Age: 31.0
Sex: F
Vaccine: HEPA, YF, HEPA, YF
Symptoms: Hepatic necrosis, Hepatomegaly, International normalised ratio, Jaundice, Nausea
Clinical narrative: Information has been reported in a published article. Title as stated above concerning a 31 year old female with no significant past medical history, no history of high-risk behavior or a family of jaundice or liver disease and no stigmata of chronic liver disease who on an unspecified date was vaccinated with a dose of HEP A vaccine (lot # not reported) (manufacturer unknown). Suspect vaccine therapy included yellow fever virus vaccine. On an unspecified she presented to the emergency room with complaints of fever, dark urine, and nausea/vomiting for 10 days. She had returned 2 days prior from a 5-day international trip. Before the trip and 11 days before the onset of her symptoms, she had received the vaccines. Symptoms of nausea/vomiting and itching started on the first day of travel and continuing to progress during the trip. She denied any pain, dyspnea, or diarrhea. On an unspecified date the patient was admitted to hospital. Her temperature on admission was normal at 99 degrees F (37 degrees C), as were her other vital signs. Her physical examination was significant for severe jaundice and mild hepatomegaly, without splenomegaly and encephalopathy. Laboratory blood examination revealed white blood cell count of 3,500/uL (normal range, 4,500 to 11,000/uL), hemoglobin of 12 g/dL (11.7 to 15.0 g/dL), platelets of 256,000/uL (150,000 to 450,000/uL), and international normalized ratio (INR) of 1.1. Electrolytes, creatinine, and blood urea nitrogen were normal. Her total (9.4 mg/dL) and direct (6.3 mg/dL ) bilirubin levels were significantly elevated, as were her levels of alanine aminotransferase (ALT) of 575 u/L  (1 to. 53 u/L) and aspartate aminotransferase (AST) of 1276 u/L (1 to 50 u/L). The patient's levels of alkaline phosphates of 162 U/L (30 to110 u/L) and gamma-glutamyl transpeptidase of 152 u/L (10 to 54 u/L) were mildly elevated. Albumin (3.4 g/dL) and total protein (6.7 g/dL) levels were within normal limits. Viral serologies for Epstein-Barr virus, leptospira, and hepatitis A, B, C and E were negative. Additionally, autoimmune markers including antinuclear antibodies, anti-liver kidney microsome antibodies, antimitochondrial antibodies, and anti-smooth muscle antibodies were negative. Serum quantitative immunoglobulin G (IgG) levels were mildly elevated at 1870 mg/dL (<1728 mg/dL). A yellow fever DNA polymerase chain reaction result was negative. She was discharged to home after several days of observation with stable, though still elevated blood tests (ALT 566 u/L, AST 192 u/L, and total bilirubin 9.7 mg/dL). Weekly follow-up blood tests showed increased (ALT 750 u/L, AST 208 u/L, total bilirubin 17.7 mg/dL). No new symptoms or signs were noted on readmission. A percutaneous liver biopsy was performed and showed acute hepatitis with bridging necrosis. She had marked expansion of the portal tracts by lymphoplasmacellular infiltrates. Eosinophils were also present. There was lobular inflammation, scattered acidophilic bodies, foci of parenchymal necrosis, perivenular necroinflammatory lesions, cholestasis and portal central bridging necrosis. Periportal hepatocyte regeneration was evident. Trichome stain confirmed absence of fibrous septa and the absence of collagen deposition in the areas with bridging necrosis. Despite the negative autoimmune serum markers, a presumptive diagnosis of autoimmune hepatitis was made. Using the group criteria, the pretreatment likelihood of the group was considered probable. She was started on PREDNISONE 40mg daily and showed a dramatic improvement in both the ALT (90 u/L) and AST (95 u/L) blood test results. She was discharged to home again on a slow PREDISONE taper and AZATHIOPRINE 50mg daily. within 3 months, she was taking only 5mg of PREDNISONE daily and 50mg of AZATHIOPRINE daily and had normal ALT (25 u/L), AST (16 u/L) and total bilirubin (0.7mg/dL) blood values. She was instructed to stop PREDINISONE and continue taking AZATHIOPRINE 50mg daily. Subsequently follow-up 2 months later revealed that she had self-discontinued AZATHIOPRINE shortly after her last visit because of nausea and vomiting. Her liver were as follows: ALT 7u/L, AST 17 u/L, total bilirubin 0.4mg/dL and IgG of 1870 mg/dL. Autoimmune markers were repeated and remained negative. Nearly a year after her initial presentation, she underwent a repeat percutaneous liver biopsy that revealed significant decreased in the portal inflammation, with focal mild interface hepatitis and minimal lobular activity. The areas of bridging necrosis had now been replaced by thin fibrous septa, which were devoid of inflammation. Ceroid-containing macrophages were present in portal tracts and rarely in the lobules, indicative of previous damage. The findings were those of chronic hepatitis with mild activity (grade 2 of 4) and fibrous septum formation (stage 2 of 4). Evidence of resolving hepatitis was noted compared with the entail biopsy. Given the biopsy results, she was restarted on PREDNISONE 10mg and AZATHIOPRINE 50mg daily to prevent disease progression. Prednisone had been tapered off and she was tolerating AZATHIPPRINE without any nausea/vomiting. Her ALT and AST remain < 20u/L. The authors felt that autoimmune hepatitis was apparently abruptly triggered by vaccination. All evidence suggests this was an idiosyncratic response to either hepatitis A virus vaccine inactivated or yellow fever virus vaccination. No further information is available. A copy of the published article is attached as further documentation of the patient's experience.