{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:19:26Z","timestamp":1792210766615,"version":"4.4.0"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Hepatic encephalopathy (HE), a neuropsychiatric complication of decompensated cirrhosis, is associated with high mortality and high risk of recurrence. Rifaximin add-on to lactulose for 3 to 6 months is recommended for the prevention of recurrent episodes of HE after the second episode. However, whether the combination for more than 6 months is superior to lactulose alone in the maintenance of HE remission is less evident. Therefore, the aim of this study is to evaluate the one-year efficacy of rifaximin add-on to lactulose for the maintenance of HE remission in Taiwan. Methods: We conducted a real-world single-center retrospective cohort study to compare the long-term efficacy of rifaximin add-on to lactulose (group R + L) versus lactulose alone (group L, control group). Furthermore, the treatment efficacy before and after rifaximin add-on to lactulose was also analyzed. The primary endpoint of our study was time to first HE recurrence (Conn score \u2265 2). All patients were followed up every three months until death, and censored at one year if still alive. Results and Conclusions: 12 patients were enrolled in group R + L. Another 31 patients were stratified into group L. Sex, comorbidity, ammonia level, and ascites grade were matched while age, HE grade, and model for end-stage liver disease (MELD) score were adjusted in the multivariable logistic regression model. Compared with group L, significant improvement in the maintenance of HE remission and decreased episodes and days of HE-related hospitalizations were demonstrated in group R + L. The serum ammonia levels were significantly lower at the 3rd and 6th month in group 1. Concerning changes before and after rifaximin add-on in group R + L, mini-mental status examination (MMSE), episodes of hospitalization, and variceal bleeding also improved at 6 and 12 months. Days of hospitalization, serum ammonia levels also improved at 6th month. Except for concern over price, no patients discontinued rifaximin due to adverse events or complications. The above results provide evidence for the one-year use of rifaximin add-on to lactulose in reducing HE recurrence and HE-related hospitalization for patients with decompensated cirrhosis.<\/jats:p>","DOI":"10.3390\/jpm11060478","type":"journal-article","created":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T04:30:46Z","timestamp":1622089846000},"page":"478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Real-World Experience of the One-Year Efficacy of Rifaximin Add-On to Lactulose Is Superior to Lactulose Alone in Patients with Cirrhosis Complicated with Recurrent Hepatic Encephalopathy in Taiwan"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1450-4245","authenticated-orcid":false,"given":"Ching","family":"Chang","sequence":"first","affiliation":[{"name":"Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hao","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan"},{"name":"College of Medicine, Chang-Gung University, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Jung","family":"Tseng","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7656-4695","authenticated-orcid":false,"given":"Rong-Nan","family":"Chien","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan"},{"name":"College of Medicine, Chang-Gung University, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/hep.27210","article-title":"Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver","volume":"60","author":"Vilstrup","year":"2014","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1056\/NEJMra1600561","article-title":"Hepatic Encephalopathy","volume":"375","author":"Wijdicks","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s40265-018-1019-y","article-title":"Impact of Hepatic Encephalopathy in Cirrhosis on Quality-of-Life Issues","volume":"79","author":"Montagnese","year":"2019","journal-title":"Drugs"},{"key":"ref_4","first-page":"142","article-title":"Hepatic Encephalopathy: An Update on the Pathophysiology and Therapeutic Options","volume":"5","author":"Elwir","year":"2017","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1053\/j.gastro.2009.05.056","article-title":"Secondary prophylaxis of hepatic encephalopathy: An open-label randomized controlled trial of lactulose versus placebo","volume":"137","author":"Sharma","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.4254\/wjh.v7.i29.2871","article-title":"Advances in cirrhosis: Optimizing the management of hepatic encephalopathy","volume":"7","author":"Liu","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.2165\/10898630-000000000-00000","article-title":"Pharmacotherapy for hepatic encephalopathy","volume":"70","author":"Phongsamran","year":"2010","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1159\/000081990","article-title":"Rifaximin, a poorly absorbed antibiotic: Pharmacology and clinical potential","volume":"51","author":"Scarpignato","year":"2005","journal-title":"Chemotherapy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/j.cgh.2013.12.021","article-title":"Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy","volume":"12","author":"Mullen","year":"2014","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1056\/NEJMoa0907893","article-title":"Rifaximin treatment in hepatic encephalopathy","volume":"362","author":"Bass","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0168-8278(02)00350-1","article-title":"Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: Results of a randomized, double-blind, double-dummy, controlled clinical trial","volume":"38","author":"Mas","year":"2003","journal-title":"J. Hepatol."},{"key":"ref_12","first-page":"269","article-title":"Efficacy of Rifaximin in prevention of recurrence of hepatic encephalopathy in patients with cirrhosis of liver","volume":"24","author":"Ali","year":"2014","journal-title":"J. Coll. Physicians Surg. Pak."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1111\/apt.14275","article-title":"Rifaximin treatment is associated with reduced risk of cirrhotic complications and prolonged overall survival in patients experiencing hepatic encephalopathy","volume":"46","author":"Kang","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_14","first-page":"42","article-title":"Comparison of Rifaximin Plus Lactulose with the Lactulose Alone for the Treatment of Hepatic Encephalopathy","volume":"65","author":"Ahire","year":"2017","journal-title":"J. Assoc. Physicians India"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1177\/0897190014566312","article-title":"Treatment of Acute Hepatic Encephalopathy: Comparing the Effects of Adding Rifaximin to Lactulose on Patient Outcomes","volume":"29","author":"Courson","year":"2016","journal-title":"J. Pharm. