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Segmental Caroli's disease. Contrast‑enhanced CT image showing segmental cystic dilatation in left hepatic lobe with " central‑dot sign " (arrow). Associated features of portal hypertension seen namely ascites (asterix)
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Ductal plate malformations are a heterogenous group of congenital fibrocystic liver diseases resulting from insult to the ductal plate at various stages of embryogenesis. As a result various biliary malformations, cysts, hamartomas and congenital hepatic fibrosis may be seen. We present a radiological pictorial of ductal plate malformations, accura...
Citations
... En 1959, Alonso-Lej (13) clasificó los quistes de colédoco; posteriormente, Todani y colaboradores (14) modificaron esta clasificación a la que es actualmente la más utilizada. Se definen cinco tipos de quiste de colédoco según el lugar y forma (Tabla 1) (15) . La presentación clínica difiere según el grupo etario. ...
Los quistes de vía biliar se caracterizan por la dilatación de los conductos biliares intrahepáticos o extrahepáticos. Es una patología congénita poco frecuente, diagnosticada principalmente en niños. La presentación clínica en adultos suele ser inespecífica, pero importante debido a su riesgo aumentado de desarrollar carcinoma. Se presenta el caso de una paciente de 37 años que consulta por dolor en epigastrio irradiado al hipocondrio derecho, asociado a emesis y coluria. La ecografía hepatobiliar resultó normal, pero debido al riesgo de coledocolitiasis se realizó una colangiopancreatografía por resonancia magnética en la que se evidenció una dilatación quística del colédoco proximal de aproximadamente 2 cm, clasificada como Todani tipo I. Los quistes de vía biliar se han asociado a varias complicaciones, y el colangiocarcinoma es la más importante. La probabilidad de malignización es mayor en adultos y en los quistes Todani tipo I.
... Dado que la mayoría de los hamartomas tienen un tamaño menor a 5 mm, a menudo no se detectan en las imágenes, como ocurrió en el presente caso. [5][6][7][8][9] El diagnóstico diferencial incluye metástasis hepáticas, que usualmente son más heterogéneas en su tamaño; quistes hepáticos simples, los cuales rara vez son peque- pacientes con colangitis recurrente es un desafío y puede requerir trasplante hepático. 21 El ácido ursodesoxicólico ha demostrado, en un estudio con un modelo animal de enfermedad poliquística hepática, la inhibición de la proliferación de colangiocitos quísticos y la disminución de los niveles de ácidos biliares citotóxicos en el hígado. ...
Introducción. Los complejos de Von Meyenburg o hamartomas biliares son una anomalía congénita benigna rara de los conductos biliares intrahepáticos. Generalmente son asintomáticos y se encuentran de manera incidental en los estudios de imágenes pero pueden ser causa de ictericia, dolor abdominal y colangitis. Caso clínico. Paciente de sexo masculino de 80 años, que ingresa en el servicio de urgencias por ictericia progresiva asociada a prurito, con hepatograma alterado y patrón de colestasis. Se le realizan estudios de imágenes en los cuales no se evidencian alteraciones en el parénquima hepático ni en las vías biliares. Se decide realizar una biopsia hepática en la que se observa colestasis canalicular perivenular y presencia de complejos de Von Meyenburg. El paciente recibió tratamiento con ácido ursodesoxicólico con normalización de la colestasis en el seguimiento ambulatorio. Conclusión. El diagnóstico de hamartomas biliares debe tenerse en cuenta en los pacientes con colestasis intrahepática en los que no se identifica la etiología con los estudios iniciales. Representan un desafío diagnóstico ya que no siempre se observan en los estudios de imágenes.
... Hepatic manifestations are due to ductal plate malformation of the portobiliary system [2] . The combination of Caroli's disease, which is ductal plate malformation of central biliary tree and congenital hepatic fibrosis, which is ductal plate malformation of the peripheral biliary system, leads to Caroli's syndrome. ...
... The combination of high-resolution ultrasound and MRCP can noninvasively provide detailed information regarding the extent of kidney and hepatobiliary involvement [51]. Patients with CHF typically have the following imaging features: dysmorphic liver (usually hypertrophic left segment and atrophic right lobe), portal hypertension, and other DPMs (e.g., biliary hamartoma and Caroli syndrome) [52]. Moreover, a systemic radiological examination is necessary to assess whether other organs are involved, particularly for neuromuscular or renal abnormalities [53]. ...
