Book Review

Hepatic Encephalopathy

N Engl J Med 1993; 328:1857-1858June 24, 1993

Article

Hepatic Encephalopathy
By Alan H. Lockwood. 151 pp., illustrated. Boston, Butterworth-Heinemann, 1992. $44.95. ISBN: 0-7506-9324-0

The last overview of hepatic encephalopathy, a clinical problem in which two distinct disciplines meet, was written by a hepatologist more than a decade ago; it was criticized for its omissions of neurochemical issues. Now Lockwood, a neurologist as well as specialist in nuclear medicine, has written a short monograph covering recent advances in the field. It has succeeded in some aspects while falling short in others.

Controversy has characterized research in hepatic encephalopathy. Of the nine chapters of this book, five deal with different candidate neurotoxins that have been studied over the past four decades. The role of ammonia, discounted in the 1980s, has been freshly reexamined by the author, using a new method (positron-emission tomography) that has led to new ideas. For example, the often cited lack of relation between blood levels of ammonia and the degree of encephalopathy can now be explained by an increased passage of ammonia into the brain. Once nervous tissue metabolizes ammonia, multiple neurotransmitter systems may be affected; in this light, much of ammonia-induced neurotoxicity occurs “downstream” from ammonia itself. The search for an endogenous benzodiazepine ligand or ligands is also unfolding. Hepatic encephalopathy has become the focus for the biologic importance of such a compound. The author reviews the literature on this subject succinctly, expanding on key studies rather than providing an exhaustive review. This allows for a quick update, a welcome opportunity at a time when the literature is growing at an exponential rate.

The brief sections on clinical aspects of the syndrome are, unfortunately, less precise. Fulminant hepatic failure is not “a syndrome that evolves to the point where cerebral function is impaired over a minimum of eight weeks,” but a syndrome in which encephalopathy develops within eight weeks of the first evidence of impaired liver function. The development of brain edema in acute liver failure, a major cause of death in this disease, is incompletely discussed; papilledema is described as a clinical sign of this condition, but papillary signs are seldom seen because of the rapidity of deterioration. The need to treat subclinical hepatic encephalopathy, as proposed by the author, is controversial at best. A chapter on therapy provides a pathophysiologic background to currently available measures; several omissions are nonetheless evident. The use of oral metronidazole as an alternative antibiotic is not discussed, the controversial results of two meta-analyses of the effectiveness of branched-chain amino acid therapy are not mentioned, and the use of lactose (a much cheaper alternative to lactulose) for patients who are lactose-intolerant is not discussed.

The monograph will be useful for those interested in a neurologic perspective on the pathogenesis of hepatic encephalopathy, a perspective that incorporates advances in methods as well as insight into the neurochemical disorder. The book will be considerably less helpful at the bedside. In the meantime, a complete review of the subject will require collaborative efforts of researchers on both sides of “the blood-brain barrier.”

Andres T. Blei, M.D.
Northwestern University, Chicago, IL 60611