Keywords
congenital hepatic fibrosis - pancreaticobiliary maljunction - cholangitis - Roux-en-Y
reconstruction - liver transplantation
Introduction
Congenital hepatic fibrosis (CHF) is a rare disorder of the portobiliary system characterized
histologically by defective remodeling of the ductal plate, abnormal branching of
the intrahepatic portal veins, and progressive fibrosis of the portal tracts.[1] Typically, CHF is associated with autosomal recessive polycystic kidney disease.[2] Although liver transplantation is curative, it should be limited to the minority
of patients with chronic cholangitis or progressive hepatic dysfunction. In most instances,
CHF is a disorder characterized by well-preserved hepatic function and a good prognosis
if complications such as variceal bleeding and cholangitis are controlled.[3]
Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a union of
the pancreatic and biliary ducts outside the duodenal wall. PBM is associated with
a high risk for biliary tract carcinoma because of the continuous reflux of pancreatic
juice into the biliary tract.[4] To prevent biliary tract carcinogenesis in PBM patients, the cystic-dilated choledochus
should be excised in childhood before the development to a precancerous stage.[5] A case of CHF and PBM who suffered recurrent fever of unknown origin not responsive
to several antibiotics after Roux-en-Y reconstruction is reported.
Case Report
A 1-year-old girl was referred to our hospital due to prolonged diarrhea. She had
mild hepatosplenomegaly. Her kidneys were not palpable. Her height and weight were
within the reference ranges, and her developmental history was age-appropriate. Her
abdominal enhanced computed tomography (CT) showed hepatomegaly, dilation of intrahepatic
bile ducts, and a polycystic kidney. Magnetic resonance cholangiopancreatography and
drip infusion cholangiographic CT revealed PBM and a choledochal cyst. She had no
variceal bleeding or jaundice. Viral markers of hepatitis A virus, hepatitis B virus,
hepatitis C virus, cytomegalovirus, and Epstein–Barr virus were all negative. Her
renal function was normal and renal biopsy was not performed. The parents were healthy,
non-consanguineous Japanese. The patient had a healthy elder sister and younger brother,
and her family had no liver or renal diseases.
At the age of 4 years, she was treated by resection of the choledochal cyst and Roux-en-Y
reconstruction because of the cyst's risk of cancer. Operative cholangiography showed
PBM and a choledochal cyst ([Fig. 1]). On liver biopsy specimen examination, portal areas greatly expanded by fibrous
tissue and increased bile ducts were seen. The bands sometimes connected with adjacent
portal tracts. Distorted irregular bile ducts in the portal tracts were noted ([Fig. 2a]). She was diagnosed as having CHF based on the histological findings. After Roux-en-Y
reconstruction, she suffered recurrent fever of unknown origin not responsive to several
antibiotics (sulbactam/cefoperazone, panipenem/betamipron, piperacillin, amikacin,
etc.). When she had a high fever, although C-reactive protein was high (∼10 mg/dL),
her aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline
phosphatase, gamma-glutamyl transpeptidase, prothrombin time, total bilirubin, direct
bilirubin, and immunoglobulin levels were all normal. She had no jaundice, cough,
nasal discharge, diarrhea, pyuria, or otitis media. Repeated blood and urine cultures
were all negative. The symptoms were intractable, and her systemic condition gradually
deteriorated and her quality of life was reduced. Therefore, she underwent living
donor liver transplantation (LDLT) from her father at the age of 6 years. The recipient
liver was dark brown and green ([Fig. 2b]). A lymph node in the hepatic portal region was enlarged. On histological examination,
neutrophilic cholangitis with diffuse infiltration of neutrophils in the bile duct
and hepatic vein and reactive lymphadenitis with infiltration of neutrophils and macrophages
in sinusoids were seen. Three species of multi-drug-resistant Pseudomonas aeruginosa were cultured in the recipient's liver. After LDLT, the patient had no episodes of
recurrent fever, and her outcome was good.
Fig. 1 Operative cholangiography shows pancreaticobiliary maljunction and a choledochal
cyst.
Fig. 2 (a) On histological examination of the liver biopsy specimen, portal areas greatly expanded
by fibrous tissue and increased bile ducts are seen. The bands sometimes connect with
adjacent portal tracts. Distorted irregular bile ducts are noted in the portal tracts
(hematoxylin and eosin stain). (b) The recipient liver shows dark brown and green.
Discussion
In the present case, complete choledochal cyst resection and Roux-en-Y reconstruction
were performed in a 4-year-old girl with PBM and a choledochal cyst. At the time of
the operation, hepatic histological findings were hyperplasia of the interlobular
bile duct and diffuse fibril formation around the portal vein, compatible with a diagnosis
of CHF. Postoperatively, the patient repeatedly suffered from fever of unknown origin.
Although an investigation was performed from various perspectives to identify the
cause of the fever, the focus could not be determined. While blood test findings did
not include elevated transaminase levels or elevated bile duct–related enzymes such
as gamma-glutamyl transpeptidase, it was considered that the cause of the fever was
ascending cholangitis with foci at the liver and bile ducts. Therefore, LDLT from
the patient's father was performed when the patient was 6 years old. In Japan, the
number of deceased donors is still extremely low, especially for pediatric recipients.
LDLT was efficacious for a patient with intractable cholangitis following Roux-en-Y
reconstruction for CHF and PBM.
Since there are risks of biliary tract carcinoma in patients with PBM and a choledochal
cyst, surgery at an early stage is recommended for such cases.[5] Choledochal cyst resection in Japan is usually performed when the patient is between
1 and 4 years of age.[6] Therefore, choledochal cyst resection and Roux-en-Y reconstruction were performed
when the patient was 4 years old, because PBM was observed in the present case.
CHF can be associated with polycystic kidney, which is a rare disease. It is considered
that CHF and Caroli disease are ductal plate malformations from an embryological point
of view.[1] CHF is often accompanied by portal hypertension. Even if portal hypertension is
clearly present, hepatic function usually remains normal, and the patient's prognosis
is relatively good.[3] Liver transplantation is indicated in those children who develop liver failure in
association with portal hypertension.[7] Also, recurrent cholangitis in CHF is an indication for liver transplantation.[8] In the present case, the patient suffered repeatedly from intractable cholangitis
after Roux-en-Y reconstruction; therefore, this may have caused the liver transplantation
to be performed earlier than otherwise. In Alagille syndrome accompanying hypoplasia
of the intrahepatic bile duct, performing the Kasai procedure may result in a poor
outcome.[9] One possible mechanism could be that exposure to intestinal contents and/or ascending
cholangitis via the portoenterostomy could result in a second hit on already abnormal
bile ducts. Therefore, in such cases, the Kasai procedure is not recommended. In ductal
plate malformation, as for CHF, the intrahepatic bile duct has a complicated form,
and, therefore, once an infection is established, it becomes intractable. Similar
to Alagille syndrome, Roux-en-Y reconstruction should be avoided for ductal plate
malformations such as CHF. If polycystic kidneys are identified, liver biopsy should
be performed before any operative intervention to rule out/diagnose CHF.
