A 61-year-old woman was suspected with AIH on September 2019 (Child-Pugh class A; MELD score, 12). On January 25, 2020, she presented with spiked fever that had persisted for seven days and she complained of tightness in her chest (Table 1). Owing to the persistent fever and ineffective antibiotic treatment, a chest CT scan was performed and revealed blurred margins in the left upper lung. A SARS-CoV-2-specific RT-PCR assay was performed, and a positive case of COVID-19 was confirmed on January 30, 2020. Her CT scan showed the hallmarks of a COVID-19 infection, namely bilateral ground-glass opacities. Further, her laboratory results on admission showed leukocytosis and elevated CRP, ALT, AST, GGT, and TB levels. In addition, her blood coagulation function parameters, including D-Dimer, activated partial thromboplastin time, and fibrinogen were elevated (Table 2).
Patient 1 was evaluated with a low AIH score (AIH score: 8) with no antinuclear antibody (ANA), smooth muscle antibody, or liver/kidney microsomal type 1 (LKM-1) antibody detected. The baseline liver characteristics refer to her liver function assessment at hospital discharge, 3 months before she was diagnosed with influenza (Table 3). As is shown in Table 3, her MELD score was 7 and R Factor for liver injury was 1.3. After the onset of the H1N1 viral infection, her liver functions remarkably worsen. Initial laboratory tests revealed obviously elevated liver enzymes: AST, 169 U/L; ALT, 201.3 U/L; GGT, 180.3 U/L; and ALP, 115 U/L. Although viral serologies for hepatitis A, B, C, and E were still negative, serum immunoglobulin was 700.2 mg/dL (Figure 2A). Post H1N1 infection, her AIH score rose to 21 with a positive ANA titer of >1:80, and her liver histology revealed features typical of interface hepatitis. In addition, her MELD score and R Factor for liver injury increased to 13 and 5.3, respectively (Table 3).
Patient 2 was diagnosed with defined AIH (AIH score: 18). Table 3 indicates her baseline liver characteristics, which refer to her liver function assessment at hospital discharge, 5 months before she was diagnosed with influenza. She was under glucocorticoid therapy until she was infected with the H1N1 virus. Due to this immunosuppressant therapy, although her ALT, AST, ALP, and total protein (TP) levels were in normal range, she had jaundice with elevated TB (29 mumol/L) and GGT (64 U/L) levels (Figure 2B). Her MELD score and R Factor for liver injury increased from 7 to 13 and from 1.3 to 1.6, respectively (Table 3).
Patient 3 was diagnosed with probable AIH (AIH score: 12). Table 3 indicates her baseline liver characteristics, which refer to her liver function assessment at hospital discharge, 3 months before she was diagnosed with COVID-19. Her MELD score and R Factor for liver injury were 10 and 1, respectively. From the onset of COVID-19 symptoms, her liver function deteriorated. Initial laboratory tests during COVID-19 hospitalization revealed evidently elevated liver enzymes: AST, 49 U/L; ALT, 142 U/L; GGT, 200 U/L; ALP, 114 U/L; and TP, 62 g/L (Figure 2C). Compared to her liver function before COVID-19, her AIH score elevated to 14 with a positive LKM-1 antibody titer>1:80. In addition, her MELD score and R Factor for liver injury increased to 12 and 3.7, respectively (Table 3). Once she was given systematic glucocorticoids normal liver function was restored. However, liver injury recurred with the highest level of ALT (163 U/L) and AST (85 U/L) after glucocorticoid withdrawal, and more liver protective drugs had to be administered.
After infection, all patients received antiviral therapy: patient 1, Oseltamivir orally [75 mg, BID]; patient 2, first Oseltamivir orally [75 mg, BID] followed by pulsed Peramivir [0.6, ivgtt, qd] due to disease deterioration; and patient 3, ritonavir orally [400 mg/100 mg, BID] and interferon alfa-2b [500 wu, BID]. All patients were given systemic glucocorticoids combined with liver protective drugs (glutathione-based therapy) and broad-spectrum antibiotics. In addition, patients 1 and 2 were administered with oxygen inhalation due to their low PaO2 (<60 mmHg). Patient 3 required endotracheal intubation due to ARDS. During hospitalization, the sputum cultures of patient 1 and patient 3 showed the presence of Candida albicans and Stenotrophomonas maltophilia. Normal liver function was restored in all patients post therapy (Figure 2), and the liver assessment score decreased (Table 3). Finally, all patients were discharged from the hospital (patient 1, 1 February 2020; patient 2, 12 February 2020; and patient 3, 10 March 2020) after two consecutive negative results of the RT-PCR assays for H1N1 and SARS-CoV-2 were obtained on nasopharyngeal swabs (Table 1).