A 64-year-old woman was admitted to our hospital on December 3th, 2021 due to the "diagnose of liver metastatic adenocarcinoma for more than 3 months and fatigue for 1 week". In early August 2021, the patient had been admitted to our hospital because of abdominal pain and low back pain. PET-CT(Positron emission tomography-computed tomography 2021/8/13): 1.Multiple hypermetabolic nodules and masses in the liver; low density shadow of portal vein, considering tumor thrombus; Multiple lymph node metastasis in mediastinum, hepatogastric space, hilar region and retroperitoneum; Multiple bone metastasis. 2.A hypermetabolic mass in the hilar region is considered to be malignant. Further pathological immunohistochemical (IHC) results showed that AE1/AE3 (+), Hepatocyte (partial +), AFP (-), GPC-3 (focal +), HSP70 (+), GS (-), Arginase-1 (focal +), IMP3 (diffuse +), CK7 (minority +), CK20 (+), CEA (-), CDX-2 (-), SATB2 (+), Villin (+), GATA-3 (-), TTF-1 (-), Napsin A (-), p53 (80% +). Ki67 (30% +). Based on the results of imaging examination and pathological immunohistochemistry, the patient was diagnosed as intrahepatic cholangiocarcinoma with multiple metastases after MDT multi-disciplinary consultation. cTNM staging: stage IV. From August 16th to November 8th, paclitaxel (albumin-bound) combined with Seggio and pembrolizumab was given to the patient for 5 cycles. Her liver function was normal before treatment. At the end of November 2021, the patient developed fatigue, anorexia, and abdominal distension, without the symptom of abdominal pain, fever, nausea, and vomiting. She was admitted to the hospital for further diagnosis and treatment. The patient has a history of hepatitis B, but no history of hypertension, diabetes, heart disease, blood transfusion, and drug allergy. Her physical examination revealed the following: The sclera and skin of the whole body were normal, no liver palm and spider nevus were seen; the breath sounds of both lungs were clear, with the absence of dry and wet sounds; the heart sounded strong, with a regular rhythm of a heart rate of 62 beats/min; the abdomen was soft, without tenderness and rebound tenderness; the liver was 4 transverse fingers below the right ribs, and the mobility dullness was negative; no edema was noted on either leg.
Laboratory examinations showed the following results: Whole blood cell analysis (2021-12-4): WBC:2.8x109/L, NEUT#:1.61x109/L, PLT:57x109/L; Coagulation (2021-12-4): PT:14.6s, INR:1.34, PTA:66%; Blood biochemical examination (2021-12-4): ALT:774IU/L, AST:1113.5IU/L, TBil:26.6mumol/L, DBil:13.5mol/L, gamma-GT:160.6IU/L, ALP:229.5IU/L;ICI was stopped immediately, intravenous magnesium isoglycyrrhizinate 200mg, reduced glutathione 1.8g once a day to protect the liver.Other examination (2021-12-4): HBsAg(+) HBeAg(+) HBcAg(-) HBsAb(-) HBeAb(+) HBcAb(+), HBV DNA:<100IU/mL, Hepatitis A antibody, Hepatitis C antibody and Hepatitis E antibody IgM were all negative.AFP:3.5ng/mL; autoantibodies were negative; Immunoglobulin IgG9.5g/L IgA 2.58g/L IgM1.2g/L. Liver biopsy was recommended, which was rejected by the family. (2021-12-10):ALT(228.4IU/L) and AST(749.3IU/L) were lower than before,TBil(119.3 umol/L) and gamma-GT(188IU/L) were higher than before, and she gradually developed yellow skin and sclera, dark urine, extreme fatigue, abdominal distension, and nausea. Considering immune-mediated hepatotoxicity, glucocorticoid(1mg/Kg/d) was given (12/10-12/20), Combined with oral mycophenolate mofetil(MMF) 0.5g twice a day (12/18-12/20). Blood biochemical examination (2021-12-20): ALT: 842.6IU/L, AST: 1249.7IU/L, TBil: 249.4mumol/L, DBil: 93.8mol/L. Coagulation (2021-12-25): PT: 26.2s, INR: 2.34, PTA: 30%, APTT: 39.1s. Abdominal CT (2021-12-26): hepatic hilar space occupying and liver metastasis of the patient was improved compared with that in the previous examination. Liver cirrhosis, enlarged spleen, widened portal vein were observed in the patient during this period of examination. Final diagnosis: Immune-related liver injury induced by ICIs, grade 4. with a subacute liver failure at an early stage. Diagnosis was confirmed based on the same results as previous ones.
Subsequently, from December 22th to 24th, she was given a double plasma molecular adsorption therapy. On December 27th, she underwent single-plex plasma exchange, replacing 2000ml of fresh frozen plasma. On December 30th, double plasma molecular adsorption combined with half-volume plasma exchange therapy was given to her, and the amount of plasma exchanged was 1000ml (see  Figure 3 ). After this treatment, her liver function returned to normal (see  Figures 2A, B ). Subsequently, the re-examination showed that her liver lesions had shrunk significantly (see  Figures 3A-D ).