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Year : 2020  |  Volume : 63  |  Issue : 1  |  Page : 138-139
Neonatal hemochromatosis: A rare cause of liver failure in infancy


Department of Pathology, GI-Pathology and Neonatology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India

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Date of Web Publication31-Jan-2020
 

How to cite this article:
Chaudhuri PM, Mandal B, Halder A, Ghosh R, Chatterjee U, Mukherjee S. Neonatal hemochromatosis: A rare cause of liver failure in infancy. Indian J Pathol Microbiol 2020;63:138-9

How to cite this URL:
Chaudhuri PM, Mandal B, Halder A, Ghosh R, Chatterjee U, Mukherjee S. Neonatal hemochromatosis: A rare cause of liver failure in infancy. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Feb 23];63:138-9. Available from: http://www.ijpmonline.org/text.asp?2020/63/1/138/277391




Neonatal cholestasis (NC) is a broad heterogeneous group of disorders characterized by persistent conjugated hyperbilirubinemia, with an incidence of 1 in 2500 live births.[1] Biliary atresia (BA) is the most common obstructive forms of NC, whereas the major nonobstructive disorders include idiopathic neonatal hepatitis, progressive familial intrahepatic cholestasis (PFIC), preterm birth, endocrinological and metabolic disorders, Alagille syndrome, and mitochondriopathy.[2] Neonatal hemochromatosis (NH) is a rare but important cause of NC, characterized by iron deposition in multiple organs except for the reticuloendothelial system, leading to end-stage liver disease even in a premature infant.[3] We elucidate a case of NH with severe bile duct proliferation that caused a diagnostic dilemma.

A 4-week-old neonate presented with a complaint of jaundice since birth, which persisted despite phototherapy. Her birth history was normal and she was delivered at term by elective caesarean section. At presentation, her bilirubin level was 18.0 mg/dL, of which the conjugated type was 13.5 mg/dL. The stools were pale yellow in color. Serum levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were found to be raised as well as the coagulation profile was deranged. An ultrasound of the upper abdomen showed a small contracted gall bladder. Based on these features, a clinical diagnosis of NC was considered. Hepatobiliary scintigraphy (HIDA scan) and a liver biopsy were planned to rule out BA. However, the baby developed progressive jaundice, ascites, and hepatic failure and died.

On autopsy, the baby had slate grey color and tense ascites. Most of the organs showed a greenish discoloration. The liver and gall bladder were contracted and were deep green in color. The cut sections of the liver revealed fine nodularity. Except for an enlarged spleen, the other organs were grossly within normal limits. Sections were taken from the different viscera for histological evaluation. On H and E staining of sections, the liver showed significant hepatic necrosis. Broad bridging fibrous bands were present with the formation of incomplete nodules. Their portal areas showed marked fibrous expansion with extensive portal and periportal bile duct proliferation. However, cholestasis within the neoductules was lacking. The small islands of hepatocytes within the nodules showed cytoplasmic and canalicular cholestasis. A reddish hue was seen in the hepatocytes, most prominent in the periportal areas as well as within the biliary epithelium and focally within Kupffer cells [Figure 1]. Significant hepatocellular distension or Kupffer cell hyperplasia was lacking. No particular storage cells were identified. In view of short progressive history and reddish hue of the hepatocytes, a Perls' Prussian blue staining was performed which showed intensely blue staining hemosiderin pigment deposition in the hepatocytes with a characteristic pericanalicular pattern and also in the bile ductular epithelium. Considerable iron deposition was noted in pancreatic acini and ducts. Focal iron deposits were also present in the myocardium [Figure 2]. Based on these histological findings, an etiological diagnosis of NH was made.
Figure 1: (a) Gross photograph showing greenish discoloration of liver and an enlarged spleen. (b) Photomicrograph showing a lobule of hepatocytes separated by fibrous tissue (H and E stain, 4×). (c) Low-power view showing the reddish hue of hepatocytes (H and E stain, 10×). (d) High-power view showing an extreme degree of bile ductular proliferation (H and E stain, 40×)

