Nitrofurantoin use tied to liver injury, leading to cirrhosis, death, liver transplantation

Long-term exposure to nitrofurantoin (NTF) can result in drug-induced liver injury (DILI), which then increases the risk of parenchymal necrosis, bridging fibrosis, cirrhosis, and death or liver transplantation, reveals a study. In addition, NTF-DILI is associated with HLA-DRB1∗11:04, a risk factor for liver injury.

Between 2004 and 2020, 78 individuals with definite, highly likely, or probable NTF-DILI were enrolled into Drug Induced Liver Injury Network studies. The research team compared HLA alleles between NTF-DILI and three control groups: population (n=14,001), idiopathic autoimmune hepatitis (n=231), and non-NDT DILI (n=661).

Among cases of liver injury, 69 percent was hepatocellular and 55 percent icteric. Aspartate transaminase > alanine transaminase was more common in the 44 long-exposure (≥1 year) NTF-DILI cases than in the 18 short (≤7 days) and 16 intermediate (>7 to <365 days) exposure cases (73 percent vs 33 percent vs 50 percent; p=0.018).

Likewise, antinuclear or smooth muscle antibody positivity (91 percent vs 44 percent vs 50 percent; p<0.001) and corticosteroid use (61 percent vs 27 percent vs 44 percent; p=0.06) were greater in long-exposure NFT-DILI cases.

Among patients with long-term NTF-DILI, 38 percent presented with bridging fibrosis, nodularity or cirrhosis, or clinical and imaging evidence for cirrhosis, with massive or sub-massive cirrhosis in 20 percent. None of those with short-term exposure died or had transplantation, while seven (12 percent) from other groups died or underwent transplantation.

Adjustments for covariates revealed that HLA-DRB1∗11:04 was more common in NTF-DILI than in population controls (odds ratio [OR], 4.29; p=1.15 x 10^-4), idiopathic autoimmune hepatitis (OR, 11.77; p=7.76x10^-5), and non-NTD DILI (OR, 3.34; p=0.003).

“To mitigate against serious liver injury associated with NTF, regulators should revise the prescribing information and consider other mitigation strategies,” the investigators said.

NTF is used for the treatment (short term) and prevention (long term) of urinary tract infections.