Encephalopathy hepatic

Behar KL, Rothman DL, Petersen KF, et al Preliminary evidence of low cortical GABA levels in localized 1FF-MR spectra of alcohol-dependent and hepatic encephalopathy patients. Am J Psychiatry 136 952-954, 1999... 

Corticosteroid therapy for patients with alcoholic hepatitis (steatonecrosis) with or without hepatic encephalopathy... 

Add protein back in 20 g increments every 3-5 d once acute hepatic encephalopathy improves and until protein caloric goal is achieved (usually 0.8-1 g/kg/d)... 

O Portal hypertension is the precipitating factor for the complications of cirrhotic liver disease—ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, and hepatic encephalopathy. Lowering portal pressure can reduce the complications of cirrhosis and decrease morbidity and mortality. 

Lactulose is the foundation of pharmacologic therapy to prevent and treat hepatic encephalopathy because its unique mechanism binds ammonia in the gut and facilitates its excretion. 

Cirrhosis is the progressive replacement of normal hepatic cells by fibrous scar tissue. This scarring is accompanied by the loss of viable hepatocytes, which are the functional cells of the liver. Progressive cirrhosis is irreversible and leads to portal hypertension that is in turn responsible for many of the complications of advanced liver disease. These consequences include (but are not limited to) spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, and variceal bleeding.1... 

Markers of hepatic encephalopathy include decreased cognition, confusion, changes in behavior, and asterixis. 

Increased blood ammonia concentration is characteristic of hepatic encephalopathy, but levels do not correlate well with the degree of impairment. 

In acute hepatic encephalopathy, temporary protein restriction to decrease the rate of ammonia production can... 

Drug therapy for portal hypertension and cirrhosis can alleviate symptoms and prevent complications but it cannot reverse cirrhosis. Drug therapy is available to treat the complications of ascites, varices, spontaneous bacterial peritonitis, hepatic encephalopathy, and coagulation abnormalities. 

Lactulose is the foundation of pharmacologic therapy to prevent and treat hepatic encephalopathy. It is a non-digestible synthetic disaccharide laxative that is hydrolyzed in the gut to an osmotically-active compound that draws water into the colon and stimulates defecation. Lactulose also lowers colonic pH, which favors the conversion of ammonia (NH3) to ammonium (NHf).48 Ammonium is ionic and cannot cross back into systemic circulation it is eliminated in the feces. Lactulose is usually initiated at 15 to 30 mL two to three times per day and titrated to a therapeutic goal of two to four soft bowel movements daily.20 49 50... 

What are the presenting signs and symptoms of hepatic encephalopathy ... 

What factors could contribute to hepatic encephalopathy in this patient ... 

What is the prognosis for this patient who has developed ascites, variceal bleeding, and hepatic encephalopathy within 3 months ... 

Evaluate for signs and symptoms of hepatic encephalopathy. Mental status changes may be subtle questioning family members or caregivers about confusion or personality changes may reveal mild hepatic encephalopathy even if the patient is unaware of the deficits. 

Blei AT, Cordoba J, and the Practice Parameters Committee of the American College of Gastroenterology. Hepatic encephalopathy practice guidelines. Am J Gastroenterol 2001 96 1968-1976. Gines P, Cardena A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med 2004 350 1646-1654. 

Chronic hepatitis (disease lasting longer than 6 months) is usually associated with hepatitis B, C, and D. Chronic viral hepatitis may lead to the development of cirrhosis, which may induce end-stage liver disease (ESLD). Complications of ESLD include ascites, edema, jaundice, hepatic encephalopathy, infections, and bleeding esophageal varices. Therefore, prevention and treatment of viral hepatitis may prevent ESLD. 

In fulminant hepatitis with hepatic encephalopathy, patients may have asterixis and coma. 

Alzheimer s disease Cerebral infarction Cerebral tumors Closed head injury Cushing s syndrome Hemodialysis Hepatic encephalopathy Huntington s disease Hyperthyroidism Ictal or post-ictal mania Multiple sclerosis Neurosyphilis... 

Crystalline amino acid bulk solutions are supplied by various manufacturers in various concentrations (e.g., 3.5%, 5%, 7%, 8.5%, 10%, 15%, and 20%). Different formulations are tailored for specific age groups (e.g., adults and infants) and disease states (e.g., renal and liver disease). Specialized formulations for patients with renal failure contain higher proportions of essential amino acids. Formulas for patients with hepatic encephalopathy contain higher amounts of branched-chain and lower amounts of aromatic amino acids. However, these specialized formulations should not be used routinely in clinical practice because their efficacy has not been clearly demonstrated. Crystalline amino acid solutions have an acidic pH (pH = 5-7) and may contain inherent electrolytes (e.g., sodium, potassium, acetate, and phosphate). 

