Portal-Systemic Encephalopathy Workup
- Author: Gagan K Sood, MD; Chief Editor: BS Anand, MD more...
Studies include the following:
- Serum calcium
- Serum ammonia, preferably arterial
- Elevated blood levels are not diagnostic of hepatic encephalopathy, and normal levels do not rule out hepatic encephalopathy. Very high levels may suggest an unsuspected urea cycle enzyme deficiency. They are helpful to suggest a diagnosis of hepatic encephalopathy when the cause is obscure.
- Serum glucose
- Serum albumin
- Serum aspartate aminotransferase: A very high aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) level (eg >1000) may suggest widespread hepatic necrosis as a consequence of acetaminophen toxicity and may help guide appropriate diagnostic evaluations and therapy accordingly (with acetaminophen levels and N -acetylcysteine). However, very high AST and ALT values may be observed in other settings (notably ischemic hepatitis and other causes of submassive or massive hepatic necrosis) and, therefore, are not specific.
- Serum alanine aminotransferase: ALT is more specific for liver origin because AST also may be released from muscle.
- Serum bilirubin
- Complete blood cell (CBC) count
- Blood and urine screen for drugs
- Blood alcohol level
- Serum electrolytes: levels may be disturbed for a variety of reasons in patients with advanced liver disease. Hyponatremia resulting from diuretic use, renal failure, water intoxication, or the syndrome of inappropriate secretion of antidiuretic hormone is particularly important to consider as a contributing cause of encephalopathy.
- Serum transaminases: This measurement is useful as an index of hepatocellular inflammation, although a poor correlation exists with respect to hepatocellular function. Very high transaminase values (eg, >500 U/L) suggest the possibility of acute hepatitis of indeterminate etiology, and, in the context of encephalopathy, consider the possibility of FHF.
- Prothrombin time, albumin, and bilirubin: Measurements are true liver function tests that provide an estimate of the severity of liver damage. They also allow the clinician to anticipate certain potential complications (eg, bleeding) and adjust therapy appropriately.
See the list below:
- Computed tomography scan of the head
- The rationale for CT scan is to exclude structural considerations in the differential diagnosis, including intracranial hemorrhage (epidural, subdural, subarachnoid, intraparenchymal), cerebral infarct, intracranial infections (brain abscess with mass effect, meningoencephalitis), and hydrocephalus.
- CT scan of the head may not be necessary in patients with well-documented liver disease and a typical history, especially if no focal or localizing signs are evident. However, if the circumstances leave any doubt, then CT scan is critical in helping exclude structural causes for encephalopathy.
- This test is more widely available than MRI and generally can be performed more rapidly. Therefore, it is the imaging modality of first choice in most instances.
- Patients may develop portosystemic encephalopathy and subsequently sustain head trauma. This is particularly common among patients with alcoholism, and the event may not be volunteered upon taking the history or may not be evident upon physical examination. However, in uncomplicated portosystemic encephalopathy, no characteristic clues or findings are present.
- Magnetic resonance imaging
- The availability and speed with which CT scans can be performed make them preferable in most instances for helping exclude mass lesions and, especially, intracranial hemorrhage. However, MRI findings may be of particular value in cases in which a diagnosis is not clear-cut based on other clinical and laboratory data.
- The presence of hyperintense-appearing regions on T1-weighted MRI studies of the brains of patients with cirrhosis is described as a characteristic feature. The increased MRI signal intensity may be the result of Mn deposition in these structures.
- The globus pallidus, putamen, and caudate nucleus of the basal ganglia and the frontal and occipital cortex of patients with cirrhosis who died with hepatic encephalopathy are demonstrated to contain increased Mn concentrations when compared to matched control specimens. Pallidal hyperintensity on T1-weighted MRI does not appear to be present in well-compensated patients with cirrhosis who do not have hepatic encephalopathy. This finding appears to correlate with blood ammonia levels but not the severity of hepatic encephalopathy itself.
- The amount of Mn deposition that can be identified at autopsy following hepatic coma appears to be independent of patient age, etiology of cirrhosis, or the presence of chronic hepatic encephalopathy. In an experimental model using both cirrhotic and portacaval-shunted rats, Mn levels in the basal ganglia were significantly elevated above control values. These levels also were significantly higher in portacaval-shunted rats when compared to those with experimental cirrhosis; therefore, while the precise etiology responsible for Mn deposition is unclear, it is enhanced by portal hypertension.
