Norfloxacin Therapy for Hepatopulmonary Syndrome: A Pilot Randomized Controlled Trial

Background & Aims The hepatopulmonary syndrome occurs in up to one-third of patients with cirrhosis. Animal models of this disease suggest that endotoxemia might cause nitric oxide–mediated vascular dilatation that can be inhibited by the antibiotic norfloxacin. We sought to test this hypothesis in humans. Methods We conducted a pilot randomized, controlled crossover trial of norfloxacin 400 mg twice daily for 4 weeks with a 4-week washout period to assess the feasibility of a larger trial. The primary clinical end point was change in alveolar-arterial oxygen gradient (AaDO2 ). Results Recruitment was challenging, and change in AaDO2 was highly variable. We recruited 9 adults (1 woman; age, 60 ± 9 years; AaDO2 , 50 ± 22 mm Hg). AaDO2 decreased by 0.8 ± 4.8 and 3.4 ± 12.4 mm Hg while on norfloxacin and placebo, respectively ( P = .59). Conclusions Recruitment difficulties and variability of the primary outcome measure suggest the need for a multicenter clinical research network for future therapeutic trials in this disease. There was no major effect of norfloxacin on gas exchange in patients with hepatopulmonary syndrome.