Follow-up Evaluation of Patients With Liver Test Abnormalities Detected During SARS-CoV2 Infection

Lidia Canillas; Teresa Broquetas; José A. Carrión; Giulia Pagano; Agnès Soriano; Esther Garrido; Rosa Fernández; Ana Viu; Judit Romero; Gemma Díaz; Nuria Cañete; Susana Coll; Dolores Naranjo; Xavier Bessa; Montserrat Garcia-Retortillo; Marc Puigvehí


J Viral Hepat. 2022;29(9):823-834. 

In This Article

Abstract and Introduction


Abnormal liver function tests (A-LFTs) during admission for coronavirus disease-19 (COVID-19) are frequent, but its evolution after COVID-19 resolution remains unexplored. We evaluated factors related to A-LFTs during COVID-19 and assessed the liver outcome after patients' discharge. This is a observational study including: (1) retrospective analysis of variables related to A-LFTs during COVID-19; and (2) follow-up evaluation with blood test, transient elastography and liver biopsy in those with persistent A-LFTs. A-LFTs were defined according to CTCAEv4.0. Among 595 patients, 366 (61.5%) showed A-LFTs. The ratio of partial pressure of oxygen and inspired oxygen fraction (P/F) below 200, ferritin ≥1000 ng/mL, male gender and antibiotic and immunomodulatory treatments were related to A-LFTs. Follow-up evaluation was performed in 153 individuals. Persistent A-LFTs at follow-up was similar in patients with/without A-LFTs during admission (14.1% vs. 4.9%, p = 0.104). Fifteen (93%) and 58 (39%) patients with/without A-LFTs at follow-up showed metabolic fatty liver disease criteria (p < 0.001), which were histologically confirmed. In conclusion, A-LFTs during COVID-19 were related to infection severity. Abnormalities remitted at follow-up in >80% of patients, and no correlation between A-LFTs at admission and at follow-up was found. Most patients with A-LFTs at follow-up had non-invasive and histologically proven fatty liver disease.


The first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) were reported in December 2019 in Wuhan, China. In Barcelona, the first cases of SARS-CoV2 infection were diagnosed at the end of February 2020. As of January 1, 2022, there have been 6.29 million cases of infection and 89,405 deaths by SARS-CoV-2 in Spain,[1] and the pandemic is having a huge damaging impact socially and economically.

Severe acute respiratory syndrome coronavirus 2 is a ribonucleic acid (RNA) virus usually transmitted among humans through the respiratory route with respiratory droplets or small particles. Angiotensin I converting enzyme 2 (ACE2) and serine proteases, such as transmembrane serine protease 2 (TMPRSS2), are key determinants for cell tropism of the virus.[2] Consequently, organs with high ACE2 and TMPRSS2 levels are the most damaged, including the respiratory tract and lungs causing acute respiratory distress syndrome (ARDS), and the digestive tract, inducing nausea, vomiting and diarrhoea.[3,4] However, COVID-19 can also affect other organs such as the brain, heart, circulatory vessels, kidneys and liver.[5]

From the beginning of the pandemic, independent cohorts of patients with SARS-CoV2 infection described liver function tests (LFTs) abnormalities, especially in transaminases levels. Increased transaminases were reported in 21%–35.5% of hospitalized patients in China,[6–8] but meta-analysis of these series estimated lower pooled prevalence rates of 15%[9] and 19%.[10] In the second half of 2020, subsequent large US series reported abnormal aspartate-aminotransferase (AST) in 74%–83.4%, and alanine-aminotransferase (ALT) in 45%–61.6% of COVID-19 patients. However, less than 20% of patients had AST or ALT more than five times the upper limit of normality (ULN).[11,12] Importantly, severe LFTs abnormalities were related to a more severe respiratory infection in all published series.[8,11–13]

Persistent symptomatology several weeks after SARS-CoV2 infection has been reported, and this new medical entity has been named post-acute COVID-19 syndrome (PACS). PACS comprises two sub-groups: first, long-COVID is the presence of symptoms after 4 weeks of infection onset; and second, the presence of sequelae is diagnosed when symptoms persist after 12 weeks of the acute infection, associated to the evidence of irreversible tissue damage.[14,15] Thus far, liver involvement in the course of PACS remains underexplored. In this regard, no data about the evolution of abnormal LFTs (A-LFTs) and liver damage after resolution of the acute infection have been reported so far.