Congenital hepatic fibrosis presenting as hepatomegaly in early infancy

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B r i e f clinical a n d l a b o r a t o r y o b s e r v a t i o n s

The Journal of Pediatrics January 1968

2. Deutsch, H. F., and Morton, J. I.: Dissociation of human serum macroglobulins, Science 125: 600, 1957. 3. Kibrick, S.: Viral infections of the fetus and newborn in Pollard, Morris: Perspectives in virology, vol. 2, Minneapolis, 1961, Burgess Publishing Co., p. 140. 4. Alford, C. A., Jr." Studies on antibody in con-

genital rubella infections, Am. J. Dis. Child. 110" 455, 1965. 5. Bellanti, J. A., Artenstein, M. S., and Olson, L. C., Buescher, E. L., Luhrs, C. E., and Milstead, K. L.: Congenital rubella. Clinieopathologic, virologic, and immunologic studies, Am. J. Dis. Child. 110: 464, 1965.

Congenital hepatic fibrosix presenting as bepatomegaly in early infancy

cm. below the right costal margin and the spleen, 2 cm. below the left costal margin. A right inguinal hernia was present. At 8 weeks of age the patient was admitted to the Naval Hospital, San Diego, Calif., for evaluation because of apparent progression of the abdominal distension and hepatosplenomegaly. There were no other symptoms. The appetite was good and stools were normal. During the hospital stay the liver was measured from 3 to 5 cm. below the right costal margin and the spleen from 6 to 7 cm. below the left costal margin. The abdominal girth varied between 42 and 46 cm. Pitting edema was present over both tibial areas. I,aboratory studies revealed a hematocrit value of 35 with a normal white-blood-cell count and differential. The urinalysis revealed a specific gravity of 1.020 and was negative for protein and reducing substances. An intravenous pyelogram and upper gastrointestinal series were normal. A flat plate of the abdomen revealed a ground glass appearance suggesting ascites; however, an abdominal paracentesis yielded no fluid. A bonemarrow examination was normal with the exception of an eosinophilia of 8 per cent. The serum glutamic oxalaeetic transaminase was 16 units; alkaline phosphatase, 3 King-Armstrong units; cholesterol, 140 mg. per cent; albumin, 3.5 Gm. per cent; globulin, 4.6 Gin. per cent; and sweat chloride, 39.2 mEq. per liter. Urine cultures for cytomegalic inclusion virus were negative, and the Sabin-Feldman dye test was negative in the mother. The patient was dischaNed from the hospital to be followed in the outpatient clinic. He remained asymptomatic, and his growth and development were normal. The hepatosplenomegaly remained unchanged. At 8 months of age the patient was readmitted to rule out type I I I glycogenosis. Glucose, glucagon, and epinephrine tolerance tests were normal. An electrocardiogram revealed right bundle branch block and nonspecific abnormal T waves.

Robert W. ten Bensel, Lieutenant Commander (MC) USNR, and Earl R. Peters, Captain (MC) USN SAN

DIEGO,

CALIF.

C o N g E N I T AL

hepatic f i b r o s i s

is a

rare

congenital disorder characterized by hepatomegaly with a proliferation of dilated bile ducts a n d extensive periportal fibrosis. T h e r e are few reports of this entity in pediatric literature. T h e purpose of this paper is to report a case of congenital hepatic fibrosis in whom abdominal distension a n d hepatospIenomegaly were first noted at 6 weeks of age. CASE REPORT J. D., a Caucasian male infant, was born March 13, 1965, following a normal pregnancy and delivery. The mother and father, 30 and 33 years of age, respectively, were in good health. Four other siblings were normal. At birth the infant weighed 3,100 grams and was 48 cm. in length. At 6 weeks of age the patient was noted to have abdominal distension; the liver was felt 3 The opinions or assertions contained herein are the private ones of the authors and are not to be construed as o~cial or reflecting the views of the Navy Department, or the Naval Service at large.

Volume 72 Number l

Fig. 1. Hepatosplenomegaly in Patient J. D. at 24 months of age. An esophagogram revealed no evidence of varices. Repeat liver function tests were normal. At 14 months of age the infant was admitted for surgical repair of the large inguinal hernia. While he was under anesthesia, an exploratory laparotomy was performed to obtain a liver biopsy. The liver was massively enlarged, yellowish-gray in color, and had a fine lace-like appearance. At the time of the wedge biopsy, its consistency was noted to be quite firm, and the bleeding was less than normal. The spleen was grossly enlarged but otherwise appeared normal. The patient remained asymptomatic. One year postoperatively, his growth and development had remained normal (Fig. 1), and repeated liverfunction studies, an esophagogram and intravenous pyelogram were normal. The liver biopsy (Figs. 2 and 3) revealed a marked increase in fibrous tissue which was periportal in location and did not distort zonal structures. Within the fibrous tissue there were many well-formed and dilated bile ducts, some of which were filled with bile pigments and others with proteinaceous debris. These dilated bile ducts were lined with cuboidal and columnar epithelial cells. The parenchymal liver cells were normal. The arteries and veins were considered normal. The slides were reviewed by Dr. Sheila Sherlock, and she concurred with the diagnosis of congenital hepatic fibrosis consist-

Brief clinical and laboratory observations

97

Fig. 2. Photomicrograph showing distorted architecture of liver with periportal fibrosis, bile duct dilatation, and proliferation. (Original magnification x20.)

