Human Metapneumovirus-associated Liver Enzyme Elevation in Children: Case Series of Nine Patients

To the Editors: Human metapneumovirus (HMPV) is an enveloped RNA virus belonging to the Paramyxoviridae family and was first identified in the Netherlands in 2001. HMPV is one of the leading causes of upper and lower respiratory tract infections in children and has a particularly high incidence in the 0–4-year age group.1 Although the infection is self-limiting in most cases, neurologic and cardiac complications and, rarely, liver involvement have been reported.2 In viral respiratory infections, hepatic involvement usually manifests as elevated serum transaminases. While well described in respiratory syncytial virus, influenza, adenovirus, and Epstein-Barr virus, marked elevation due to HMPV is rare and may result from direct viral invasion, immune-mediated injury, or systemic inflammation.3 In this study, we present 9 pediatric cases with confirmed HMPV infection by respiratory tract polymerase chain reaction panel and concomitant marked transaminase elevation. Our aim is to raise awareness of hepatic involvement as a rare but clinically significant manifestation of HMPV infection. The clinical and demographic summary of the cases is presented in Table 1. TABLE 1. - Clinical and Demographic Characteristics of the Cases No Age(Year) Sex Disease ALT (U/L) AST (U/L) Time to Normalization (Days) 1 10 Male None 1499 775 13 2 1 Male None 686 542 8 3 1 Male None 4145 3382 17 4 7 Male HydrocephalusLaryngomalaciaTracheostomy 99 167 6 5 6 Male Hodgkin lymphoma 131 137 5 6 0.75 Female LaryngomalaciaSitus inversus totalis 68 94 10 7 0.75 Male None 741 926 75 8 2 Female Sandhoff 145 194 8 9 1,5 Male None 142 121 10 Median 145 194 Mean 850.6 704.2 ALT indicates alanine aminotransferase; AST, aspartate aminotransferase. This study represents one of the largest pediatric case series in the literature demonstrating marked transaminase elevation associated with HMPV infection. While previous reports have mostly described mild elevations in transaminases related to HMPV, in our series alanine aminotransferase (ALT) and/or aspartate aminotransferase levels were observed to reach much higher values, in some cases approaching levels suggestive of viral hepatitis. Furthermore, a significant proportion of our patients were otherwise healthy children, in whom transaminase elevation emerged as the only additional systemic finding accompanying respiratory symptoms. In this respect, our study provides a unique contribution by demonstrating that HMPV may present with a broader clinical spectrum than expected and that hepatic involvement can occur in the absence of underlying serious liver disease. Transaminase elevation associated with HMPV infection has been reported in only a few cases. Kamin et al4 evaluated transaminase levels in 1010 children diagnosed with respiratory viral infections and found liver enzyme elevation in 14.6% of the HMPV group; however, this elevation was mostly mild, with a median ALT of 40 U/L. In a multicenter study conducted in 2018, HMPV was detected in 16 (2.6%) of 613 patients with elevated transaminase levels, and normalization occurred within a median of 12.5 days.5 In our study, the median ALT and aspartate aminotransferase levels were 145 and 194 U/L, respectively. This difference may be explained by the fact that, unlike the study by Kamin et al, which included all HMPV cases in the population, our cohort consisted exclusively of patients who were specifically referred due to elevated transaminase levels. This case series demonstrates that HMPV infection can sometimes present with marked transaminase elevation, which may occur both in otherwise healthy children and in those with underlying diseases. Our findings highlight the importance of assessing liver function tests during clinical follow-up in such cases. Furthermore, although the prognosis is generally favorable, the presence of concomitant severe systemic diseases may increase the risk of mortality.