Real-World Setting of Efficacy and Safety of 3 Years of Rifaximin Administration in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study

Abstract

Background/Objectives: Rifaximin is a therapeutic agent for patients with hepatic encephalopathy (HE); however, there is little data on the effects of its long-term (>1 year) administration in Japanese patients with cirrhosis. The effects and safety of 3-year rifaximin treatment on HE was investigated in Japan. Methods: A total of 190 Japanese patients with cirrhosis who were continuously administered rifaximin for more than 1 year suffered overt or covert HE, which was diagnosed by a physician. Laboratory data were collected at baseline, 3, 6, 12, 18, 24, 30, and 36 months following rifaximin administration. We examined the cumulative overt HE incidences, overall survival rates, and hepatic functional reserves following rifaximin treatment. The occurrence of adverse events was also assessed. Results: The levels of ammonia improved significantly after 3 months of rifaximin administration, which continued for 3 years. Serum albumin and prothrombin activity also significantly improved 3 years after initiation of rifaximin treatment. Cumulative overt HE incidences were 12.1%, 19.7%, and 24.9% at 1, 2, and 3 years, respectively. The survival rates following rifaximin treatment were 100%, 88.9%, and 77.8% at 1, 2, and 3 years, respectively. In contrast, renal function and electrolytes did not change following rifaximin administration. Only three (1.6%) patients discontinued rifaximin therapy because of severe diarrhea after 1 year of rifaximin administration. No other serious adverse events were observed. Conclusions: Three years of continuous rifaximin (RFX) treatment was both effective and safe for patients with hepatic encephalopathy. Liver function improved and did not worsen during treatment.

Keywords: Japanese; hepatic encephalopathy; long-term administration; multicentered; rifaximin.

Figure 1

Flowchart of the present study.

Figure 2

Serum ammonia and albumin levels and prothrombin time (%) after RFX administration. (a) NH₃, Ammonia levels significantly decreased after RFX treatment from 100.0 (66.5–141.5) μg/dL at baseline to 74.0 (49.8–111.3) μg/dL, 75.4 (49.5–105.0) μg/dL, 74.4 (48.5–105.0) μg/dL, 70.2 (42.0–99.0) μg/dL, 67.0 (41.0–99.0) μg/dL, 70.0 (35.3–97.5) μg/dL, and 69.0 (40.0–99.8) μg/dL after 3, 6, 12, 18, 24, 30, and 36 months, respectively. A statistically significant difference was observed between baseline and after 3 months and more. Pre, before rifaximin treatment.; M, months. (b) Alb, albumin; The serum Alb levels significantly increased after RFX treatment from 3.2 (2.9–3.5) g/dL at baseline to 3.3 (2.9–3.6) g/dL, 3.3 (3.0–3.6) g/dL, 3.3 (3.0–3.6) g/dL, 3.4 (3.0–3.8) g/dL, 3.4 (3.1–3.7) g/dL, 3.4 (3.1–3.8) g/dL, 3.5 (3.1–3.8) g/dL after 3,6, 12, 18, 24, 30, and 36 months, respectively. A statistically significant difference was observed between baseline and after 3 months and more. Pre, before rifaximin treatment.; M, months. (c) PT (%), prothrombin time (%); PT activity significantly increased after RFX treatment from 69.0 (57.0–80.1) % at baseline to 69.5 (59.0–84.3) %, 71.0 (59.4–84.2) %, 72.0 (60.0–83.7) %, 73.0 (62.2–84.0) %, 72.8 (62.0–84.0) %, 79.0 (64.6–88.7) %, 80.6 (66.1–89.1) % after 3,6, 12, 18, 24, 30, and 36 months, respectively. A statistically significant difference was observed between baseline and after 3 months and more. Pre, before rifaximin treatment.; M, months.

Figure 2

Serum ammonia and albumin levels and prothrombin time (%) after RFX administration. (a) NH₃, Ammonia levels significantly decreased after RFX treatment from 100.0 (66.5–141.5) μg/dL at baseline to 74.0 (49.8–111.3) μg/dL, 75.4 (49.5–105.0) μg/dL, 74.4 (48.5–105.0) μg/dL, 70.2 (42.0–99.0) μg/dL, 67.0 (41.0–99.0) μg/dL, 70.0 (35.3–97.5) μg/dL, and 69.0 (40.0–99.8) μg/dL after 3, 6, 12, 18, 24, 30, and 36 months, respectively. A statistically significant difference was observed between baseline and after 3 months and more. Pre, before rifaximin treatment.; M, months. (b) Alb, albumin; The serum Alb levels significantly increased after RFX treatment from 3.2 (2.9–3.5) g/dL at baseline to 3.3 (2.9–3.6) g/dL, 3.3 (3.0–3.6) g/dL, 3.3 (3.0–3.6) g/dL, 3.4 (3.0–3.8) g/dL, 3.4 (3.1–3.7) g/dL, 3.4 (3.1–3.8) g/dL, 3.5 (3.1–3.8) g/dL after 3,6, 12, 18, 24, 30, and 36 months, respectively. A statistically significant difference was observed between baseline and after 3 months and more. Pre, before rifaximin treatment.; M, months. (c) PT (%), prothrombin time (%); PT activity significantly increased after RFX treatment from 69.0 (57.0–80.1) % at baseline to 69.5 (59.0–84.3) %, 71.0 (59.4–84.2) %, 72.0 (60.0–83.7) %, 73.0 (62.2–84.0) %, 72.8 (62.0–84.0) %, 79.0 (64.6–88.7) %, 80.6 (66.1–89.1) % after 3,6, 12, 18, 24, 30, and 36 months, respectively. A statistically significant difference was observed between baseline and after 3 months and more. Pre, before rifaximin treatment.; M, months.

Figure 3

Cumulative incidence of OHE and survival rate of patients after RFX administration. (a) The rate of overt HE was 12.1%, 19.7%, and 24.9% at 1, 2, and 3 years, respectively. M, months. (b) Survival rate of the patients after RFX treatment. Survival rate after 1 year of RFX treatment was 100% and the survival rates after 2 and 3 years of RFX treatment were 88.9% (95%CI: 0.830–0.926) and 77.8% (95%CI: 0.703–0.831), respectively. M, months.