A two-year-old girl was hospitalized for "hepatic dysfunction and recurring oral candidiasis for more than ten months." She was hospitalized at a local hospital with "bronchitis" at the age of one year and one month, where she was found to have liver dysfunction with ALT and AST levels of 624 U/l and 644 U/l, respectively. Her condition improved after one week of treatment with glutathione and bicyclol. After continuing glutathione and bicyclol for more than one week, the liver enzyme levels returned to normal. At the age of one year and five months, she was treated at a local clinic for approximately three days due to oral candidiasis and poor appetite, and her ALT and AST levels were 1,019 U/L and 898 U/L respectively. She was admitted to the hospital. A liver, gallbladder, pancreas, and spleen ultrasound indicated gallbladder wall edema and splenomegaly. The child was then given anti-infective ceftezole and ganciclovir antiviral therapy. The treatment, however, proved ineffective, and the patient was moved to our hospital. Laboratory tests were performed during hospitalization with the following results: LDH 638 U/L (120-300 U/L), AST 1539 U/L (<=40 U/L), ALT 607 U/L (<=41 U/L), gamma-GT 109 U/L (10-71 U/L), total cholesterol 2.52 mmol/L (<5.18), and total bile acid 58.3 micromol/L. There was no obvious coagulation abnormality. Screening for antibodies against hepatitis C virus (HCV), HAV, HEV, HIV, PVB, Treponema pallidum (TP), and hepatitis B virus (HBV) were negative; The concentration of Immunoglobulin A was 0.15 g/L (0.11-1.45 g/L), Immunoglobulin G was 8.8 g/L (3.3-12.3 g/L), Immunoglobulin M was 0.79 g/L (0.33-1.75 g/L), Complement C3 was 0.81 g/L (0.65-1.39 g/L), and Complement C4 was 0.23 g/L (0.16-0.38 g/L). The levels of blood ammonia (57 micromol/L) and ceruloplasmin (0.498 g/L), and the results of the lymphocyte subset analysis [T cells, B cells, and natural killer (NK) cells] indicated no significant abnormalities (Supplementary material Table S1). The level of anti-CMV-IgM and anti-CMV-IgG was 2.85 AU/ml and 89.74 AU/ml, respectively. IgG antibody against Epstein-Barr virus early antigen and nuclear antigen was <5.0 U/ml and 140.0 U/ml, respectively. The levels of IgG and IgM antibodies against Epstein-Barr virus capsid antigen were 39.2 U/ml and <10.0 U/ml, respectively. The Epstein-Barr virus DNA assay showed 9.08E + 002 copy/ml (0-500 copy/mL). Mycobacterium tuberculosis was not cultured either in a solid or liquid medium. The analysis of autoantibodies revealed cytoplasmic antinuclear antibodies as granule 1:100 and anti-liver cytosol-1 antibody (ALC-1) as suspicious, whereas screening for anti-GP210 antibody was weakly positive (Supplementary material Table S2). Retest The child was diagnosed with liver dysfunction, oral candidiasis, acute bronchial pneumonia, and cytomegalovirus infection. Liver protection was provided by administering enzyme-lowering (glutathione, bicyclol, magnesium isoglycyrrhizinate) and anti-infective (cefoperazone and sulbactam sodium, voriconazole) substances. Then the child was discharged and was orally administered bicyclol and glutathione tablets to reinforce treatment. For the next four months, liver function was measured in conventional outpatient clinics and was high (ALT: 50 U U/L, AST: 137 U/L). Since the cause for this elevated liver function remained unclear, the child was readmitted to the hospital. Liver biopsy and high-precision clinical display PLUS detection were conducted with the consent of the guardians. Liver perfusion analysis revealed incomplete lobular structure, partial hydrolysis of some hepatocytes, infiltration of a few lymphocytes into the portal area, and mild hyperplasia of the fibers. These observations were consistent with the pathological changes observed in G1S1 chronic hepatitis (Figure 1). A liver biopsy under an electron microscope showed that the liver tissue was slightly swollen with a reduced endoplasmic reticulum, slight hyperplasia, expansion of the smooth endoplasmic reticulum, and blurred mitochondrial structures. Most of the hepatocytes showed a slight increase in the number of small lipid droplets in their cytoplasm, with few showing depositions of not many cholestatic pigment particles. The gaps between hepatocyte surfaces were slightly wider, and a few capillary bile ducts were somewhat dilated and cholestatic. Hepatic stellate cells were prominent in the Disse cavity, and focal bundles of collagen fibers were deposited. Kupffer cells were observed in the hepatic sinusoids with no portal area (Figure 2). High-precision clinical display PLUS detection revealed a heterozygous GOF mutation (p.R274W) in the coiled-coil (CC) domain of the transcription factor STAT1 (Figure 3). The legal guardian provided written informed consent to participate in this study.
We monitored the clinical progress of this child for more than three years. After multiple treatments (antifungal voriconazole, nystatin treatment for oral Candida, antibiotics against bacterial infection, and liver protection with bicyclol and glutathione), the child still exhibited splenomegaly. Serial radiological investigations of the chest were conducted (Figure 4). We intermittently gave the child glutathione, bicyclol treatment, and oral antifungal therapy during this period. The child's family members were very cooperative with the doctor's treatment and brought her to the hospital regularly for re-examination to evaluate her liver function. Fortunately, the child's condition is stable, with no further clinical progress.