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Figure 2: (a and b) Perls' Prussian blue staining showing extensive iron deposition in hepatocytes and within bile ductules in scanner power (4×) and high power (40×). (c and d) Iron deposition also noted within pancreatic acini and ducts as shown in low power (10×) and high power (40×) photomicrographs (Perls' Prussian blue stain)

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NH is an extremely rare disease presenting immediately after birth, with only a little more than 100 cases being described in the literature.[4] In NH, the liver disease begins in-utero and end-stage liver disease is established even in a prematurely born infant.[3] Besides liver failure, the other clinical presentations include growth retardation, coagulopathy, anemia, thrombocytopenia, ascites, and generalized edema. Morphologically, the liver is often bile stained with extensive fibrosis, giant cell, or pseudoglandular transformation with focal nodular regeneration and varying degrees of cholestasis. Severe bile ductular proliferation is an extremely rare finding in NH.[5],[6] For diagnosis of NH, a lip biopsy to show iron deposition in ducts and acini of minor salivary glands and estimation of serum ferritin levels are important, but unfortunately, none of the two was done in our case. Severe bile ductular proliferation in NH can simulate obstructive etiologies like BA, but bile plugs within the neoductules are characteristically absent in NH, as in our case. Normal neonatal liver contains significant iron, and pathological hepatic siderosis can also be seen in a variety of other neonatal liver diseases, but none of these entities is associated with extrahepatic siderosis, except NH.[3] Our case showed iron deposition in the pancreas and heart, which clinched the diagnosis of NH. The causes of bile duct proliferation in neonates and infants are outlined in [Table 1].
Table 1: Causes of bile duct proliferation in neonates and infants

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Most cases of NH can be attributed to gestational alloimmune liver disease and hence is also known as fetal alloimmune hepatitis.[3],[5] Management of NH is supportive that consists of exchange transfusion and administration of intravenous immunoglobulin. Liver transplantation is indicated in failed cases. As NH can recur in subsequent pregnancies, parental counseling is of utmost importance. After one affected pregnancy, high doses of intravenous immunoglobulins administered at 14 weeks onwards have shown to improve neonatal outcome in subsequent pregnancies.[3],[5],[6]

So to conclude, bile ductular proliferation is an important morphological sign to distinguish between the obstructive and nonobstructive causes of NC that have separate management strategies. Bile plug formation within neoductules is an important sign in favor of the obstructive causes. NH is a rare but important cause of liver failure in infancy characterized by extrahepatic siderosis multiple organs. Careful assessment of all the clinical and morphological features taken together is required to correctly distinguish NH from the other nonobstructive and obstructive causes of NC.

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Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
McKiernan PJ. Neonatal cholestasis. Semin Neonatol 2002;7:153-65.  Back to cited text no. 1
    
2.
Hoerning A, Raub S, Dechêne A, Brosch MN, Kathemann S, Hoyer PF, et al. Diversity of disorders causing neonatal cholestasis- the experience of a tertiary pediatric center in Germany. Front Pediatr 2014;23:65.  Back to cited text no. 2
    
3.
Feldman AG, Whitington PF. Neonatal hemochromatosis. J Clin Exp Hepatol 2013;3:313-20.  Back to cited text no. 3
    
4.
Murray KF, Kowdley KV. Neonatal HC. Pediatrics 2001;108:960-4.  Back to cited text no. 4
    
5.
Whitington PF, Kelly S, Ekong UD. Neonatal hemochromatosis: Fetal liver disease leading to liver failure in the fetus and newborn. Pediatr Transplant 2005;9:640-5.  Back to cited text no. 5
    
6.
Knisely AS, Mieli-Vergani G, Whitington PF. Neonatal hemochromatosis. Gastroenterol Clin North Am 2003;32:877-89.  Back to cited text no. 6
    

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Correspondence Address:
Aniket Halder
430/2 Ratnavilla, Nabatirtha, PO Hridaypur, Barasat, 24 Pgs (N), West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_526_18

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