A. M. A. ABDULLAH ET AL.
Congenital Hepatic Fibrosis in Saudi Arabia by A. M. A. Abdullah,* H. Nazer,* M. Atiyeh,** and M. A. AH*** Departments of* Paediatrics, ** Medicine, and *** Pathology, King Faisal Specialist Hospital and Research Centre P.O. Box 3354, Riyadh 11211, Saudi Arabia
Introduction
King Faisal Specialist Hospital and Research Centre (KFSH & RC).
Congenital hepatic fibrosis (CHF) has been recognized as an inherited, rare disorder characterized by periportal fibrosis with irregularly shaped proliferating bile ducts. Affected children are prone to suffer from portal hypertension without significant impairment of liver functions.1'2 The common hepatic manifestations of CHF were first described in 1856 by Bristowe.3 Thereafter, the varied clinical spectrum of CHF was more widely recognized.4-' The name 'congenital hepatic fibrosis' was introduced by Kerr and Colleagues in 1961.6 The diagnosis of CHF is usually confirmed by its typical histological features on a percutaneous liver biopsy or a surgical wedge liver biopsy. Liver function tests in CHF are characteristically normal except for an occasional high alkaline phosphatse.7 The exact incidence and prevalence of CHF are not known. By 1981, only 200 patients with CHF had been reported in the literature.1 The disease appears in both sporadic and familial forms. It is probably inherited as an autosomal recessive.8 In Saudi Arabia, where a high incidence of consanguineous marriage prevails, the disease may not be as rare as previously thought. It is possible that a large proportion of affected patients remains undiagnosed until they present with gastrointestinal haemorrhage from bleeding oesophageal varices which may be fatal. This report describes the varied clinical presentation of CHF as experienced at
Fourteen children (eight males, six females) met the criteria for the diagnosis of CHF. Their mean age at diagnosis was 7.5 years (range 1.8-14 years). Seven cases were the offspring of consanguineous marriages. Five families had a history of more than one affected child, but siblings were not included in the study. The main clinical features at presentation are shown in Table 1. Liver function tests were normal in all patients
240
Journal of Tropical Pediatrics
© Oxford University Press 1991
Patients and Methods
The medical records for patients up to the age of 14 years seen at KFSH & RC with the diagnosis of CHF were reviewed. The study analysed patients retrospectively and prospectively from 1981 to 1988. Only patients with confirmed histological changes of CHF were included (Fig. 1). Each case was reviewed for age, sex, time from onset of symptoms to diagnosis, consanguinity, similarly affected children in the family, and main clinical features at presentation. The patients were subjected to various investigations including liver function tests, hepatitis B screen, blood biochemistry, abdominal ultrasound, endoscopy, and angiography. Results
Vol.37
October 1991
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on July 13, 2015
Summary Congenital hepatic fibrosis (CHF) is a recognized cause of portal hypertension with oesophageal varices, gastro-intestinal haemorrhage and cholangitis in children without significant impairment of hepatic or renal function. This report describes the varied clinical presentation of CHF as seen at King Faisal Specialist Hospital and Research Centre (KFSH & RC) and emphasizes the clinical patterns that should enable a pediatrician to consider the diagnosis. Fourteen children with CHF were diagnosed between 1981 and 1988. The age at presentation ranged from 1.8-14 years (mean: 7.5 years); clinical manifestations at diagnosis were splenomegaly (12), hepatomegaly (11), failure to thrive (10), marked abdominal distention (4), and fever (4). Liver function tests were normal except for high alkaline phosphatase. Eight patients had polycystic kidneys confirmed on ultrasound examination. Upper gastro-intestinal endoscopy showed oesophageal varices of variable severity in all eight patients examined. Splenoportography revealed splenic vein occlusion in one patient. One patient died within days of admission with convulsions, coma, and aspiration pneumonia. One patient was lost to follow-up. The remaining 12 patients are all alive and receive regular follow-up. Two patients required splenorenal shunt. In view of the prevalence of consanguinity in Saudi Arabia, the diagnosis of CHF should be considered in children with hepatomegaly despite normal liver function tests, and particularly in those with renal abnormalities and/or evidence of portal hypertension.