- Therefore, signs of extrapyramidal toxicity in hepatic encephalopathy conceivably may result from Mn deposition. The neurologic and radiologic changes may resolve gradually with time following liver transplantation. Deposition of Mn also may potentiate the effects of BZPs, natural or otherwise, by increasing the number of available peripheral-type BZP binding sites (possibly by promoting receptor expression).
- These intriguing issues unveiled by the advent of MRI are complemented by metabolic data derived from the application of MRS. This technique has demonstrated findings of altered glutamine metabolism. Its role in clinical evaluation and management of hepatic encephalopathy is unclear. In one series, MRS findings (ie, decreased myoinositol, increased glutamine) correlated poorly with neurological status. These markers were suggested to be more representative of the underlying chronic hepatic dysfunction.
- Positron emission tomography scanning has demonstrated reduced metabolic activity for glucose utilization in the parietal cortex of patients with cirrhosis with mild hepatic encephalopathy. At present, this technique is best reserved for research applications because no clear clinical guidelines are available for its use and its availability is limited.
See the list below:
- Psychometric testing
- Psychometric evaluations are of value for establishing the diagnosis and perhaps for monitoring response to therapy in subclinical portosystemic encephalopathy. The number-connection test and the Trail-Making Test are pragmatic approaches and are used widely at the bedside.
- More formal testing may not be feasible with many patients, in part due to the length of time taken to administer the tests, and also because of uncooperativeness. However, the results of psychometric testing in subclinical portosystemic encephalopathy may be of prognostic value independent of the Child-Pugh score of disease severity.
- Patients with alcohol-induced liver disease exhibit poorer test scores than those with liver disease from other causes, presumably due to cerebral toxicity intrinsic to chronic alcohol use and independent of the hepatic insufficiency.
- A grading scheme that incorporates the level of consciousness, personality and intellect, neurologic signs, and electroencephalogram (EEG) abnormalities is proposed for hepatic encephalopathy. The clinical portion of this grading approach has the advantage of being easily administered at the bedside, and it is helpful as a guide to progress.
- EEG studies of patients in portosystemic encephalopathy grades 1-3 may demonstrate high voltage and low-frequency triphasic waves of 1-3 Hz. These also may be seen in uremia but are characteristic of hepatic encephalopathy. With progression to coma, the EEG typically shows delta-wave activity, representing a generalized slowing of the cortex, a nonspecific pattern seen in toxic and metabolic encephalopathies.
- The EEG is most helpful in excluding the presence of other causes for encephalopathies, such as status epilepticus and akinetic seizures, or the demonstration of postictal slowing with or without focal spike and wave activity that suggests prior seizures.
- EEG monitoring frequently is useful in assisting with the diagnosis of hepatic encephalopathy, especially subclinical hepatic encephalopathy. Computer-assisted or spectral EEG analysis may demonstrate characteristic abnormalities, but the incremental benefit over conventional EEG is unclear.
- Evoked potentials
- Further electrophysiologic assessment may be performed with evoked-potential studies, but whether this approach is of value remains unclear, except when significant doubt exists with respect to the underlying diagnosis of portosystemic encephalopathy as the cause for neuropsychiatric dysfunction. This is rarely the case in practice. These studies include visual-evoked potentials, somatosensory-evoked potentials, or brainstem auditory–evoked potentials, and they represent the externally recorded voltage from synchronous firing of neurons in a network response to specific stimuli.
- The chief value of this approach may be to document abnormal cortical function in subclinical portosystemic encephalopathy and establish the diagnosis. Brainstem auditory–evoked responses appear particularly sensitive as a marker of perturbed cortical function. Evoked-potential studies in acute hepatic encephalopathy conceivably may be useful for monitoring clinical response to treatment; however, the use of these electrophysiologic diagnostic modalities currently is not widespread.
In neuropathological studies of hepatic encephalopathy, Alzheimer type II astrocytosis is typical and likely represents the end result of these mechanisms. Astrocytes demonstrate swollen nuclei, margination of the chromatin, and a prominent nucleolus.
Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010. 362(12):1071-1081.
Mullen KD, Poordad F, Rossaro L, et al. Long term efficacy and survival in patients treated with the gut-selective antibiotic rifaximin (550 mg BID) for the maintenance of remission from overt hepatic encephalopathy. Gastroenterol Hepatol. 2011. 7(6 Suppl 9):1-15.
