Long-term effects of L-carnitine on hyperammonemia and hepatic encephalopathy in patients with liver cirrhosis: a multicenter retrospective study

Objective Long-term efficacy data for L-carnitine in managing blood ammonia concentration (BAC) and preventing hepatic encephalopathy recurrence remain limited. This multicenter study examined the long-term effects of L-carnitine on BAC, hepatic encephalopathy–related events, and clinical outcomes in patients with liver cirrhosis. Methods Of 444 patients who received L-carnitine between April 2012 and March 2021, we enrolled 242 patients with hyperammonemia or hepatic encephalopathy (median Child–Pugh score 9) in this retrospective study across four institutions. Results Median BAC decreased from baseline 123 μg/dl to 95.5, 88, 83, 96, and 86 μg/dl at 12, 24, 48, 96, and 192 weeks, respectively (all P < 0.05). BAC normalization occurred at a median of 100 days overall, but significantly faster at 63 days with initial doses more than 1500 mg/day versus 4.7 months with less than or equal to 1500 mg/day ( P = 0.0034). Among 113 patients followed for 2 years pre- and posttreatment, hepatic encephalopathy–related hospitalizations decreased dramatically from 183 to 62 ( P < 0.001). Cumulative hepatic encephalopathy–related event incidence at 6, 12, and 24 months was 15.5, 18.1, and 23.7%, respectively. Model for End-Stage Liver Disease scores improved significantly at 1 year ( P = 0.0059). Multivariate analysis identified ascites, albumin–bilirubin score, and HCC as independent prognostic factors for survival. Only 2.1% of patients experienced mild, transient gastrointestinal adverse events (all grade 1). Conclusion Long-term L-carnitine administration effectively reduces BAC and hepatic encephalopathy–related hospitalizations with excellent safety. Higher initial doses (>1500 mg/day) achieve more rapid BAC normalization and should be considered for patients with significant hyperammonemia.