Abstract
Objective: Identify molecular basis of cholestatic cirrhosis with hepatocellular carcinoma (HCC) in a 55-year-old woman Design: Case study Settings: Center of Cardiovascular Surgery and Transplantation, Brno, Czech Republic Material and Methods: A woman aged 60y had pruritus and icterus as an infant, with normal-range serum gamma-glutamyl transpeptidase activity, that were palliated effectively by biliary diversion and pharmacotherapy. Cirrhosis (diagnosed at age 20y) was complicated by portal hypertension with variceal bleeding (29y) and hypersplenism requiring splenectomy (34y).
Jaundice recurred after a viral illness treated with acetaminophen, and worsened; serum alpha-fetoprotein was elevated, and magnetic resonance imaging found a 22mm left-lobe mass. At transplant hepatectomy (55y), HCC arisen in cirrhosis was confirmed.
Immunostaining for bile salt export pump (BSEP), encoded by ABCB11, was conducted and ATP8B1, ABCB11 and TJP2 were analyzed in the patient and her first-degree relatives. Results: BSEP was unremarkably expressed in the explanted liver.
Compound heterozygosity for 2 pathogenic point mutations in ABCB11, encoding bile salt export pump (BSEP), was identified (c.2495G>A [p.Arg.832His] and c.2629G>A [p.Gly877Arg]), without ATP8B1 lesions. Both mutations are reported in association with progressive familial intrahepatic cholestasis.
Conclusion: HCC associated with PFIC due to ABCB11 mutations is recognized in children. To our knowledge, no report in an adult has yet appeared.
Our patient had PFIC with functional but not absolute deficiency of BSEP. Unusually slow progression of her disease can be attributed to residual BSEP function, assisted by surgical and medical palliative interventions.