Sex: F
Vaccine: COVID19
Symptoms: Herpes simplex test, Human papilloma virus test, Influenza virus test, International normalised ratio, Investigation
Clinical narrative: A Rare Case of COVID-19 Vaccination-Induced Cholangiopathic Liver Injury; This is a literature report.  An 89-year-old woman with a medical history of anxiety and atrial fibrillation, currently receiving apixaban, presented to the emergency department with yellowing of the skin for the past week. In addition, the patient reported a reduction in oral intake, weight loss, and constipation. There was no recent history of rash, fever, travel, alcohol overuse, antibiotics use, over-the-counter medications including herbal supplements, or illicit or recreational drug use. The patient had not undergone any medication changes, except for receiving the first shot of the tozinameran COVID-19 vaccine 2 weeks before presentation. She had never tested positive for COVID-19. Her only home medications were alprazolam and apixaban, which she had been taking for years without any adverse effects. The patient was hemodynamically stable, at rest, without any acute distress, and showed no indications of chronic liver disease such as hepatosplenomegaly, ascites, or encephalopathy on physical examination. Comprehensive metabolic panel revealed elevated liver enzymes, including a total bilirubin level of 23.4 mg/dL (reference range: 0.2-1.3 mg/dL), direct bilirubin level of 10 mg/dL, aspartate aminotransferase of 46, alanine aminotransferase of 59, and gamma-glutamyl transpeptidase of 113 U/L. The R factor was 0.7, indicative of cholestatic injury. Despite undergoing an extensive workup, all potential causes of elevated liver enzymes were negative. Abdominal ultrasound and computed topography scan were unremarkable. Magnetic resonance cholangiopancreatography demonstrated diffuse hypointensities of the liver and spleen on T2-weighted sequences, with concern for hemochromatosis. A panel for hereditary hemochromatosis was performed, revealing only 1 copy of the H63D pathogenic variant of the HFE gene, along with a serumferritin level of 200.7 and a transferrin saturation of 40%. Moreover, the negative Prussian blue stain on the liver tissue biopsy ruled out the presence of tissue deposition of iron, thereby eliminating the possibility of hemochromatosis. The liver biopsy findings of the patient revealed severe cholestasis and bile duct damage, indicating liver injury attributed to COVID-19 vaccine-induced cholangiopathy. Based on the clinical history, biopsy results, and a Causality Assessment Method score of 6, the patient was diagnosed with DILI caused by the COVID-19 vaccine. During hospitalization, the patient's laboratory values showed gradual improvement with supportive management, and she was discharged in a stable condition with a resumption of her prehospitalizationmedications, except for the COVID-19 vaccine. A follow-up appointment was scheduled 12 weeks (84 days) after the initial presentation, and the patient's results demonstrated complete resolution of jaundice and liver chemistries. DILI is the leading cause of acute liver failure, with intrinsic and idiosyncratic types and a multifactorial etiology involving drugs, genetics, and environmental factors. The study by authors across 18 countries found that COVID-19 vaccines commonly cause a hepatocellular pattern of injury, with 84% of patients displaying this injury pattern after vaccination. This case is notable for highlighting the occurrence of a cholangiopathic pattern of DILI after COVID-19 vaccination, which has rarely been reported. The cholestatic-type drug-induced liver injury observed in our case was not unexpected because cholangiocytes have a high concentration of ACE2 receptors. SARS-CoV-2 specifically targets ACE2-expressing tissues and binds to receptors through its spike protein. COVID-19 vaccines like tozinameran use mRNA technology to produce a spike protein that is specific to SARS-CoV-2. This spike protein is recognized by the immune system, triggering an immune response to prevent or mitigate COVID-19 infection. There is a strong possibility of an idiosyncratic reaction between theCOVID-19 vaccine and cholangiocytes rich in ACE2 expression, possibly because of cross-reactivity between the ACE2 expression by cholangiocytes and the spike protein produced by the mRNA vaccines. To diagnose DILI, it is crucial to establish a correlation between drug exposure and the onset of liver disease, while eliminating any other potential causes. In this particular case, patients did not take any new medications or over-the-counter supplements and potential causes related to hepatitis were also ruled out. Given the temporal relationship between vaccine administration and symptom onset, there is a suspicion that the patients may have developed DILI because of the vaccine. In addition, although the usefulness of liver biopsy as a diagnostic tool is uncertain, it aided in both diagnosing DILI and eliminating other causes of liver damage in our patient. At present, the prompt identification and discontinuation of the precise diagnosis, identification, and cessation of the causative agent. Although drug withdrawal is the primary strategy, outcomes can range from complete resolution to acute liver failure, and severe cases may necessitate liver transplantation. This report stresses the significance of monitoring for DILI as a COVID-19 vaccine complication in high-risk patients. Further research is needed to understand the mRNA vaccine's spike protein impact on ACE2 expression in cholangiocytes. Timely detection and management of DILI is critical, and drug cessation is the primary treatment. Ongoing research is required to develop effective therapeutic interventions and comprehend the complex etiology of DILI. Causative agent stand as the primary therapeutic approach for the management of DILI because no pharmacological interventions have been authorized for this condition. Although the evidence is insufficient, steroids are recommended for the management of DILI and acute liver failure. Corticosteroids are frequently used and backed by the observations of the Drug-Induced Liver Injury Network. The findings demonstrate that corticosteroids were administered to 82% of patients who died or underwent liver transplants, as well as 36.6% of patients who were alive with the native liver at 6 months. The management of DILI requires precise diagnosis, identification, and cessation of the causative agent. Although drug withdrawal is the primary strategy, outcomes can range from complete resolution to acute liver failure, and severe cases may necessitate liver transplantation. This report stresses the significance of monitoring for DILI as a COVID-19 vaccine complication in high-risk patients. Further research is needed to understand the mRNA vaccine's spike protein impact on ACE2 expression in cholangiocytes. Timely detection and management of DILI is critical, and drug cessation is the primary treatment. Ongoing research is required to develop effective therapeutic interventions and comprehend the complex etiology of DILI.; Sender's Comments: Based on the known the information available the Causal relation between the events Drug-induced liver injury and suspect drug cannot be excluded completely The impact of this report on the benefit/risk profile of the Pfizer drug is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees, and Investigators, as appropriate.