Submitted:
06 April 2026
Posted:
08 April 2026
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Abstract
Background: Drug-induced liver injury (DILI) is a leading cause of acute liver dysfunction and acute liver failure in the United States. Nitrofurantoin is a well-recognized cause of DILI and is associated with both acute and chronic hepatitis-like syndromes. Case Presentation: A 77-year-old male with hypertension, hyperlipidemia, and chronic obstructive pulmonary disease developed severe hepatocellular injury after two days of nitrofurantoin therapy for a suspected urinary tract infection. He presented with generalized weakness, difficulty ambulating, and mild abdominal discomfort. Laboratory evaluation revealed markedly elevated transaminases. Nitrofurantoin was discontinued, and supportive care was initiated, resulting in rapid biochemical improvement. Conclusion: Nitrofurantoin-induced hepatotoxicity may occur even after short-term exposure. Early recognition and prompt discontinuation are essential to prevent progression. This case highlights the need for vigilance when prescribing nitrofurantoin in elderly patients.
Keywords:
acute liver injury
; drug-induced liver injury
; hepatotoxicity
; nitrofurantoin
Introduction
Drug-induced liver injury (DILI) remains a major cause of acute liver dysfunction and is a leading indication for acute liver failure in the United States [1]. Nitrofurantoin, a commonly prescribed antibiotic for uncomplicated urinary tract infections, is a well- recognized cause of DILI and may produce both acute and chronic hepatitis-like syndromes [2,3]. The spectrum of injury ranges from mild asymptomatic transaminase elevations to severe acute liver failure and autoimmune-like hepatitis [2,4].
The pathogenesis of nitrofurantoin-induced hepatotoxicity is believed to be immune- mediated, involving reactive metabolites that trigger hepatocellular injury [2,4]. Although hepatotoxicity is more frequently associated with prolonged exposure, clinically significant liver injury has also been reported after short-term use, particularly in elderly patients and those with comorbid conditions [3,5].
We present a case of severe acute hepatocellular injury occurring after only two days of nitrofurantoin therapy, highlighting the potential for rapid-onset DILI and the importance of early recognition.
Case Presentation
A 77-year-old male with a history of hypertension, hyperlipidemia, and non-oxygen- dependent chronic obstructive pulmonary disease presented with generalized weakness, difficulty ambulating, and mild diffuse abdominal discomfort. He denied nausea, vomiting, jaundice, alcohol use, acetaminophen overuse, new herbal supplements, or recent medication changes.
Two days prior to presentation, he had been prescribed nitrofurantoin for a suspected urinary tract infection. Baseline liver function tests at that time were within normal limits (ALT 51 U/L, AST 37 U/L).
On presentation, he was hemodynamically stable. Physical examination revealed mild diffuse abdominal tenderness without guarding or rebound. There were no jaundice, rash, hepatosplenomegaly, or stigmata of chronic liver disease.
Table 1.
Initial Laboratory Findings.
| Parameter | Patient Value | Reference Range |
|---|---|---|
| Alanine aminotransferase (ALT) | 6147 U/L | 7–56 U/L |
| Aspartate aminotransferase (AST) | 4202 U/L | 10–40 U/L |
| Alkaline phosphatase (ALP) | 144 U/L | 44–147 U/L |
| Gamma-glutamyl transferase (GGT) | 47 U/L | 9–48 U/L |
| Total bilirubin | 1.4 mg/dL | 0.1–1.2 mg/dL |
| Direct bilirubin | 0.6 mg/dL | 0–0.3 mg/dL |
| Albumin | 4.1 g/dL | 3.5–5.0 g/dL |
| Creatinine | 1.4 mg/dL | 0.6–1.3 mg/dL |
| International Normalized Ratio (INR) | 1.3 | 0.8–1.2 |
| Acetaminophen level | <8 µg/mL | <20 µg/mL |
Evaluation for alternative etiologies was unremarkable, including negative viral hepatitis serologies and absence of alcohol misuse, herbal supplementation, or exposure to other hepatotoxic medications.
Given the strong temporal relationship between nitrofurantoin initiation and symptom onset, drug-induced liver injury was suspected. Nitrofurantoin was discontinued, and supportive care with intravenous fluids was initiated.
Table 2.
Liver Enzyme Trend Hospital Day AST (U/L) ALT (U/L).
| Day 1 | 4202 | 6147 |
| Day 2 | 3020 | 4350 |
| Day 3 | 1850 | 2650 |
| Day 5 | 640 | 920 |
The patient demonstrated rapid biochemical improvement and was discharged with outpatient follow-up.
Discussion
Nitrofurantoin is a well-recognized cause of drug-induced liver injury and may manifest as acute hepatocellular injury, cholestatic hepatitis, chronic active hepatitis, or autoimmune-like hepatitis [2,4,5]. Although more commonly associated with long-term use, clinically significant hepatotoxicity has also been reported after short-term exposure [3].
The mechanism is believed to be immune-mediated, involving reactive metabolites that bind to hepatocellular proteins and trigger inflammatory responses [2,4]. Elderly patients may be particularly susceptible due to age-related changes in hepatic metabolism and increased comorbidity burden [1].
In this case, severe hepatocellular injury developed within two days of nitrofurantoin initiation, with rapid improvement following drug discontinuation. This clinical course is consistent with previously reported cases of acute nitrofurantoin-induced hepatotoxicity [3,5].
Causality assessment using the Roussel Uclaf Causality Assessment Method (RUCAM) yielded a score of 10, consistent with a probable diagnosis of drug-induced liver injury.
Table 3.
RUCAM Causality Assessment.
| Criterion | Score |
|---|---|
| Time to onset after drug initiation | +2 |
| Course after drug withdrawal | +3 |
| Risk factors (age >55 years) | +1 |
| Concomitant drugs | 0 |
Criterion Score
Exclusion of alternative causes → +2 Known hepatotoxicity of nitrofurantoin +2 Re-exposure → 0
Total Score → 10 (Probable DILI)
Current clinical guidelines emphasize early recognition and prompt discontinuation of the offending agent to prevent progression to acute liver failure [1].
This case highlights the potential for extremely rapid onset of severe hepatocellular injury following short-term nitrofurantoin exposure and underscores the importance of maintaining a high index of suspicion in patients presenting with abrupt transaminase elevations after medication initiation.
Conclusion
Nitrofurantoin-induced liver injury may occur even after brief exposure and can result in severe hepatocellular damage. Early recognition, medication review, and prompt discontinuation are essential for favorable outcomes. Clinicians should remain vigilant when prescribing nitrofurantoin, particularly in elderly patients.
Funding
None.
Ethics Statement
Written informed consent was obtained from the patient.
Conflict of Interest
The authors declare no conflicts of interest.
References
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