Age: 64.0
Sex: F
Vaccine: COVID19
Symptoms: Chromaturia, Fatigue, Hyposmia, Liver function test increased, Malaise
Clinical narrative: transabdominal liver biopsy was obtained and showed mixed portal inflammation, bile duct injury and endotheliitis consistent with ACR (Rejection Activity Index [RAI] score 4) with central venular dilation and sinusoidal congestion; possible hepatic venous outflow obstruction; sinusoidal obstruction syndrome; darkened urine; malaise; Reduced sense of smell; elevated liver tests; fatigue; mild myalgias; local soreness at injection site; reduced range in motion at injection site; reduced sense of smell; This non-study case was reported in an article and describes the occurrence of TRANSPLANT REJECTION (transabdominal liver biopsy was obtained and showed mixed portal inflammation, bile duct injury and endotheliitis consistent with ACR (Rejection Activity Index [RAI] score 4) with central venular dilation and sinusoidal congestion), VENOOCCLUSIVE LIVER DISEASE (possible hepatic venous outflow obstruction) and VENOOCCLUSIVE LIVER DISEASE (sinusoidal obstruction syndrome) in a 64-year-old female patient who received mRNA-1273 (Moderna COVID-19 Vaccine) for COVID-19 vaccination. The occurrence of additional non-serious events is detailed below.      The patient's past medical history included Cirrhosis of liver, Hepatitis C, Hepatocellular carcinoma and Infection (Cured with direct acting antiviral medications four years earlier.). Concurrent medical conditions included Liver transplant (Received from a decreased donor.) since 18-Aug-2020. Concomitant products included TACROLIMUS, AZATHIOPRINE SODIUM (AZATHIOPRINE [AZATHIOPRINE SODIUM]) and PREDNISONE for Immunosuppression NOS.    In February 2021, the patient received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (Intramuscular) 1 dosage form. On an unknown date, the patient experienced TRANSPLANT REJECTION (transabdominal liver biopsy was obtained and showed mixed portal inflammation, bile duct injury and endotheliitis consistent with ACR (Rejection Activity Index [RAI] score 4) with central venular dilation and sinusoidal congestion) (seriousness criterion medically significant), VACCINATION SITE PAIN (local soreness at injection site), VACCINATION SITE MOVEMENT IMPAIRMENT (reduced range in motion at injection site), HYPOSMIA (reduced sense of smell), MYALGIA (mild myalgias), CHROMATURIA (darkened urine), FATIGUE (fatigue), MALAISE (malaise), HYPOSMIA (Reduced sense of smell), LIVER FUNCTION TEST INCREASED (elevated liver tests), VENOOCCLUSIVE LIVER DISEASE (possible hepatic venous outflow obstruction) (seriousness criterion medically significant) and VENOOCCLUSIVE LIVER DISEASE (sinusoidal obstruction syndrome) (seriousness criterion medically significant). The patient was treated with METHYLPREDNISOLONE (METHYLPREDNISOLONE WITH AZATHIOPRINE) (intravenous) for Sinusoidal obstruction syndrome, at a dose of 3 day course; MYCOPHENOLATE MOFETIL for Sinusoidal obstruction syndrome, at a dose of 1 dosage form and IMMUNOGLOBULIN ANTI-THYMOCYTE at a dose of 1 milligram/kilogram once a day. At the time of the report, TRANSPLANT REJECTION (transabdominal liver biopsy was obtained and showed mixed portal inflammation, bile duct injury and endotheliitis consistent with ACR (Rejection Activity Index [RAI] score 4) with central venular dilation and sinusoidal congestion) was resolving, VACCINATION SITE PAIN (local soreness at injection site), VACCINATION SITE MOVEMENT IMPAIRMENT (reduced range in motion at injection site), HYPOSMIA (reduced sense of smell), MYALGIA (mild myalgias), VENOOCCLUSIVE LIVER DISEASE (possible hepatic venous outflow obstruction) and VENOOCCLUSIVE LIVER DISEASE (sinusoidal obstruction syndrome) had resolved and CHROMATURIA (darkened urine), FATIGUE (fatigue), MALAISE (malaise), HYPOSMIA (Reduced sense of smell) and LIVER FUNCTION TEST INCREASED (elevated liver tests) outcome was unknown.        