It is well known that liver failure and/or portal-systemic blood flow shunting have a detrimental effect on the brain, causing the syndrome of hepatic encephalopathy (HE). Individuals with liver cirrhosis and/or portal-blood shunting who do not have overt signs of HE can nonetheless present signs of brain dysfunction. Such signs include: (i) alteration of brain metabolism or functioning, detectable by: functional neuroimaging, clinical neurophysiology and the reduced ability to perceive flickering light; (ii) behavioural alterations concerning cognitive function or fine motor control.1 Given that all these dysfunctions represent a condition of minimal hepatic encephalopathy (MHE), coming to a cohesive definition of this condition has been problematic. The concept is, in fact, polysemic—it has many meanings.

Due to the fact that the various dimensions of MHE are not parallel in their decline, recognition of MHE and its prevalence are debatable.2–5 Its detection varies according to both the examinable dimensions of the disease and the fixed diagnostic cut-offs. In neurology, it is well accepted that the behavioural consequences of a disease depend on the severity of brain damage, the presence of confounders, and the pre-morbid conditions of the individual.6 Therefore, depending on the level of brain toxicity, the degree of cognitive function can vary, given the interplay of confounders and co-factors.

Minimal hepatic encephalopathy is under scrutiny for its real-life implications that are in part recognized and in part still under investigation. Briefly, MHE might: (i) be a risk factor for bouts of overt HE or for death (therefore potentially playing a part in transplant selection);3,7,8 (ii) increase the risk in activities such as driving;9 and (iii) be a condition having a direct detrimental effect on health related quality of life (HRQoL).10

Since MHE is associated with mild cognitive dysfunction, it is reasonable to suspect that this would have a detrimental effect on HRQoL. If the Peterson's conceptual framework and lexicon11,12 were to be applied to MHE, then we would see that its cognitive dimension is a ‘hepatic mild cognitive impairment’. In contrast, the pathophysiological changes occurring in the brain might have less of a relationship to HRQoL than patient cognition. This is because (i) cognition is related to behaviour, as well as the perception of HRQoL and (ii) cognitive dysfunction is an objective limit to the global performance of an individual. On the other hand, behavioural relationships are less evident using functional neuroimaging or neurophysiological tests. If any, their link with HRQoL could reflect metabolic alterations—possibly in catecholaminergic tone—causing a reduction in mood level. However, Tarter et al.13 excluded the existence of mood changes in MHE. Given that, the issue has not been examined in detail, but it may be worth studying further.

A great goal for clinical research in this area would be to understand the implication of the alterations in each dimension of MHE, before pooling the alterations under the unique definition of MHE.

In this issue of Journal of Gastroenterology and Hepatology, Ying-qun Zhou et al.14 used a diagnostic criterion for MHE, which takes into account both electroencephalographic (EEG) changes and psychometric tests, that provided a dichotomous classification of MHE. This approach, though valuable in detecting patients with MHE,15 can lead to loss of information due to the different domains of EEG and psychometric testing. Analysis of disaggregated and quantified data (both for the EEG and psychometric tests) would be preferable in future research, so that the outcomes related to each feature of MHE can be separately assessed. Furthermore, research into the effect that MHE has on HRQoL should include a clear description of the patients' cognitive profile, since this is the feature of MHE that is expected to be more closely related to HRQoL. Moreover, the quantifying of psychometric alterations along a scale is preferable to the simple dichotomy ‘yes’ or ‘no’. Some psychometric tools, such as the Psychometric Hepatic Encephalopathy Score (PHES)5 or the use of age and education adjusted Z score,16,17 allow both a dichotomous judgment and damage scoring. This might be important since, a priori, no one can predict which dysfunction levels and cognitive domains influence HRQoL.

Ying-qun Zhou et al.14 deal with HRQoL, which, together with survival, is a highly important clinical outcome for the study of any chronic disorder. Chronic liver disease is not an exception: both generic and specific questionnaires are used to assess HRQoL. All of them have proven that liver cirrhosis impairs quality of life. However, the influence of a disease is modulated by the expectations of the individual. For instance, liver cirrhosis has the highest detrimental effect on the QoL of young men,18 possibly due to the damage on sexual life. For this reason, the proper development by Ying-qun Zhou et al.14 of a questionnaire oriented to estimate HRQoL in the peculiar Chinese cultural background is an important achievement. They were able to tailor the questionnaire to be more appropriate, since it reflects the expectations and asks the proper questions for this population. This approach can be a model for the development of other questionnaires tailored for specific cultural areas that are highly different from western countries.

The intrinsic link between MHE and liver disease is an important item that should be considered when examining the effect of MHE on HRQoL. Any cross-sectional study can not discriminate for sure, despite accurate statistical tools,19 between a spurious association (due to the fact that both MHE and HRQoL depend on liver function) and a true influence of MHE on HRQoL. Interventional trials to improve the cognitive status without improving liver function would help answer this question. A single study properly designed to achieve this aim17 supports the existence of a true relationship between MHE and HRQoL. Therefore, a clear improvement to the study by Ying-qun Zhou et al.,14 which is based on a mere cross-sectional evaluation, would be the measurement of the changes inducible by interventional trials. Otherwise, it is difficult to assume for sure that the questionnaire is specifically oriented to detect HRQoL deflection related to MHE, or, alternatively, whether it is generically oriented to detect HRQoL deflection related to chronic liver disease.

At any rate, the work by Ying-qun Zhou et al.,14 despite some limits, deserves the utmost respect and attention, since it provides a well designed procedure to produce a questionnaire that will improve research on MHE and chronic liver disease in China and, possibly, other cultural similar countries.


  1. Top of page
  2. References