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Antibiotics for the treatment of hepatic encephalopathy

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Abstract

The treatment of hepatic encephalopathy (HE) is complex and therapeutic regimens vary according to the acuity of presentation and the goals of therapy. Most treatments for HE rely on manipulating the intestinal milieu and therefore antibiotics that act on the gut form a key treatment strategy. Prominent antibiotics studied in HE are neomycin, metronidazole, vancomycin and rifaximin. For the management of the acute episode, all antibiotics have been tested. However the limited numbers studied, adverse effects (neomycin oto- and nephrotoxicity, metronidazole neurotoxicity) and potential for resistance emergence (vancomycin-resistant enterococcus) has limited the use of most antibiotics, apart from rifaximin which has the greatest evidence base. Rifaximin has also demonstrated, in conjunction with lactulose, to prevent overt HE recurrence in a multi-center, randomized trial. Despite its cost in the US, rifaximin may prove cost-saving by preventing hospitalizations for overt HE. In minimal/covert HE, rifaximin is the only systematically studied antibiotic. Rifaximin showed improvement in cognition, inflammation, quality-of-life and driving simulator performance but cost-analysis does not favor its use at the current time. Antibiotics, especially rifaximin, have a definite role in the management across the spectrum of HE.

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References

  • Alcorn J (2008) Review: rifaximin is equally or more effective than other antibiotics and lactulose for hepatic encephalopathy. ACP J Club 149(5):11

    PubMed  Google Scholar 

  • Atterbury CE, Maddrey WC, Conn HO (1978) Neomycin-sorbitol and lactulose in the treatment of acute portal-systemic encephalopathy: a controlled, double-blind clinical trial. Am J Dig Dis 23:398–406

    Article  PubMed  CAS  Google Scholar 

  • Bajaj JS (2010) Review article: the modern management of hepatic encephalopathy. Aliment Pharmacol Ther 31(5):537–547

    Article  PubMed  CAS  Google Scholar 

  • Bajaj JS, Riggio O (2010) Drug therapy: rifaximin. Hepatology 52(4):1484–1488

    Article  PubMed  CAS  Google Scholar 

  • Bajaj JS, Heuman DM, Wade JB, Gibson DP, Saeian K, Wegelin JA, Hafeezullah M, Bell DE, Sterling RK, Stravitz RT, Fuchs M, Luketic V, Sanyal AJ (2011) Rifaximin improves driving simulator performance in a randomized trial of patients with minimal hepatic encephalopathy. Gastroenterology 140(2):478–487

    Article  PubMed  CAS  Google Scholar 

  • Bajaj JS, Hylemon PB, Ridlon JM, Heuman DM, Daita K, White MB, Monteith P, Noble NA, Sikaroodi M, Gillevet PM (2012a) Colonic mucosal microbiome differs from stool microbiome in cirrhosis and hepatic encephalopathy and is linked to cognition and inflammation. Am J Physiol Gastrointest Liver Physiol 303(6):G675–G685

    Article  PubMed  CAS  Google Scholar 

  • Bajaj JS, O’Leary JG, Reddy KR, Wong F, Olson JC, Subramanian RM, Brown G, Noble NA, Thacker LR, Kamath PS (2012b) Second infections independently increase mortality in hospitalized patients with cirrhosis: the north american consortium for the study of end-stage liver disease (NACSELD) experience. Hepatology 56(6):2328–2335

    Article  PubMed  CAS  Google Scholar 

  • Bajaj JS, Pinkerton SD, Sanyal AJ, Heuman DM (2012c) Diagnosis and treatment of minimal hepatic encephalopathy to prevent motor vehicle accidents: a cost-effectiveness analysis. Hepatology 55(4):1164–1171

    Article  PubMed  Google Scholar 

  • Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, Sigal S, Sheikh MY, Beavers K, Frederick T, Teperman L, Hillebrand D, Huang S, Merchant K, Shaw A, Bortey E, Forbes WP (2010) Rifaximin treatment in hepatic encephalopathy. N Engl J Med 362(12):1071–1081

    Article  PubMed  CAS  Google Scholar 

  • Blei AT, Cordoba J (2001) Hepatic encephalopathy. Am J Gastroenterol 96:1968–1976

    Article  PubMed  CAS  Google Scholar 

  • Brigidi P, Swennen E, Rizzello F, Bozzolasco M, Matteuzzi D (2012) Effects of rifaximin administration on the intestinal microbiota in patients with ulcerative colitis. J Chemother 14(3):290–295

    Google Scholar 

  • Bucci L, Palmieri GC (1993) Double-blind, double-dummy comparison between treatment with rifaximin and lactulose in patients with medium to severe degree hepatic encephalopathy. Curr Med Res Opin 13:109–118

