Year : 2009 | Volume
: 52 | Issue : 1 | Page : 10--13
Liver needle biopsy in Iraninan pediatric patients: Diagnostic significance and pattern of liver diseases
Maryam Monajemzadeh1, Hedieh Moradi Tabriz1, Fatemeh Mahjoub1, Gholamhossein Fallahi2, Fatemeh Farahmand2,
1 Department of Pathology, Children Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Pediatrics and Gastroenterology, Children Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
Hedieh Moradi Tabriz
Department of Pathology, Children Medical Center Hospital, Tehran University of Medical Sciences, Keshavarz Boulevard, Tehran
We aimed at determining the pattern of liver disease in the Iranian children referred to the Medical Center of Children affiliated with the Tehran University of Medical Sciences. Materials and Methods: In a cross-sectional study conducted over 2 years, 425 liver needle biopsies were sent to the pathology laboratory of our center. Slides were prepared from paraffin-embedded blocks, stained by routine H & E and special stains and were then reviewed. The frequency of each disorder, separately and in combination with the age group or gender of the patients was calculated and compared with other similar studies. Results: The male to female ratio was 1.42:1. The age range was between 1 month and 18 years old and 41.4% were less than 2 years old. The most common histological diagnosis was iron overload due to major thalassemia (17.5%) followed by biliary atresia (9.7%), no significant pathologic change (8.7%), neonatal hepatitis (8.7%), chronic hepatitis (8.5%), cirrhosis (6.5%), metabolic disease (5.5%) and progressive familial intrahepatic cholestasis (5%). Results of the hemosiderosis grading in patients with thalassemia revealed no or minimal, mild, medium, or marked increase in 10%, 27.1%, 10%, 21.4% and 31.5% of the cases, respectively and the degree of iron deposition rose in parallel with age and also the stage of fibrosis (p<0.05). Conclusion: A liver biopsy is a useful and practical tool for the appropriate diagnosis of pediatric liver diseases. Also, we found that in non thalassemic children, biliary atresia, chronic hepatitis and neonatal hepatitis, in the stated order, are the most prevalent histologic diagnoses in Iranian pediatrics.
|How to cite this article:|
Monajemzadeh M, Tabriz HM, Mahjoub F, Fallahi G, Farahmand F. Liver needle biopsy in Iraninan pediatric patients: Diagnostic significance and pattern of liver diseases.Indian J Pathol Microbiol 2009;52:10-13
|How to cite this URL:|
Monajemzadeh M, Tabriz HM, Mahjoub F, Fallahi G, Farahmand F. Liver needle biopsy in Iraninan pediatric patients: Diagnostic significance and pattern of liver diseases. Indian J Pathol Microbiol [serial online] 2009 [cited 2022 Sep 28 ];52:10-13
Available from: https://www.ijpmonline.org/text.asp?2009/52/1/10/44953
Liver disease in pediatrics is one of the most significant causes of morbidity and mortality in this age group and includes a broad spectrum of disorders such as infections, developmental abnormalities and metabolic and neoplastic disorders that finally result in hepatic dysfunction and cirrhosis. Biliary atresia and neonatal hepatitis are the two most common causes of cholestasis in the neonatal period. , Treatment modalities differ among each condition; therefore, it is obvious that an early and correct diagnosis has a crucial role in the proper management of these children. Various diagnostic tools including liver function tests, enzyme assays, or imaging techniques are available for the evaluation of liver disorders, but although liver biopsy is an invasive method, it is the corner stone for a precise diagnosis and differentiates between the foregoing conditions. 
In our study, we aimed at determining the frequency of different patterns of liver needle biopsies performed in Iranian children and compared them with other studies.
