Table 2.
Randomized controlled trials published since 2010 regarding the effect of rifaximin in patients with decompensated liver cirrhosis. MHE: minimal hepatic encephalopathy; BT: bacterial translocation; OHE: overt hepatic encephalopathy; sMR: soluble mannose receptor; HRS: hepatorenal syndrome.
| Author (Year) | Treatment | Design | Target Patients | n | Primary Endpoint | Main Result |
|---|---|---|---|---|---|---|
| Schulz C, et al. (2019) [129] | Rifaximin 550 mg twice daily alone continuously for 3 months vs. rifaximin combined with lactulose 30–60 mL daily for 3 months | RCT | Decompensated LC with MHE | 5 | MHE improvement | Significant improvement of MHE in all patients. No statistically significant changes in the bacterial community profile at each time point. |
| Kimer N, et al. (2018) [130] | Rifaximin for 4 weeks vs. placebo | RCT | Decompensated LC | 54 | BT and inflammation | No impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition |
| Nutt NI, et al. (2018) [131] | Lactulose vs. Lactulose+ rifaximin 550 mg twice daily |
RCT | HE due to decompensated LC | 130 | HE | No significant difference on HE (p = 0.276). |
| Mekky MA, et al. (2018) [132] | Rifaximin vs. metronidazole | RCT | Decompensated LC with an acute episode of OHE | 120 | OHE improvement | OHE improvement: 46 patients (76.7%) in the metronidazole group vs. 45 (75%) in the rifaximin group (p = 0.412). |
| Higuera-de-la-Tijera F, et al. (2018) [133] | Lactulose vs. L-ornithine L-aspartate (LOLA) vs. rifaximin vs. placebo | RCT | Decompensated LC with variceal bleeding | 87 | HE development | Lactulose vs. placebo: 54.5% vs. 27.3%, p = 0.06 LOLA vs. placebo: 54.5% vs. 22.7%, p = 0.03 Rifaximin vs. placebo: 54.5% vs. 23.8%, p = 0.04. |
| Kimer N, et al. (2018) [134] | Rifaximin for 4 weeks vs. placebo | RCT | Decompensated LC | 54 | Macrophage markers s CD163, sMR |
sCD163 and sMR were associated with liver disease severity. No effect of rifaximin on sCD163 and sMR. |
| Goyal O, et al. (2017) [135] | Rifaximin (1200 mg/day) vs. lactulose (30–120 mL/day) for 3 months | RCT | Decompensated LC with MHE | 112 | MHE reversal | MHE reversal at 3 months: 73.7% (42/57) in the rifaximin group and 69.1% (38/55) in the lactulose group (p = 0.677). |
| Lauridsen MM, et al. (2017) [136] | Lactulose plus BCAAs plus rifaximin vs. triple placebos for 3 months | RCT | Decompensated LC without clinically manifest HE | 44 | Continuous reaction test time (CRT) | ΔCRT: 0.50 ± 0.20 vs. 0.13 ± 0.12 (p = 0.06). |
| Lim YL, et al. (2017) [137] | Propranolol monotherapy vs. rifaximin and propranolol combination therapy | RCT | Decompensated LC | 64 | HVPG | HVPG response rates: 56.2% in the propranolol vs. 87.5% in the combination, (p = 0.034). |
| Ibrahim ES, et al. (2017) [138] | Rifaximin 550 mg twice daily for 12 weeks vs. placebo | RCT | Decompensated LC | 80 | HRS occurrence | HRS occurrence: 9 (22.5%) in the control group vs. 2 (5%) in the rifaximin group; p = 0.048. |
| Kimer N, et al. (2017) [139] | Rifaximin for 4 weeks vs. placebo | RCT | Decompensated LC | 54 | HVPG | No significant difference on HVPG (p = 0.94). |
| Elfert A, et al. (2016) [140] | Rifaximin 1200 mg daily vs. norfloxacin 400 mg daily for 6 months | RCT | Decompensated LC with a previous episode of SBP | 262 | Prevention of SBP | Recurrence rate of SBP: 3.88% in the rifaximin vs. 14.13% in the norfloxacin (p = 0.04) Mortality: 13.74% in the rifaximin vs. 24.43% in the norfloxacin (p = 0.044). |
| Sidhu, et al. (2016) [141] | Rifaximin 400 mg thrice a day vs. lactulose 30–120 mL/day | RCT | MHE due to decompensated LC | 112 | MHE improvement | MHE reversal at 3 months: 73.7% (42/57) in the rifaximin arm and 69.1% (38/55) in the lactulose arm (p > 0.05). |
