Sub-clinical hepatic encephalopathy is an independent risk factor for survival in patients with cirrhosis

Manifest or clinical hepatic encephalopathy (HE) is an end-stage complication of cirrhotic patients associated with poor survival. If patients with sub-clinical HE carry the same poor prognosis is unclear. The aim of the study was to investigate the survival of cirrhotic patients with sub-clinical HE in comparison to cirrhotic patients without HE.

Methods: In 338 patients with cirrhosis sub-clinical HE was detected by measurement of visual event-related P300 potentials. A latency of ≥320ms was considered as sub-clinical HE. In addition, patients underwent a diagnostic work-up including measurement of Child-Pugh score, MELD, and hepatic venous pressure gradient (HVPG). Patients with clinical HE, HCC, TIPS, and concurrent illness were excluded. Kaplan-Meier survival (KM) curves and Cox regression were performed.

Results: 197 patients were included in the statistical examination. 97 of these patients had a P300 latency of ≥320ms (mean±SD: Child-Pugh score 7.8±2.1; MELD 13.3±5.8; HVPG 15.4±5.7mmHg) and were therefore classified as sub-clinical HE. The remaining patients (Child-Pugh score 7.9±2.1; MELD 14.0±6.2; HVPG 15.0±6.1mmHg) had no signs of sub-clinical or clinical HE (no HE). KM curves of both groups are shown in figure 1. Multivariate Cox regression revealed HVPG (p=0.004), MELD (p=0.006), and sub-clinical HE (0.033) as independent prognostic factors.

Conclusion: Cirrhotic patients with sub-clinical hepatic encephalopathy have a shorter survival compared to patients without hepatic encephalopathy. As a potential sign of hepatic decompensation, sub-clinical HE should receive more clinical attention.

Figure 1: Kaplan-Meier survival curves comparing cirrhotic patients without hepatic encephalopathy (no HE) and with sub-clinical hepatic encephalopathy (sub-clinical HE)