A. M A. ABDULLAH ET AL
sodes not responding satisfactorily to sclerotherapy together with supportive medical measures.
except for high alkaline phosphatase with a mean of 440 u/1 (range 133-1636). The mean haemoglobin level at initial presentation was 95 g/1 (range 47-120). Eight patients had associated polycystic kidneys as shown on ultrasound examination. The liver was enlarged (11 patients) and hyperechoic because of fibrosis and ductular proliferation. Other associated clinical conditions were congenital lymphagiectasia (one patient) and gluten sensitive enteropathy (one patient). Upper gastro-intestinal endoscopy showed oesophageal varices in all eight patients examined, three of whom had associated fundal varices. One patient had mild oesphageal varices on barium swallow examination, but did not require endoscopic confirmation at KFSH & RC. Splenoportography revealed splenic vein occlusion in one patient. Sclerotherapy with 1 per cent polidocanal was performed in six cases. The number of sclerotherapy sessions was 6, 4, 2, in one patient each, and 1 in the remaining three patients. The patients were followed up for a mean period of 2.2 years (range 0.5-7 years). One patient died within days of admission with convulsions, coma, and pneumonia, and one was lost to follow-up. The remaining 12 patients are all alive and receive regular assessment. Two patients have had splenorenal shunts because of massive bleeding epi-
TABLE 1
Clinical features Cinical presentation Failure to thrive Haematemesis and/or Melaena Abdominal distention Fever
Journal of Tropical Pediatrics
Vol. 37
of congenital No. of pts (%) 10 7 4 4
(71.4) (50) (28.5) (28.5)
October 1991
hepatic fibrosis (14 cases) Clinical findings Splenomegaly Hepatomegaly Oesophageal varices Renal mass
No. of pts (%) 12 11 9 2
(85.7) (87.5) (64.2) (14.2)
241
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on July 13, 2015
FIG. 1. Liver biopsy shows enlarged portal triad with increased fibrous tissue and bile ducts. Lobular and portal inflammation is absent (H&E).
Discussion This is the first report on C H F in Saudi Arabia emphasizing its main clinical features as experienced at KFSH & RC. It is possible that the disease occurs with a similar or even higher incidence in Saudi Arabia than what has been reported in the developed countries. 9 This is quite likely because of the high rate of consanguineous marriage in this country. Seven cases (50 per cent) in this series were the product of consanguineous marriages. Congenital hepatic fibrosis is considered a rare autosomal recessive disease8 that is diagnosed essentially by its morphological features with diffuse portal fibrosis separating normal hepatic lobules. The presence of widened portal tracts with bile ductular proliferation is an essential feature of the disease. 10 It has been suggested that this may result from a disproportionate overgrowth of biliary epithelium, however, in some cases, such spaces are rare and may be detected only by a surgical wedge liver biopsy. CHF is occasionally segmental or limited to one lobe, usually the left lobe of the liver. Liver function tests were essentially normal in all our patients except for high levels of alkaline phosphatase. A large proportion of affected children could have remained undetected or misdiagnosed as cirrhosis. It should be possible to be highly suspicious of the diagnosis of CHF on the basis of clinical, laboratory, and radiological data in children with hepatomegaly and associated renal anomalies, before embarking on performing liver biopsies which may have to be surgical wedge liver biopsies." The typical histopathological changes in CHF are quite distinct from those of cirrhosis. The disease might manifest in the early months of life or late in childhood or in the adults. 10 The course of the disease is dominated by recurrent episodes of gastro-intestinal bleeding which are often well tolerated and usually not followed by hepatic encephalopathy. The gastro-intestinal bleeding may first appear in infancy or be delayed up to the age of 60 years. Portal hypertension is a common and serious sequel of CHF. The causes of portal hypertension in CHF had not been well established, but it has been suggested to be secondary to presinusoidal block. The
A. M. A. ABDULLAH ET AL