Background. Congenital hepatic fibrosis is a hereditary fibropolycystic disease caused by ductal plate malformation. It is characterized by portal hypertension, but the manifestations, management, and outcome vary in children and adults. To raise awareness of medical staff, we have comprehensively compared the clinical features of congenital hepatic fibrosis between children and adults. Methods. We retrospectively enrolled all patients diagnosed with congenital hepatic fibrosis at the Huashan Hospital from August 2015 to August 2017 and analyzed their familial, clinical, laboratory, imaging, treatment, and follow-up data in detail. In addition, we reviewed cases with congenital hepatic fibrosis reported in the past 20 years in China and analyzed them according to the patients’ age. Results. A total of eight patients were diagnosed with congenital hepatic fibrosis in the study, including four children and four adults. The onset age of the children, who suffered from severe complications of portal hypertension and needed liver transplantation, ranged from 1 to 15 years old. The disorder developed in adults aged 26 to 60 years old. Three adults complained of recurrent abnormal liver function at the onset of illness, and they mainly received conservative treatments. The literature review included 30 children and 33 adults. In comparison, hepatomegaly was more common in children than in adults (57% vs. 21%, ). Malformation of kidneys and bile duct abnormalities were common, and multisystem involvement included eyes, other digestive organs, and genital and central nervous systems. Conclusions. Serious complications of portal hypertension developed in children requiring liver transplantation, while adults often had mild-to-moderate liver injuries upon onset. Adults with CHF varied a lot in clinical manifestations. Multiorgan involvement and unusual course are helpful to make a diagnosis. Timely histological assessment by liver biopsy and multidisciplinary cooperation are crucial for definitive diagnosis and early intervention.
1. Introduction
Congenital hepatic fibrosis (CHF) is a rare developmental disorder pathologically based on ductal plate malformation (DPM), namely, ciliopathy or fibrocystic liver disease. It is characterized by hepatosplenomegaly and portal hypertension. The prevalence of the disease is 1/10000–20000 [1, 2]. CHF rarely presents as a single entity but is often concomitant with a wide range of disorders caused by various gene mutations like autosomal recessive polycystic kidney disease (ARPKD) and Caroli syndrome. Nowadays, pediatric-onset liver disorders are increasingly common in adult hepatology practices due to latent pathogenesis and more awareness about congenital disease [3]. The severity and prognosis of this disease differ according to onset ages, and the therapeutic regimens vary accordingly. Therefore, we retrospectively analyzed and compared the clinical features of four children and four adults definitively diagnosed with CHF by liver histopathology. Furthermore, we reviewed and analyzed 63 cases with CHF reported in the past 20 years in China according to onset age.
2. Materials and Methods
We retrospectively enrolled all of the CHF cases that were diagnosed pathologically at the Huashan Hospital in Shanghai, China, from August 2015 to August 2017, and then collected the clinical data, including demographic information, family history, clinical manifestations, laboratory indexes, imaging findings, treatment, and follow-up. Then, we summarized and compared the clinical features of CHF according to onset age.
Liver histopathology is the gold standard for CHF diagnosis, which was performed by postliver transplant biopsy or ultrasound-guided percutaneous biopsy using a 16 g Tru-Cut needle (USA, Argon). All CHF cases in our study met the pathological characteristics of CHF, including the following: (1) defective remodeling of the ductal plate manifesting as abnormally shaped small bile ducts in the portal area and the cubic or columnar bile duct epithelia form elongated or cystic cavities, (2) dense fibrous septa of different widths separate liver parenchyma into hepatic islands containing normal vasculature and portal-portal bridging fibrosis and intact hepatic lobule, and (3) potentially abnormal changes to the intrahepatic portal vein branches. Cystic expansions of the intrahepatic bile ducts (microscopic and medium-sized bile ducts) are characteristics of Caroli syndrome, which was considered to be a different stage of the same disease as CHF in which microscopic bile ducts are involved [4]. Genetic testing was performed for 2 patients, in whom the candidate gene selected on the basis of clinical features and family history was tested by Sanger sequencing (ABCB4 gene for Patient 4 and PKHD1 gene for Patient 5).
