Background: Several lines of evidence suggest that SARS-CoV-2 infection impacts liver function; however, the evaluation of these changes over time according to the disease timeline remains unclear. Objectives: The objective of this study was to identify potential alterations in liver function parameters during the first to fifth waves of COVID-19 and compare these alterations with the demographic and clinical outcomes of patients across the waves. Methods: This cross-sectional study included 1501 hospitalized patients with a confirmed RT-PCR diagnosis of COVID-19, referred to Shahid Sadoughi Hospital, Yazd, Iran, between November 20, 2019, and November 20, 2021. Liver function parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, direct bilirubin, and albumin, were assessed using standard clinical laboratory methods. Statistical analyses were conducted to evaluate differences in liver function parameters across the five pandemic waves, with significance set at P < 0.05. Results: The median age of the hospitalized patients (N = 1501) was 61 ± 21.8 years, with the majority being male (816, 54.3%). The Kruskal-Wallis test showed a significant increase in the median levels of ALP, total bilirubin, and direct bilirubin in the first wave; the AST and ALT in the third wave; and serum albumin in the second wave (P < 0.001). The median serum levels of total bilirubin and direct bilirubin were significantly higher in older patients compared to younger patients (P < 0.001), and the median ALT and serum albumin were significantly lower in older patients (P < 0.0001). In males, the median values of AST, ALT, total bilirubin, and direct bilirubin were significantly higher than in females (P < 0.0001). The median values of all parameters, except serum albumin, in deceased patients were significantly higher compared to discharged patients, and serum albumin was significantly lower. Conclusions: In this descriptive study, we observed that older and male patients were more frequently hospitalized than females. Our findings showed variations in liver parameters across different pandemic waves, suggesting distinct behaviors of various SARS-CoV-2 strains.
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