major clinical sequelae of CHF are portal hypertension, hypersplenism, and renal failure. Cholangiocarcinoma and amyloidosis are recognized late sequelae of CHF. 12 Over the past few years there has been an increasing recognition of the association of CHF not only with congenital renal anomalies and in particular infantile polycystic disease of the kidneys, but also with saccular dilatation of intraphepatic bile ducts (Caroli's disease). 13~13 Further reports have demonstrated the association of CHF with pulmonary fibrosis, congenital heart disease,16 pulmonary hypertension with coronary arterial fistula17 and dilation of pancreatic ducts withfibrosis.CHF has also been associated with increased copper deposition that exceeded 550 //g per gram dry liver tissue which could contribute to liver damage.18 The association of CHF with intestinal lymphangiectasia has been described in an adult.19 In our study, one child had evidence of intestinal lymphangiectasia. Pelletier et al.20 described in 1986 a new syndrome with such an association in a child with secretory diarrhoea. One of our patients had glutensensitive enteropathy which has not been previously reported in congenital hepatic fibrosis. Congenital hepatic fibrosis continues to have good prognosis if bleeding from varices can be controlled and renal failure does not occur. Haematemesis and melaena due to bleeding varices are the most common complications which determine the prognosis of CHF. Ultrasound examination will contribute further in assessing portal hypertension, the intra- and extrahepatic bile ducts and the kidneys21 and will gradually replace endoscopy for the detection of varices. This will permit selection of patients at high risk of bleeding who need endoscopic confirmation and management.22 Early surgery with splenorenal or porto caval shunting may be required in recurrent bleeding episodes not responding to sclerotherapy, oesophageal tamponade together with supportive medical treatment.23 Two patients in this study required spleno-renal shunting which prevented further bleeding and improved life expectancy. Liver transplantation is also considered in the management of CHF especially in patients with recurrent uncontrolled cholangitis.1 Episodes of ascending cholangitis with or without lithiasis are recognized complications of CHF. Medical treatment with trimethoprimsulphamethozaxole has been considered a very useful treatment regimen.24 Knowledge about CHF is expanding rapidly with more recognition of associated conditions. The critieria for the diagnosis of CHF have not changed. It is hoped that with increasing recognition of the varied clinical manifestations of CHF, a higher index of suspicion for its diagnosis should enable a pediatrician to detect affected children especially in the presence of hepatomegaly splenomegaly, normal liver function tests in association with renal abnormalities and/or evidence of portal hypertension.
1. De vos M, Barbier F, Cuvenlier C. Congenital hepatic fibrosis. J Hepato! 1988; 6: 222-8. 2. Mowat AP. Liver disorders in childhood. Second edition, Butterworth and Co. (Publisher) Ltd. London, Boston, Toronto, Sydney, 1987. 3. Bristowe F. Cystic disease of the liver associated with similar disease of the kidney. Trans Pathol Soc Lond 1856; 7: 229. 4. McMahon HE. Congenital anomalies of the liver. Am J Pathol 1929; 5: 499. 5. Parker RGF. Fibrosis of the liver as a congenital anomaly. J Pathol Bacteriol 1956; 71: 359. 6. Kerr DNS, Harrison CV, Sherlock S, Milnes Walker R. Congenital hepatic fibrosis. Q J Med 1961; 30: 91-117. 7. Kerr DNS, Okonkwo S, Choa RG. Congenital hepatic fibrosis: The long-term prognosis. Gut 1978; 19: 514-20. 8. Kaplan BS, et al. Variable expression of autosomal recessive polycystic kidney disease and congenital hepatic fibrosis within a family. Am J. Med Genet 1988; 29: 639-47. 9. Kocak N, Ozsoylus S, Caglar M, Gogus S. Congenital hepatic fibrosis in Turkish children. Turk J Pediatr 1986; 28: 165-9. 10. Summerfield JA, et al. Hepatobiliary fibropolycystic disease: A clinical and histological review of 51 patients. J Hepatol 1986; 2: 141-56. 11. Alvarez F, et al. Congenital hepatic fibrosis in children. J Pediatr 1981; 99: 370-5. 12. Gallagher J, Millis RR, Mitchison MJ. Congenital dilatation of intrahepatic duct with cholangiocaranoma. J Clin Patho 1972; 25: 804-8. 13. Caroli J, el al. Une affection nou-velle, Sans doute congenital, des voies biliaries: La dilatation kystique unilobaire des canaux hepatiques. Sem Hop Paris 1958; 14: 496-502. 