In addition, we searched Chinese databases (China National Knowledge Internet, WanFang Data, and SinoMed) and reviewed 63 cases with CHF reported in the past 20 years in China. Comparisons between the clinical features of the children and adults were made through the chi-squared and Fisher’s exact tests using IBM SPSS Statistics 22 (IBM).
3. Results
3.1. Study Population
A total of four pediatric patients and four adult-aged patients were enrolled. All of the adults and the oldest child were diagnosed with CHF by ultrasound-guided percutaneous liver biopsy, and the other children’s diagnoses were ultimately confirmed after liver transplantation owing to liver decompensation. All four pediatric patients were admitted to the department of liver surgery, including a 13-month-old boy (P1), a 4-year-old girl (P2), a 15-year-old boy (P3), and a 9-year-old girl (P4). All four adult patients were hospitalized in the internal medicine department, including three female patients aged 26, 26, and 60 years (P5, P7, and P8, respectively) and a 26-year-old male patient (P6).
3.2. Case Reports
Patients 1-4 were all pediatric patients. Patient 1 developed cholangitis and hepatosplenomegaly at the 7th month after Kasai surgery for congenital biliary atresia (CBA), and then, he accepted the operation of piggyback liver transplantation and cholangioenteric anastomosis. Patient 2 suffered from severe liver injury and repeated hematemesis caused by gastric fundus varicosis. So she underwent living donor liver transplantation (LDLT) for liver decompensation. Patient 3 had a history of polycystic liver and kidneys. Recurrent hematemesis and melena happened for 8 years, and eventually, he was diagnosed as Caroli syndrome based on radiology and histology. In Patients 1-3, posttransplant pathology confirmed the diagnosis of CHF. Patient 4 presented with repeated melena, bloating, and itching for two months and then developed severe anemia, cholestasis, and ascites. ABCB4 mutation indicated the probability of progressive familial intrahepatic cholestasis-type 3 (PFIC3). Liver biopsy histologically conformed to features of CHF. This patient has been awaiting liver transplantation until now.
Patients 5-8 were adult patients. Patient 5 had of a history of chronic hepatitis B (CHB) and polycystic kidneys. This patient rapidly developed ascites, hypoalbuminemia, and oliguria under regular antiviral treatment. Thus, the previous pathological section was assessed again and considered to be CHB overlapping CHF. Patient 6, Patient 7, and Patient 8 presented with mildly-to-moderately elevated transaminase and bilirubin levels and progressive spleen enlargement. Patient 6 was initially diagnosed with intrahepatic cholestasis of pregnancy (ICP), yet there was no improvement after parturition and taking ursodeoxycholic acid. So liver puncture was performed in these three adults, through which they were diagnosed with CHF and at a long-term follow-up.
3.3. Clinical Manifestations
The eight cases presented with different symptoms and durations (Table 1). The youngest child (P1) previously suffered from obstructive jaundice caused by CBA and underwent Kasai operation at 3 months old. He was hospitalized again because of a high postoperatively fever, hepatosplenomegaly, and cholestatic liver injury. The other three pediatric cases (P2, P3, and P4) all suffered from repeated hematemesis or melena, suggestive of upper gastrointestinal bleeding. Unlike the children, the majority of adults (P6, P7, and P8) were hospitalized due to abnormal liver function. Notably, Patient 5 had a 20-year history of polycystic kidney and untreated CHB with pathological grade G3S4 and then underwent splenectomy for severe hypersplenism and esophageal varices. She mainly presented with abdominal distension, edema, oliguria, and anemia. Only one patient (P3) had a suspicious family history, namely, an older sister who developed cirrhosis at 29 years old and a younger sister who underwent a splenectomy for hypersplenism at 27 years old.
No.
