Progressive familial intrahepatic cholestasis : Clinical, biochemical, genetic and histopathological aspects

摘要: In the early 1980’s, most cases of neonatal cholestasis (often referred to as hepatitis) remained unexplained. By today, many these diseases have been characterized in detail. Progressive familial intrahepatic (PFIC) is one cholestatic entities with onset, where new techniques genetics and molecular biology contributed substantially our understanding. The aims this thesis were further extend knowledge PFIC terms disease genetics, effects surgical diversion bile, distribution bile flows during episodes remission. We studied a total 18 patients. Genetic linkage analysis excluded involvement known locus at 18q2122, suggested that genetically heterogeneous disease. After identification gene ABCB11, which causes type 2, genetic characterization showed homozygous missense mutation (c.890A>G) causing an amino acid shift (p.E297G) majority Swedish children studied. One compound heterozygous child carried microdeletion had not previously reported, two negative for mutations coding sequence ABCB11. A presented signs coagulopathy, ranging severity from bruises or nose bleeds bleeding lung brain, consequence vitamin K malabsorption due hampered hepatobiliary excretion. Complete relief pruritus was observed 7 13 operated within month after partial external biliary (PEBD). Six treated increased stomal losses first 2-6 weeks surgery. patient underwent liver transplantation months PEBD end-stage disease, died hepatocellular carcinoma 14 PEBD. At follow-up 11 21 improved growth, biochemical markers significantly reduced. All suffered more episode(s) varying duration followup period 5 12 years. correlated positively stage fibrosis recent biopsy (r=0.62, p<0.05). statistically significant regress histologic noted 3 years PEBD, than 10 scintigraphic examinations performed on 9 (n=5) remission (n=8). When we compared fractions isotopic activity lost through stoma, urine remaining body remission, found larger fraction stoma (median 90% vs. 22%, p<0.05), smaller into 2.5% 15%, p<0.05) cholestasis. conclude encompasses one, but several diseases, all caused by different defects formation bile. Most ABCB11 who undergo favorable long-term prognosis including histological improvement survival without need transplantation.