Fig. 3. Photomicrograph showing "micro-hamartoma" or "bile duct adenoma." Note normal liver parenchymal cells. (Original magnification x50.)

ent with microhamartomas of the bile ducts (yon Meyenburg complexes). DISCUSSION Congenital h e p a t i c fibrosis is considered to be a v a r i a n t of cystic disease of the liver, the cystic m a l f o r m a t i o n s developing from the congenital fibrosis. 1-~ T h e histological

98

Brie] clinical and laboratory observations

picture is characterized by a marked increase of periportal fibrous tissue and proliferation of dilated bile ducts. These areas of dilated bile ducts have been called "von Meyenburg complexes ''4 or "multiple bile duct adenomas." T h e liver parenchymal cells are normal, and liver function tests are usually normal in spite of the frequent association of portal hypertension, a, ~, 7 Most children present with abdominal enlargement or hematemesis after one year of age? Hepatomegaly was noted at 6 weeks of age in our patient, the earliest such finding in any reported case of congenital hepatic fibrosis. Polycystic kidneys are frequently associated with congenital hepatic fibrosis and appear to be the primary determinant of prognosis, s-l~ Other associated malformations which may affect prognosis have included subarachnoid hemorrhage from a cerebellar hemangioma 'J and progressive pulmonary fibrosis. 'z The heredity of the condition is not clearly known. Affected siblings have been reported, 1 but it has never appeared in successive generations? ~

SUMMARY A case of congenital hepatic fibrosis has been presented in which the hepatospleno.megaly was noted at 6 weeks of age. There was no evidence of portal hypertension, and liver function remained normal. This case emphasizes the value of liver biopsy in

Single umbilical artery Robert J. Harris, M.D., and G. Van Leeuwen, M.D. COLUMBIA~ MO. R E c E N T L Y we have reviewed the literature, with respect to single umbilical artery and its association with other anomalies, and reported our experience with 2,000 consecutively born infants, 6 of w h o m had a single umbilical artery. 1 Of these infants 4 had no

The Journal of Pediatrics January 1968

evaluating cases of idiopathic hepatosplenomegaly in infants.

REFERENCES 1. Kerr, D. N. S., Harrison, C. V., Sherlock, S., and Walker, R. M.: Congenital hepatic fibrosis, The Quart. J. Med. 30: 91, 1961. 2. Mac Mahan, H. W.: Congenital anomalies of the liver, Am. J. Path. 5: 499, 1929. 3. Parker, R. B. F.: Fibrosis of the liver as a congenital anomaly, J. Path. & Bact. 71: 359, 1956. 4. Von Meyenburg: Uber die Cystenleber, Bacts. Path. & Anat. 64: 477, 1918. 5. Popper, H. P., and Schoffner, F.: Liver: Structure and function, New York, 1957, Blakiston Division, McGraw-Hill Book Company. 6. Boley, S. J., Arlen, M., and Mogilner, L. J.: Congenital hepatic fibrosis causing portal hypertension in children, Surgery. 54: 356, 1963. 7. Me Carthy, L. G., Boggenstoss, A. H., and Logan, G. B.: Congenital hepatic fibrosis, Gastroenterology 49: 27, 1965. 8. Kerr, D. N. S., Warrick, C. K., and HartMercer, J.: A liver resembling medullary sponge kidney in patients with congenital hepatic fibrosis, Clin. Radiol. 13: 85, 1962. 9. Reilly, B. J., and Neuhauser, E. B. D.: Renal tubular ectasia in cystic disease of the kidneys and liver. Am. J. Roentgenol. 84: 546, 1960. 10. Grossman, H., and Seed, W.: Congenital hepatic fibrosis, bile duct dilatation and renal lesion resembling medullary sponge kidney, Radiology 87: 46, 1966. 11. Wagenvoort, C. A., Boggenstoss, A, H., and Love, J. G.: Subarachnoid hemorrhage due to cerebellar hemangioma associated with congenital hepatic fibrosis and polycystic kidneys. Staff Meeting of the Mayo Clinic, 37: 301, 1962. 12. Sherlock, S.: Personal communication.

recognized congenital anomalies; 2 had 16 - 18 chromosomal trisomy. Subsequent to the above study we have accumulated data on 2,800 additional infants born in 2 hospitals (Table I ) . O f the 2,800 infants 11 had a single umbilical artery which was detected by careful inspection of the umbilical cord at the point of entry into the infant, Histological confirmation was obtained in all instances of single umbilical artery. T h e infants were carefully examined; the procedures included a hemogram, urinalysis, chest x-ray, and intravenous pyelography. T h e infants have