A 14-year-old boy (weight: 90 kg; height: 175 cm; BMI: 29.39 kg/m2) was admitted to our hospital on 22 June 2020 with symptoms of yellow eyes and diarrhea for more than 20 days. The child had been treated with a Chinese patent cold medicine (that included acetaminophen) for an upper respiratory tract infection 30 days prior. He had never taken the medicine before, and during treatment, a maculopapular rash developed on the trunk. The local hospital's laboratory studies on June 4 showed a total bilirubin (TBil) of 277 mumol/L, direct bilirubin (DBIL) of 150.2 mumol/L, alanine aminotransferase (ALT) of 580 U/L, and aspartic acid aminotransferase (AST) of 320 U/L. On June 14, he was treated with methylprednisolone 40 mg/d intravenously for 3 days, and the rash improved. Liver function was noted to be aggravated 1 week later, and he was treated with prednisone acetate 20 mg orally every day from 22 June 2020, but his condition did not improve.
He was allergic to penicillin, and there was no history of any significant disease in his family. Moderate jaundice of the skin and sclera was noted, and no cardiopulmonary abnormalities were found.
A liver biopsy was performed on June 24, and pathological examinations were consistent with DILI (G3 S1) (Figure 1A). Pathological sections were sent to Renji Hospital, School of Medicine, Shanghai Jiao Tong University, for consultation, and after review, the diagnosis was autoimmune hepatitis (acute-severe). Mycophenolate mofetil (MMF) 750 mg/d (250 mg t.i.d.) orally began on 3 July 2020, and after 4 days, his TBil, PT, and INR levels had increased to 250.30 mumol/L, 23.2 s, and 2.12, respectively. Based on the laboratory studies and his condition, he had progressed to subacute liver failure (SALF). He was placed on the liver transplant list, and a complete pre-liver transplantation workup was performed.
Prednisone acetate was changed to methylprednisolone 30 mg q12 h ivgtt on 9 July 2020, and hepatic encephalopathy was diagnosed on July 10. MMF was discontinued on July 11, and he was given intravenous gamma globulin 20 g/d, but there was no improvement in his condition after 5 days of treatment. He was given treatment with a non-bioartificial liver (NBAL) starting on July 21, and after 5 treatments (from July 21 to August 3, once every 3-4 days) in combination with integrative medical treatments including liver protection, plasma infusion, and human albumin, his symptoms improved.
On 7 August 2020, the patient experienced sudden chills, shivering, and hyperpyrexia. Sputum culture revealed Candida albicans, and chest computed tomography (CT) showed multiple nodules in the lungs (Figures 2A,B). The 1,3-beta-D glucan test (G test) and galactomannan antigen detection test (GM test) were negative. Due to poor coagulation, tracheoscopy was not performed. Pulmonary candidiasis was diagnosed, and the patient's fever persisted after a week of treatment with fluconazole 400 mg/d ivgtt. A repeat sputum culture on 14 August 2020 revealed Aspergillus niger, resulting in a diagnosis of invasive pulmonary aspergillosis (IPA). Fluconazole was changed to voriconazole (loading dose on 18 August 2020 of 400 mg q12 h ivgtt, and maintenance dose of 200 mg q12 h ivgtt was started on D2. The regimen was adjusted according to the clinical situation and therapeutic drug monitoring (TDM) results), and his condition improved.
His chest CT showed resolution of the lung lesions after 85 days of treatment, and voriconazole was discontinued on 10 November 2020. On 31 May 2021, laboratory studies revealed TBil, 11.9 mumol/L; ALT, 52 U/L; AST, 40 U/L; ALP, 204 U/L; and gamma-GT, 93 U/L. A repeat liver biopsy after 24 weeks of treatment was consistent with autoimmune-like phenomenon liver failure (G3 S3) (Figures 1B,C). A diagnosis was made according to the Roussel Uclaf Causality Assessment Method (RUCAM), and a probable diagnosis of autoimmune hepatitis was made based on 2008 International Autoimmune Hepatitis Group's (IAIHG) criteria: (1) DILI, cholestatic, acute, and RUCAM score calculated as 10 (highly likely); (2) IAIHG score 4, combined with liver pathology, the diagnosis of the teenager is drug-induced liver injury with autoimmune-like phenomenon (AL-DILI), drug-induced autoimmune hepatitis (DI-AIH) is not excluded.