Sex
Age
Chief complaint
Course
Principal diagnosis
Hb (g/L)
WBC (10⁹/L)
PLT (10⁹/L)
ALT (U/L)
AST (U/L)
ALP (U/L)
GGT (U/L)
TBil (mmol/L)
INR
Alb (g/L)
P1
M
1 yr
Hyperpyrexia
1 month
CHF§
CBA
Cholangitis after Kasai operation
110
9.13
205
51
68
553
265
6.2
1.04
37
P2
F
4 yr
Hematemesis
1.5 month
CHF§
86
3.71
189
268
230
813
500
12.3
0.94
39
P3
M
15 yr
Hematemesis and melena
8 years
CHF§
Caroli disease
52
5.63
649
17
19
129
26
3.7
1.15
27
P4
F
9 yr
Melena and bloating
2 months
CHF§
PFIC3
68
2.25
226
317.9
274.1
382
233
14.7
0.87
28.8
P5
F
26 yr
Bloating, edema, and oliguria
7 years
CHF
CHB
Intrahepatic biliary duct cystic dilation
Polycystic kidneys§§
83
7.04
329
15
20
91
22
12
1.08
37
P6
F
26 yr
Isolated abnormal liver function
6 years
CHF
134
4.81
66
67
51
156
177
46.1
1.12
46
P7
M
26 yr
Isolated abnormal liver function
9 months
CHF
Intrahepatic biliary duct cystic dilation
147
4.19
75
20
21
45
64
17.5
1.20
45
P8
F
60 yr
Abnormal liver function and edema
4 years
CHF
136
3.82
72
46
55
139
24
31.8
1.19
32
Abbreviations and normal range of each lab index in parentheses: P = patient; M = male; F = female; yr = years old; CHF = congenital hepatic fibrosis; CHB = chronic hepatitis B; CBA = congenital biliary atresia; PFIC3 = progressive familial intrahepatic cholestasis-type 3; Hb = hemoglobin (male: 130-175 g/L, female: 115-150 g/L); WBC = white blood cell (-); PLT = platelet (-); ALT = alanine aminotransferase (male: 9-50 U/L, female: 7-40 U/L); AST = aspartate aminotransferase (male: 15-40 U/L, female: 13-35 U/L); ALP = alkaline phosphatase (1~4 yrs: <281 U/L; 5~6 yrs: <269 U/L; 7~12 yrs: <300 U/L; male 13~17 yrs: <390 U/L; male 18~19 yrs: 40-129 U/L; : 45-125 U/L; female 13~17 yrs: <187 U/L; female 18~19 yrs: 35-104 U/L; female 20~49 yrs: 35-100 U/L; female 50~79 yrs: 35-100 U/L; and : 50-135 U/L); GGT = γ-glutamyl transpeptidase (male: 10-60 U/L, female: 7-45 U/L); TBil = total bilirubin (3.4-20.4 μmol/L); INR = international normalized ratio (0.88-1.12); Alb = albumin (40-55 g/L). §CHF: combined with liver decompensation; §§polycystic kidneys combined with chronic renal dysfunction; IDA: iron deficiency anemia; RA: renal anemia.
... DPM results, depending on the timing or stage of development, in a spectrum of abnormalities including: • multiple hamartomas or biliary microhamartomas (Von Meyenburg complexes, VMC) -the failure of involution of embryonic bile ducts; • congenital hepatic fibrosis (CHF) -the failure of microscopic bile ducts involution; • Caroli syndrome (CS; Caroli disease in association with CHF) -the failure of involution of microscopic and medium size bile ducts; • Caroli disease (CD) -the failure of involution of medium and large bile ducts; • isolated liver cysts in polycystic liver disease (PCLD) -result of malformation of the embryonic ductal plate with formation of von Meyenburg complexes lined with functional biliary epithelium [2][3][4][5]. ...
... It is worth emphasizing, that more than one form of DPMs can coexist in the same patients [2]. ...
Introduction: Autosomal recessive polycystic kidney disease (ARPKD) is a ciliopathy with kidney and liver
manifestations. Children with ARPKD usually remain only under the care of nephrologist due to silent liver
involvement characterized by congenital hepatic fibrosis with or without bile ducts dilatation. The aim of this
study is to pay attention on the occurrence of the abnormalities of the biliary tract in ARPKD patients.