McGee RG, Bakens A, Wiley K, Riordan SM, Webster AC. Probiotics for patients with hepatic encephalopathy. Cochrane Database Syst Rev. 2011. (11):CD008716. [Medline].
Agrawal A, Sharma BC, Sharma P, Sarin SK. Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis: An Open-Label, Randomized Controlled Trial of Lactulose, Probiotics, and No Therapy. Am J Gastroenterol. 2012 Jun 19. [Medline].
Pockros P, Hassanein T, Vierling J, et al. Phase 2, multicenter, randomized study of AST-120 (spherical carbon adsorbent) vs. lactulose in the treatment of lowgrade hepatic encephalopathy. J Hepatol. 2009. 50(Suppl 1):S43-4.
Simón-Talero M, García-Martínez R, Torrens M, et al. Effects of intravenous albumin in patients with cirrhosis and episodic hepatic encephalopathy: a randomized double-blind study. J Hepatol. 2013 Dec. 59(6):1184-92. [Medline].
Laleman W, Simon-Talero M, Maleux G, et al. Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy. Hepatology. 2013 Jun. 57(6):2448-57. [Medline].
Albrecht J, Hilgier W, Rafalowska U. Activation of arginine metabolism to glutamate in rat brain synaptosomes in thioacetamide-induced hepatic encephalopathy: an adaptative response?. J Neurosci Res. 1990 Jan. 25(1):125-30. [Medline].
Amaral OB, Quevedo J, Walz R, et al. Flumazenil and hepatic encephalopathy. Hepatology. 1999 Apr. 29(4):1338-9. [Medline].
Amodio P, Del Piccolo F, Marchetti P, et al. Clinical features and survivial of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests. Hepatology. 1999 Jun. 29(6):1662-7. [Medline].
Avallone R, Zeneroli ML, Venturini I, et al. Endogenous benzodiazepine-like compounds and diazepam binding inhibitor in serum of patients with liver cirrhosis with and without overt encephalopathy. Gut. 1998 Jun. 42(6):861-7. [Medline].
Bansky G, Meier PJ, Riederer E, et al. Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans. Gastroenterology. 1989 Sep. 97(3):744-50. [Medline].
Barbaro G, Di Lorenzo G, Soldini M, et al. Flumazenil for hepatic coma in patients with liver cirrhosis: an Italian multicentre double-blind, placebo-controlled, crossover study. Eur J Emerg Med. 1998 Jun. 5(2):213-8. [Medline].
Basile AS, Jones EA. Ammonia and GABA-ergic neurotransmission: interrelated factors in the pathogenesis of hepatic encephalopathy. Hepatology. 1997 Jun. 25(6):1303-5. [Medline].
Bianchi GP, Marchesini G, Fabbri A, et al. Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison. J Intern Med. 1993 May. 233(5):385-92. [Medline].
Bickford RG, Butt HR. Hepatic coma: the electroencephalographic pattern. J Clin Invest. 1955. 34:790-9.
Bircher J, Buhrer M, Franz K, et al. [1st use of lactitol in the treatment of porto-systemic encephalopathy]. Schweiz Med Wochenschr. 1982 Sep 18. 112(38):1306-7. [Medline].
Bresci G, Parisi G, Banti S. Management of hepatic encephalopathy with oral zinc supplementation: a long-term treatment. Eur J Med. 1993 Aug-Sep. 2(7):414-6. [Medline].
Butterworth RF. Pathogenesis of acute hepatic encephalopathy. Digestion. 1998 Jul. 59 Suppl 2:16-21. [Medline].
Chan H, Hazell AS, Desjardins P. Neurotoxins generated in liver failure cause altered expression of genes coding for key astrocytic proteins. Hepatology. 1999. 30(4):234A.
Charlton MR. Branched chains revisited. Gastroenterology. 1996 Jul. 111(1):252-5. [Medline].
Child CG. Ligature of the portal vein (translation of original by Eck, 1877). Surg Gynecol Obstet. 1953. 375-6.
Conn HO. Trailmaking and number-connection tests in the assessment of mental state in portal systemic encephalopathy. Am J Dig Dis. 1977 Jun. 22(6):541-50. [Medline].
