LAUSR

Coronavirus Disease 2019 (COVID-19), due to infection with the virus termed SARS-CoV-2, has complicated the evaluation of elevated liver enzymes. Elevated liver enzymes occur in a median of 15% [1] and up to 58% [2] of patients with COVID-19. Though the most common patterns of liver enzyme abnormalities in patients with SARS-CoV-2 include elevated aminotransferases, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) typically 1–2 times the upper limit of normal [2], the prognostic significance of abnormal liver biochemistries remains uncertain. There are many potential contributing etiologies to elevated liver enzymes in patients with SARS-CoV-2 including direct liver injury, associated inflammatory responses, congestive hepatopathy, hepatic ischemia, drug-induced liver injury (DILI), and muscle breakdown [3, 4]. In one meta-analysis, an estimated 3% of patients had recognized chronic liver disease at the time of COVID-19 infection [5]. As a result, consultations for abnormal liver biochemistries in patients with COVID-19 are likely common and difficult to resolve. Clarifying a diagnosis is further complicated by the desire to limit exposure of staff assisting with or performing diagnostic testing (e.g., abdominal ultrasound or liver biopsy). In this context, there is need for more information on how best to evaluate these patients. In the current issue of Digestive Diseases and Sciences, Bloom et al. [6] demonstrate the diagnostic difficulties of evaluating elevated liver enzymes in patients with COVID19. The authors identified twenty adult inpatients at Massachusetts General and Brigham and Women’s Hospitals who were PCR-positive for SARS-CoV-2 and received inpatient hepatology consultations for abnormal liver biochemistries. Laboratory and clinical data were retrospectively reviewed by three senior hepatologists who assigned a rank-order list of the top three potential etiologies, providing recommendations for additional evaluations. Patients with COVID-19 in this study were middle-aged (median 46 years), 90% male, 55% Hispanic, and 40% had underlying chronic liver disease. Most had a hepatocellular (64%) or cholestatic (29%) pattern of liver biochemistries. Blood chemistries reflective of liver synthetic function were generally normal. The most common diagnoses for these patients were COVID-related liver injury and DILI, but agreement on the most likely diagnosis was low among the three hepatologists and the original consultant (κ agreement 0.10). Conversely, all were in general agreement with the diagnostic work-up, which included liver enzyme monitoring for all patients. Abdominal ultrasound was recommended for a minority and was often discouraged. Similarly, cross-sectional imaging and liver biopsy were not recommended for any patients. This investigation of the diagnosis and work-up of elevated liver enzymes in patients with COVID-19 provides a timely glimpse into the difficulties encountered caring for these patients. However, study results should be interpreted in the context of potential limitations. This study included a small patient sample, and results may lack generalizability to other settings given that it was conducted at a large academic medical center early in the US COVID-19 epidemic (March–April 2020), when understanding of the hepatic effects of SARS-CoV-2 was limited. Furthermore, restricting this cohort to patients with a hepatology consultation may have selected for more complex patients, which could account for the large proportion of included patients with chronic liver disease. Lastly, without follow-up data in these patients, it is impossible to evaluate the accuracy of the ranked diagnoses. These potential limitations do not diminish the immediate clinical implications of this study. These results underscore the immense diagnostic challenge of elevated liver enzymes in COVID-19, given the large degree of disagreement among * Andrew M. Moon [email protected]