Hepatic encephalopathy treatment

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. 

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]. 

Testa R, Eftimiadi C, Sukkar GS, De Leo C, Rovida S, Schito GC, Celle G A non-absorb-able rifamycin for treatment of hepatic encephalopathy. Drugs Exp Clin Res 1985 11 387-392. 

Williams R, James OF, Warnes TW, Morgan MY Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy A double-blind, randomized, dosefinding multi-centre study. Eur J Gastroenterol Hepatol 2000 12 203-208. 

Rifaximin is available in Europe for the treatment of acute intestinal bacterial infections, hepatic encephalopathy, bacterial overgrowth syndrome, diverticular disease of the colon, and for the prevention of infections after colorectal surgery [3, 4]. Rifaximin is also licensed in Mexico, Asia and Northern Africa and has recently been approved in USA for the treatment of traveler s diarrhea. 

Rifaximin has been shown to possess good antibacterial activity against a variety of anaerobic bacteria (table 3) [24, 27, 28], Anaerobes have been shown to be capable of producing ammonia (especially Clostridia), which has been incriminated in the pathogenesis of hepatic encephalopathy [29], The authors suggested that since rifaximin is a nonabsorbable and effective antibiotic against anaerobic flora, it would be an ideal treatment for patients with compromised hepatic function. Eubacterium is inhibited by rifaximin with an MIC90 < 2 pg/ml [27]. 

Eftimiadi C, Deleo C, Schito GC Treatment of hepatic encephalopathy with U105, a new nonabsorbable rifamycin. Drugs Exp Clin Res 1984 10 691-696. 

As outlined in the excellent review by Gilles and Brogden [9], the current indications for rifaximin include surgical prophylaxis and the treatment of hepatic encephalopathy, infectious diarrhea and intestinal bacterial overgrowth syndromes. As such, rifaximin is aimed only at enteric flora. Owing to its lack of absorption, rifaximin will likely not be used for other conditions or indications. Such limited indications should help preserve the activity of the agent, since overuse for common conditions like urinary or respiratory tract infections will naturally not occur. Limited use should help retard the development of resistance among enteric flora. 

Butterworth RF, Lavoie J, Peterson C, Cotman CW, Szerb J Excitatory amino acids and hepatic encephalopathy in Pomier Larargue G, Butterworth RF (eds) Hepatic Encephalopathy Pathophysiology and Treatment. Clifton, Humana Press, 1989, pp 417-433. 

Lanthier PL, Morgan MY Lactitol in the treatment of chronic hepatic encephalopathy An open comparison with lactulose. Gut 1985 26 415-420. 

Morgan MH, Read AE, Speller DCE Treatment of hepatic encephalopathy with metronidazole. Gut 1982 23 1-7. 

Tarao K, Ikeda T, Hayashi K, Sakurai I A Successful use of vancomycin hydrochloride in the treatment of lactulose-resistant chronic hepatic encephalopathy. J Gastroenterol Hepatol 1989 4 284-286. 

Festi D, Mazzella G, Parini P, Ronchi M, Cipolla A, Orsini M, Sangermano A, Bazzoli F, Aldini R, Roda E Treatment of hepatic encephalopathy with non-absorbable antibiotics. Ital J Gastroenterol 1992 24 14-16. 

Massa MD, Vallerino MD, Dodero MD Treatment of hepatic encephalopathy with rifaximin Double blind, double dummy study versus lactulose. Eur J Clin Res 1993 4 7-18. 

FeraG, AgostinacchioF,NigroM, SchiraldiO, Ferrieri A Rifaximin in the treatment of hepatic encephalopathy. Eur J Clin Res 1993 4 57-66. 

Bucci L, Palmieri GC Double-blind, doubledummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy. Curr Med Res Opin 1993 13 109—118. 

Miglio F, Valpiani D, Rossellini SR, Ferrieri A Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial. Curr Med Res Opin 1997 13 593-601. 

