A boy who was 10 years and 6 months old was admitted to the hospital due to abdominal pain that persisted for 4 days. The patient also vomited three times without concomitant fever or diarrhea. He was found to have jaundice when referred to a local hospital. The biochemical tests showed exceptionally high levels of alanine aminotransferase [(ALT) 2330 U/L], aspartate aminotransferase [(AST) 1326 U/L], and total bilirubin [(TB) 74.2 mumol/L]. The patient received no intervention or treatment before being transferred to our hospital. He was previously in good health, denied taking any medications or having a history of exposure to patients with COVID-19, and received the second dose of inactivated COVID-19 vaccine 3 months before admission. At admission, the physical examination revealed that the child had scleral icterus, jaundice, hepatosplenomegaly, upper abdominal tenderness, and a positive Murphy's sign.
The patient underwent infectious pathogen screening. Evidence of hepatitis A, B, C, and E viruses, CMV, HSV, and EBV infection is not found by serology (Hepatitis A, B, C, and E virus, CMV, and EBV), immunohistochemical (EBV), and PCR (HSV and EBV) analyses. The autoimmune hepatitis-related antibodies (17 common antibodies including ANA, SSA, AMA M2, and ss-DNA) and metabolism disease-related tests (including blood glucose, blood ammonia, lactate, alpha-fetoprotein, and ceruloplasmin) were also negative. Abdominal ultrasound indicated hepatosplenomegaly, pericholecystic edema, and thickening of the gallbladder wall. Magnetic resonance cholangiopancreatography (MRCP) showed edema of the first porta hepatis, the periportal region, and the gallbladder, as well as stenosis of the choledoch (Figures 1A-C,G). To further clarify the potential cause, the patient underwent trio-based next-generation sequencing (Trio-NGS) and liver biopsy. Trio-NGS did not detect any abnormalities, while liver biopsy showed mild interfacial hepatitis and fibrosis of portal area (G1S1) (Figures 2A,B), and further classification of the intrahepatic lymphocytes predominantly suggested CD8 + cells (Figure 2C). Tests for HBsAg, HBcAg, CMV, IgG4, and EBER in liver tissue remained negative. Although some interlobular bile ducts were very small, the number of intrahepatic bile ducts was normal. Finally, torque teno virus (TTV) sequences were detected by metagenomic NGS (mNGS) in whole blood sample (Figure 3A) and liver tissue (Figure 3B). The result of electron microscopy (Figure 2D) indicated chronic active hepatitis, which was shown as follows: hepatic cells were swollen, rough endoplasmic reticulum and smooth endoplasmic reticulum were slightly expanded, and lipid droplets were observed in hepatocytes (upper image), as well as lymphocytosis were observed in hepatic sinusoidal (lower image). However, no viral inclusions were found.
After hospitalization, the patient received ceftazidime (based on cholecystitis), lipid-soluble vitamins, and reduced glutathione treatment. Unfortunately, the patient's situation deteriorated with rapid progressive jaundice (peak TB: 173 mumol/L), underwent plasmapheresis once, and was administered methylprednisolone. The patient's liver function was improved after the administration of steroids (Figures 4A-C). MRCP tests showed that the narrow bile duct was not relieved, but the hepatosplenomegaly and gallbladder edema had disappeared (Figures 1D-F,H). The patient was discharged after one month of treatment. Two weeks post-discharge, he revisited the hospital. He was clinically stable without any adverse and unanticipated events. The biochemical tests showed that ALT was 163 U/L, AST was 60 U/L, and TB was 11.6 mumol/L.
As a whole, this case report follows the CARE Case Report Guidelines. Our adherence to these reporting guidelines has been listed in the Supplementary material.