13 In this open-label, randomized, controlled trial of 125 patients, randomly assigned to either lactulose or non-lactulose treatment, 20% (12/61) and 47% (30/64) developed overt hepatic encephalopathy, respectively (P = 0.001).13 In this study, non-response to lactulose was reported in

patients with hyponatremia and very high venous ammonia levels.13 The study by Sharma et al. in this issue of the Journal of Gastroenterology and find more Hepatology14 examined the effectiveness of lactulose in the prevention of hepatic encephalopathy following an acute variceal bleed. The study involved the randomization of 70 patients to either 30 mL lactulose three to four times per day (ultimately to ensure 2–3 semiformed stools per day) or non-lactulose. Inclusion criteria included admission within 24 h of gastrointestinal bleed, no history of lactulose intake in the preceding 6 weeks, and no significant distracting comorbidity.14 The inclusion of patients with a prior history of encephalopathy rendered it

as neither a primary nor secondary prophylaxis study. Bleeding was assessed and managed in accordance with Baveno IV guidelines, and hepatic encephalopathy was assessed as per West Haven criteria by two independent assessors. Approximately one-sixth of patients in each group received terlipressin instead of somatostatin as a vasoactive drug. Nineteen patients developed clinically-overt hepatic encephalopathy; 14% (5/35) in the lactulose group and 40% (14/35) in the non-lactulose group (P = 0.03), giving Selleck Ulixertinib a relative risk reduction of

66%.14 The resultant increase in length of hospital stay of those who developed encephalopathy was also significant (11 ± 2.2 vs 7 ± 1.8 days, P = 0.001).14 Those in the control group were treated with lactulose therapy once hepatic encephalopathy did develop. Confounding precipitants of hepatic encephalopathy are difficult to separate, although there were no significant Meloxicam biochemical differences between the two groups. Alternative therapies for hepatic encephalopathy include antibiotics, such as neomycin, that reduce ammonia-producing bacteria. These have been used in the long-term treatment of hepatic encephalopathy.4 However, more recently, they have lost favor secondary to their side-effect profiles. Rifaximin is a semisynthetic rifamycin-based antibiotic with gut-specific action as a result of its poor solubility and absorption.15 The negligible plasma levels of rifaximin bode well for avoiding potential drug resistance.15 Solid evidence for the use of rifaximin in the treatment of hepatic encephalopathy is largely a consequence of the randomized, controlled trial conducted by Bass et al.16 In that study, rifaximin was compared to placebo in patients in remission from recurrent hepatic encephalopathy, with breakthrough episodes reported in 22% (31/140) of patients in the rifaximin group and 46% (73/159) in the placebo group (P < 0.001).