    Article  PubMed  CAS  Google Scholar 

  • Conn HO, Leevy CM, Vlahcevic ZR, Rodgers JB, Maddrey WC, Seeff L, Levy LL (1977) Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology 72(4 Pt 1):573–583

    PubMed  CAS  Google Scholar 

  • Fera G, Agostinacchio F, Nigro M, Schiraldi O, Ferrieri A (1993) Rifaximin in the treatment of hepatic encephalopathy. Eur J Clin Res 4(1):57–66

    Google Scholar 

  • Fernández J, Acevedo J, Castro M, Garcia O, de Lope CR, Roca D, Pavesi M, Sola E, Moreira L, Silva A, Seva-Pereira T, Corradi F, Mensa J, Ginès P, Arroyo V (2012) Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology 55(5):1551–1561

    Article  PubMed  Google Scholar 

  • Festi D, Mazzella G, Orsini M, Scottili S, Sangermano A, Li Bassi S, Ferrieri A, Falcucci M, Grossi L, Marzio L, Roda E (1993) Rifaximin in the treatment of chronic hepatic encephalopathy: results of a multicenter study of efficacy and safety. Curr Ther Res 54(5):598–609

    Article  Google Scholar 

  • Gustot T, Durand F, Lebrec D, Vincent JL, Moreau R (2009) Severe Sepsis in cirrhosis. Hepatology 50(6):2022–2033

    Article  PubMed  CAS  Google Scholar 

  • Huang E, Esrailian E, Spiegel BMR (2007) The cost-effectiveness and budget impact of competing therapies in hepatic encephalopathy: a decision analysis. Aliment Pharmacol Ther 26:1147–1161

    Article  PubMed  CAS  Google Scholar 

  • Jalan R (2010) Rifaximin in hepatic encephalopathy: more than just a non-absorable antibiotic? J Hepatol 53(3):580–582

    Article  PubMed  Google Scholar 

  • Jiang ZD, DuPont HL (2005) Rifaximin: in vitro and in vivo antibacterial activity–a review. Chemotherapy 51(Suppl 1):67–72

    Article  PubMed  CAS  Google Scholar 

  • Kalambokis GN, Mouzaki A, Rodi M, Pappas K, Fotopoulos A, Xourgia X, Tsiansos EV (2012) Rifaximin improves systemic hemodynamics and renal function in patients with alchol-related cirrhosis and ascites. Clin Gastroenterol Hepatol 10(7):815–818

    Article  PubMed  CAS  Google Scholar 

  • Leevy CB, Phillips JA (2007) Hospitalizations during the use of rifaximin versus lactulose for the treatment of hepatic encephalopathy. Dig Dis Sci 52:737–741

    Article  PubMed  CAS  Google Scholar 

  • Loft S, Sonne J, Dossing M, Andreasen PB (1987) Metronidazole pharmacokinetics in patients with hepatic encephalopathy. Scand J Gastroenterol 22(1):117–123

    Article  PubMed  CAS  Google Scholar 

  • Mantry PS, Munsaf S (2010) Rifaximin for the treatment of hepatic encephalopathy. Transplant Proc 42(10):4543–4547

    Article  PubMed  CAS  Google Scholar 

  • Marco F, Amato PS, D’Arienzo A (1984) Rifaximin in collateral treatment of portal-systemic encephalopathy: a preliminary report. Curr Ther Res 36:668–674

    Google Scholar 

  • Mas A, Rodés J, Sunyer L, Rodrigo L, Planas R, Vargas V, Castells L, Rodríguez-Martínez D, Fernández-Rodríguez C, Coll I, Pardo A (2003) Spanish Association for the Study of the Liver Hepatic Encephalopathy Cooperative Group. 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 38(1):51–58

    Article  PubMed  CAS  Google Scholar 

  • Massa P, Vallerino E, Dodero M (1993) Treatment of hepatic encephalopathy with rifaximin: double-blind, double-dummy study versus lactulose. Eur J Clin Res 4:7–18

    Google Scholar 

  • Morgan MH, Read AE, Speller DC (1982) Treatment of hepatic encephalopathy with metronidazole. Gut 23(1):1–7

    Article  PubMed  CAS  Google Scholar 

  • Neff GW, Kemmer N, Kaiser T, Zacharias V, Majoras N, Safdar K (2007) Outcomes in adult and pediatric liver transplantation among various ethnic groups. Transplant Proc 39(10):3204–3206

    Article  PubMed  CAS  Google Scholar 

  • Neff GW, Jones M, Broda T, Jonas M, Ravi R, Novick D, Kaiser TE, Kemmer N (2012) Durability of rifaximin response in hepatic encephalopathy. J Clin Gastroenterol 46(2):168–171

    Article  PubMed  CAS  Google Scholar 

  • Orlandi F, Freddara U, Candelaresi MT, Morettini A, Corazza GR, Di Simone A, Dobrilla G, Cavallini G (1981) Comparison between neomycin and lactulose in 173 patients with hepatic encephalopathy: a randomized clinical study. Dig Dis Sci 26(6):498–506

