S3067 Liver Histology Findings in COVID-19 Vaccine-Induced Hepatitis: A Case Series

Abstract

Introduction: There have been reported cases of hepatitis after COVID-19 vaccination. The previously described clinical presentations and histology findings have been heterogenous, making it difficult to identify a definitive pattern of liver injury. We present a series of three patients with elevated liver enzymes after Pfizer COVID-19 vaccination who underwent liver biopsy. Case Description/Methods: Patient 1, a 32-year-old male in good health, presented with elevated liver enzymes on routine outpatient labs. He was asymptomatic and physical exam was unremarkable. He had received his second dose of the COVID vaccine 27 days prior. Serologic liver workup and biopsy findings can be found in Table 1. He was treated with ursodiol 500 mg twice daily, with significant improvement in liver enzymes after 30 days. Patient 2, a 56-year-old male with history of diabetes presented with nausea, pruritis and painless jaundice. Jaundice and diffuse excoriations were seen on exam. Liver enzymes were elevated and serologic liver workup and biopsy findings can be found in Table 1. His third COVID-19 vaccination was 5 days prior to presentation. The patient was treated with IV steroids for 5 days, with short term improvement in liver enzymes. Patient 3, an 85-year-old male with history of dyslipidemia and NSTEMI presented with dark urine and poor oral intake. Scleral icterus was noted on physical exam. Liver enzymes were elevated, and serologic liver workup and biopsy findings can be found in Table 1. He received his third COVID-19 vaccine 4 days prior. He was treated with prednisone taper with complete resolution of liver enzymes after 3 months. Discussion: This case series suggests a possible correlation between Pfizer COVID-19 vaccination and hepatitis as demonstrated by liver biopsy findings. All three patients had no prior history of underlying liver disease, alcohol use or identifiable risk factors. Patient presentation was variable in terms of clinical symptoms, serologic workup and even histology findings. The common thread was elevated immunoglobulins suggesting an immune component without findings of autoimmune hepatitis. This is consistent with a previously published case series of COVID-19 vaccine-induced hepatitis. We share our findings to add to the collective repository of COVID-19 vaccine-induced hepatitis to add to existing literature and with the hope of increasing awareness. Table 1. - This table depicts demographic information, pertinent work up, and treatment of each case Case Age, Sex, BMI Pertinent Medical History Vaccine Type, Dose, Timing* Associated Symptoms Peak Lab Values Pertinent Work Up (negative unless listed) Liver Biopsy Clinical Course AST (U/L) ALT (U/L) ALP (U/L) T bili (mg/dL) INR (ratio) 1 32 male25.1 NoneNo prior liver disease Pfizer-BioNTechDose #227 days None 222 372 666 1.4 1.1 IgG 1,670 mg/dLCross-sectional imaging within normal limits Chronic hepatitis with mild-moderate fibrosis (Grade 1-2, Stage 2) Mild centrilobular changes with steatosis Treatment with ursodiol 500 mg twice daily for 30 daysImproving 2 56 male30.5 Recent acute cholecystitis, type 2 diabetes mellitusNo prior liver disease Pfizer-BioNTechDose #3 (booster)5 days Nausea, vomiting, jaundice, scleral icterus, pruritis, dark urine, weight loss 474 395 860 23.6 1.4 IgA 640 mg/dLIgG 2,230 mg/dL, IgG subclass 4,153 mg/dL+ANA 1:640, +ASMA 1:320Ferritin 3,775 ng/mLMRCP: cholelithiasis with possible acute cholecystitis, no biliary duct dilatation, no choledocholithiasis Mild nonspecific periportal edema with mildly prominent periportal lymph nodes Cholestatic hepatitis, stage 3 out of 4 NASH, tissue IgG4 immunostains unremarkable (1+ out of 4) Treatment with IV methylprednisolone 100 mg x5 days, followed by 60 mg prednisone daily for 30 days with short term improvement 3 85 male27.8 Hypo-thyroidism dyslipidemiaNo prior liver disease Pfizer-BioNTechDose #3 (booster) 4 days Dark urine 2354 2221 313 15.9 1.2 IgG 1,770 mg/dL, IgG4 212 mg/dLANA+, ASMA+ 1:20CT scan A/P with IV contrast: acute interstitial pancreatitis, gallbladder wall thickeningMRI: normal liver contour & size, without evidence of hepatic steatosis Acute hepatitisSteatohepatitis, moderate inflammation, marked ballooning degeneration and no significant sinusoidal fibrosis Treatment with prednisone 40 mg daily, then tapered over 3 months Normalized AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; T bili, total bilirubin; IgG, immunoglobulin G; IgA, immunoglobulin A; ANA, anti-nuclear antibody; ASMA, anti-smooth muscle antibodies; MRCP, magnetic resonance cholangiopancreatography; DILI, drug-induced liver injury; NASH, non-alcoholic steatohepatitis *In association with COVID vaccine