Progressive Familial Intrahepatic Cholestasis in Korea: A Clinicopathological Study of Five Patients

Abstract

Background Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive liver diseases that present as neonatal cholestasis. Little is known of this disease in Korea. Methods The records of five patients histologically diagnosed with PFIC, one with PFIC1 and four with PFIC2, by liver biopsy or transplant were reviewed, and ATP8B1 and ABCB11 mutation status was analyzed by direct DNA sequencing. Clinicopathological characteristics were correlated with genetic mutations. Results The first symptom in all patients was jaundice. Histologically, lobular cholestasis with bile plugs was the main finding in all patients, whereas diffuse or periportal cholestasis was identified only in patients with PFIC2. Giant cells and ballooning of hepatocytes were observed in three and three patients with PFIC2, respectively, but not in the patient with PFIC1. Immunostaining showed total loss of bile salt export pump in two patients with PFIC2 and focal loss in two. Lobular and portal based fibrosis were more advanced in PFIC2 than in PFIC1. ATP8B1 and ABCB11 mutations were identified in one PFIC1 and two PFIC2 patients, respectively. One PFIC1 and three PFIC2 patients underwent liver transplantation (LT). At age 7 months, one PFIC2 patient was diagnosed with concurrent hepatocellular carcinoma and infantile hemangioma in an explanted liver. The patient with PFIC1 developed steatohepatitis after LT. One patient showed recurrence of PFIC2 after 10 years and underwent LT. Conclusions PFIC is not rare in patients with neonatal cholestasis of unknown origin. Proper clinicopathologic correlation and genetic testing can enable early detection and management.

Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review

“…After screening titles and abstracts, 563 articles were retrieved for full-text evaluation. Ultimately, 67 non-overlapping studies [ 11 , 12 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ,…”

Progressive Familial Intrahepatic Cholestasis: A Study in Children From a Liver Transplant Center in India

“…On the other hand, both the cases of PFIC3 presented in 1 st decade, at 5 years and 9 years respectively. The main function of TJP2 is to prevent back diffusion of bile salts from canaliculi to the blood circulation (3,4). In this study, 2 out of 3 cases with TJP2 presented in infancy while one presented in childhood.…”

Morphology of transplanted liver in recurrent progressive familial intrahepatic cholestasis type 2

“…Только в одной сравнительно давней публикации [14] было сообщено о шести пациентах с ПСВХ-2, у которых развился возврат заболевания. Остальные публикации на эту тему посвящены единичным наблюдениям [3,[10][11][12][13].…”

“…При гистологическом исследовании биоптата трансплантированной печени было найдено увеличение размеров гепатоцитов в несколько раз из-за отека, что связано с отсутствием белка BSEP, который обеспечивает транспорт солей желчи из гепатоцитов [3,[10][11][12][13]. Присутствовали также многоядерные гепатоциты, которые, по данным литературы [13], являются отличительным гистологическим признаком именно ПСВХ-2. Внутриклеточное скопление желчных кислот привело к развитию склероза портальных трактов и появлению септ (F2).…”

“…Однако сравнительно недавно появились сообщения о том, что у пациентов с ПСВХ-2 после трансплантации печени развивается рецидив холестаза вместе с клиническими и гистологическими признаками первичной болезни. Рецидив заболевания связывают с появлением аутоантител против белка BSEP, которые ингибируют транспортную активность насоса солей желчи и вызывают тяжелый холестаз [3,[10][11][12][13].…”