    Article  PubMed  CAS  Google Scholar 

  • Paik YH, Lee KS, Han KH, Song KH, Kim MH, Moon BS, Ahn SH, Lee SJ, Park HJ, Lee DK, Chon CY, Lee SI, Moon YM (2005) Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study. Yonsei Med J 46(3):399–407

    Article  PubMed  CAS  Google Scholar 

  • Parini P, Cipolla A, Ronci M, Antionio M, Salzetta A, Mazzella G, Roda E (1992) Effect of paromomycin in the treatment of portal-systemic encephalopathy. Curr Ther Res 52:34

    Article  Google Scholar 

  • Poh Z, Chang PE (2012) A current review of the diagnostic and treatment strategies of hepatic encephalopathy. Int J Hepatol 2012:480309

    PubMed  CAS  Google Scholar 

  • Poordad FF (2007) Review article: the burden of hepatic encephalopathy. Aliment Pharmacol Ther 1:3–9

    Article  Google Scholar 

  • Prakash R, Mullen KD (2010) Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 7:515–525

    Article  PubMed  Google Scholar 

  • Riggio O, Mannaioni G, Ridola L, Angeloni S, Merli M, Carlà V, Salvatori FM, Moroni F (2010) Peripheral and splanchnic indole and oxindole levels in cirrhotic patients: a study on the pathophysiology of hepatic encephalopathy. Am J Gastroenterol 105(6):1374–1381

    Article  PubMed  CAS  Google Scholar 

  • Sanyal A, Bass N, Poorad F, Sheikh MY, Mullen K, Sigal S, Frederick T, Brown, Jr R, Bhandari B, Sedghi S, Merchant K, Huang S, Shaw A, Bortey E, Forbes W (2010) Rifaximin decreases venous ammonia concentrations and time-weighted average ammonia concentrations correlate with overt hepatic encephalopathy (HE) as assessed by Conn Score in a 6-months study. Program and abstracts of the 45th Annual Meeting of the European Association for the Study of the Liver Abstract 195

  • Sanyal A, Younossi ZM, Bass NM, Mullen KD, Poordad F, Brown RS, Vemuru RP, Mazen Jamal M, Huang S, Merchant K, Bortey E, Forbes WP (2011) Randomised clinical trial: rifaximin improves health-related quality of life in cirrhotic patients with hepatic encephalopathy – a double-blind placebo-controlled study. Aliment Pharmacol Ther 34(8):853–861

    Article  PubMed  CAS  Google Scholar 

  • Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA (2011) Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol 54:640–649

    Article  PubMed  CAS  Google Scholar 

  • Sidhu SS, Goyal O, Mishra BP, Sood A, Chhina RS, Soni RK (2011) Rifaximin improves psychometric performance and health-related quality of life in patients with minimal hepatic encephalopathy (the RIME Trial). Am J Gastroenterol 106(2):307–316

    Article  PubMed  CAS  Google Scholar 

  • Stepanova M, Mishra A, Venkatesan C, Younossi ZM (2012) In-hospital mortality and economic burden associated with hepatic encephalopathy in the United States from 2005 to 2009. Clin Gastroenterol Hepatol 10(9):1034–1041

    Article  PubMed  Google Scholar 

  • Strauss E, Tramote R, Silva EP, Caly WR, Honain NZ, Maffei RA, de Sá MF (1992) Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology 39(6):542–545

    PubMed  CAS  Google Scholar 

  • Tarao K, Ikeda T, Hayashi K, Sakurai A, Okada T, Ito T, Karube H, Nomoto T, Mizuno T, Shindo K (1990) Successful use of vancomycin hydrochloride in the treatment of lactulose resistant chronic hepatic encephalopathy. Gut 31(6):702–706

    Article  PubMed  CAS  Google Scholar 

  • Testa R, Eftimiadi C, Sukkar GS, De Leo C, Rovida S, Schito GC, Celle G (1985) Drugs Exp Clin Res 11(6):387–392

    PubMed  CAS  Google Scholar 

  • U.S. Food and Drug Administration (2010) Briefing Document for Gastrointestinal Drugs Advisory Committee Meeting 23 February 2010. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/GastrointestinalDrugsAdvisoryCommittee/UCM201081.pdf. Accessed 3 December 2012

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  1. Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA, USA

    Kavish R. Patidar & Jasmohan S. Bajaj

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  1. Kavish R. Patidar
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  2. Jasmohan S. Bajaj
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Correspondence to Jasmohan S. Bajaj.

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Patidar, K.R., Bajaj, J.S. Antibiotics for the treatment of hepatic encephalopathy. Metab Brain Dis 28, 307–312 (2013). https://doi.org/10.1007/s11011-013-9383-5

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