Immune‐mediated liver injury following COVID‐19 vaccination: A systematic review

Immune‐mediated liver injury (ILI) following coronavirus disease 2019 (COVID‐19) vaccination is not well‐characterized. Therefore, we systematically reviewed the literature on ILI after COVID‐19 vaccination. We searched PubMed, Cochrane, Ovid, Embase, and gray literature to include articles describing ILI following COVID‐19 vaccination. Reports without confirmatory evidence from liver biopsy were excluded. Descriptive analysis, and study quality were reported as appropriate. Of the 1,048 articles found, 13 (good/fair quality; 23 patients) were included. Studies were primarily from Europe (n = 8), America (n = 2), Asia (n = 2), or Australia (n = 1). Patients were predominantly females (62.5%) of age 55.3 years (49.1–61.4), with an antecedent exposure to Moderna messenger RNA (mRNA)–1273 (47.8%), Pfizer‐BioNTech BNT162b2 mRNA (39.2%), or ChAdOx1 nCoV‐19 vaccine (13%). Pre‐existing comorbidities (69.6%) were common, including liver disease in 26.1% and thyroid disorders in 13% of patients. About two‐thirds of the patients were on concurrent medications (paracetamol, levothyroxine, statins, and non‐steroidal anti‐inflammatory drugs). Jaundice was the most common symptom (78.3%). Peak bilirubin, alanine aminotransferase, and alkaline phosphatase levels were 10.8 (6.8–14.8) mg/dl, 1,106.5 (757.0–1,702.5) U/L, and 229 (174.6–259.6) U/L, respectively. Histological findings were intense portal lymphoplasmacytic infiltrate with interface hepatitis. Steroids were used in 86.9% of patients, and complete response, recovering course, and death were reported in 56.5%, 39.1%, and 4.3% of patients, respectively. ILI following COVID‐19 vaccination is rare. The diagnosis is established on temporal correlation, biochemical findings, and histopathology. Prognosis is excellent with corticosteroids. Causality establishment remains a challenge.