Loguercio C, Federico A, De Girolamo V, Ferrieri A, Del Vecchio Blanco C Cyclic treatment of chronic hepatic encephalopathy with rifaximin. Minerva Gastroenterol Dietol 2003 49 53-62... 

Mas A, Rodes J, Sunyer L, Rodrigo L, Planas R, Vargas V, Castells L, Rodriguez-Martinez D, Fernandez-Rodriguez C, Coll I, Pardo A Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy Results of a randomized, double-blind, doubledummy, controlled clinical trial. J Hepatol 2003 38 51-58. 

Rifaximin, a nonabsorbable derivative of rifamycin, has shown promising bactericidal action against both aerobes and anaerobes, such as bacterioides, lactobacilli and clostridia [33, 34], The development of resistance to this antibiotic can occur, but resistant strains rapidly disappear from the intestine thus allowing cyclic administration of rifaximin. Controlled clinical trials showed efficacy of rifaximin in adult and pediatric patients with infectious diarrhea [36,37], hepatic encephalopathy [38], post-surgical complications [39] and colonic diverticulosis [40], Only recently was the efficacy of rifaximin in the treatment of SIBO demonstrated [41-43]. 

Treatment Goals Acute and Chronic Hepatic Encephalopathy... 

Osmotic laxatives (e.g., lactulose, sorbitol) are poorly absorbed or nonabsorbable compounds that draw additional fluid into the GI tract. Lumen osmolality increases, and fluid movement occurs secondary to osmotic pressure. Lactulose is a synthetic disaccharide that is poorly absorbed from the GI tract, since no mammalian enzyme is capable of hydrolyzing it to its monosaccharide components. It therefore reaches the colon unchanged and is metabolized by colonic bacteria to lactic acid and to small quantities of formic and acetic acids. Since lactulose does contain galactose, it is contraindicated in patients who require a galactose-free diet. Metabolism of lactulose by intestinal bacteria may result in increased formation of intraluminal gas and abdominal distention. Lactulose is also used in the treatment of hepatic encephalopathy. 

This is a semisynthetic disaccharide which is not absorbed from the GI tract. It produces an osmotic diarrhoea of low pH, and discourages the proliferation of ammonia-producing bacteria. It is therefore useful in the treatment of hepatic encephalopathy. Osmotic laxatives like lactulose, sorbitol, and lactilol rarely cause significant adverse effects. Glycerol suppositories are useful in softening and lubricating passage of inspissated faeces. 

Lactitol 40 is a disaccharide that has been used in the management of hepatic encephalopathy, a major neuropsychiatric complication of both acute and chronic liver failure. It has mild laxative properties and is used to reduce the production and absorption of gut-derived neurotoxic substances symptomatic of hepatic encephalopathy. Although long considered a first-line pharmacological treatment, there is a lack of sufficient evidence to support lactitol s efficacy and continued use when weighed against other suitable therapeutic alternatives such as oral antibiotics <2006MI94>. 

List two treatment options for the management of Mrs MW s hepatic encephalopathy. Describe the mechanism of action for one of these. 

Treatment goals for hepatic encephalopathy include provision of supportive care, identification and removal of precipitating factors, reduction in the nitrogenous load from the gut and optimisation of long-term therapy. 

Treatment of hepatic encephalopathy (portal systemic encephalopathy) hepatic coma. 

Case study level 1 - Alcoholic cirrhosis alcohol withdrawal 338 Case study level 2 - Alcoholic cirrhosis management of bleeding risk and treatment for the maintenance of alcohol abstinence 339 Case study level 3 - Hepatic encephalopathy and ascites 341 Case study level Ma - Pulmonary tuberculosis 342 Case study level Mb - Liver failure 344... 

Treatment and prophylaxis of hepatic encephalopathy Start with 30-45 ml (20 gm/30 ml) p.o. 3-4 times daily, then adjusted to achieve 2-3 soft formed stools/day or 300 ml (200 g) mixed with 700 ml of water or saline rectally as a retention enema (retain for 30-60 min) every 4-6 h. as needed... 

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