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Clinical and Pathophysiological Characteristics of Cirrhotic Patients with Grade 1 and Minimal Hepatic Encephalopathy
Karen Louise Thomsen1, Jane Macnaughtan1, Giovanni Tritto1
1Liver Failure Group, UCL Institute for Liver and Digestive Health, University College London Medical School, London, United Kingdom.
Insights
Covert hepatic encephalopathy (HE) is not a single entity. Grade 1 HE patients experienced more hospitalizations and mortality than minimal HE (mHE) patients, indicating distinct clinical trajectories.
Area of Science:
- Hepatology
- Gastroenterology
- Clinical Medicine
Background:
- The EASL/AASLD guidelines propose 'Covert HE' encompassing minimal HE (mHE) and Grade 1 HE.
- Longitudinal data are lacking to support mHE and Grade 1 HE as a single entity.
- This study investigates clinical outcomes in these subgroups.
Purpose of the Study:
- To determine if complications and mortality rates are similar between mHE and Grade 1 HE patients.
- To evaluate the heterogeneity within the proposed 'Covert HE' classification.
Main Methods:
- 106 clinically stable cirrhotic patients without prior Overt HE were classified into no HE (n=23), mHE (n=39), or Grade 1 HE (n=44).
- Patients were followed for a mean of 230 days, with measurements of biochemistry, ammonia, bacterial DNA, and neutrophil function.
- Outcomes assessed included hospital admissions for complications and mortality.
Main Results:
- Grade 1 HE patients showed significantly higher rates of hospitalization (P=0.02) and mortality (P=0.04) compared to no HE and mHE groups.
- Ammonia levels were similar in mHE and Grade 1 HE but higher than in the no HE group.
- Grade 1 HE patients exhibited increased bacterial translocation and neutrophil dysfunction compared to mHE patients.
Conclusions:
- 'Covert HE' is a heterogeneous classification, with Grade 1 HE patients facing significantly worse outcomes than mHE patients.
- These findings suggest that mHE and Grade 1 HE should be considered distinct entities.
- Further long-term studies are needed before full implementation of current EASL/AASLD guidance.
Background And Aims:
EASL/AASLD hepatic encephalopathy (HE) guidelines proposed the alternative use of the term 'Covert HE' combining minimal HE (mHE) and Grade 1 HE into a single entity. However, longitudinal data to indicate that these are indeed a single entity are lacking. The aims of this study were to determine whether the occurrence of complications of cirrhosis requiring hospital admission and mortality were similar in these sub-groups of patients.
Methods:
Clinically-stable cirrhotic patients (n = 106) with no previous history of 'Overt HE' were included over a 2-year period and classified as having no HE (n = 23), mHE (n = 39) or Grade 1 HE (n = 44). Standard biochemistry, venous ammonia, bacterial DNA and neutrophil function were measured at inclusion and the patients were followed for a mean of 230±95 days.
Results:
Patients with Grade 1 HE had significantly more complications requiring hospitalisation (infection 9/18/34%; HE 4/8/18%; other 13/10/11%; P = 0.02) and significantly greater mortality (4/5/20%; P = 0.04) compared to patients with no HE or mHE respectively. Patients with mHE and grade 1 HE had similar ammonia levels, but higher than the no HE group (P<0.001). MELD score was similar between groups but Grade 1 HE patients had increased frequency of bacterial translocation (P = 0.06) and neutrophil spontaneous respiratory burst (P = 0.02) compared to patients with mHE.
Conclusions:
The results of this study show for the first time that 'Covert HE' is a heterogeneous entity with significantly greater hospitalisations and mortality in the Grade 1 HE patients compared with mHE. Further prospective longer-term studies are required before EASL/AASLD guidance is fully implemented.
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