14. David CH, Stringer DA, Whyte H, Daneman A, Mancer K. Congenital hepatic fibrosis with saccular dilatation of intrahepatic bile ducts and infantile polycystic kidneys. Pediat Radiol 1986; 16: 302-5. 15. Dusol M, Levi JU, Glasser K, Schiff ET. Congenital hepatic fibrosis with dilatation of of intrahepatic bile ducts. Gastroenterology 1976; 71: 839-43. 16. Naveh Y, et al. Congenital hepatic fibrosis with congenital heart disease. Gut 1980; 21: 799-807. 17. Dewhurst NG, Colledge NR, Miller HC. Severe pulmonary hypertension and mutiple coronary arterial fistulas in association with congenital hepatic fibrosis. Br Heart J 1987; 58: 525-7. 18. Evans J, Harris O, Van Deth AG. Congenital hepatic fibrosis associated with mallory bodies and copper retention. Aust NZ J Med 1984; 14: 500-3. 19. Chagnon JP, et al. Fibrose hepatique congenitales, Polykystose renale et lymphangiectasies intestinales primitives. Gastroenterol Clin Biol 1982; 6: 325-32. 20. Pelletier VA, el al. Secretory diarrhoea with proteinlosing, enteropathy, enterocolitis cystica superficialis, intestinal lymphangiectasia and congenital hepatic fibrosis: A new syndrome. J Pediatr 1986; 107: 61-5. 21. Glazer GM, Laing FC, Brownth W, Gooding GA. Sonographic demonstration of portal hypertension. The patient umbilical vein. Radiology 1980; 136: 561. 22. De Giacomo C, et al. Ultrasonographic prediction of the
242
Journal of Tropical Pediatrics
References
October 1991
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on July 13, 2015
Vol.37
A. M. A. ABDULLAH ET AL.
presence of severity of esophageal varices in children. J Pediatr Gastroenterol Nutr 1989; 9: 431-5. 23. Summerschild HC, Langmark F, Maurseth K. Congenital hepatic fibrosis: Report of two new cases and review of the literature. Surgery 1973; 73; 53-8.
24. Sanchez C, Gonzalez E, Garnai J. Trimethoprimsulfamethoxazole treatment of cholangitis complicating congenital hepatic fibrosis. Pediat Infect Dis 1986; 5: 360-3.
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on July 13, 2015
Journal of Tropical Pediatrics
Vol.37
October 1991
243
Congenital Hepatic Fibrosis in Saudi Arabia by A. M. A. Abdullah,* H. Nazer,* M. Atiyeh,** and M. A. AH*** Departments of* Paediatrics, ** Medicine, and *** Pathology, King Faisal Specialist Hospital and Research Centre P.O. Box 3354, Riyadh 11211, Saudi Arabia
Introduction
King Faisal Specialist Hospital and Research Centre (KFSH & RC).
Congenital hepatic fibrosis (CHF) has been recognized as an inherited, rare disorder characterized by periportal fibrosis with irregularly shaped proliferating bile ducts. Affected children are prone to suffer from portal hypertension without significant impairment of liver functions.1'2 The common hepatic manifestations of CHF were first described in 1856 by Bristowe.3 Thereafter, the varied clinical spectrum of CHF was more widely recognized.4-' The name 'congenital hepatic fibrosis' was introduced by Kerr and Colleagues in 1961.6 The diagnosis of CHF is usually confirmed by its typical histological features on a percutaneous liver biopsy or a surgical wedge liver biopsy. Liver function tests in CHF are characteristically normal except for an occasional high alkaline phosphatse.7 The exact incidence and prevalence of CHF are not known. By 1981, only 200 patients with CHF had been reported in the literature.1 The disease appears in both sporadic and familial forms. It is probably inherited as an autosomal recessive.8 In Saudi Arabia, where a high incidence of consanguineous marriage prevails, the disease may not be as rare as previously thought. It is possible that a large proportion of affected patients remains undiagnosed until they present with gastrointestinal haemorrhage from bleeding oesophageal varices which may be fatal. This report describes the varied clinical presentation of CHF as experienced at
Fourteen children (eight males, six females) met the criteria for the diagnosis of CHF. Their mean age at diagnosis was 7.5 years (range 1.8-14 years). Seven cases were the offspring of consanguineous marriages. Five families had a history of more than one affected child, but siblings were not included in the study. The main clinical features at presentation are shown in Table 1. Liver function tests were normal in all patients
240
Journal of Tropical Pediatrics
© Oxford University Press 1991