Conn HO, Leevy CM, Vlahcevic ZR, et al. Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology. 1977 Apr. 72(4 Pt 1):573-83. [Medline].
Costa E, Guidotti A. Diazepam binding inhibitor (DBI): a peptide with multiple biological actions. Life Sci. 1991. 49(5):325-44. [Medline].
Córdoba J, Mínguez B. Hepatic encephalopathy. Semin Liver Dis. 2008 Feb. 28(1):70-80. [Medline].
Dasani BM, Sigal SH, Lieber CS. Analysis of risk factors for chronic hepatic encephalopathy: the role of Helicobacter pylori infection. Am J Gastroenterol. 1998 May. 93(5):726-31. [Medline].
de Bruijn KM, Blendis LM, Zilm DH, et al. Effect of dietary protein manipulation in subclinical portal-systemic encephalopathy. Gut. 1983 Jan. 24(1):53-60. [Medline].
Deschenes M, Dufresne MP, Bui B, et al. Predictors of clinical response to transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with refractory ascites. Am J Gastroenterol. 1999 May. 94(5):1361-5. [Medline].
Eck NV. Ligature of the portal vein. Voen Med J St-Petersburg (Russo). 1877. 130:1-2.
Elkington SG, Floch MH, Conn HO. Lactulose in the treatment of chronic portal-systemic encephalopathy. A double-blind clinical trial. N Engl J Med. 1969 Aug 21. 281(8):408-12. [Medline].
Fabbri A, Magrini N, Bianchi G, et al. Overview of randomized clinical trials of oral branched-chain amino acid treatment in chronic hepatic encephalopathy. JPEN J Parenter Enteral Nutr. 1996 Mar-Apr. 20(2):159-64. [Medline].
Felipo V, Hermenegildo C, Montoliu C, et al. Neurotoxicity of ammonia and glutamate: molecular mechanisms and prevention. Neurotoxicology. 1998 Aug-Oct. 19(4-5):675-81. [Medline].
Ferenci P. Hepatic Encephalopathy. McIntyre N, Benhamou JP, Bircher J, Rizzetto M, Rodes J, eds. Textbook of Clinical Hepatology. Oxford, England: Oxford University Press; 1991. Vol 1: 473-83.
Fischer JE, Baldessarini RJ. False neurotransmitters and hepatic failure. Lancet. 1971 Jul 10. 2(7715):75-80. [Medline].
Flannery DB, Hsia YE, Wolf B. Current status of hyperammonemic syndromes. Hepatology. 1982 Jul-Aug. 2(4):495-506. [Medline].
Genesca J, Gonzalez A, Segura R, et al. Interleukin-6, nitric oxide, and the clinical and hemodynamic alterations of patients with liver cirrhosis. Am J Gastroenterol. 1999 Jan. 94(1):169-77. [Medline].
Germain L, Frexinos J, Louis A, et al. [Double blind study of lactulose in 8 patients with chronic hepatic encephalopathy after portocaval shunt]. Arch Fr Mal App Dig. 1973 Jun. 62(4):293-302. [Medline].
Girard G, Butterworth RF. Effect of portacaval anastomosis on glutamine synthetase activities in liver, brain, and skeletal muscle. Dig Dis Sci. 1992 Jul. 37(7):1121-6. [Medline].
Gitlin N. Hepatic encephalopathy. Zakim D, Boyer T, eds. Hepatology: a textbook of liver disease. 3rd ed. Philadelphia, Pa: WB Saunders; 1996. Vol 1: 605-17.
Groeneweg M, Gyr K, Amrein R, et al. Effect of flumazenil on the electroencephalogram of patients with portosystemic encephalopathy. Results of a double blind, randomised, placebo-controlled multicentre trial. Electroencephalogr Clin Neurophysiol. 1996 Jan. 98(1):29-34. [Medline].
Guarner C, Soriano G, Tomas A, et al. Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. Hepatology. 1993 Nov. 18(5):1139-43. [Medline].
Hassanein TI, Tofteng F, Brown RS Jr, et al. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology. 2007 Dec. 46(6):1853-62. [Medline].
Haussinger D, Laubenberger J, vom Dahl S, et al. Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy. Gastroenterology. 1994 Nov. 107(5):1475-80. [Medline].