End-stage liver disease Liver failure that is usually accompanied by complications such as ascites or hepatic encephalopathy. 

Hepatic encephalopathy Change in mental or neurologic status secondary to progressive liver disease or confusion and disorientation that a patient with advanced liver disease experiences due to accumulation of ammonia. 

A. M. Herneth, A. Puspok, R. Steindl, and G. Yurdaydin in Advances in Hepatic Encephalopathy and Metabolic Nitrogen Exchange , L. Capocaccia, M. Merli, and O. Riggo, Eds. GRG Press, Boca Raton, 1995, p. 254. 

Liu Q, Duan ZP, Ha DK, Bengmark S, Kurto-vic J, Riordan SM Symbiotic modulation of gut flora Effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatololy 2004 39 1441-1449. 

Rifaximin Rifamycin Antibiotic Gut bacteria Enteric infection Diarrhea, infectious Hepatic encephalopathy Small intestine bacterial overgrowth Inflammatory bowel disease Colonic diverticular disease Irritable bowel syndrome Constipation Clostridium difficile infection Helicobacter pylori infection Colorectal surgery Bowel decontamination, selective Pancreatitis, acute Bacterial peritonitis, spontaneous Nonsteroidal anti-inflammatory drug enteropathy... 

A large number of human studies [71, 77-80] performed in patients with infectious diarrhea or other GI diseases (e.g. hepatic encephalopathy, small bowel bacterial overgrowth, IBD, colonic diverticular disease) have confirmed the antibacterial activity of rifaximin demonstrated in vitro and in laboratory animals. 

On the basis of log bacterial survival rates, the antibacterial activity of rifaximin was greater than that of paromomycin against Enterococcus spp., anaerobic cocci, Bac-terioides spp. and Clostridium spp. isolated in fecal samples from 20 patients with subclinical hepatic encephalopathy (fig. 4) [81]. On the other hand, E. coli dead Klebsiella spp. appeared more susceptible to paromomycin while both antibiotics showed equal potency against Proteus spp. [81]. Here again it should be pointed out that stool concentrations of rifaximin are 250-500 times higher than the MIC90 values [71], which makes the in vitro differences of activity between this and other antimicrobials meaningless from a clinical standpoint. 

Antimicrobial resistance to rifamycins develops rapidly both in vitro and in vivo [65,85,86], As a consequence, all the three members of the family (i.e. rifampicin, rifabutin and rifapentine) are used clinically as components of combination therapies [65,87], Being structurally related, rifaximin could share this potential. And indeed resistance rates, recorded in fecal strains of Enterobacteriaceae, Enterococcus, Bacteroides, Clostridium and anaerobic cocci, ranged between 30 and 90% after short-term (5 days) antibiotic (800 mg daily) treatment [82], A similar pattern was observed in 10 patients with hepatic encephalopathy after treatment with rifaximin 1,200 mg/day for 5 days [80]. 

Nevertheless, a rapid disappearance of resistant bacteria was observed after stopping the antibiotic treatment (fig. 5). Different kinetics of disappearance were, however, observed. The aerobic species showed a more rapid return to the baseline sensitive status whereas the anaerobic bacteria, especially the Gram-negative rods, regained sensitivity to rifaximin more slowly. In any case, 3 months after the end of treatment resistant strains were no longer detectable in the feces [82], These results support the cyclic use of rifaximin that has been adopted by the investigators in the treatment of hepatic encephalopathy [77] and colonic diverticular disease [79]. 

Fig. 4. Changes in anaerobic flora population following oral administration of rifax-imin or paromomycin in patients with hepatic encephalopathy (from Testa et al. [81]). 

Although the pharmacokinetics of rifaximin in patients with renal insufficiency has not been specifically studied, its very low renal excretion makes any dose adjustment unnecessary. The same holds true for patients with hepatic insufficiency. In fact, the mean peak drug plasma concentrations (i.e. 13.5 ng/ml) detected in subjects with hepatic encephalopathy patients given rifaximin 800 mg 3 times daily for 7 days [34, 108] were not dissimilar to those found in healthy subjects [102] and patients with IBD [98], Indeed, in all the trials performed in this condition the drug has been well tolerated [33, 77],... 

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