Patterns of Acute Liver Injury and Post‐Acute Liver Sequelae of COVID‐19

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ABSTRACT Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is known to cause acute liver injury (ALI) in COVID‐19 patients. This study explores the association between ALI patterns and the occurrence of long‐term hepatic complications in patients with and without existing chronic liver disease (CLD). Methods Within the Veterans Health Administration system, we identified patients testing positive for SARS‐CoV‐2. ALI was categorised based on injury type within the first 30 days post‐infection into hepatocellular, cholestatic, or mixed patterns. Cox regression was employed to analyse the link between ALI types and hepatic complications post‐acute COVID‐19 phase in patients with and without pre‐existing CLD. Results Of 173 111 COVID‐19 patients, 1843 (1.1%) suffered from ALI: 1542 hepatocellular, 180 cholestatic and 121 mixed. Among these, 51 291 (29.6%) had pre‐existing CLD. Post‐acute hepatic dysfunction was notably higher in ALI patients, with adjusted hazard ratios (aHR) of 2.19 for hepatocellular, 1.57 for cholestatic and 5.75 for mixed injuries. Patients with pre‐existing alcohol‐associated liver disease had a significantly increased risk of decompensation (aHR = 6.86), followed by those with Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD) (aHR = 1.56). Conclusions COVID‐19–associated ALI was associated with increased risk of post‐acute hepatic dysfunction and decompensation, with the highest risk observed among patients with a mixed hepatocellular‐cholestatic injury pattern. Among patients with pre‐existing CLD, ALD was most strongly associated with subsequent hepatic decompensation, while MASLD showed a more modest association.

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