Safety and utility of liver biopsy after pediatric hematopoietic stem cell transplantation

Liver dysfunction is common after pediatric hematopoietic stem cell transplantation (HSCT) and liver biopsy may be necessary to diagnosis the cause of liver dysfunction and institute therapy. We report our liver biopsy experience in 356 consecutive patients. During the study period, 16 (4.5%) patients underwent 18 biopsies, all after allogeneic HSCT. The median time from HSCT to biopsy was 205.5 days. All patients had transaminase elevation and 67% had hyperbilirubinemia. The most commonly used method of biopsy was the imaging-guided percutaneous approach, performed in 12 of 18 cases. Five biopsies were done transjugularly and 1 was performed during laparotomy. In all the cases a histopathologic diagnosis was made. The most common diagnosis was graft-versus-host disease (GVHD) followed by iron overload. In 12 cases, management was modified based on biopsy results. Complications occurred after 5 biopsies, 4 of which were performed transjugularly. The most common complication was hemorrhage. Two patients required transfer to the intensive care unit for related complications. No complications were observed after percutaneous biopsies. In 2 cases a second procedure was required to manage the complication. We conclude that while liver biopsy yields a high-rate of diagnoses, it is accompanied by high rates of complications, particularly when the transjugular approach is used.     

Effects of isolated small bowel transplantation on liver dysfunction caused by intestinal failure and long-term total parenteral nutrition

It has not been fully determined whether isolated small bowel transplantation (ISBTx) can reverse liver dysfunction caused by intestinal failure requiring long-term total parenteral nutrition (TPN). A boy with congenital microvillus inclusion disease presented with vomiting and severe diarrhea since the first day of life and had been managed by TPN since then. He suffered from catheter-related sepsis several times. At 14 yr of age he developed progressive hepatosplenomegaly with thrombocytopenia and coagulopathy. He underwent ISBTx with an ileal graft from his blood-identical grandmother at the age of 16 yr. Oral feeding was started on the 14th day after ISBTx and gradually increased. TPN was completely withdrawn after 5 months. Liver was palpated 5 cm below the costal margin before ISBTx, while it became non-palpable 5 months after ISBTx. Serum liver enzyme levels and prothrombin time normalized in the 5 months following ISBTx. Liver biopsy showed marked steatosis, slight cholestasis, and mild bridging fibrosis before ISBTx. Although histological examination of liver biopsy revealed complete disappearance of steatosis 7 and 11 months after ISBTx, liver fibrosis remained unchanged. This clinical experience has shown that although steatosis and cholestasis are reversible after successful ISBTx and withdrawal of TPN, liver fibrosis may remain unchanged.     

Auto-immune cholangiopathy in a juvenile patient with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multi-system inflammatory disease characterized by the presence of auto-antibodies. Liver enzyme abnormalities are common but clinical liver dysfunction with jaundice is rare. We report a juvenile female patient with SLE who developed jaundice 9 months after her initial presentation. Further investigations including liver biopsy and magnetic resonance cholangio-pancreatography revealed two likely pathologies for her liver dysfunction; amoxicillin-clavulanic acid induced cholestasis and auto-immune cholangiopathy. The hyperbilirubinaemia resolved spontaneously 3 months after exposure to amoxicillin-clavulanic acid; however, the elevation in Alanine transaminase and Gamma-glutamyl transpeptidase persisted until intensive immunosuppressive therapy achieved complete remission. CONCLUSION: We report a rare case of a juvenile patient with SLE and auto-immune cholangiopathy. The use of cholangio-pancreatography as part of the diagnostic work-up achieved the final diagnosis.     

Fanconi-Bickel syndrome

We present here the first case of Fanconi-Bickel syndrome, a rare type of glycogen storage disease, from India. A 17-month-old female child presented with severe growth retardation and abdominal distention. Clinical examination revealed a "doll-like" face, massive hepatomegaly, and rickets. Laboratory investigations confirmed severe hypophosphatemic rickets and proximal renal tubular dysfunction. Liver biopsy showed glycogen accumulation in the hepatocytes.     

Phenobarbital can aggravate a cholestatic bile acid pattern in infants with obstructive cholangiopathy

The effect of phenobarbital on urinary bile acid excretion in intrahepatic cholestasis was studied in four boys 4-43 months of age who received 10 mg/kg of body weight of phenobarbital for a period of 3 weeks-3 years. One child was observed at two different periods: with and without histologically proven cirrhosis. Before the treatment period, the infants excreted 10-fold higher amounts of bile acids in urine than healthy children. The primary bile acids predominated, and there were also increased amounts of polyhydroxylated bile acids, 3 beta-hydroxy-5-cholenoic acid, and ketonic bile acids but small amounts of secondary bile acids. After the phenobarbital treatment, the patients further increased their urinary bile acid excretion, including all kinds of bile acids except the secondary ones. The sulfated fraction did not increase in absolute amounts, and its relative percentage decreased from a mean of 60-33%. Liver function test results generally did not improve, although serum concentration of bilirubin decreased. Most of these changes suggested a worsening of the cholestatic state after phenobarbital treatment. The results indicate that at our present state of knowledge, phenobarbital should not be given routinely to infants or children with intrahepatic cholestasis.     

