Case Presentation: A 42- year- old woman with a past medical history of major depressive disorder presented to the clinic with elevated transaminases after starting duloxetine one month prior. She denied abdominal pain, sick contacts, recent travel, alcohol use, and use of herbal supplements. Her labs were notable for an ALT of 649 U/L and AST of 355 U/L (both had been normal 2 months prior), with normal total bilirubin and alkaline phosphatase. Duloxetine was held, but the transaminases continued to uptrend over the course of a month with a peak AST of 826 U/L and peak ALT of 1,118 U/L. The patient was then admitted and placed on N-Acetylcysteine for 48 hours followed by a decrease in her transaminases over the next month to an ALT of 234 U/L and AST of 83 U/L, and eventually to 12 U/L and 17 U/L, respectively over the next 2 months.
Discussion: Duloxetine can cause a delayed hepatocellular injury from 1 to 6 months of initiation. NAC has long been used as a treatment for DILIcaused by acetaminophen. N-acetyl-p-benzoquinone imine (NAPQI) is a metabolite of acetaminophen and requires glutathione for its metabolism, but when the liver’s glutathione is depleted, NAPQI causes hepatocellular necrosis. NAC restores the liver’s glutathione, thus preserving it from further damage from the metabolite. NAC increases guanylate cyclase, thus increasing the antioxidant effects of the medication and improving blood flow to the liver. Other mechanisms of action include decreasing malondialdehyde and homocysteine levels, and an overall reduction in pro-inflammatory cytokines, including interleukin-8, interleukin-6, and tumor necrosis factor-α. Reducing Reactive Oxygen Species (ROS) via the Toll-like receptors in the Kupffer cells is another mechanism of reducing liver injury. Although there are no standard guidelines for non-acetaminophen related liver injury, studies have shown that NAC, when given intravenously, improved transplant-free survival rates in these patients if they had early liver failure.
Conclusions: Given the rise in LFTs after initiating duloxetine, our patient’s DILI was likely associated with the medication. This case highlights the importance of NAC as a therapeutic agent in patients with non-acetaminophen related DILI given its properties of restoring hepatic glutathione and improving blood flow.