Hazell AS, Desjardins P, Butterworth RF. Chronic exposure of rat primary astrocyte cultures to manganese results in increased binding sites for the 'peripheral-type' benzodiazepine receptor ligand 3H-PK 11195. Neurosci Lett. 1999 Aug 13. 271(1):5-8. [Medline].
Howard ER. Encephalopathy without cirrhosis: hunt the shunt. Gut. 1999 Sep. 45(3):329-30. [Medline].
Häussinger D. Hepatic glutamine transport and metabolism. Adv Enzymol Relat Areas Mol Biol. 1998. 72:43-86. [Medline].
Häussinger D. Low grade cerebral edema and the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology. 2006 Jun. 43(6):1187-90. [Medline].
Ito S, Miyaji H, Azuma T, et al. Hyperammonaemia and Helicobacter pylori. Lancet. 1995 Jul 8. 346(8967):124-5. [Medline].
Jalan R, Olde Damink SW, Hayes PC, et al. Diagnosis of hepatic encephalopathy: will in vivo proton MRS play a role?. Hepatology. 1999 May. 29(5):1605-7. [Medline].
Jenkins RL, Gedaly R, Pomposelli JJ, et al. Distal splenorenal shunt: role, indications, and utility in the era of liver transplantation. Arch Surg. 1999 Apr. 134(4):416-20. [Medline].
Kale RA, Gupta RK, Saraswat VA, et al. Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy. Hepatology. 2006 Apr. 43(4):698-706. [Medline].
Keeling PW, Jones RB, Hilton PJ, et al. Reduced leucocyte zinc in liver disease. Gut. 1980 Jul. 21(7):561-4. [Medline].
Kircheis G, Nilius R, Held C, et al. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double-blind study. Hepatology. 1997 Jun. 25(6):1351-60. [Medline].
Kircheis G, Quack G, Erbler H. L-ornithine L-aspartate in the treatment of hyperammonemia and hepatic encephalopathy. Conn HO, Bircher J, eds. Hepatic encephalopathy: syndromes and therapies. Bloomington, Ill: Medi-Ed; 1994. 373-83.
Kullmann F, Hollerbach S, Holstege A, et al. Subclinical hepatic encephalopathy: the diagnostic value of evoked potentials. J Hepatol. 1995 Jan. 22(1):101-10. [Medline].
Köstler H. Proton magnetic resonance spectroscopy in portal-systemic encephalopathy. Metab Brain Dis. 1998 Dec. 13(4):291-301. [Medline].
Larsen FS, Ejlersen E, Clemmesen JO. Preservation of cerebral oxidative metabolism in fulminant hepatic failure: an autoregulation study. Liver Transpl Surg. 1996 Sep. 2(5):348-53. [Medline].
Larsen FS, Olsen KS, Ejlersen E, et al. Cerebral blood flow autoregulation and transcranial Doppler sonography in patients with cirrhosis. Hepatology. 1995 Sep. 22(3):730-6. [Medline].
Lata J, Hulek P, Fejfar T, et al. [Rifaximin in the treatment of hepatic encephalopathy]. Vnitr Lek. 2002 Jun. 48(6):578-82. [Medline].
Laubenberger J, Haussinger D, Bayer S, et al. Proton magnetic resonance spectroscopy of the brain in symptomatic and asymptomatic patients with liver cirrhosis. Gastroenterology. 1997 May. 112(5):1610-6. [Medline].
Layrargues GP, Rose C, Spahr L, et al. Role of manganese in the pathogenesis of portal-systemic encephalopathy. Metab Brain Dis. 1998 Dec. 13(4):311-7. [Medline].
Lee FY, Lu RH, Tsai YT, et al. Plasma interleukin-6 levels in patients with cirrhosis. Relationship to endotoxemia, tumor necrosis factor-alpha, and hyperdynamic circulation. Scand J Gastroenterol. 1996 May. 31(5):500-5. [Medline].
Lee JH, Seo DW, Lee YS, et al. Proton magnetic resonance spectroscopy (1H-MRS) findings for the brain in patients with liver cirrhosis reflect the hepatic functional reserve. Am J Gastroenterol. 1999 Aug. 94(8):2206-13. [Medline].
Lockwood AH. Early detection and treatment of hepatic encephalopathy. Curr Opin Neurol. 1998 Dec. 11(6):663-6. [Medline].
Lockwood AH, Yap EW, Rhoades HM, et al. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy. J Cereb Blood Flow Metab. 1991 Mar. 11(2):331-6. [Medline].
