Sex: F
Vaccine: COVID19
Symptoms: Alanine aminotransferase, Alpha 1 foetoprotein, Alpha-1 antitrypsin deficiency, Antibody test, Antinuclear antibody
Clinical narrative: Drug-Induced Liver Injury; This is a literature report.  A 61 year-old female patient received bnt162b2 (PFIZER-BIONTECH COVID-19 VACCINE), administration date Jan2021 (Batch/Lot number: unknown) as dose 2, single for covid-19 immunisation. Relevant medical history included: "Irritable bowel disease" (unspecified if ongoing); "cholecystectomy" (unspecified if ongoing); "fatty liver disease" (unspecified if ongoing), notes: This patient has underlying fatty liver disease. The patient's concomitant medications were not reported. Vaccination history included: Covid-19 vaccine (DOSE 1; MANUFACTURER UNKNOWN), for COVID-19 immunisation. The following information was reported: DRUG-INDUCED LIVER INJURY (hospitalization) with onset Jan2021, outcome "recovered" (2021), described as "Drug-Induced Liver Injury". The patient was hospitalized for drug-induced liver injury (start date: Jan2021, discharge date: Feb2021). The event "drug-induced liver injury" was evaluated at the emergency room visit. The patient underwent the following laboratory tests and procedures: alanine aminotransferase: (06Apr2018) 20, notes: U/L; (29Jan2021) 37, notes: U/L; (30Jan2021) 30, notes: U/L; (31Jan2021) 22, notes: U/L; (01Feb2021) 22, notes: U/L; (02Feb2021) 20, notes: U/L; (03Feb2021) 22, notes: U/L; (04Feb2021) 20, notes: U/L; (05Feb2021) 19, notes: U/L; (06Feb2021) 20, notes: U/L; (19Feb2021) 25, notes: U/L; (09Mar2021) 16, notes: U/L; (08Apr2021) 11, notes: U/L; (02Jun2021) 11, notes: U/L; alpha 1 foetoprotein: (unspecified date) negative; alpha-1 antitrypsin deficiency: (unspecified date) negative; antibody test: (unspecified date) negative, notes: less than or equal to 20 = negative, reference range; (unspecified date) negative, notes: less than or equal to 20 = negative, reference range; antinuclear antibody: (unspecified date) negative; aspartate aminotransferase: (06Apr2018) 16, notes: U/L; (29Jan2021) 37, notes: U/L mildly elevated; (30Jan2021) 28, notes: U/L; (31Jan2021) 20, notes: U/L; (01Feb2021) 20, notes: U/L; (02Feb2021) 29, notes: U/L; (03Feb2021) 36, notes: U/L; (04Feb2021) 34, notes: U/L; (05Feb2021) 29, notes: U/L; (06Feb2021) 30, notes: U/L; (19Feb2021) 35, notes: U/L; (09Mar2021) 24, notes: U/L; (08Apr2021) 15, notes: U/L; (02Jun2021) 14, notes: U/L; bilirubin conjugated: (unspecified date) 3.9 mg/dl; biopsy liver: (unspecified date) minimal pallor suggesting slight edema, notes: minimal pallor suggesting slight edema along with scattered inflammatory cells consisting of small lymphocytes, scattered polymorphonuclear leukocytes, and few eosinophils, no evidence of florid duct lesion on interface hepatitis, and no evidence of fibrosis on trichrome and reticulin stain; blood albumin: (06Apr2018) 3.7 g/dl; (29Jan2021) 3 g/dl; (30Jan2021) 3 g/dl; (31Jan2021) 4.4 g/dl; (01Feb2021) 3.1 g/dl; (02Feb2021) 2.8 g/dl; (03Feb2021) 3.1 g/dl; (04Feb2021) 3 g/dl; (05Feb2021) 2.8 g/dl; (06Feb2021) 2.9 g/dl; (19Feb2021) 3.9 g/dl; (09Mar2021) 4.1 g/dl; (08Apr2021) 4.1 g/dl; (02Jun2021) 4.1 g/dl; blood alkaline phosphatase: (06Apr2018) 91, notes: U/L; (29Jan2021) 207, notes: U/L; (30Jan2021) 181, notes: U/L; (31Jan2021) 208, notes: U/L; (01Feb2021) 254, notes: U/L; (02Feb2021) 293, notes: U/L; (03Feb2021) 367, notes: U/L; (04Feb2021) 348, notes: U/L; (05Feb2021) 329, notes: U/L; (06Feb2021) 366, notes: U/L; (19Feb2021) 231, notes: U/L; (09Mar2021) 162, notes: U/L; (08Apr2021) 130, notes: U/L; (02Jun2021) 96, notes: U/L; blood bilirubin: (06Apr2018) 1 mg/dl; (29Jan2021) 6.2 mg/dl; (30Jan2021) 6.5 mg/dl; (31Jan2021) 5.7 mg/dl; (01Feb2021) 3.6 mg/dl; (02Feb2021) 3.6 mg/dl; (03Feb2021) 3.3 mg/dl; (04Feb2021) 2.5 mg/dl; (05Feb2021) 2 mg/dl; (06Feb2021) 1.7 mg/dl; (19Feb2021) 1.2 mg/dl; (09Mar2021) 0.9 mg/dl; (08Apr2021) 1 mg/dl; (02Jun2021) 1.3 mg/dl; body temperature: (unspecified date) 99.9 Fahrenheit; ceruloplasmin (18-53): (unspecified date) 38 (negative); computerised tomogram abdomen: (unspecified date) showed no acute abnormalities; gamma-glutamyltransferase (1-24): (unspecified date) 103, notes: U/L; heart rate: (unspecified date) between 90 and 110, notes: Beats per minute, tachycardia; hepatitis a antibody: (unspecified date) negative; hepatitis b core antibody: (unspecified date) negative; hepatitis b surface antigen: (unspecified date) negative; hepatitis c antibody: (unspecified date) negative; investigation: (unspecified date) negative; magnetic resonance cholangiopancreatography: (unspecified date) no filling defect within t, notes: no filling defect within the biliary duct, status post cholecystectomy, bile duct diameter within a normal range and unremarkable liver; physical examination: (unspecified date) conjunctival icterus, mild generalized abdominal t, notes: conjunctival icterus, mild generalized abdominal tenderness without guarding, or rigidity; serum ferritin (10.0-291.0): (unspecified date) 975.2 ng/ml; smooth muscle