Article Case report Congenital hepatic fibrosis: case report and review of literature Brahim El Hasbaoui, Zainab Rifai, Salahiddine Saghir, Anas Ayad, Najat Lamalmi, Rachid Abilkassem, Aomar Agadr Corresponding author: Zainab Rifai, Department of Pediatrics, Children’s Hospital, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco. [email protected] Received: 19 Jan 2021 - Accepted: 03 Feb 2021 - Published: 18 Feb 2021 Keywords: Fibrosis, hyper-transaminasemia, cholestasis, ciliopathy, case report Copyright: Brahim El Hasbaoui et al. Pan African Medical Journal (ISSN: 1937-8688). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cite this article: Brahim El Hasbaoui et al. Congenital hepatic fibrosis: case report and review of literature. Pan African Medical Journal. 2021;38(188). 10.11604/pamj.2021.38.188.27941 Available online at: https://www.panafrican-med-journal.com//content/article/38/188/full Congenital hepatic fibrosis: case report and review &Corresponding author of literature Zainab Rifai, Department of Pediatrics, Children’s Hospital, Faculty of Medicine and Pharmacy, Brahim El Hasbaoui1, Zainab Rifai2,&, Salahiddine University Mohammed V, Rabat, Morocco Saghir1, Anas Ayad1, Najat Lamalmi3, Rachid 1 1 Abilkassem , Aomar Agadr 1Department of Pediatrics, Military Teaching Hospital Mohammed V, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco, 2Department of Pediatrics, Children’s Hospital, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco, 3Department of Histopathologic, Avicenne Hospital, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco Article characterized histologically by defective Abstract remodeling of the ductal plate (DPM). DPM refers Congenital hepatic fibrosis (CHF) is a rare the histologic changes seen in the liver of a autosomal recessive disease derived from biliary heterogeneous group of genetic disorders, in which dysgenesis secondary to ductal plate malformation; segmental dilation of the intrahepatic bile duct are it often coexists with Caroli’s disease, von associated with fibrosis. The persistence of Meyenburg complexes, autosomal dominant immature embryonic bile ducts incites excess polycystic kidney disease (ADPKD), and autosomal proliferation of fibrous tissue in portal areas, recessive polycystic kidney disease (ARPKD). leading to portal hypertension, splenomegaly, Although CHF was first named and described in hyper-splenism, upper gastrointestinal varices, and detail by Kerr et al. in 1961. Its pathogenesis still ascites. Meantime hepatomegaly is an important remains unclear. The exact incidence and sign that can be detected in almost of patients; prevalence are not known, and only a few hundred these patients have relatively well-preserved liver patients with CHF have been reported in the function [1]. Congenital hepatic fibrosis is also literature to date. However, with the development frequently associated with ciliopathies (disorders of of noninvasive diagnostic techniques such as primary cilia) and the phenotype may involve ultrasound, computed tomography (CT), and kidneys, collectively termed hepatorenal fibrocystic magnetic resonance imaging (MRI), CHF may now disease. Autosomal recessive polycystic kidney be more frequently detected. Anatomopathological disease (ARPKD) is the most likely concomitant examination of liver biopsy is the gold standard in ailment, as opposed to juvenile nephronophthisis, diagnosis of CHF. Patients with CHF exhibit variable various syndromic conditions (meckel-gruber, clinical presentations, ranging from no symptoms Bardet-biedl, jeune, or joubert), and related to severe symptoms such as acute hepatic disorders that present with less frequency [2,3]. decompensation and even cirrhosis. The most Here, we present two cases of congenital hepatic common presentations in these patients are fibrosis according to the results of medical imaging splenomegaly, esophageal varices, and (CT or MRI), a liver biopsy, and genetic testing. gastrointestinal bleeding due to portal hypertension. In addition, in younger children, CHF Patient and observation often is accompanied by renal cysts or increased renal echogenicity. Great variability exists among Case 1: we report the 2-years-old girl who had been the signs and symptoms of the disease from early referred for evaluation of an abdominal distension childhood to the 5th or 6th decade of life, and in most with persistent hyper-transaminasemia and patients the disorder is diagnosed during cholestasis. She was born at full term of non- adolescence or young adulthood. Here, we present consanguineous parentage with no antenatal or two cases