{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:31:39Z","timestamp":1777419099397,"version":"3.51.4"},"reference-count":17,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE:<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of combination therapy for the treatment and prevention of hepatic encephalopathy (HE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATA SOURCES:<\/jats:title>\n                    <jats:p>A PubMed MEDLINE search was conducted (1947-June 2012) using the key terms lactulose, lactitol, nonabsorbable disaccharide, metronidazole, rifaximin, neomycin, probiotics, and hepatic encephalopathy. Searches were limited to include articles published in English.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY SELECTION AND DATA EXTRACTION:<\/jats:title>\n                    <jats:p>Study selection included published trials, case reports, and case series of humans with HE who were treated with combination therapy of rifaximin, lactulose, lactitol, metronidazole, neomycin, and\/or probiotics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATA SYNTHESIS:<\/jats:title>\n                    <jats:p>Only 6 studies that evaluated the benefits of combination drug therapy in the treatment or prevention of HE were available for review. Four studies addressed the treatment of HE, 2 found no significant difference between lactulose\/neomycin versus placebo or rifaximin\/lactulose, 1 assessed the use of rifaximin\/lactulose without a control group, and the fourth found no significant difference between lactulose\/probiotics versus either drug alone, although each group showed improvement from baseline. In the 2 prevention trials, both of which stemmed from the same data, the combination of rifaximin\/lactulose was superior to lactulose alone, showing significant improvement in mental status, blood ammonia levels, and health-related quality of life and reductions in HE recurrence and hospitalization. Currently, there are no available clinical studies evaluating dual antibiotic therapy, metronidazole with nonabsorbable disaccharides, or antibiotics with probiotics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>The evidence evaluating the use of combination therapy for the treatment of HE does not support its widespread use. The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy. The combination of rifaximin and lactulose should be considered for the prevention of HE, especially after the second episode of HE recurrence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1345\/aph.1r146","type":"journal-article","created":{"date-parts":[[2012,10,24]],"date-time":"2012-10-24T01:43:41Z","timestamp":1351043021000},"page":"1559-1563","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Combination Therapy for the Treatment and Prevention of Hepatic Encephalopathy"],"prefix":"10.1177","volume":"46","author":[{"given":"Rima A","family":"Mohammad","sequence":"first","affiliation":[{"name":"Rima A Mohammad PharmD BCPS, Assistant Professor of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA; Clinical Specialist, Internal Medicine\/Hepatology, University of Pittsburgh Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randolph E","family":"Regal","sequence":"additional","affiliation":[{"name":"Randolph E Regal PharmD, Clinical Associate Professor of Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI; Clinical Pharmacist, University of Michigan Hospitals and Health Centers; Consultant Pharmacist, VPH Pharmacy, Swartz Creek, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar","family":"Alaniz","sequence":"additional","affiliation":[{"name":"Cesar Alaniz PharmD, Clinical Associate Professor of Pharmacy, College of Pharmacy, University of Michigan; Clinical Pharmacist, Critical Care Medicine Unit, University of Michigan Hospitals and Health Centers"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,11,1]]},"reference":[{"key":"bibr1-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1159\/000089783"},{"key":"bibr2-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2001.03964.x"},{"key":"bibr3-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e3283417567"},{"key":"bibr4-aph.1R146","first-page":"1063","volume":"18","author":"Blanc P","year":"1994","journal-title":"Gastroenterol Clin Biol"},{"key":"bibr5-aph.1R146","first-page":"403","volume":"23","author":"Di Piazza S","year":"1991","journal-title":"Ital J Gastroenterol"},{"key":"bibr6-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1185\/03007999509111552"},{"key":"bibr7-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e3282f3e6f5"},{"key":"bibr8-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907893"},{"key":"bibr9-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(10)60197-3"},{"key":"bibr10-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04808.x"},{"key":"bibr11-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)70239-7"},{"key":"bibr12-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(65)90002-4"},{"key":"bibr13-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5498.1267"},{"key":"bibr14-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(95)80309-2"},{"key":"bibr15-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1177\/030006058701500602"},{"key":"bibr16-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2004.07.029"},{"key":"bibr17-aph.1R146","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04590.x"}],"container-title":["Annals of Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.1R146","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1345\/aph.1R146","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1345\/aph.1R146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:09:23Z","timestamp":1777374563000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1345\/aph.1R146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":17,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1345\/aph.1R146"],"URL":"https:\/\/doi.org\/10.1345\/aph.1r146","relation":{},"ISSN":["1060-0280","1542-6270"],"issn-type":[{"value":"1060-0280","type":"print"},{"value":"1542-6270","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11]]}}}