Nitrofurantoin-induced liver injury: long-term follow-up in two prospective DILI registries

Abstract

Nitrofurantoin is a synthetic antibiotic that is recommended as first-choice treatment for uncomplicated urinary tract infections. The prescription of this drug has increased dramatically, especially in Latin American countries. We described the demographics, clinical characteristics, biochemical features, and outcome of nitrofurantoin-induced liver injury. We analyzed 23 cases from the Latin American DILI Network (LATINDILI) and the Spanish DILI Registry. Causality was assessed with the RUCAM and RECAM scale. Of the 23 DILI cases included in our series, 96% patients were women, and the mean age of the whole cohort was 61 years. The median time of drug exposure was 175 days (interquartile range [IQR] 96–760), with 11 patients who were prescribed nitrofurantoin for more than six months. Hepatocellular damage was the most frequent pattern of liver injury (83%), and nearly half of the patients had an asymptomatic presentation (52%). Neither death nor liver transplantation was documented in this series. Overall, 65% of the patients (n = 15) presented with positive autoantibody titres. The median time to resolution was 81 days (IQR 57–141), and 15 patients (83%) recovered within six months. Five patients (22%) developed nitrofurantoin-induced autoimmune-like hepatitis (NI-AILH), of whom two were characterized by a persistent increase in transaminases that required immunosuppressive treatment to achieve normalization of liver enzymes. Clinicians who prescribe nitrofurantoin should be aware that patients who had taken nitrofurantoin for a long term may be at risk of developing nitrofurantoin-induced autoimmune-like hepatitis.

Clinical presentation, causative drugs and outcome of patients with autoimmune features in two prospective DILI registries

“…In addition, unlike other studies, the female sex was also significantly less represented in our cohort (58%) compared with other findings in retrospective analysis in an AIH registry (92%), 6 or the DILIN cohort (91%) 7 . These discrepancies might be related to the differences in the drugs causing liver injury, with nitrofurantoin and α‐methyldopa (more often used in female patients) being more frequently reported as causative agents in other studies 21,22 …”

“…7 These discrepancies might be related to the differences in the drugs causing liver injury, with nitrofurantoin and α-methyldopa (more often used in female patients) being more frequently reported as causative agents in other studies. 21,22 d Three patients were treated with ursodeoxycholic acid, and two patients refused to receive immunosuppressive treatment.…”

Hepatotoxicity of Antibiotics and Antifungals and Their Safe Use in Hepatic Impairment

“…4 Nitrofurantoin DILI has been recently well characterized by large prospective registries. 164 165 The American cohort consisted of 78 patients who were predominantly female with hepatocellular injury, jaundice, and autoantibody positivity at diagnosis. 164 A combined cohort from the Latin American DILI Network and the Spanish DILI Registry composed of 23 cases described similar findings as well.…”

“…164 A combined cohort from the Latin American DILI Network and the Spanish DILI Registry composed of 23 cases described similar findings as well. 165 Interestingly, in the American cohort, participants had a long latency to injury with a median of 463 days and experienced significant morbidity and mortality with 8% death or liver transplantation rate, 164 whereas the latency was much shorter in the combined cohort (median: 143 days) and no death or liver transplantation was reported. 165 Patients taking nitrofurantoin can develop an acute or chronic form of liver injury.…”

“…165 Interestingly, in the American cohort, participants had a long latency to injury with a median of 463 days and experienced significant morbidity and mortality with 8% death or liver transplantation rate, 164 whereas the latency was much shorter in the combined cohort (median: 143 days) and no death or liver transplantation was reported. 165 Patients taking nitrofurantoin can develop an acute or chronic form of liver injury. 166 Chalasani and colleagues described differences between acute versus chronic liver injury from nitrofurantoin in the American DILIN cohort.…”