Patients and Methods
The medical records for patients up to the age of 14 years seen at KFSH & RC with the diagnosis of CHF were reviewed. The study analysed patients retrospectively and prospectively from 1981 to 1988. Only patients with confirmed histological changes of CHF were included (Fig. 1). Each case was reviewed for age, sex, time from onset of symptoms to diagnosis, consanguinity, similarly affected children in the family, and main clinical features at presentation. The patients were subjected to various investigations including liver function tests, hepatitis B screen, blood biochemistry, abdominal ultrasound, endoscopy, and angiography. Results
Vol.37
October 1991
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on July 13, 2015
Summary Congenital hepatic fibrosis (CHF) is a recognized cause of portal hypertension with oesophageal varices, gastro-intestinal haemorrhage and cholangitis in children without significant impairment of hepatic or renal function. This report describes the varied clinical presentation of CHF as seen at King Faisal Specialist Hospital and Research Centre (KFSH & RC) and emphasizes the clinical patterns that should enable a pediatrician to consider the diagnosis. Fourteen children with CHF were diagnosed between 1981 and 1988. The age at presentation ranged from 1.8-14 years (mean: 7.5 years); clinical manifestations at diagnosis were splenomegaly (12), hepatomegaly (11), failure to thrive (10), marked abdominal distention (4), and fever (4). Liver function tests were normal except for high alkaline phosphatase. Eight patients had polycystic kidneys confirmed on ultrasound examination. Upper gastro-intestinal endoscopy showed oesophageal varices of variable severity in all eight patients examined. Splenoportography revealed splenic vein occlusion in one patient. One patient died within days of admission with convulsions, coma, and aspiration pneumonia. One patient was lost to follow-up. The remaining 12 patients are all alive and receive regular follow-up. Two patients required splenorenal shunt. In view of the prevalence of consanguinity in Saudi Arabia, the diagnosis of CHF should be considered in children with hepatomegaly despite normal liver function tests, and particularly in those with renal abnormalities and/or evidence of portal hypertension.
A. M A. ABDULLAH ET AL
sodes not responding satisfactorily to sclerotherapy together with supportive medical measures.
except for high alkaline phosphatase with a mean of 440 u/1 (range 133-1636). The mean haemoglobin level at initial presentation was 95 g/1 (range 47-120). Eight patients had associated polycystic kidneys as shown on ultrasound examination. The liver was enlarged (11 patients) and hyperechoic because of fibrosis and ductular proliferation. Other associated clinical conditions were congenital lymphagiectasia (one patient) and gluten sensitive enteropathy (one patient). Upper gastro-intestinal endoscopy showed oesophageal varices in all eight patients examined, three of whom had associated fundal varices. One patient had mild oesphageal varices on barium swallow examination, but did not require endoscopic confirmation at KFSH & RC. Splenoportography revealed splenic vein occlusion in one patient. Sclerotherapy with 1 per cent polidocanal was performed in six cases. The number of sclerotherapy sessions was 6, 4, 2, in one patient each, and 1 in the remaining three patients. The patients were followed up for a mean period of 2.2 years (range 0.5-7 years). One patient died within days of admission with convulsions, coma, and pneumonia, and one was lost to follow-up. The remaining 12 patients are all alive and receive regular assessment. Two patients have had splenorenal shunts because of massive bleeding epi-
TABLE 1
Clinical features Cinical presentation Failure to thrive Haematemesis and/or Melaena Abdominal distention Fever
Journal of Tropical Pediatrics
Vol. 37
of congenital No. of pts (%) 10 7 4 4
(71.4) (50) (28.5) (28.5)
October 1991
hepatic fibrosis (14 cases) Clinical findings Splenomegaly Hepatomegaly Oesophageal varices Renal mass
No. of pts (%) 12 11 9 2
(85.7) (87.5) (64.2) (14.2)
241
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on July 13, 2015
FIG. 1. Liver biopsy shows enlarged portal triad with increased fibrous tissue and bile ducts. Lobular and portal inflammation is absent (H&E).
