Abnormal liver chemistry in patients with influenza A H1N1

To the Editor: Liver chemistry abnormalities during influenza A H1N1 infections have been poorly characterized. An observational study of liver tests was conducted on patients with influenza A H1N1 in Shanghai during the 2009 pandemic. From 30 May to 14 July 2009, all laboratory-confirmed cases of influenza A H1N1 admitted to the hospital were reviewed. Blood samples for liver tests were taken on admission, before patients received oseltamivir treatment (75 mg b.i.d. for 5 days for adults, 2 mg/kg b.i.d. for 5 days for children). Liver tests consisted of liver enzymes, bilirubin, bile acids and others (Table 1). Samples were quantified by the Roche Modular P-800 system (Roche Diagnostics Ltd, Shanghai, China). Correlations between any two variables were determined by Spearman’s rank correlation. Classification of indices was analysed by hierarchical cluster (between groups linkage, squared Euclidean distance). Statistical analysis was performed using SPSS 18. All 224 patients had undetectable H1N1 RNA after the treatment and were discharged from hospital within a week. One hundred and thirty-one patients (58%) had abnormal liver tests. Seventy-eight per cent were Chinese, and 55% were males. The age was 21 6 years (median interquartile range). There were 46 children (2–18 years) and 85 adults (4 18 years). The time of onset was 2 0.5 days. No abnormal liver test correlated with age or gender. Only an abnormal pre-albumin was significantly related to the time of onset (Po 0.01). Pre-albumin was the most frequent abnormal index. Abnormal pre-albumin was correlated negatively with alanine transaminase (ALT) and g-glutamyl transpeptidase (Po 0.05). Pre-albumin and LDH composed the cluster that had the highest number of patients. Abnormal g-globulin was correlated positively with total serum protein (Po 0.01), and negatively with pre-albumin (Po 0.01). g-Globulin, total serum protein and albumin were isolated from clusters of other indices. The incidence of abnormal liver tests in this study is higher than the 26.6 or 20% reported in the previous study where only aminotransferases were measured (1). This is because pre-albumin was the most frequent abnormal test in our patients. Pre-albumin is synthesized in the liver and lasts for 2 days in the human body. It suggests that dysfunction of protein synthesis is a sign of early liver injury caused by influenza A H1N1. Abnormal pre-albumin, which often appeared in isolation, was associated with the time of onset. This suggests that indices of hepatic dysfunction vary with time during the period of H1N1 infection. Another clue is that abnormalities of the repeat liver tests were different from the first tests. However, without repeating liver tests on all the patients and performing liver biopsies, it is difficult to confirm this hypothesis. g-Globulin is synthesized by B lymphocytes. Abnormal g-globulin did not correlate with other liver tests except total serum protein. It suggests that humoral immunity has no influence on liver function during influenza A H1N1 infection, although the rise in influenza antibody titre had been more frequent in case of abnormal ALT in the previous research (2). This is because ALT cannot independently represent hepatic dysfunction very well. A mouse model has shown that hepatic inflammation is related to T-cell activation instead of a direct cytopathic effect of the H1N1 virus itself (1). Therefore, an indirect effect of immune activity may be the pathogenesis of liver dysfunction in influenza A H1N1 infection.