Materials and Methods
In a cross-sectional study conducted over 2 years (2004 to 2006), 401 liver biopsies were sent to the pathology laboratory of the Medical Center of Children affiliated with the Tehran University of Medical Sciences. Indications for liver needle biopsies included abnormal liver function tests, jaundice, unexplained hepatosplenomegaly and the evaluation of iron storage in major thalassemia. Patients with thalassemia who are candidates for bone marrow biopsies must be evaluating for the amount of iron overload by liver needle biopsy. The biopsies were taken by the use of menghini needles and were immediately fixed in 10% formalin solution. Alcohol was used as another fixative solution except for the evaluation of hemochromatosis in patients with thalassemia. After processing in an automated tissue processor, paraffin-embedded blocks were serially sectioned and were then stained by H & E, trichrome and PAS with and without diastase methods. Other special stains such as perls stain, rhodanin stain and reticulin stain were used when required. Slides showed less than three portal spaces considered as inadequate specimens. The frequency of each disorder, separately and in combination with the age group or gender of the patients was calculated and compared with other similar studies. In cases of chronic hepatitis, the Histological Activity Index (HIA) scoring system was used for grading and staging the disease. The evaluation of iron storage was performed according to Marx and Sindram hepatic iron scoring. 
A total of 425 liver biopsies belonging to 401 cases were studied with a male to female ratio of 1.42:1. A total of 80 cases were thalassemia cases that underwent biopsies in order to estimate the iron overload. The age range was from 1 month to 18 years old. Patients from 1 month to 1 year old composed the most frequent age group (41.4%). A total of 26.9% were between 2 and 5 years old, 16% were between 6 and 10 years old and 13.7% were above 11 years old.
The most common histological diagnosis was iron overload due to major thalassemia (17.5%) followed by biliary atresia (9.7%). There were no significant pathologic changes (8.7%) and neonatal hepatitis (8.7%), chronic hepatitis (8.5%), cirrhosis (6.5%), metabolic disease (5.5%) and progressive familial intrahepatic cholestasis (5%) were the other histological diagnoses. [Table 1] shows the frequency of each diagnosis, separately and in combination with age groups in non thalassemic patients. We found that biliary atresia and neonatal hepatitis, in order, are the two most common diagnoses from 1 month to 1 year old. In non thalassemic patients, as age increased, chronic hepatitis became the dominant diagnosis.
A total of 3 out of 7 patients with the diagnosis of granulomatous hepatitis showed acid fast bacilli in their special staining.
Results on the grading of hemosiderosis in patients with thalassemia revealed no or a minimal, mild, medium, or marked increase in 10%, 27.1%, 10%, 21.4% and 31.5% of the patients, respectively and the degree of iron deposition rose in parallel with age and also the stage of fibrosis (p  In this regard, information on the patient's medical history, physical examinations, biochemical tests and viral and autoimmune markers may be helpful and valuable. In addition, we believe that epidemiologic and national criteria can play an important role in the primary evaluation of these patients. In this regard, we evaluated liver biopsies in Iranian pediatrics to estimate the frequency of different patterns of livers disease. There were similar studies in India,  South Africa,  and Pakistan ,, and we have a comparison between our results and other countries. Furthermore, the number of our cases was higher than the others.
In our study, secondary hemochromatosis in patients with thalassemia composed the most prevalent histological diagnoses (17.5%) most of which showed a mild to moderate increase in liver iron storage. Ahmad, et al. performed a similar study on 100 children in Rawalpindi and achieved the same predominance but in a higher frequency (30%). A total of 65% of their patients had moderate to severe hemochromatosis.  Because of frequent transfusions, it is reasonable and predictable that as the age of patients with thalassemia increases, the degree of iron deposition also rises. With progressing siderosis, fibrosis develops in portal spaces that finally expand as septal fibrosis and cirrhosis. This event and the correlation of the stage of fibrosis with the degree of iron deposition emphasizes the importance of close monitoring of patients and the performance of a bone marrow transplantation as soon as possible to lessen the frequency of transfusions.
The next common group of disorders in our study was biliary atresia (11.8%). Our result was quite similar to Ahmad, et al. in Rawalpindi  and Muthupei  in South Africa. In contrast, previous investigations in Pakistan showed a lower incidence of biliary atresia, 8%,  5%,  and 9%.  In a study in Nigeria, hepatic schistosomiasis (37.5%) was the most frequent lesion and only two cases of biliary atresia were noted in 48 liver needle biopsies. They concluded that in sharp contrast to European countries where neonatal hepatitis or biliary atresia are the most common diagnoses, in tropical and subtropical regions, infections are prevalent. 
