S5745 Gastroenteritis as a Trigger for Acute Flare-Ups of BRIC in the Setting of ABCB11 Mutation

Introduction: Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are rare autosomal recessive genetic disorders caused by defects in the bile secretion pathway. The estimated prevalence ranges from 1 in 50,000 to 1 in 100,000 births. These disorders typically present in childhood with signs and symptoms of cholestasis. BRIC is usually benign with recurrent episodes of acute symptoms with periods of asymptomatic phase, but it can also progress with liver fibrosis and develop failure similar to PFIC. Case Description/Methods: A 29-year-old man presented with 3 months of worsening pruritus that started after a suspected episode of Norovirus. Other symptoms included 10-pound weight loss, mild right upper quadrant pain, jaundice, dark orange urine, and loose, pale green stools over the 4 weeks prior to presentation, Labs were notable for alkaline phosphatase 334; total bilirubin increase within one month (4.7 to 30 mg/dL), direct bilirubin 24.6, international normalized ratio 2.2, and a negative viral hepatitis and autoimmune panel. A GI Biofire panel detected Shigella/EIEC and Campylobacter. CT and MRI showed mild diffuse steatosis, no pancreatitis, or biliary ductal dilation. A liver biopsy was performed to evaluate if there is advanced fibrosis as seen in PFIC, suggesting a progressive disease. The biopsy showed cholestasis, an acute feature of BRIC2 with stage 0-1 fibrosis. Patient’s serum bilirubin improved to 14.3 mg/dl in the subsequent 5 weeks. Gene analysis in the past found missense mutations in 2 alleles of the ABCB11 gene, which is observed in PFIC2/BRIC2. Ten years prior, the patient had a post-mononucleosis flare; liver biopsy then showed no fibrosis. He had normalized biochemical values and was asymptomatic until the current episode. Discussion: This case illustrates infectious diarrhea as a potential trigger for PFIC/BRIC flare and emphasizes the need for timely evaluation. In this patient’s case, there was no significant progression of liver fibrosis over 10 years. He had a spontaneous improvement clinically and in laboratory values. This, along with asymptomatic periods between acute episodes, favors a diagnosis of BRIC2 as opposed to PFIC2. However, what may appear as benign pruritus can reveal a severe underlying disorder, and our case underscores the importance of prompt diagnosis and proactive management to improve outcomes in genetic intrahepatic cholestatic disorders.