antibody: (unspecified date) negative; ultrasound abdomen: (unspecified date) increased echogenicity, notes: increased echogenicity within the liver compatible with fatty infiltrates, and common duct diameter was measured to be 6 mm; vital signs measurement: (unspecified date) stable except for tachycardia; white blood cell count: (unspecified date) 17.2 x10 9/l; (unspecified date) trended down. Therapeutic measures were taken as a result of drug-induced liver injury. Clinical course and discussion: A 61-year-old female with a known history of irritable bowel disease and cholecystectomy presented to the emergency department with generalized weakness, body aches, dry heaving, and a low-grade temperature of 99.9 Fahrenheit. The patient received a second dose of the Pfizer COVID-19 vaccine nine days before the start of symptoms. She was noted to have conjunctival icterus, mild generalized abdominal tenderness without guarding, or rigidity on physical examination. On admission, the patient's vitals were stable except for tachycardia with a heart rate between 90 and 110 beats/min. Laboratory analysis was remarkable for elevated alkaline phosphatase (ALP) of 207 U/L, total bilirubin of 6.2 mg/dL, direct bilirubin of 3.9 mg/dL, white blood cell (WBC) count of 17.2 x 10^9 /L, and mildly elevated aspartate transaminase of 37 U/L (Table 1 "Liver function tests trend" and Figure 1 "Graphs showing liver function test trends"). Abdominal ultrasound showed increased echogenicity within the liver compatible with fatty infiltrates, and common duct diameter was measured to be 6 mm. At the same time, CT of the abdomen with contrast showed no acute abnormalities. The patient was admitted to the hospital and started on empiric antibiotics for presumed cholangitis. Gastroenterology consultation was obtained. Magnetic resonance cholangiopancreatography without contrast showed no filling defect within the biliary duct, status post cholecystectomy, bile duct diameter within a normal range, and unremarkable liver. The patient remained afebrile, WBC trended down, and abdominal pain improved over the course of the hospital stay. Given these findings, infectious disease specialist recommended discontinuing antibiotics. Antibodies to liver/kidney microsomal type 1, smooth muscle, anti-mitochondrial, alpha-1 antitrypsin came back negative, and, additionally, ceruloplasmin, antinuclear antibody, alpha fetoprotein, and viral serologies for hepatitis A, B, and C came back negative (Table 2 "Immunologic and infectious work-up for liver disease"). Liver biopsy showed minimal pallor suggesting slight edema along with scattered inflammatory cells consisting of small lymphocytes, scattered polymorphonuclear leukocytes, and few eosinophils, no evidence of florid duct lesion on interface hepatitis, and no evidence of fibrosis on trichrome and reticulin stain. Given that all work-up for infection, autoimmune diseases, and any obstruction came back negative, the patient's clinical picture and laboratory findings were attributed as a liver injury due to the COVID-19 vaccine. Her liver function levels continued to trend down, and she was discharged from the hospital after a week of hospitalization. On the patient's follow-up with a gastroenterologist, abdominal pain was resolved, and her liver function test values normalized (Table 1 and Figure 1). In this case, the review of medications and history did not reveal any other reason for hepatotoxicity. She also denied the use of any over-the-counter medications or supplements. Although it is rare with vaccination, the COVID-19 vaccine is likely the cause of hepatotoxicity in our patient based on a diagnosis of exclusion. In this case, the patient had a cholestatic pattern with elevated ALP and bilirubin with mild elevation in the transaminases. This patient has underlying fatty liver disease. It is unclear if that was a likely risk factor for hepatotoxicity in this case. Hepatotoxicity can occur with vaccines, even though it is more common with prescription and nonprescription drugs. So, the clinician should be watchful in patients showing clinical signs and symptoms after a vaccine. In summary, we presented a case of liver injury after the COVID-19 vaccine. We attributed the cause of liver injury to the COVID-19 vaccine, given no other cause in our patient after extensive work-up. There are reports of drug-induced liver injury and abnormal liver function analysis from the spontaneous reports from patients who received Pfizer/BioNTech BNT162b2 mRNA COVID-19 vaccine. The purpose of this manuscript is to raise awareness of potential side effects; it should not alter the recommendation of healthcare providers regarding vaccinations.   No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: Based on the information provided a contributory role of BNT162B2 to the event liver injury cannot be fully excluded. Underlying fatty liver may also be contributory. The impact of this report on the benefit/risk profile of the Pfizer product 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.