Acta Paediatr 81: 937. 1992
SHORT COMMUNICATION
Alagille syndrome and hepatocarcinoma: a case report Antonio Chiaretti, Giuseppe Zampino, Lorenzo Botto and Giancarlo Polidori Department of Pediatrics. Catholic University of Rome, Italy
Alagille syndrome is characterized by a benign chroAlagille syndrome is an autosomic dominant form of intrahepatic cholestasis associated with characteristic nic cholestasis which begins typically at 4-5 months of facies, peripheral stenosis of the pulmonary artery, eye age. On light microscopy, a decrease in the size and defects, anomalies of the hand and vertebral arches, number of the small intrahepatic biliary ducts may be hypogonadism and growth delay. Deletion of the short noted. Approximately 15% of patients develop liver arm of chromosome 20 has been reported in some cases, cirrhosis. Hepatocarcinoma is a very rare event in these while a primary defect of biliary acid excretion has been patients. Most cases of hepatocarcinoma in patients proposed as the pathogenetic mechanism of the disease. with Alagille syndrome follow the development of Liver cirrhosis develops in 12-14% of cases. Hepatocar- cirrhosis (2,3). The present case developed hepatocarcicinoma is a very rare complication of this disease (1-3). noma without cirrhosis. We believe, together with other We report the case of a 17-year-old male with Alagille authors (l), that chronic cholestasis could have played an important role in the development of the liver syndrome who developed hepatocellular carcinoma. At physical examination the patient showed the neoplasia, possibly inducing dysplastic features in the following: marked growth delay (weight - 6 SD; height hepatocytes. Moreover, cirrhosis does not appear to be a necessary intermediate step of the process. From a - 6 SD); facial anomalies, including high and broad forehead, long beaked nose, pointed chin and micro- clinical standpoint, we feel that all patients with Alagille gnathia; systolic murmur; kyphosis and scoliosis; and syndrome should undergo periodic investigations for short fingers. The liver was enlarged with a hard mass in early detection of hepatocarcinoma, including determithe right hypochondrium. Laboratory investigations nation of serum levels of alpha-fetoprotein and liver revealed increased levels of triglycerides, cholesterol, echography . lipemia, ALP, AST, ALT and GGT. Total bilirubin was 6 mg/dl and direct bilirubin 4 mg/dl; alpha-fetoprotein was 400 ng/ml. High-resolution karyotype was 46 XY. A posterior ocular embryotoxon was detected by gonioscopy. Two-dimensional and Doppler echocardio- References graphy was negative. Skeletal X-rays showed a bone age 1. Adams P. Hepatocellular carcinoma associated with arteriohepatic of 9-10 years. An abdominal CT showed hepatomegaly dysplasia. Dig Dis Sci 1986;31:438-42 and a mass in the left hepatic lobe. Liver biopsy showed 2. Kaufman S, Wood P, Shaw B, Markin R, Gridelli B, Vanderhoff J. Hepatocarcinoma in a child with Alagille syndrome. Am J Dis the presence of hepatocarcinoma and a reduction in the 1987;141 :698-700 number of biliary ducts in the portal areas with 3. Child Rabinowitz M, Imperial JC, Schade R, et al. Hepatocellular prominent intralobular cholestasis. No sign of cirrhosis carcinoma in Alagille’s syndrome. A family study. J Pediatr Gastroenterol Nutr 1989;8:26-30 was noted. The patient died 17 months after the beginning of Received July 23, 1991. Accepted June 10, 1992. chemotherapy.
SHORT COMMUNICATION
Alagille syndrome and hepatocarcinoma: a case report Antonio Chiaretti, Giuseppe Zampino, Lorenzo Botto and Giancarlo Polidori Department of Pediatrics. Catholic University of Rome, Italy
Alagille syndrome is characterized by a benign chroAlagille syndrome is an autosomic dominant form of intrahepatic cholestasis associated with characteristic nic cholestasis which begins typically at 4-5 months of facies, peripheral stenosis of the pulmonary artery, eye age. On light microscopy, a decrease in the size and defects, anomalies of the hand and vertebral arches, number of the small intrahepatic biliary ducts may be hypogonadism and growth delay. Deletion of the short noted. Approximately 15% of patients develop liver arm of chromosome 20 has been reported in some cases, cirrhosis. Hepatocarcinoma is a very rare event in these while a primary defect of biliary acid excretion has been patients. Most cases of hepatocarcinoma in patients proposed as the pathogenetic mechanism of the disease. with Alagille syndrome follow the development of Liver cirrhosis develops in 12-14% of cases. Hepatocar- cirrhosis (2,3). The present case developed hepatocarcicinoma is a very rare complication of this disease (1-3). noma without cirrhosis. We believe, together with other We report the case of a 17-year-old male with Alagille authors (l), that chronic cholestasis could have played an important role in the development of the liver syndrome who developed hepatocellular carcinoma. At physical examination the patient showed the neoplasia, possibly inducing dysplastic features in the following: marked growth delay (weight - 6 SD; height hepatocytes. Moreover, cirrhosis does not appear to be a necessary intermediate step of the process. From a - 6 SD); facial anomalies, including high and broad forehead, long beaked nose, pointed chin and micro- clinical standpoint, we feel that all patients with Alagille gnathia; systolic murmur; kyphosis and scoliosis; and syndrome should undergo periodic investigations for short fingers. The liver was enlarged with a hard mass in early detection of hepatocarcinoma, including determithe right hypochondrium. Laboratory investigations nation of serum levels of alpha-fetoprotein and liver revealed increased levels of triglycerides, cholesterol, echography . lipemia, ALP, AST, ALT and GGT. Total bilirubin was 6 mg/dl and direct bilirubin 4 mg/dl; alpha-fetoprotein was 400 ng/ml. High-resolution karyotype was 46 XY. A posterior ocular embryotoxon was detected by gonioscopy. Two-dimensional and Doppler echocardio- References graphy was negative. Skeletal X-rays showed a bone age 1. Adams P. Hepatocellular carcinoma associated with arteriohepatic of 9-10 years. An abdominal CT showed hepatomegaly dysplasia. Dig Dis Sci 1986;31:438-42 and a mass in the left hepatic lobe. Liver biopsy showed 2. Kaufman S, Wood P, Shaw B, Markin R, Gridelli B, Vanderhoff J. Hepatocarcinoma in a child with Alagille syndrome. Am J Dis the presence of hepatocarcinoma and a reduction in the 1987;141 :698-700 number of biliary ducts in the portal areas with 3. Child Rabinowitz M, Imperial JC, Schade R, et al. Hepatocellular prominent intralobular cholestasis. No sign of cirrhosis carcinoma in Alagille’s syndrome. A family study. J Pediatr Gastroenterol Nutr 1989;8:26-30 was noted. The patient died 17 months after the beginning of Received July 23, 1991. Accepted June 10, 1992. chemotherapy.
