A 61-year-old woman complaining of scleral icterus for 2 months was admitted to a local hospital on 3 December, 2019. She was treated with choleretics and hepatoprotective drugs, but the specific drugs were unknown; however, the symptoms recurred easily. She was referred to the outpatient department of our hospital with scleral icterus, yellowing urine, itchy skin, and weakness. Liver function tests showed alanine aminotransferase (ALT) 118U/L, aspartate aminotransferase (AST) 84U/L, alkaline phosphatase (ALP) 272U/L, total serum bilirubin (TBIL) 123.4 mumol/L, direct bilirubin (DBIL) 72.4 mumol/L, indirect bilirubin (IBIL) 51 mumol/L, and gamma-glutamyl transferase (gamma-GT) of 128U/L. Computed tomography (CT) of the abdomen revealed common bile duct wall thickening and severe biliary obstruction. Magnetic resonance cholangiopancreatography (MRCP) was performed to further characterize the structure of the bile duct in the hilar area is unclear, as well as diffuse irregular mural thickening and lesions of the extrahepatic bile duct. A diagnosis of obstructive jaundice was made, and the patient was hospitalized for future treatment on 19 December, 2019. The patient had been on Salmeterol Xinafoate and Fluticasone Propionate Powder for Inhalation for 30 years; past medical procedures included appendectomy 27 years ago, hysterectomy 20 years ago, and cholecystectomy 10 years ago.
The patient has a history of significant weight loss the months preceding admission to hospital. On admission to our department, few positive findings were noted on physical examination, except that the patient was visibly icteric. No neurological symptoms or evidence of neurological disturbance were detected, and there was no abdominal distension or organomegaly. Vital signs, bowel movement, chest, and cardiovascular observations were normal. Murphy's sign was negative. Laboratory investigations showed a white blood count of 10.82x109/L with 75% neutrophils. Liver function tests revealed abnormalities consistent with obstructive jaundice. ALT 53U/L, AST 54U/L, ALP 225U/L, TBIL level 412.7mol/L, DBIL 334.7 mol/L, IBIL 78 mol/L, gamma-GT 50U/L. Coagulation factors, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) levels were normal. The carbohydrate antigen 19-9 (CA19-9) level was obviously elevated (8358 U/L). Anti-hepatitis viruses, anti-HIV, autoimmune antibodies, and anti-neutrophil plasma antibodies were normal or negative.
We administered magnesium isoglycyrrhizinate, polyene phosphatidylcholine, amino acids, vitamin C and potassium hydrogen phosphate for symptomatic treatment. For further evaluation Endoscopic Retrograde Cholangiopancreatography (ERCP) was performed at the digestive intervention center, radiography showed a stricture of the bile duct in the hilar area (Bismuth IV) on 20 December, 2019. Two biopsies from the bile duct stricture were collected for pathological examination. Multiple stents were inserted into the bile duct to relieve the obstruction, and nasobiliary duct drainage was performed. There was no evidence of bile duct calculus, cirrhosis, or focal lesions in the liver. Pathological examination after the surgery showed numerous round bodies in the fibrous tissue of the bile duct in the hilar area and suggestive fungal (Cryptococcus) infection by morphology. Hematoxylin and eosin as well as Grocott's methenamine silver and Periodic acid-Schiff (PAS) staining of the specimen obtained from the stricture place were positive (Figure 1). Immunohistochemistry demonstrated the CD-68, a major antigen expressed on the membrane of mononuclear macrophages and Langerhans cells, was positive. The serum for cryptococcal antigen test was also positive. The diagnosis of biliary cryptococcosis was confirmed. 
Clinicians invited clinical pharmacist consultation the use of drugs for cryptococcosis infection on 29 December, 2019. The patient was treated with oral fluconazole 400 mg/day (800 mg/day on the first day) for 4-6 months. The liver function improved and the temperature normalized, and the patient was discharged with continual oral fluconazole on 4 January, 2020.
Subsequently, 3 days after discharged, the patient visited the local hospital again for deepened skin and scleral icterus; the patient was experiencing chills and fever, a maximum temperature of 39.2 C, no limb twitching, no unconsciousness, and blood pressure of 80/50 mmHg. She was hospitalized in our department on the basis of biliary infection. Laboratory investigations showed a white blood count of 11.91x109/L with 85.9% neutrophils, C reactive protein (CRP) 32.18 mg/L, Procalcitonin (PCT) 1.32 ng/L, and Interleukin-6 (IL-6) 22.93 pg/mL; liver function showed ALT 59U/L, AST 50U/L, ALP 130U/L, TBIL level 216.5mol/L, DBIL 169.1 mol/L, IBIL 47.4 mol/L, and gamma-GT of 45U/L on 9 January, 2020. We administered Biapenem as an anti-infective treatment, and suggested oral fluconazole 400 mg/day because of the patient adjust the fluconazole 200 mg q12h by herself, but the patient did not show any improvement. Liver function indexes were continued to increase, ALT 73U/L, AST 85U/L, ALP 157U/L, TBIL level 402.2mol/L, DBIL 295.4 mol/L, IBIL 106.8mol/L, and gamma-GT 56U/L on 16 January, 2020. Again, the patient underwent ERCP at our digestive intervention center, and purulent secretions overflowed from the duodenal papilla. Based on the biopsy results, cholangitis was diagnosed, and biapenem was administered as anti-infective treatment. After 5 days of treatment, the liver function of the patient improved, and the temperature returned to normal. The patient discharged and continue with oral fluconazole 400 mg/day. The biliary stents were replaced on April 2020, December 2020, and June 2021, respectively. Ultimately, the patient achieved complete recovery, and no complications were observed during the 2 years of follow-up. Bilirubin changes showed in Figure 2. Cryptococcus Antigen Agglutination Titer showed in Figure 3. Conditions recommended by clinical pharmacist for treatment showed in Table 1.