Hepatosplenic Candidiasis in Children with Cancer. Three Cases in Leukemic Children and a Literature Review

Three children with acute leukemia presented with prolonged fever and neutropenia after cytostatic therapy, which was followed by abdominal pain, hepatomegaly, and hepatic dysfunction with raised serum alkaline phosphatase. Abdominal CT scan and ultrasound demonstrated multiple small lesions compatible with the hepatosplenic candidiasis syndrome. Liver biopsies showed microabscesses with a granulomatous appearance, but evidence of yeasts and pseudohyphae was present in 1 case only. Cultures were negative. Treatment with amphotericin B and 5-fluorocylosine was successful in two children. At autopsy, one child had signs of active infection. Hi reviewed the literature on 27 children with hepatosplenic candidiasis. Abdominal symptomatology and prolonged fever, despite antibiotic therapy, in a patient with previous or present neutropenia after cytotoxic exposure, should lead to a careful evaluation, including noninvasive imaging studies, open liver biopsy, and prompt aggressive antifungal treatment, the response to which requires close follow-up.     

Progressive Liver Fibrosis in Late-onset Argininosuccinate Lyase Deficiency

A 4-month-old boy, with late-onset argininosuccinate lyase (ASL) deficiency with hepatomegaly, was treated by protein restricted diet and arginine supplementation; he was followed for 3 years. Hepatomegaly and mild liver dysfunction persisted without significant hyperammonemia. He maintained normal psychomotor development to the age of 12 months, but, at 3 years of age, his developmental status is in the borderline normal range. Liver biopsy performed at 12 months of age demonstrated swollen and pale hepatocytes with abnormal glycogen deposition and mild periportal fibrosis. A subsequent liver biopsy at 3 years of age showed progressive liver fibrosis in the periportal and central areas, which extended into the liver lobule. These findings suggest that liver impairment in ASL deficiency may advance without significant hyperammonemia and underline the importance of repeated liver biopsy in this disorder, even when the plasma ammonia level is well controlled.     

Liver retransplantation with external biliary diversion for progressive familial intrahepatic cholestasis type 1: a case report

Abstract:  PFIC1, originally described as "Byler disease," is characterized by cholestatic feature and chronic diarrhea. Many patients require LT for the cure, but intractable diarrhea and prolonged growth retardation after LT are serious complications limiting the ultimate outcome of LT for this disease. EBD has recently been shown to be a promising and effective treatment. Recently, we successfully treated a five-yr-old boy with PFIC1 employing EBD after re-transplantation. The patient received LDLT at the age of one yr. Six months after initial transplantation, he developed repeated attacks and diarrhea followed by the development of liver dysfunction and ascites. Liver biopsy at three yr after LDLT revealed the features of chronic graft rejection. With a diagnosis of chronic graft rejection with liver failure, we performed a repeat LDLT with EBD in which the jejunal loop used for hepaticojejunostomy was taken out of the body surface through the abdominal wall. Ten months after surgery, he is doing well, having no attack of diarrhea.     

Clinical manifestations of congenital syphilitic hepatitis: implications for pathogenesis

To study the clinical course and biochemical features of congenital syphilitic hepatitis, the records of all 22 pediatric patients admitted to North Carolina Memorial Hospital between 1969 and 1979 with a positive maternal, cord blood, or serum VDRL were reviewed. Of the seven infants identified with symptomatic congenital syphilis, five had clinical and biochemical evidence of liver dysfunction. All five were jaundiced (peak bilirubin ranged from 8.4 to 29.8 mg/dl, in each case greater than 40% conjugated). Peak transaminase elevation ranged from seven to 150 times normal. Serum glutamic-oxaloacetic transaminase exceeded serum glutamic-pyruvic transaminase in each infant, the difference ranging to 7,400 U. The onset of illness did not occur until after treatment had been initiated in two of these five cases. Liver dysfunction increased with treatment in all four infants with serial enzyme determinations. Liver dysfunction also persisted for more than 6 weeks after adequate treatment in two cases. Liver biopsy 5 weeks after treatment in another infant showed giant cell hepatitis. These observations suggest that treatment can potentiate liver dysfunction in congenital syphilis and that viable treponemes are not necessarily essential in the pathogenesis of the hepatitis.     

