Abstract
Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8-3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.
Keywords: COVID-19; DILI; RUCAM; Roussel Uclaf Causality Assessment Method; drug-induced liver injury.
【저자키워드】 COVID-19, DILI, RUCAM, Roussel Uclaf Causality Assessment Method, drug-induced liver injury., 【초록키워드】 Treatment, coronavirus disease, Clinical characteristics, India, antiviral drugs, diagnostic, Diagnosis, systematic review, drug, outcome, virus, liver diseases, Clinical features, antiviral drug, China, Characteristics, Algorithm, male, female, Spain, Aspartate aminotransferase, Liver injury, Japan, AST, drug treatment, assessment, Causality, patients, clinical feature, COVID-19 patients, ALT, Drug-induced liver injury, DILI, Liver disease, COVID-19 patient, alanine aminotransferase, Liver tests, confounding variable, Most patients, COVID-19 case, median age, therapeutic efficacy, aspartate, confounders, Alanine, Abnormalities, abnormality, Undetermined, ALT/AST, country, feature, Montenegro, hepatocellular injury, Established diagnosis, robust, defined, caused, reported, provided, searched, the mean, ranged, liver test, patients treated, 【제목키워드】 review, drug, assessment, Causality,