Usefulness of Needle Biopsy in the diagnosis

Objective: To see the usefulness of liver biopsy in the diagnosis and to document the spectrum of paediatric liver diseases. Methods: A retrospective, cross sectional survey at Histopathology department of Army Medical College Rawalpindi from January 2000 to December 2003. The liver biopsies were taken with Menghini needle. The fixed tissues were processed under standard conditions. Results: During four years period, a total of 100 cases with age range of 1.5 months to 16 years were studied. The most common histological findings in order of frequency were secondary haemochromatosis (30%), biliary atresia (20%), storage disorders (16%), cirrhosis of liver (10%) and neonatal hepatitis (10%). The less common entities were chronic hepatitis (6%), nonspecific reactive hepatitis (3%) and granulomatous hepatitis (1%). One case each of hepatoblastoma, haemophagocytic lymphohistiocytosis and congenital fibrosis was also noted. These findings have been compared with local and international histological studies. Conclusion: Liver biopsy is a useful diagnostic technique in the diagnosis of paediatric liver diseases. Biliary atresia, strorage disorders and neonatal hepatitis are the most common entities in our set up (JPMA 55:24;2005). (H&E) stain. The special stains like PAS with and without diastase, Reticulin stain and Perl's stain were also used when required. The sections which showed less than three portal areas were excluded from the study. For chronic hepatitis, Knodell8 histological activity index (HAI), scoring system was used to know the grade and stage of the disease. Results A total of 100 cases with age range from 1.5 month to 16 years were studied during a period of four years. The male to female ratio was 1.2:1. The histopathological findings of children of both sexes are shown in Table 1. The most common histological diagnoses were secondary haemochromatosis due to Thalassaemia Major (30%) followed by biliary atresia (20%) and storage disorders (16%). The major share amongst the storage disorders was due to glycogen storage disease (12%). The less common disorders were neonatal hepatitis (10%), chronic hepatitis (6%) and nonspecific reactive hepatitis (3%). One case each of hepatoblastoma, haemophagocytic lymphohistiocytosis (HLH), congenital hepatic fibrosis and metastatic Hodgkin's lymphoma was also noted. Sixty percent of Thalassaemic children had Knodell HAI score between 13/22 to 18/22 and 65% patients revealed grade 3-4 haemosiderosis. Only three thalassaemic children showed full developed cirrhotic changes. Age wise distribution of various disorders is shown in Table 2. Discussion The liver in children is afflicted with the same pathologies as that of adults with some differences in etiology and prevalence. Many genetic metabolic disorders like glycogen storage disease, galactosaemia and phenylketonuria are prevalent in paediatric age group. A few malignancies like neuroblastoma, hepatoblastoma or haemangiomas cause enlargement of liver. Some acquired lesions such as neonatal hepatitis and biliary atresia are also seen in infancy or newborn period.9 The most common disorder in this study was secondary haemochromatosis (30%) due to Thalassaemia Major. This figure is not the actual representative of relative frequency of liver diseases. The finding is biased because of recent establishment of Armed Forces Bone Marrow Transplantation Center (AFBMTC) Rawalpindi. Liver biopTable 1. Histological Spectrum (Sex-wise distribution) of paediatric liver diseases (n = 100). S. No. Diagnosis Male Female Total Cases % 1. Secondary Haemochromatosis 14 16 30 30.0 (Thalassaemia Major) 2. Biliary Atresia 13 7 20 20.0 3. Hepatitis 12 8 a. Chronic Hepatitis 3 3 6 6.0 b. Neonatal Hepatitis 7 3 10 10.0 c. Granulomatous Hepatitis 1 1 1.0 d. Nonspecific Reactive Hepatitis 1 2 3 3.0 4. Metabolic / Storage Disorders 7 9 16 16.0 a. Glycogen Storage Disease 5 7 12 12.0 b. Galactosaemia 1 1 1.0 c. Alpha-1 antitrypsin deficiency 1 1 1.0 d. Fatty change 1 1 2 2.0 5. Cirrhosis Liver 6 4 10 10.0 6. Tumours 1 1 2 2.0 a. Hepatoblastoma 1 1 1.0 b. Metastatic Hodgkin's Disease 1 1 1.0 7. Miscellaneous 1 1 2 2.0 Haemophagocytic 1 1 1.0 Lymphohistiocytosis Congenital Hepatic Fibrosis 1 1 1.0 Total 54 46 100 100% biopsies of Thalassaemic children were done at MH Rawalpindi being a referral centre, for selection of suitable cases before undergoing bone marrow transplantation. Valuable information about degree of haemosiderosis, histological activity of chronic hepatitis and extent of fibrosis were gathered. Sixty percent of our cases showed 13/22 to 18/22 score as per Knodell8 histological activity index (HAI) and 65 percent of our children had 3-4 grade haemosiderosis. Whereas in a Chinese study10 (2002), 30% patients revealed HAI stage-3 and 44% children were having grade 3-4 haemosiderosis. Three Thalassaemic cases in this series developed cirrhotic changes as early as 6-7 years of age which is similar to a previous study by Jean et al11 where age range for cirrhosis was 7-8 years. However no case of cirrhosis was detected in a study by Lie et al10, probably because of better hepatitis screening program and availability of effective and prompt iron chelation therapy. The next common group of disorders in this series was neonatal cholestasis due to biliary atresia (20%). Similarly biliary atresia was the most common disease noted in Ga-Rankuwa Hospital Histopathology Laboratory, South Africa.12 This incidence is quite high when compared with three previous local Pakistani studies.13-15 Neonatal hepatitis was noted in 10% cases within one year of age with male dominance. In contrast to our study the variable frequencies of 2.7%, 3.3%, 13%, 15%, and 18% have been reported from different centers in Pakistan13-15 and India16 (Table 3). In our set up the common cause of chronic hepatitis are Hepatitis 'B' or Hepatitis 'C' viruses. We detected a total of six (6%) cases of chronic hepatitis, which is closer to two other studies by Anwar et al13 (1988) and Shakoor KA15 (1987). Four of six cases were due to hepatitis 'C' and two due to hepatitis 'B' infection. Infants, who acquire hepatitis perinataly, have upto 90% risk of developing chronic Hepatitis B infection.17 The prevalence of hepatitis C viral infection is relatively low in childhood and most chronically infected children are asymptomatic and show milder histological derangements.18,19 Same was our observation where children infected with hepatitis C were asymptomatic at presentation and showed mild hepatitis activity with slightly raised ALT level. One of the indications for liver biopsy is to find out the underlying cause for pyrexia of unknown origin.3 In this study we detected one case of "PUO" with chronic granulomatous inflammation, most likely due to tuberculosis. This patient responded well to anti-tuberculosis treatment. The nonspecific reactive hepatitis in the present Table 2. Age-wise distribution of childhood hepatic diseases (n=100). Disorders of Liver Number of cases in different age groups 1 Month 1 year 2-5 years 6-10 years 11-16 years Total Secondary Haemochromatosis 7 19 4 30 (Thalassaemia Major) Biliary Atresia 16 4 1 20 Glycogen Storage Disease 4 7 1 12