of congenital hepatic fibrosis in 2-years- perinatal complications, she was on exclusively old girl and 12-year-old male who had been referred breast-fed, food diversification was started at 6 for evaluation of an abdominal distension with months old, the child was described as a good persistent hyper-transaminasemia and cholestasis, eater, she was on a normal diet, and was thriving the diagnostic was made according to the results of appropriately. Furthermore, the girl presented an medical imaging (CT or MRI), a liver biopsy, and abdominal distension with recurrent episodes of genetic testing. mild diarrhea, bloating and loss of appetite since last 3 months. On the other side there was no history of jaundice, or gastro-intestinal bleeding. At Introduction the admission both her growth and development Congenital hepatic fibrosis (CHF) is a were normal for her age. However, hepatomegaly developmental disorder of the portobiliary system, and splenomegaly were noted. The liver Brahim El Hasbaoui et al. PAMJ - 38(188). 18 Feb 2021. - Page numbers not for citation purposes. 2 Article biochemical profile revealed elevated alkaline cholestasis. Like the first patient, further tests were phosphatase (ALK) of 704 U/L (reference range, 38- performed to established etiology of this disorder; 126 U/L), alanine aminotransferase (ALT) of 264 the results for serum ceruloplasmin, ferritin, viral U/L (reference range, 10-40 U/L), and aspartate markers, and antinuclear antibodies (ANA) were all aminotransferase (AST) of 153U/L (reference within normal limits, and the T spot test was range, 5-34 U/L). negative. However, abdominal computed tomography (CT) and magnetic resonance imaging Total and direct bilirubin, prothrombin time (PT), (MRI), showed hepatomegaly, splenomegaly, activated partial thromboplastin time (PTT) levels dilatations of intrahepatic bile ducts but the liver were normal. No thrombocytopenia was noticed at parenchymal heterogeneity appeared non- the blood count cell. Based on laboratory data for cirrhotic. On the other hand, two cysts were seen in chronic hepatitis, further tests were performed to the left kidney. The histopathologic exam of liver established etiology and included the biopsy revealed proliferation of collagen fibers determination of hepatitis B surface antigen surrounding the portal area, a finding that was (HBsAg) and hepatitis C virus (HCV), cytomegalo compatible with congenital hepatic fibrosis. Like virus (CMV), Epstein-Barr virus (EBV) antibodies, the first patient, he was discharged after his examination of serum ceruloplasmin, 24h urine symptoms improved with supportive treatment, copper, serum copper, serum iron, ferritin, and he remained alive over 1 year of follow-up until transferrin saturation, smooth muscle actin (SMA) he developed an acute liver and renal failure, antibodies, liver-kidney microsomal (LKM) unfortunately he died 2 months later. antibodies, and anti-nuclear antibodies (ANA) were done and were negatives. Abdominal ultrasound Discussion showed hepatosplenomegaly with normal liver echotexture, no nodular or steatosis liver were Congenital hepatic fibrosis (CHF) is a fibrocystic observed, there were no signs for portal disease affecting mainly the kidneys and liver. It is hypertension at the doppler. No fibrosis or hepatic characterized by fusiform dilatations of the renal cirrhosis, no dilatations of intrahepatic bile ducts collecting duct and ductal plate malformation of and no renal lesions were observed in abdominal the liver. The incidence is approximately 1: 20,000 CT and MRI. On the other hand, there were no live births. The majority of cases are caused by esophageal varices on upper gastrointestinal mutations in the PKHD1 gene, which encodes for endoscopy. Liver biopsy was performed and the fibrocystin/polycystin. This protein is expressed by histopathologic exam demonstrating disordered the renal and biliary epithelium and is postulated to hepatic acini and fibrous parenchymal banding bile maintain 3-dimensional tubular architecture. ductular proliferation and dilation, consistent with Autosomal recessive polycystic kidney disease can the diagnosis of congenital hepatic fibrosis be divided into 4 subgroups. The first group, (Figure 1, Figure 2). Our patient was put on a “perinatal,” presents in infancy with severe renal waiting list for liver transplantation, her clinical disease, congestive heart failure, and pulmonary condition remained stable, she is followed hypoplasia. The second group, “neonatal,” has regularly, until now without any complications such progressive renal disease, whereas the third as