Discussion This is the first report on C H F in Saudi Arabia emphasizing its main clinical features as experienced at KFSH & RC. It is possible that the disease occurs with a similar or even higher incidence in Saudi Arabia than what has been reported in the developed countries. 9 This is quite likely because of the high rate of consanguineous marriage in this country. Seven cases (50 per cent) in this series were the product of consanguineous marriages. Congenital hepatic fibrosis is considered a rare autosomal recessive disease8 that is diagnosed essentially by its morphological features with diffuse portal fibrosis separating normal hepatic lobules. The presence of widened portal tracts with bile ductular proliferation is an essential feature of the disease. 10 It has been suggested that this may result from a disproportionate overgrowth of biliary epithelium, however, in some cases, such spaces are rare and may be detected only by a surgical wedge liver biopsy. CHF is occasionally segmental or limited to one lobe, usually the left lobe of the liver. Liver function tests were essentially normal in all our patients except for high levels of alkaline phosphatase. A large proportion of affected children could have remained undetected or misdiagnosed as cirrhosis. It should be possible to be highly suspicious of the diagnosis of CHF on the basis of clinical, laboratory, and radiological data in children with hepatomegaly and associated renal anomalies, before embarking on performing liver biopsies which may have to be surgical wedge liver biopsies." The typical histopathological changes in CHF are quite distinct from those of cirrhosis. The disease might manifest in the early months of life or late in childhood or in the adults. 10 The course of the disease is dominated by recurrent episodes of gastro-intestinal bleeding which are often well tolerated and usually not followed by hepatic encephalopathy. The gastro-intestinal bleeding may first appear in infancy or be delayed up to the age of 60 years. Portal hypertension is a common and serious sequel of CHF. The causes of portal hypertension in CHF had not been well established, but it has been suggested to be secondary to presinusoidal block. The
A. M. A. ABDULLAH ET AL
major clinical sequelae of CHF are portal hypertension, hypersplenism, and renal failure. Cholangiocarcinoma and amyloidosis are recognized late sequelae of CHF. 12 Over the past few years there has been an increasing recognition of the association of CHF not only with congenital renal anomalies and in particular infantile polycystic disease of the kidneys, but also with saccular dilatation of intraphepatic bile ducts (Caroli's disease). 13~13 Further reports have demonstrated the association of CHF with pulmonary fibrosis, congenital heart disease,16 pulmonary hypertension with coronary arterial fistula17 and dilation of pancreatic ducts withfibrosis.CHF has also been associated with increased copper deposition that exceeded 550 //g per gram dry liver tissue which could contribute to liver damage.18 The association of CHF with intestinal lymphangiectasia has been described in an adult.19 In our study, one child had evidence of intestinal lymphangiectasia. Pelletier et al.20 described in 1986 a new syndrome with such an association in a child with secretory diarrhoea. One of our patients had glutensensitive enteropathy which has not been previously reported in congenital hepatic fibrosis. Congenital hepatic fibrosis continues to have good prognosis if bleeding from varices can be controlled and renal failure does not occur. Haematemesis and melaena due to bleeding varices are the most common complications which determine the prognosis of CHF. Ultrasound examination will contribute further in assessing portal hypertension, the intra- and extrahepatic bile ducts and the kidneys21 and will gradually replace endoscopy for the detection of varices. This will permit selection of patients at high risk of bleeding who need endoscopic confirmation and management.22 Early surgery with splenorenal or porto caval shunting may be required in recurrent bleeding episodes not responding to sclerotherapy, oesophageal tamponade together with supportive medical treatment.23 Two patients in this study required spleno-renal shunting which prevented further bleeding and improved life expectancy. Liver transplantation is also considered in the management of CHF especially in patients with recurrent uncontrolled cholangitis.1 Episodes of ascending cholangitis with or without lithiasis are recognized complications of CHF. Medical treatment with trimethoprimsulphamethozaxole has been considered a very useful treatment regimen.24 Knowledge about CHF is expanding rapidly with more recognition of associated conditions. The critieria for the diagnosis of CHF have not changed. It is hoped that with increasing recognition of the varied clinical manifestations of CHF, a higher index of suspicion for its diagnosis should enable a pediatrician to detect affected children especially in the presence of hepatomegaly splenomegaly, normal liver function tests in association with renal abnormalities and/or evidence of portal hypertension.