The action taken with mRNA-1273 (Moderna COVID-19 Vaccine) (Intramuscular) was unknown.   For mRNA-1273 (Moderna COVID-19 Vaccine) (Intramuscular), the reporter considered TRANSPLANT REJECTION (transabdominal liver biopsy was obtained and showed mixed portal inflammation, bile duct injury and endotheliitis consistent with ACR (Rejection Activity Index [RAI] score 4) with central venular dilation and sinusoidal congestion), VACCINATION SITE PAIN (local soreness at injection site), VACCINATION SITE MOVEMENT IMPAIRMENT (reduced range in motion at injection site), HYPOSMIA (reduced sense of smell), MYALGIA (mild myalgias), CHROMATURIA (darkened urine), FATIGUE (fatigue), MALAISE (malaise), HYPOSMIA (Reduced sense of smell), LIVER FUNCTION TEST INCREASED (elevated liver tests), VENOOCCLUSIVE LIVER DISEASE (possible hepatic venous outflow obstruction) and VENOOCCLUSIVE LIVER DISEASE (sinusoidal obstruction syndrome) to be possibly related.    Patient was advised to begin tapering off concomitant medication prednisone; she decreased it to 2.5 mg daily for two weeks starting one day after vaccination and then discontinued it entirely. The liver test elevation did not improve after intravenous steroid therapy, and a repeat liver biopsy showed similar histology to the initial biopsy, with persistent ACR (Reject activity index (RAI) score 5) and slightly reduced central venular dilation and sinusoidal congestion. Patient was treated with anti-thymocyte globulin 1 mg/kg daily for a 6-day duration, and the liver tests gradually decreased. A third liver biopsy after completion of anti-thymocyte globulin showed improved ACR (RAI score 2) and no central venular dilation or sinusoidal congestion. Fifteen days after vaccination, Aspartate aminotransferase (AST): 229 U/L, Alanine aminotransferase (ALT): 199 U/L, Alkaline phosphatase (ALP): 576 U/L, Bilirubin: 6.0 mg/dl, Albumin: 3.3 g/dl, Tacrolimus, 12-hour trough: 8.3 ng/ml; negative for Cytomegalovirus DNA, Hepatitis C RNA, Herpes Simplex Virus-1/2 DNA, Adenovirus DNA, SARS-CoV-2 RNA, Donor Specific Antibodies, SARS-CoV-2 Spike Protein Antibodies Receptor Binding Domain; positive for SARS-CoV-2 Spike Protein Antibodies S1 Subunit. Twenty-one days after vaccination, AST: 191 U/L, ALT: 195 U/L, ALP: 522 U/L, Bilirubin: 4.9 mg/dl, Albumin: 2.0 g/dl, Tacrolimus, 12-hour trough: 7.0 ng/ml. Twenty-five days after vaccination, AST: 188 U/L, ALT: 245 U/L, ALP: 449 U/L, Bilirubin: 5.5 mg/dl, Albumin: 2.6 g/dl, Tacrolimus, 12-hour trough: 8.3 ng/ml; negative for Donor Specific Antibodies, SARS-CoV-2 Spike Protein Antibodies Receptor Binding Domain; positive for SARS-CoV-2 Spike Protein Antibodies S1 Subunit. Twenty-nine days after vaccination, AST: 125 U/L, ALT: 229 U/L, ALP: 467 U/L, Bilirubin: 5.2 mg/dl, Albumin: 2.6 g/dl, Tacrolimus, 12-hour trough: 11.3 ng/ml. Thirty-six days after vaccination, patient's AST: 94 U/L, ALT: 145 U/L, ALP: 437 U/L, Bilirubin: 2.7 mg/dl.  Company Comment: Transplant rejection is the body's inherent response to foreign body, veno-occlusive liver disease , elevated liver enzyme test, involves a pre-existing underlying condition , Con-med Tacrolimus is a high risk for chromaturia and as such these events are unlikely related to mRNA-1273.  The remaining events show temporal association with product use and as such cannot be excluded although malaise and fatigue are confounded by patient's condition and treatment for condition.; Sender's Comments: Transplant rejection is the body's inherent response to foreign body, veno-occlusive liver disease , elevated liver enzyme test, involves a pre-existing underlying condition , Con-med Tacrolimus is a high risk for chromaturia and as such these events are unlikely related to mRNA-1273.  The remaining events show temporal association with product use and as such cannot be excluded although malaise and fatigue are confounded by patient's condition and treatment for condition.