| Assem M, et al. (2016) [142] | Alternating use of norfloxacin and rifaximin vs. norfloxacin or rifaximin alone | RCT | Decompensated LC | 334 | Primary prophylaxis of SBP | Primary prophylaxis of SBP: 74.7% vs. 56.4% vs. 68.3%, (p < 0.048). |
| Zeng X, et al. (2015) [143] | Low dose rifaximin (800 mg/day, 2 weeks) vs. high dose rifaximin (1200 mg/day, 2 weeks) vs. placebo | RCT | Decompensated LC | 43 | Endotoxemia | 1.1 ± 0.8 EU/mL in the low dose rifaximin (p < 0.05) 1.0 ± 0.8 EU/mL in the high dose rifaximin (p < 0.05) 2.5 ± 1.8 EU/mL in the control group. |
| Mostafa T, et al. (2015) [144] | Rifaximin vs. norfloxacin for 6 months | RCT | Decompensated LC | 70 | Inflammatory markers | No significant difference on TNF-α, IL-6, and IL-10. |
| Khokhar N, et al. (2015) [145] | Rifaximin 550 mg once a day vs. rifaximin 550 mg twice daily | RCT | Decompensated LC with at least one episode of HE | 306 | HE recurrence | Twenty-seven patients in rifaximin 550 mg once a day and 54 patients in rifaximin 550 mg twice daily with breakthrough episode of HE (p = 0.088). |
| Sharma K, et al. (2014) [146] | L-ornithine l-aspartate (LOLA) vs. rifaximin vs. probiotics vs. placebo for 2 months | RCT | Decompensated LC with MHE | 124 | MHE improvement | Critical flicker frequency scores and improvement in psychometric tests after treatment were significantly higher (p < 0.05) for LOLA, rifaximin, and probiotics as compared with placebo group. |
| Ali B, et al. (2014) [147] | Rifaximin 550 mg twice daily for 6 months vs. placebo | RCT | Decompensated LC with at least one episode of HE | 126 | HE recurrence | Free of hepatic encephalopathy during study period: 40 out of 63 patients in the placebo group and 35 patients out of 63 patients in the rifaximin group (p = 0.56). |
| Sharma BC, et al. (2013) [148] | Lactulose plus rifaximin 1200 mg/day vs. lactulose plus placebo | RCT | Decompensated LC with OHE | 120 | Complete reversal of HE | Forty-eight (76%) in lactulose plus rifaximin compared with 29 (50.8%) in lactulose plus placebo had complete reversal of HE (p < 0.004). |
| Kalambokis GN, et al. (2012) [149] | Rifaximin 1200 mg/day vs. no treatment | RCT | Alcoholic LC with thrombocytopenia | 23 | Thrombocytopenia | In the rifaximin group, platelet counts increased significantly (83,100 ± 9700 vs. 99,600 ± 11,200/μL; p = 0.006) with significant reductions in endotoxin (1.28 ± 0.41 vs. 2.54 ± 0.86 EU/mL; p = 0.005). |
| Sidhu SS, et al. (2011) [150] | Placebo vs. rifaximin (1200 mg/day) for 8 weeks | RCT | Decompensated LC with MHE | 94 | MHE improvement | Significantly more patients in the rifaximin group presented reversal of MHE (75.5% (37/49) vs. 20% (9/45) in the placebo group; p < 0.0001). |
| Bajaj JS, et al. (2011) [151] | Rifaximin 550 mg twice daily vs. placebo for 8 weeks | RCT | Decompensated LC with MHE and current drivers | 42 | Improvement in driving performance | Rifaximin group made significantly greater improvements than placebo group in avoiding total driving errors (76% vs. 31%; p = 0.013), speeding (81% vs. 33%; p = 0.005), and illegal turns (62% vs. 19%; p = 0.01). |
| Sanyal A, et al. (2011) [152] | Rifaximin 550 mg twice daily vs. placebo for 6 months | RCT | Decompensated LC with a documented history of recurrent HE | 219 | Chronic Liver Disease Questionnaire (CLDQ) score | The time-weighted averages of the overall CLDQ score and each domain score were significantly higher in the rifaximin group vs. placebo (p-values ranged from 0.0087 to 0.0436). |
| Bass NM, et al. (2010) [153] | Rifaximin 550 mg twice daily vs. placebo for 6 months | RCT | Decompensated LC with remission from HE | 299 | First breakthrough episode of HE | Rifaximin significantly reduced the risk of an episode of HE compared with placebo over 6 months (HR with rifaximin, 0.42; 95% CI, 0.28 to 0.64; p < 0.001). |