI, 1.8-7.1; P < 0.001), and sodium (sHR, 0.9; 95% CI, 0.8-0.9; P < 0.001) were independent predictors of 6-month mortality. In HE+ patients, short-term mortality increased across the entire MELD spectrum (range, 6-40). The results were unchanged by including or excluding patients with hepatocellular carcinoma or stratifying patients according to HE characteristics. The higher 6-month mortality of HE+ versus HE- patients was confirmed also in the Canadian cohort (P < 0.001; n = 300, 33% HE+; 33 died, 104 transplanted). A similar and statistically significant C-index increase derived by the incorporation of HE in MELD was observed both in the Italian (from 0.67 to 0.75) and Canadian (from 0.69 to 0.74) cohorts. A score based on MELD plus 7 points (95% CI, 4-10) for HE+ patients optimally predicted 6-month mortality in the 2 cohorts. According to the net reclassification index, by not considering HE, 29% of overall patients were misclassified by MELD score. In conclusion, the incorporation of HE in MELD score might improve the listing and allocation policy in LT. Liver Transplantation 22 1333-1342 2016 AASLD.

Overt hepatic encephalopathy impairs learning on the EncephalApp stroop which is reversible after liver transplantation

“…Therefore, the OHE patients’ inability to demonstrate a learning effect from prior task stimuli exposure during the EncephalApp On runs may represent a harbinger of a dementing process in cirrhotic patients. This poor correlation with OHE episode characteristics replicates a prior study in which the development of OHE, rather than relevant medical phenomenology was associated with poor survival(25). Therefore, reaching the OHE stage may mark a major milestone, not only with regard to overall clinical endpoints, but perhaps also in terms of higher cortical dysfunction despite our current standard of care therapy.…”

Hepatic Encephalopathy Is Associated with Persistent Learning Impairments Despite Adequate Medical Treatment: A Multicenter, International Study

“…The pattern remained within the prior HE patients regardless of the number of prior HE episodes, prior HE severity, or infectious versus other precipitating factors. This is similar to a recent multicenter study that showed that increased risk from HE from a pre-transplant listing standpoint remains independent of number of episodes and severity of the prior HE [31]. These findings demonstrate that development of HE itself may be sufficient to reduce learning.…”

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

“…Hepatic encephalopathy (HE) is a debilitating and common complication of cirrhosis . HE is independently associated with decreased health‐related quality of life and reduced survival . Sedating and psychoactive medications such as opioids may contribute to the risk of HE through multiple mechanisms.…”