Lockwood AH, Yap EW, Wong WH. Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy. J Cereb Blood Flow Metab. 1991 Mar. 11(2):337-41. [Medline].
Loguercio C, Abbiati R, Rinaldi M, et al. Long-term effects of Enterococcus faecium SF68 versus lactulose in the treatment of patients with cirrhosis and grade 1-2 hepatic encephalopathy. J Hepatol. 1995 Jul. 23(1):39-46. [Medline].
Manzoni O, Prezeau L, Marin P, et al. Nitric oxide-induced blockade of NMDA receptors. Neuron. 1992 Apr. 8(4):653-62. [Medline].
Mas A, Rodes J, Sunyer L, et al. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. 2003 Jan. 38(1):51-8. [Medline].
Mehndiratta MM, Sood GK, Sarin SK, et al. Comparative evaluation of visual, somatosensory, and auditory evoked potentials in the detection of subclinical hepatic encephalopathy in patients with nonalcoholic cirrhosis. Am J Gastroenterol. 1990 Jul. 85(7):799-803. [Medline].
Mendenhall CL, Rouster S, Marshall L, et al. A new therapy for portal systemic encephalopathy. Am J Gastroenterol. 1986 Jul. 81(7):540-3. [Medline].
Michalopoulos GK, DeFrances MC. Liver regeneration. Science. 1997 Apr 4. 276(5309):60-6. [Medline].
Montague PR, Gancayco CD, Winn MJ, et al. Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex. Science. 1994 Feb 18. 263(5149):973-7. [Medline].
Moore JW, Dunk AA, Crawford JR, et al. Neuropsychological deficits and morphological MRI brain scan abnormalities in apparently healthy non-encephalopathic patients with cirrhosis. A controlled study. J Hepatol. 1989 Nov. 9(3):319-25. [Medline].
Moorman AF, Vermeulen JL, Charles R, et al. Localization of ammonia-metabolizing enzymes in human liver: ontogenesis of heterogeneity. Hepatology. 1989 Mar. 9(3):367-72. [Medline].
Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut. 1982 Jan. 23(1):1-7. [Medline].
Morgan MY. Cerebral magnetic resonance imaging in patients with chronic liver disease. Metab Brain Dis. 1998 Dec. 13(4):273-90. [Medline].
Morgan MY, Jakobovits AW, James IM, et al. Successful use of bromocriptine in the treatment of chronic hepatic encephalopathy. Gastroenterology. 1980 Apr. 78(4):663-70. [Medline].
Mullen KD, Szauter KM, Kaminsky-Russ K. "Endogenous" benzodiazepine activity in body fluids of patients with hepatic encephalopathy. Lancet. 1990 Jul 14. 336(8707):81-3. [Medline].
Ong J, Kerr DI. Clinical potential of GABAB receptor modulators. CNS Drug Rev. 2005 Autumn. 11(3):317-34. [Medline].
Perney P, Butterworth RF, Mousseau DD, et al. Plasma and CSF benzodiazepine receptor ligand concentrations in cirrhotic patients with hepatic encephalopathy: relationship to severity of encephalopathy and to pharmaceutical benzodiazepine intake. Metab Brain Dis. 1998 Sep. 13(3):201-10. [Medline].
Pogun S, Dawson V, Kuhar MJ. Nitric oxide inhibits 3H-glutamate transport in synaptosomes. Synapse. 1994 Sep. 18(1):21-6. [Medline].
Pomier-Layrargues G. TIPS and hepatic encephalopathy. Semin Liver Dis. 1996 Aug. 16(3):315-20. [Medline].
Pomier-Layrargues G, Giguere JF, Lavoie J, et al. Flumazenil in cirrhotic patients in hepatic coma: a randomized double-blind placebo-controlled crossover trial. Hepatology. 1994 Jan. 19(1):32-7. [Medline].
Quero JC, Hartmann IJ, Meulstee J, et al. The diagnosis of subclinical hepatic encephalopathy in patients with cirrhosis using neuropsychological tests and automated electroencephalogram analysis. Hepatology. 1996 Sep. 24(3):556-60. [Medline].
Rao VL, Butterworth RF. Neuronal nitric oxide synthase and Hepatic Encephalopathy. Metab Brain Dis. 1998 Sep. 13(3):175-89. [Medline].
