New Perspectives inHepatic Encephalopathy

Kevin D. Mullen, MD, FRCPI*, Ravi K. Prakash, MBBS, MD, MRCP (UK)

KEYWORDS

� Hepatic encephalopathy � Terminology � Cirrhosis� Spectrum of neurocognitive impairment in cirrhosis

The terminology of hepatic encephalopathy (HE) remained poorly defined for decades.One major problem was the lack of definition of what constituted acute versus chronicHE.1,2 Many physicians assumed acute HE was a term used for the fast onset of a boutof alteration in consciousness in patients with underlying cirrhosis. Others thoughtacute HEwas the encephalopathy seen only in patients with acute liver failure. ChronicHE caused even more confusion because it was proposed by some to signify any boutof HE in patients with chronic liver disease, whereas others thought it denoted a pro-tracted (length of time specified) period of loss of consciousness. Numerous otherconfusions were rampant; at times, articles were being turned down by journalsbecause of inexact terminology when, in fact, standardized terminology had neverbeen established.This mass confusion was solved, to a significant extent, by the report of the Hepatic

Encephalopathy Consensus Group at the World Congress of Gastroenterology inVienna in 1998. This report led to an entirely new multiaxial definition for the termi-nology of HE (Fig. 1).As noted, 3 broad types of HE were defined. Type A signified the HE associated with

acute liver failure. Type B was designated to represent the rare form of HE associatedwith portosystemic bypass in the absence of any intrinsic liver disease. Finally, type CHE referred to the encephalopathy associated with chronic liver disease, which isprimarily cirrhosis. Under the categories of type B and C HE, there are further termssubdividing HE into episodic HE, persistent HE and subtle form called minimal HE.As it turned out, the recommendation of the termminimal HE, along with acceptable

diagnostic criteria for this form of HE, had a major impact on the field of HE. Multiplearticles have appeared using this terminology and diagnostic criteria.3 Minimal HE isnow known to be associated with the reduction in quality of life4,5; reduced drivingskills6–8; reduced ability to hold certain kinds of employment9,10; and, most impor-tantly, predicts the subsequent onset of overt HE.11 Such has been the impact of these

Division of Gastroenterology, MetroHealth Medical Center, Case Western Reserve University,2500 MetroHealth Drive, Cleveland, OH 44109, USA* Corresponding author.E-mail address: kevin.mullen@case.edu

Clin Liver Dis 16 (2012) 1–5doi:10.1016/j.cld.2012.01.001 liver.theclinics.com1089-3261/12/$ – see front matter � 2012 Published by Elsevier Inc.

Type A HE

Type B HE

Type C HE

Precipitated

Spontaneous

Recurrent

Persistent HE

Severe HE

Mild HE

Covert HE

HE associated with

Acute Liver Failure

HE associated with

Porto-systemic

shunting with no

intrinsic liver disease

HE associated with

Chronic Liver Disease

Episodic HE

Treatment

Dependent

HE

Fig. 1. Multiaxial classification of HE. This classification system was introduced by theHepatic Encephalopathy Consensus Group at the World Congress of Gastroenterologymeet in Vienna (1998). The term minimal HE is now replaced by covert HE as shown here.

Mullen & Prakash2

findings that consideration is being given to treat patients with minimal HE before overtHE has ever occurred. Before that can be endorsed, some other issues need to beconsidered.The spectrum of neurocognitive impairment in cirrhosis (SONIC) is a term coined

by Bajaj and colleagues12 to describe the prevailing status of brain function inpatients with cirrhosis (Fig. 2). As noted, this concept views the spectrum asa continuum rather than as discrete, separate entities. There is good evidence forthe evolution from normal mental status through minimal HE to overt HE and evenpotentially to hepatocerebral degeneration. Recently the term covert HE has beenintroduced, which encompasses the area formerly designated as minimal HE andis usually diagnosed by a psychometric test battery. However, because of the diffi-culty in getting standardization of what is stage I HE of New Haven scale, the authorshave chosen to include this stage within the term covert HE.13 The hepatic enceph-alopathy scoring algorithm and low-grade/high-grade HE distinctions have alsoattempted to address the problem of the subjective scoring of stage I HE on theold New Haven scale.14,15

Normal

Covert HE

(Minimal HE + Stage I Overt HE)

Moderate Overt HE

(Stage II Overt HE)

Severe Overt HE

(Stage III Overt HE)

Comatose Overt HE

(Stage IV Overt HE)

Hepatocerebral

Degeneration

Fig. 2. Spectrum of neurocognitive impairments in cirrhosis. The range of cognitive impair-ments that are encountered with patients with cirrhosis from normal at one end to covert,overt, and severe irreversible stages, such as hepatocerebral degeneration, at the other. Thisspectrum is a continuum, and patients can fluctuate between various stages of HE basedon several factors. However, development of hepatocerebral degeneration is usuallyirreversible.

New Perspectives in Hepatic Encephalopathy 3

The authors briefly mentioned the hepatocerebral syndromes (as shown in Fig. 2)that represent an extreme form of HE.16 Essentially evidence of brain atrophy andmicrocavitation in some patients is very pronounced. Despite the damage to braintissue, this neurodegenerative disorder does seem to be reversible, to a degree.17

One spectacular case of brain regeneration is published in the literature, but generallyfar less prominent restoration of brain anatomy is noted.18

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Conventionally, for purity sake, it is stated that patients with prior bouts of overt HEshould not be classified as minimal or covert HE. This definition is only an operationaldefinition. With the advent of the concept of SONIC and widespread psychometrictesting of patients with cirrhosis, we are more likely to encounter patients who havecovert HE with or without a history of prior bouts of overt HE. There is some concernthat patients with prior overt HE have persistent cognitive impairments.19 However, forall practical purposes, they should be labeled as overt, covert, or normal depending ontheir cognitive performance at the time of testing.

REFERENCES

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