Reduction in Gastrointestinal Cancers in Cirrhotic Patients Receiving Rifaximin vs Lactulose Only Therapy for Hepatic Encephalopathy

Abstract

Background Rifaximin and/or lactulose therapy is widely used in cirrhotic patients for the prevention and treatment of hepatic encephalopathy. The incidence of gastrointestinal cancers in these patients on lactulose, rifaximin, and/or combination therapy is unknown. We investigated the possible effect of lactulose and rifaximin on cancer risk in patients with cirrhosis using the MarketScan database. Methods A retrospective cohort study was conducted using the Truven Health MarketScan Commercial Claims databases from 2007-2017. An index date was defined for each participant as the earliest date of cirrhosis diagnosis. A baseline period for each participant was defined as the 12 months prior to the first medication date while the study follow-up period represented the period from the initiation of the medication to its cessation. ANOVA was used to compare all continuous measures of age and duration of medication. Wald Chi-square tests were performed to test the associations between the study groups. Results A total of 12,409 patients were included in our study. The rifaximin only cohort had the greatest reduction in risk of developing colon cancer, esophageal cancer, and stomach cancer compared to the other groups. Rifaximin reduced the risk of colon cancer and esophageal cancer by 59.42% and 70.37%, respectively, compared to patients taking lactulose only. Patients in the lactulose plus rifaximin cohort had the highest rate of development of pancreatic cancer (lactulose plus rifaximin vs rifaximin only vs lactulose only, 0.45% vs 0.24% vs 0.21%; P < 0.0001) and liver and intrahepatic bile duct cancers (11.73% vs 5.84% vs 5.49%; P < 0.0001). Conclusion Colon, esophageal, and gastric cancers had a marked incidence reduction in the rifaximin only cohort compared to the other cohorts studied.

Rifaximin Alfa and Liver Diseases: More Than a Treatment for Encephalopathy, a Disease Modifier

“…69 Rifaximin reduced the risk of colon cancer and esophageal cancer by 59.42% and 70.37%, respectively, compared to patients taking lactulose only. 69,70 This observation is consistent with investigations in animals with experimental colon cancer, in which activation of pregnane X by RFX may protect against neoplasia. 29…”