Read AE, McCarthy CF, Heaton KW, et al. Lactobacillus acidophilus (enpac) in treatment of hepatic encephalopathy. Br Med J. 1966 May 21. 1(5498):1267-9. [Medline].
Riggio O, Efrati C, Catalano C, et al. High prevalence of spontaneous portal-systemic shunts in persistent hepatic encephalopathy: a case-control study. Hepatology. 2005 Nov. 42(5):1158-65. [Medline].
Riggio O, Masini A, Efrati C, et al. Pharmacological prophylaxis of hepatic encephalopathy after transjugular intrahepatic portosystemic shunt: a randomized controlled study. J Hepatol. 2005 May. 42(5):674-9. [Medline].
Riggio O, Merlli M, Pedretti G, et al. Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Incidence and risk factors. Dig Dis Sci. 1996 Mar. 41(3):578-84. [Medline].
Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med. 1997 Aug 14. 337(7):473-9. [Medline].
Rose C, Butterworth RF, Zayed J, et al. Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction. Gastroenterology. 1999 Sep. 117(3):640-4. [Medline].
Rose C, Michalak A, Pannunzio P, et al. L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action. Metab Brain Dis. 1998 Jun. 13(2):147-57. [Medline].
Sandford SL, Tarter RE, Sclabassi R, et al. Sensory information processing in patients with nonalcoholic cirrhosis. Short-latency visual, auditory, and somatosensory event-related potentials. J Neurol Sci. 1987 Sep. 80(2-3):269-76. [Medline].
Sanyal AJ, Freedman AM, Shiffman ML, et al. Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt: results of a prospective controlled study. Hepatology. 1994 Jul. 20(1 Pt 1):46-55. [Medline].
Schumacher IK, Okamoto T, Kim BH, et al. Transplantation of conditionally immortalized hepatocytes to treat hepatic encephalopathy. Hepatology. 1996 Aug. 24(2):337-43. [Medline].
Stauch S, Kircheis G, Adler G, et al. Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study. J Hepatol. 1998 May. 28(5):856-64. [Medline].
Strauss E, Tramote R, Silva EP, et al. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology. 1992 Dec. 39(6):542-5. [Medline].
Sushma S, Dasarathy S, Tandon RK, et al. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. 1992 Jul. 16(1):138-44. [Medline].
Taylor-Robinson SD, Oatridge A, Hajnal JV, et al. MR imaging of the basal ganglia in chronic liver disease: correlation of T1-weighted and magnetisation transfer contrast measurements with liver dysfunction and neuropsychiatric status. Metab Brain Dis. 1995 Jun. 10(2):175-88. [Medline].
Unseld E, Krishna DR, Fischer C, et al. Detection of desmethyldiazepam and diazepam in brain of different species and plants. Biochem Pharmacol. 1989 Aug 1. 38(15):2473-8. [Medline].
Uribe M, García-Ramos G, Ramos M, et al. Standard and higher doses of bromocriptine for severe chronic portal-systemic encephalopathy. Am J Gastroenterol. 1983 Aug. 78(8):517-22. [Medline].
Van der Rijt CC, Schalm SW, De Groot GH, et al. Objective measurement of hepatic encephalopathy by means of automated EEG analysis. Electroencephalogr Clin Neurophysiol. 1984 May. 57(5):423-6. [Medline].
Weissenborn K, Kolbe H. The basal ganglia and portal-systemic encephalopathy. Metab Brain Dis. 1998 Dec. 13(4):261-72. [Medline].
Weissenborn K, Scholz M, Hinrichs H, et al. Neurophysiological assessment of early hepatic encephalopathy. Electroencephalogr Clin Neurophysiol. 1990 Apr. 75(4):289-95. [Medline].
Yen CL, Liaw YF. Somatosensory evoked potentials and number connection test in the detection of subclinical hepatic encephalopathy. Hepatogastroenterology. 1990 Jun. 37(3):332-4. [Medline].
Yurdaydin C, Karavelioglu D, Onaran O, et al. Opioid receptor ligands in human hepatic encephalopathy. J Hepatol. 1998 Nov. 29(5):796-801. [Medline].
Zullo A, Rinaldi V, Meddi P, et al. Helicobacter pylori infection, plasma ammonia levels, and psychometric testing in cirrhotic patients. Am J Gastroenterol. 1999 Aug. 94(8):2214-8. [Medline].