Detecting the spontaneous resistance mutations will benefit the clinical management of CHB patients. “
“Purpose: Evaluate the efficacy of nontransplant surgery in Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC)−1 & −2. Methods/Results: At 14 Childhood Liver Disease Research and Education Network centers, 57 children (20 ALGS, 16 PFIC1, 15 PFIC2, & 6 others with GGT<100 U/L) were identified. Mean ages at surgery were 65±65 months (ALGS) & 28±37 months (PFIC). Data were retrospectively collected: pre-op (0), 6-12 months post-op (12m), 12-24 months post-op (24m), & >24m. Longitudinal lab data were analyzed using repeated measures
mixed models. Symptom data were analyzed using McNamara’s test. 39 patients (15 ALGS, 12 PFIC1, 10 PFIC2,
2 GGT<100) underwent partial external biliary diversion (PEBD). Serum total bilirubin decreased post- DNA Methyltransferas inhibitor PEBD in PFIC1 (0=8.1 JNK inhibition ±4.0, 24m=2.9±4.1 mg/dL, p<0.0001) but not in ALGS (0=5.3±5.4, 24m=4.9±4.1 mg/dL) or PFIC2 (0=2.7±2.9, 24m=2.1 ±2.5 mg/dL). Total serum cholesterol decreased in ALGS patients (0=695±465, 12m=365±152, 24m=457±319 mg/dL, p<0.05). Alanine aminotransferase levels were higher in ALGS (0=182±70, 24m=260±73 IU/L) compared to PFIC1 (0=113±134, 24m=56±32) and PFIC2 (0=123±112, 24m=99±83)(p<0.01). ALGS patients experienced less severe pruritus (0=100%, 12m=7%, 24m=12%, >24m=8%, p<0.001) and greater freedom from pruritus (0=0%, 12m=21%, 24m=35%, >24m=46%, p<0.001). PFIC1 & 2 patients similarly were less pruritic (p<0.001). Xanthoma-free ALGS patients increased (0=37%, >24m=69%, NS). 11 patients (4 ALGS, 2 PFIC1, 3 PFIC2, 2 GGT<100) underwent ileal exclusion (IE). Severe pruritus trended downward in ALGS patients (0=4/4,12m=1/4) without change in xanthomas (4/4 at 0&12m). No trend in severe pruritus was seen in PFIC (0=3/5, 12m=1/3, & 24m=1/2). 2 patients with GGT<100 required conversion from IE to PEBD due to persistent severe pruritus. Both improved post-revision. 7 patients underwent gallbladder to colon diversion (GBC; 1 ALGS, 2 PFIC1, 2 PFIC2, 2 GGT<100) and had less postop pruritus (0=7/7, 12m=0/6, 24m=3/6). Complications
were few (PEBD: 4 electrolyte abnormalities/dehydration, 2 bowel obstructions, 1 bowel ischemia, 2 stoma prolapses, 4 stoma revision; IE: 2 electrolyte abnormalities/dehydration; GBC: 2 electrolyte abnormalities, 1 intestinal obstruction, 1 bowel ischemia). 12 liver transplants Y-27632 order were subsequently performed: 3 ALGS (2 PEBD, 1 IE), 3 PFIC1 (2 PEBD, 1 IE), 6 PFIC2 (3 PEBD, 3 IE); PELD>19 were 3 PFIC2/PEBD. Summary/Conclusion: This is the first multi-center analysis of nontransplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally result in improvement of pruritus and cholestasis. Disease specific responses may exist. Disclosures: Benjamin L. Shneider – Consulting: Bristol Myers Squibb, Vertex; Grant/Research Support: Hyperion Therapeutics; Stock Shareholder: Bristol Myers Squibb Lee M.