Chronic hepatitis was noted in 10.3% of children referred to our center within 2 years. Most of them were more than 2 years old. Our result was close to Ahmad, et al.  but in contrast to Ahmad, et al.,  we detected a higher incidence of chronic hepatitis in children. One limitation in our study was that patients' medical reports about viral and autoimmune markers were incomplete, thus we could not differentiate the causes of chronic hepatitis. Zhang, et al. found that chronic hepatitis is the major pathologic feature in Chinese children and viral hepatitis, especially due to HBV, is the major leading cause for it.  Hanif evaluated the etiology of chronic liver diseases in children from Karachi and reached a similar result.  A total of 10.9% of children showed neonatal hepatitis in their histological examinations. All of them were under 2 years old with male predominance (M:F ratio was 4/1). Some authors, such as Ramakrishna, et al. were from India  and Akinbami , et al. from Omani  report the higher incidence of neonatal hepatitis, as the most common diagnosis before the age of 2. Ahmad, et al. found this disorder in 10% of their patients with male dominance. 
In patients with thalassemia, we saw an increase in the iron content with age as we expected.
Other rare diagnoses such as metabolic disease, glycogen, or lipid storage disease, etc. should be kept in mind during the investigation of a liver disorder, because with proper management, we can prevent the progression to cirrhosis. The predominance of biliary atresia in Iranian pediatrics may be because our hospital is a referral center. Proportionally, the high incidence of chronic hepatitis may indicate the infants who acquired viral hepatitis in their prenatal period and would later develop a chronic disease. As a conclusion, liver biopsies are a useful and practical tool for the appropriate diagnosis of pediatric liver disease and insufficient specimens are negligible (3.3% in our study). Also, we found that in non thalassemic children, biliary atresia, chronic hepatitis and neonatal hepatitis are the most prevalent histologic diagnoses in Iranian pediatrics.
|1||Ahmad M, Afzal S, Roshan E, Mubarik A, Bano S, Khan SA et al . Usefulness of needle biopsy in the diagnosis of pediatric liver disorders. J Pak Med Assoc 2005;55:24-8.|
|2||Lai MW, Chang MH, Hsu HC, Hsu HC, Su CT, Kao CL et al . Differential diagnosis of extra hepatic biliary atresia from neonatal hepatitis: A prospective study. J Paediatr Gastroenterol Nutr 1994;18:121-7.|
|3||Lee GR. Storage and metabolic disorders. In: Lee GR, editor. Diagnostic liver pathology. 1st ed. St. Louis: Mosby; 1994. p. 237-80.|
|4||Bazerra JA, Balistreri WF. Cholestatic syndromes of infancy and childhood. Semin Gastrointest Dis 2001;12:54-65.|
|5||Muthuphei MN. Childhood liver diseases in Ga-Rankuwa Hospital, South Africa. East Afr Med J 2000;77:508-9.|
|6||Anwar CM, Malik IA, Muzaffar M, Ali S, Hassan N, Khalilullah et al . A histological study of clinically unexplained hepatomegaly in children. Pak J Pathol 1990;1:79-82.|
|7||Ahmed TM, Khan MN, Maqbool S, Khan SK. Evaluation of liver biopsy in undiagnosed cases of liver enlargement. Pak Paedtr J 1988;3:171-5.|
|8||Shakoor KA. Histological diagnosis of paediatric liver diseases. Pak Paediatr J 1987;2:73-80.|
|9||Obafunwa JO, Elesha SO. Childhood liver diseases in Jos, Nigeria: A retrospective histopathological study. East Afr Med J 1991;68:702-6.|
|10||Zhang HF, Yang XJ, Zhu SS, Zhao JM, Zhang TH, Xu ZQ, et al . Pathological changes and clinical manifestations of 1020 children with liver diseases confirmed by biopsy. Hepatobiliary Pancreat Dis Int 2004;3:395-8.|
|11||Hanif M, Raza J, Qureshi H, Issani Z. Etiology of chronic liver disease in children. J Pak Med Assoc 2004;54:119-22.|
|12||Ramakrishna B, Date A, Kirubakaran C, Raghupathy P. The pattern of liver disease in Indian children: A review of 128 biopsied cases. Ann Trop Paediatr 1993;13:159-63.|
|13||Akinbami FO, Venugopalan P, Nirmala V, Suresh J, Abiodun P. Pattern of chronic liver disease in Omani children: A clinicopathological review. West Afr J Med 2004;23:162-6.|