Other therapies have limited data to support their
use. One theory of hepatic encephalopathy is that an
increased ratio of aromatic to branched-chain amino
acids may serve to increase the level of false neurotransmitters, which may inhibit neurotransmission.
Branched-chain amino acid supplements have been
studied, with a potential benefit detected, though
further research is needed to establish this therapy
as effective.119 Another theory is that zinc deficiency
contributes to hepatic encephalopathy, as zinc may
modulate neurotransmission and zinc deficiency is
common in patients with cirrhosis.120 There is limited
evidence for the effectiveness of zinc supplementa-tion for hepatic encephalopathy.121 Because of the
importance of GABA neurotransmission in hepatic
encephalopathy, the benzodiazepine receptor antagonist flumazenil has also been studied for hepatic
encephalopathy.122 Although it does improve hepatic
encephalopathy, the effects are short-lived, and the
medication can precipitate seizures. It is therefore not
recommended for routine use in this setting.
The traditional teaching that protein restriction
would reduce nitrogenous substrate for ammonia
production has not played out in clinical studies. Protein restriction does not reduce hepatic encephalopathy, but does result in more protein breakdown.123
Malnutrition is common in advanced liver disease,
and can be worsened with protein restriction. For
those who have hepatic encephalopathy sensitive
to protein intake, substitution of animal proteins with
vegetable proteins may be beneficial.124
The chief complications of cirrhosis and portal
hypertension are ascites, varices, and hepatic encephalopathy. These complications are highly morbid and require careful monitoring and treatment to
improve the quality and duration of patients’ lives.
Adherence to evidence-based therapies offers the
best chance of obtaining favorable outcomes. Most
importantly, the development of these complications
heralds a poor prognosis, and liver transplantation
should be considered for those who are eligible.
1. Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology
2. Williams JW Jr, Simel DL. The rational clinical examination.
Does this patient have ascites? How to divine fluid in the
abdomen. JAMA 1992;267:2645–8.
3. De Gottardi A, Thevenot T, Spahr L, et al. Risk of complications after abdominal paracentesis in cirrhotic patients:
a prospective study. Clin Gastroenterol Hepatol 2009;
4. Runyon BA, Montano AA, Akriviadis EA, et al. The serum-ascites albumin gradient is superior to the exudate-transu-date concept in the differential diagnosis of ascites. Ann
Intern Med 1992;117:215–20.
5. Planas R, Montoliu S, Balleste B, et al. Natural history of
patients hospitalized for management of cirrhotic ascites.
Clin Gastroenterol Hepatol 2006;4:1385–94.
6. Chinnock B, Hendey GW, Minnigan H, et al. Clinical impression and ascites appearance do not rule out bacterial
peritonitis. J Emerg Med 2013;44:903–9.
7. Runyon BA. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis 2012.
8. Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia
and mortality among patients on the liver-transplant waiting
list. N Engl J Med 2008;359:1018–26.
9. Sheer TA, Joo E, Runyon BA. Usefulness of serum N-terminal-ProBNP in distinguishing ascites due to cirrhosis from ascites due to heart failure. J Clin Gastroenerol
10. Colli A, Fraquelli M, Casazza G, et al. Accuracy of ultrasonography, spiral CT, magnetic resonance, and alpha-fetoprotein in diagnosing hepatocellular carcinoma: a sys-
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