Material and methods: Data on laboratory (serum total and direct bilirubin concentration, gamma-glutamyltranspeptidase
[GGT] activity, serum bile acids concentration) and imaging examinations findings (intrahepatic
and extrahepatic bile ducts dilatation, biliary cysts), as well as data on history of cholangitis, were analysed
retrospectively in 17 patients (14 male and 3 female, aged from 2.5 to 42 years) with molecularly confirmed
diagnosis of autosomal recessive polycystic kidney disease (ARPKD).
Results: Increased GGT activity was noticed in 7 patients and slightly increased direct bilirubin in 8 (46.7
and 53.3% respectively). Only one patient had a history of cholangitis. Dilatation of intrahepatic bile ducts
and common bile duct on ultrasound examination was described in 10 and 5 patients respectively. There was
no close correlation between laboratory and imaging examination findings. Four our patients with dilated
bile ducts had normal laboratory results, while two patients had abnormalities only in laboratory tests. Both,
laboratory and imaging abnormalities were found in 6 and none of them in 5 patients.
Conclusions: In patients with ARPKD abnormalities of the biliary tract can occur even when standard laboratory
tests findings stay within normal limits. Detailed biliary tree imaging evaluation should be performed
in each patients with increased GGT activity/bile acid concentration, history of cholangitis, before kidney
transplantation, as well as in adolescents and young adults due to increased risk of cholangiocarcinoma.
... The index case presented during neonatal period with features of cholangitis and improved with supportive management. Typical hepatic imaging findings included caudate lobe hypertrophy, periportal T2 hyper intensities and biliary duct anomalies in cases with Caroli syndrome (20). Liver biopsy was not done in the index case but MRCP findings in association with ARPKD were diagnostic of CHF. ...
Goldston syndrome (GS) is a rare association of Dandy-Walker malformation (DWM) and cystic renal dysplasia with or without hepatic fibrosis. It is considered to be a milder variant of Meckel Gruber syndrome (MGS) and shares features with Miranda syndrome. We reported a 22 day old infant with DWM and autosomal recessive polycystic kidney disease (ARPKD) who presented with cholestasis and acholic stools. Ultrasonography and magnetic resonance cholangiopancreatography (MRCP) confirmed the diagnosis of congenital hepatic fibrosis (CHF). The child improved with supportive treatment. CHF is a rare condition which may present as a syndromic association.
... Hepatic involvement comprises of ductal plate malformation leading to abnormal proliferation and dilatation of bile ducts and fibrosis of portal tracts. [5,6] Historically, childhood PKD was classified into four types, namely perinatal, neonatal, infantile, and juvenile forms using clinical and histologic findings. [7] The most severe form of renal disease presents in the perinatal period. ...
Autosomal recessive polycystic kidney disease (ARPKD) affects the liver and the kidney. Renal involvement presents early in life, whereas hepatic involvement manifests slightly later with portal hypertension. A male toddler came with chronic abdominal distension, prominent abdominal wall vessels, and umbilical protuberance. Ultrasonography findings of hepatic fibrosis with portal hypertension, mildly prominent biliary radicals, bilateral cystic renal enlargement, and a striated nephrogram on contrast-enhanced computed tomography suggested the diagnosis. Congenital hepatic fibrosis is invariably associated with ARPKD leading to portal hypertension and the development of portosystemic collaterals; those located in the umbilical region appear as caput medusae.
Clinically relevant macroscopic and microscopic anatomy of the liver and nutrient metabolism in the liver have been discussed. This chapter includes focussed discussion on various aetiologies of liver cirrhosis, management of liver failure and portal hypertension, and acute liver failure management. Recent advances in the treatment of chronic viral hepatitis, fatty liver, and hepatocellular carcinoma have been covered.
Fibropolycystic liver disease is a continuum of disorders that result from insults to the ductal plate at different stages of development and are often associated with each other. Caroli's syndrome, polycystic liver disease, biliary hamartomas, and congenital hepatic fibrosis are included in this complex spectrum that also shows frequent association with renal anomalies, such as polycystic kidney disease and medullary sponge kidney. Choledochal cysts are a controversial point in this topic since they have long been considered part of this spectrum due to morphological similarities, but studies have shown different pathogenesis. This article's purpose is to review these abnormalities through a multimodality radiological perspective offering correlation with its key embryological aspects. Knowing these numerous anomalies and their possible associations may ease an accurate diagnosis and prompt management.