1. De vos M, Barbier F, Cuvenlier C. Congenital hepatic fibrosis. J Hepato! 1988; 6: 222-8. 2. Mowat AP. Liver disorders in childhood. Second edition, Butterworth and Co. (Publisher) Ltd. London, Boston, Toronto, Sydney, 1987. 3. Bristowe F. Cystic disease of the liver associated with similar disease of the kidney. Trans Pathol Soc Lond 1856; 7: 229. 4. McMahon HE. Congenital anomalies of the liver. Am J Pathol 1929; 5: 499. 5. Parker RGF. Fibrosis of the liver as a congenital anomaly. J Pathol Bacteriol 1956; 71: 359. 6. Kerr DNS, Harrison CV, Sherlock S, Milnes Walker R. Congenital hepatic fibrosis. Q J Med 1961; 30: 91-117. 7. Kerr DNS, Okonkwo S, Choa RG. Congenital hepatic fibrosis: The long-term prognosis. Gut 1978; 19: 514-20. 8. Kaplan BS, et al. Variable expression of autosomal recessive polycystic kidney disease and congenital hepatic fibrosis within a family. Am J. Med Genet 1988; 29: 639-47. 9. Kocak N, Ozsoylus S, Caglar M, Gogus S. Congenital hepatic fibrosis in Turkish children. Turk J Pediatr 1986; 28: 165-9. 10. Summerfield JA, et al. Hepatobiliary fibropolycystic disease: A clinical and histological review of 51 patients. J Hepatol 1986; 2: 141-56. 11. Alvarez F, et al. Congenital hepatic fibrosis in children. J Pediatr 1981; 99: 370-5. 12. Gallagher J, Millis RR, Mitchison MJ. Congenital dilatation of intrahepatic duct with cholangiocaranoma. J Clin Patho 1972; 25: 804-8. 13. Caroli J, el al. Une affection nou-velle, Sans doute congenital, des voies biliaries: La dilatation kystique unilobaire des canaux hepatiques. Sem Hop Paris 1958; 14: 496-502. 14. David CH, Stringer DA, Whyte H, Daneman A, Mancer K. Congenital hepatic fibrosis with saccular dilatation of intrahepatic bile ducts and infantile polycystic kidneys. Pediat Radiol 1986; 16: 302-5. 15. Dusol M, Levi JU, Glasser K, Schiff ET. Congenital hepatic fibrosis with dilatation of of intrahepatic bile ducts. Gastroenterology 1976; 71: 839-43. 16. Naveh Y, et al. Congenital hepatic fibrosis with congenital heart disease. Gut 1980; 21: 799-807. 17. Dewhurst NG, Colledge NR, Miller HC. Severe pulmonary hypertension and mutiple coronary arterial fistulas in association with congenital hepatic fibrosis. Br Heart J 1987; 58: 525-7. 18. Evans J, Harris O, Van Deth AG. Congenital hepatic fibrosis associated with mallory bodies and copper retention. Aust NZ J Med 1984; 14: 500-3. 19. Chagnon JP, et al. Fibrose hepatique congenitales, Polykystose renale et lymphangiectasies intestinales primitives. Gastroenterol Clin Biol 1982; 6: 325-32. 20. Pelletier VA, el al. Secretory diarrhoea with proteinlosing, enteropathy, enterocolitis cystica superficialis, intestinal lymphangiectasia and congenital hepatic fibrosis: A new syndrome. J Pediatr 1986; 107: 61-5. 21. Glazer GM, Laing FC, Brownth W, Gooding GA. Sonographic demonstration of portal hypertension. The patient umbilical vein. Radiology 1980; 136: 561. 22. De Giacomo C, et al. Ultrasonographic prediction of the
242
Journal of Tropical Pediatrics
References
October 1991
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on July 13, 2015
Vol.37
A. M. A. ABDULLAH ET AL.
presence of severity of esophageal varices in children. J Pediatr Gastroenterol Nutr 1989; 9: 431-5. 23. Summerschild HC, Langmark F, Maurseth K. Congenital hepatic fibrosis: Report of two new cases and review of the literature. Surgery 1973; 73; 53-8.
24. Sanchez C, Gonzalez E, Garnai J. Trimethoprimsulfamethoxazole treatment of cholangitis complicating congenital hepatic fibrosis. Pediat Infect Dis 1986; 5: 360-3.
Downloaded from http://tropej.oxfordjournals.org/ at University of Birmingham on July 13, 2015
Journal of Tropical Pediatrics
Vol.37
October 1991
243