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jgh.12070","article-title":"Long-term administration of rifaximin improves the prognosis of patients with decompensated alcoholic cirrhosis","volume":"28","author":"Vlachogiannakos","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S148","DOI":"10.1097\/00004836-200411003-00006","article-title":"Cost of chronic hepatitis B virus infection in Taiwan","volume":"38","author":"Hsieh","year":"2004","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1111\/j.1365-2036.2006.03105.x","article-title":"Cost-utility analysis of different peg-interferon alpha-2b plus ribavirin treatment strategies as initial therapy for naive Chinese patients with chronic hepatitis C","volume":"24","author":"Lin","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"887","DOI":"10.3111\/13696998.2012.681332","article-title":"Economic burden of hepatitis C-associated diseases: Europe, Asia Pacific, and the Americas","volume":"15","author":"Wallace","year":"2012","journal-title":"J. Med. Econ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.jceh.2014.06.004","article-title":"Pathogenesis of hepatic encephalopathy: Role of ammonia and systemic inflammation","volume":"5","author":"Aldridge","year":"2015","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s12072-017-9812-3","article-title":"Hepatic encephalopathy: A critical current review","volume":"12","author":"Hadjihambi","year":"2018","journal-title":"Hepatol. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/hep.29410","article-title":"L-ornithine L-aspartate in bouts of overt hepatic encephalopathy","volume":"67","author":"Sidhu","year":"2018","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1001\/jamainternmed.2014.4746","article-title":"Lactulose vs polyethylene glycol 3350--electrolyte solution for treatment of overt hepatic encephalopathy: The HELP randomized clinical trial","volume":"174","author":"Rahimi","year":"2014","journal-title":"JAMA Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/ajg.2011.9","article-title":"Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: A randomized study","volume":"106","author":"Les","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/ajg.2012.113","article-title":"Secondary prophylaxis of hepatic encephalopathy in cirrhosis: An open-label, randomized controlled trial of lactulose, probiotics, and no therapy","volume":"107","author":"Agrawal","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/hep.29306","article-title":"Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial","volume":"66","author":"Bajaj","year":"2017","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1002\/hep.21930","article-title":"Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis","volume":"46","author":"Hassanein","year":"2007","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/hep.26185","article-title":"Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: The RELIEF trial","volume":"57","author":"Banares","year":"2013","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1002\/hep.31496","article-title":"A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder","volume":"73","author":"Bajaj","year":"2021","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1746-6342.2006.03215.x","article-title":"Review article: The burden of hepatic encephalopathy","volume":"25","author":"Poordad","year":"2007","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_31","first-page":"S51","article-title":"Considerations for the cost-effective management of hepatic encephalopathy","volume":"24","author":"Flamm","year":"2018","journal-title":"Am. J. Manag. Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1007\/s40273-018-0641-6","article-title":"Systematic Review of the Economic Burden of Overt Hepatic Encephalopathy and Pharmacoeconomic Impact of Rifaximin","volume":"36","author":"Neff","year":"2018","journal-title":"Pharmacoeconomics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1016\/j.transproceed.2006.10.107","article-title":"Analysis of hospitalizations comparing rifaximin versus lactulose in the management of hepatic encephalopathy","volume":"38","author":"Neff","year":"2006","journal-title":"Transplant. Proc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.jhep.2017.10.020","article-title":"Clinical states of cirrhosis and competing risks","volume":"68","author":"Morabito","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/apt.15326","article-title":"Rifaximin reduces the incidence of spontaneous bacterial peritonitis, variceal bleeding and all-cause admissions in patients on the liver transplant waiting list","volume":"50","author":"Salehi","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1111\/j.1572-0241.2003.07466.x","article-title":"Relationship of the model for end-stage liver disease (MELD) scale to hepatic encephalopathy, as defined by electroencephalography and neuropsychometric testing, and ascites","volume":"98","author":"Yoo","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1007\/s10620-008-0238-6","article-title":"Acetyl-L-carnitine treatment in minimal hepatic encephalopathy","volume":"53","author":"Malaguarnera","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Koziarska, D., Wunsch, E., Milkiewicz, M., Wojcicki, M., Nowacki, P., and Milkiewicz, P. (2013). Mini-Mental State Examination in patients with hepatic encephalopathy and liver cirrhosis: A prospective, quantified electroencephalography study. BMC Gastroenterol., 13.","DOI":"10.1186\/1471-230X-13-107"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jceh.2013.12.005","article-title":"Covert hepatic encephalopathy: Does the mini-mental state examination help?","volume":"4","author":"Corrias","year":"2014","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2147\/CEOR.S30675","article-title":"Update on the management of cirrhosis\u2014Focus on cost-effective preventative strategies","volume":"5","author":"Neff","year":"2013","journal-title":"Clinicoecon. Outcomes Res."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/11\/6\/478\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:08:39Z","timestamp":1760162919000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/11\/6\/478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,27]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["jpm11060478"],"URL":"https:\/\/doi.org\/10.3390\/jpm11060478","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,27]]}}}