Urosodeoxycholic Acid Therapy in a Child with Trimethoprim-Sulfamethoxazole-induced Vanishing Bile Duct Syndrome
A previously healthy 7-year-old boy was hospitalized with jaundice. Two weeks before admission, he had developed mucous diarrhea and mild fever. At that time, he was treated with oral TMP-SMX (trimethoprim 80 mg and sulfamethoxazole 400 mg [Septrin; Samil Pharmaceutical Co., Seoul, Korea], 0.83 tablet twice a day, trimethoprim 8 mg/kg) for 4 days under a presumptive diagnosis of infectious colitis at a private clinic. One day later, he showed icteric sclera, followed by progression of jaundice. After 8 days of the onset of icteric sclera, he was referred to our hospital because jaundice and pruritus became aggravated.\nHe had no previous history of hepatitis, hepatobiliary diseases, or chronic illness. Family history was nonspecific. Three months before the appearance of jaundice, he received amoxicillin-clavulanic acid for 5 days because of acute tonsillitis at a private clinic.\nAt admission, he had jaundice and complained of mild epigastric pain and pruritus. On physical examination, his body temperature was 37℃, heart rate 95 beat/min, respiratory rate 22/min, and blood pressure 100/60 mmHg. His growth and development were normal. Although his whole body was icteric, he was not so ill-looking. There was no pharyngotonsillar inflammation and cervical lymph enlargement. Heart and lung sounds on auscultation were normal. The abdomen was soft and flat without tenderness. The liver was palpable 3 finger breath below the right subcostal margin. There was no splenomegaly.\nThe initial hematologic study showed hemoglobin 11.0 g/dL, white blood cell 4,450/mL (eosinophil 4.3%), platelet 412,000/µL, reticulocyte 1.47%, prothrombin time 10.8 seconds, and partial prothrombin time 27.8 seconds. Liver function tests were as follows: aspartate transaminase (AST)/alanine transaminase (ALT) 231/220 IU/L, total bilirubin (TB)/direct bilirubin (DB) 8.4/7.5 mg/dL, alkaline phosphatase (ALP) 1,028 IU/L, gamma-glutamyl-transpeptidase (GGT) 708 IU/L, and albumin 3.8 g/dL. The total cholesterol level was 490 mg/dL. The Coomb test for direct and indirect was negative. Other serologic tests showed ceruloplasmin 45 mg/dL, immunoglobulin G 851 mg/dL, complement 3/4 each 165/37 mg/dL, antinuclear antibody (-), and antineutrophil cytoplasmic antibody (-). Viral markers for A, B, C, Epstein Barr virus, cytomegalovirus, herpes simplex virus, mycoplasma, and parvovirus were all negative.\nLiver ultrasonography and abdominal computed tomography showed normal enhancement patterns of hepatomegaly with no visualization of the common biliary duct and gallbladder. Hepatobiliary scan demonstrated normal liver uptake, but no visualization of the gallbladder and duodenum on 150-minute delayed images ().\nTreatment with UDCA (20 mg/kg/day [Ursa; Daewoong Pharmaceutical Co., Seoul, Korea]) was started on hospital day 2. On hospital day 12, liver function test results were similar to those of the admission day showing AST/ALT 103/100 IU/L and TB/DB 8.8/8.0 mg/dL. After discharge from the hospital, he was maintained on UDCA.\nLiver biopsy was performed 36 days after the onset of jaundice due to no improvement of cholestasis: TB/DB 8.7/8.6 mg/dL, ALP 709 IU/L, and GGT 548 IU/L. Histologic examination revealed bile plugs and biliary stasis around the central vein with the disappearance of the interlobular bile ducts. Cytokeratins (CKs) 7 and CK 19 were negative by immunohistochemistry. These findings were consistent with those of VBDS ().\nAfter confirmation of VBDS, UDCA was increased to 30 mg/kg/day. Afterwards, there was improvement in cholestasis. Nine weeks after the onset of jaundice, liver tests at the outpatient clinic showed AST/ALT 77/64 IU/L, TB/DB 1.29/0.66 mg/dL, ALP 815 IU/L, GGT 529 IU/L, and total cholesterol 385 mg/dL. Two weeks later, AST/ALT and total cholesterol normalized. Seven weeks later, ALP and GGT were within the normal range. Clinical progression and treatment course are shown in . Three months after recovery of VBDS, he received amoxicillin-clavulanic acid for 7 days due to acute rhinosinusitis. After that, there was no clinical and laboratory abnormalities associated with VBDS for 1 year. The patient has been followed regularly at the outpatient clinic.