On 1 December 2021, a previously healthy 59-year-old man was diagnosed with stage IV lung adenocarcinoma harboring L858R mutation. He denied a history of hypertension, diabetes, coronary heart disease, liver diseases, or infectious diseases such as tuberculosis. A 40 x 33 x 46 mm mass in the paramediastinal of the upper lobe of the left lung is shown in  Figure 1A . The patient had no family history of cancer and other diseases and no history of drugs or food allergies. He had a long history of smoking (15-25 cigarettes/day) and drinking (150-200 ml/day) for more than 30 years and quit smoking and drinking after his diagnosis of lung cancer. At the time, he had normal liver function with laboratory indicators as follows: alanine aminotransferase (ALT) at 10 U/L (normal range, 9-50 U/L), aspartate aminotransferase (AST) at 14 U/L (normal range, 15-40 U/L), alkaline phosphatase (ALP) at 73 U/L (normal range, 30-120 U/L), gamma-glutamyltransferase (GGT) at 14 U/L (normal value, 8-57 U/L), total bilirubin (TBil) at 9.8 micromol/L (normal value, 5-21 micromol/L), direct bilirubin (DBil) at 2.1 micromol/L (normal value, 0-7 micromol/L), indirect bilirubin (IBil) at 7.7 micromol/L (normal value, 1.5-18 micromol/L), prothrombin time activity (PTA) at 84% (normal value, 80-130%), and international normalized ratio (INR) at 1.11 (normal value, 0.85-1.15). Five days later, he received one dose of cisplatin (40 mg, intrapleural perfusion) and initiated targeted therapy with dacomitinib (45 mg daily, oral). He was then discharged on day 16.
On the 37th day of dacomitinib administration, the patient was readmitted with jaundice. As shown in  Figure 1B , the tumor size was significantly reduced compared with pre-treatment ( Figure 1A ). He had no other symptoms except for obvious yellowing of the skin and sclera. Laboratory examinations indicated liver injury: ALT at 324 U/L, AST at 176 U/L, ALP at 739 U/L, GGT at 523 U/L, TBil at 160.2 micromol/L, DBil at 95.8 micromol/L, IBil at 64.4 micromol/L, and bilirubin detected in urine. The patient tested negative for hepatitis A virus antibody (anti-HAV-IgM), hepatitis B virus antigen and DNA (HBsAg, HBV DNA), hepatitis C virus antigen and RNA (HCV cAg, HCV RNA), hepatitis E virus antibody (anti-HEV-IgM/IgG), and autoantibodies (including antinuclear antibodies, smooth muscle antibodies, antibodies to the liver-kidney microsome type 1, antimitochondrial antibodies, antibodies to liver cytosol type 1, and antibodies to soluble liver antigen). With 4.27 ng/ml of alpha-fetoprotein (AFP) in the normal range (0.89-8.78 ng/ml), abdominal ultrasound and computed tomography (CT), liver magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) show no abnormality.
The Naranjo score for dacomitinib-induced liver injury was 5, indicating probable adverse drug reactions. It was determined that dacomitinib was a "probable" cause of DILI based on a Roussel Uclaf Causality Assessment Method (RUCAM) score of 8. In addition, the cholestatic type of DILI caused by dacomitinib was diagnosed according to DILI guidelines. A liver biopsy was not performed due to the poor general condition of the patient.
The timeline is shown in  Figure 2 . Dacomitinib was discontinued on the first day of readmission. The patient then received drug and non-drug therapy, including magnesium isoglycyrrhizinate at 100 mg daily, S-adenosylmethionine at 1 g daily, and ursodeoxycholic acid at 250 mg three times daily throughout the hospital stay; N-acetylcysteine at 8 g daily between the 12th and 17th hospital days and infusion of plasma on the 16th hospital day because of a sudden deterioration of coagulation function; and once artificial liver therapy on the 26th hospital day due to high levels of bilirubin. The patient was discharged on the 29th hospital day (29 days after dacomitinib termination) and continued ursodeoxycholic acid treatment outside the hospital. He was followed up for 4 months.
During hospitalization, the patient remained sane without signs of hepatic encephalopathy. However, he developed a change in taste, poor appetite, abdominal distension, generalized itching, aggravated yellowing of the skin and sclera, yellow urine, and white stool. The serum levels of the laboratory parameters in the patient are shown in  Figure 3 . After the discontinuation of dacomitinib, the liver enzyme (ALT, AST, ALP, GGT) levels decreased obviously. However, bilirubin (TBil, DBil, IBil) levels showed an upward trend, reaching the highest (18-fold) level on day 26 after dacomitinib termination. It subsequently decreased partly after artificial liver therapy, followed by a gradual downward trend, and finally normalized on day 146 after dacomitinib discontinuation. Coagulation function (PTA) was relatively stable initially, decreased significantly (PTA<30%) on day 15 after dacomitinib termination, recovered, and remained in the normal range after an infusion of fresh frozen plasma (350 ml) on day 16 after dacomitinib termination. The severity of DILI was assessed as acute liver failure (ALF) based on DILI guidelines.
Fifty days after dacomitinib termination, a lung CT image showed an increased tumor size ( Figure 1C ), and the patient received afatinib 30 mg daily the next day. 34 and 95 days after afatinib administration, lung CT showed a reduced tumor size without tumor progression and metastasis ( Figure 1D ). The patient achieved stable disease (SD) based on imaging assessment and continued to receive afatinib treatment. The patient showed agreement on the risk, medication, and treatment plan with the clinician throughout the entire treatment.