Graft versus host-like illness in a child with phenobarbital hypersensitivity

A child in whom a phenobarbital hypersensitivity drug reaction developed which consisted of fever, a pruritic desquamating erythrodermic rash, alopecia, icterus, protein-losing enteropathy, myositis, and nephritis, is described. Laboratory studies demonstrated eosinophilia, elevated serum IgE, and elevated T suppressor/cytotoxic cells in the peripheral blood. Findings from biopsy specimens of skin and jejunum suggested a cell-mediated pathogenesis, and lymphoproliferative studies of the patient's mononuclear cells revealed a positive response to phenobarbital. The clinical findings and laboratory studies suggested an autoimmune cell-mediated hypersensitivity reaction triggered by phenobarbital.     

Case of an infant with hepatic cirrhosis caused by mitochondrial respiratory chain disorder

The patient had hepatomegaly with liver dysfunction at the age of 1 month. Magnetic resonance imaging performed at the age of 1 year showed multiple nodules of varying size in his liver. We were able to examine the mitochondrial respiratory chain function in the liver biopsy samples because all other differential diagnoses for hepatic cirrhosis had been ruled out. Complex I and IV activities were below the normal level (<30%) of the citrate synthase (CS) ratio. Liver blue native polyacrylamide gel electrophoresis showed an extremely weak complex I and IV band. Liver respiratory chain complexes I and IV were found to be deficient in this patient. The histologic findings were highly suggestive of mitochondrial respiratory chain disorder. Findings of progressive liver cirrhosis changes were observed in magnetic resonance imaging at the age of 5 years. An examination of the mitochondrial respiratory chain function should be performed along with a liver biopsy if mitochondrial respiratory chain disorder is suspected as a possible differential diagnosis of idiopathic hepatitis.     

Severe immune haemolytic anaemia due to ceftriaxone in a patient with congenital nephrotic syndrome

Aim: To describe the first case of ceftriaxone‐related haemolysis in a patient with congenital nephrotic syndrome (CNS). Background: Severe haemolysis caused by an immune reaction to ceftriaxone has mostly been described in patients with underlying haematological or immune dysfunction. Case report: The authors present a 20‐month‐old boy with CNS of the Finnish type with several previous severe infections treated with ceftriaxone, admitted for suspected sepsis. Following ceftriaxone administration he developed shock secondary to an acute haemolytic reaction, with severe anaemia. Hypersensitivity to ceftriaxone was documented through positive agglutination tests. Conclusion: Onset of haemolysis following ceftriaxone administration, particularly in a patient previously exposed to the drug, must raise the suspicion of a possible immune reaction.     

Pretreatment liver biopsy in 20 children with histiocytosis X: a clinicopathologic correlation

Liver biopsies were done on 20 patients with histiocytosis X (HX) as part of pretreatment evaluation prior to entry on two Childrens Cancer Study Group protocols. Seventeen patients had hepatomegaly, and seven had one or more abnormal laboratory parameters using Lahey's criteria for liver dysfunction. Nineteen of 20 specimens showed various abnormalities of the portal triads. A single biopsy revealed normal liver. Among the changes were triaditis, bile duct proliferation, variable fibrosis with histiocytic infiltrates, and cirrhosis. One patient had typical granulomas of HX within the liver parenchyma in addition to portal triaditis. Patients with larger livers and dysfunction tended to show more marked histologic abnormalities in the portal triads. However, correlations among liver size, function, and pathology showed considerable overlap. Early death among these patients was more likely to be associated with progressive HX in other sites and/or infection. Death from cirrhosis and liver failure per se occurred in one patient 4 years after initial biopsy, but five other children had evidence of cirrhosis on biopsy or at autopsy. The majority of patients with triaditis initially did not have clinical evidence of progressive liver disease although four expired with other manifestations of HX or infection. Conversely, patients showing fibrohistiocytic changes or cirrhosis initially were likely to have continuing or progressive liver disease. Although the liver histology was not diagnostic of HX, the types of portal changes usually predicted the subsequent course of liver disease.     

Treatment of a biliary-venous fistula following percutaneous biopsy in a pediatric living related liver transplant patient

Liver biopsy is a common study performed after hepatic transplantation. Most centers routinely perform a biopsy 1 week after surgery to evaluate for the possibility of acute rejection. Subsequent biopsies are based on clinical symptoms and routine hepatic function laboratory testing. We report the clinical presentation and treatment of a biliary-venous fistula resulting in sepsis and bilhemia (elevated serum bilirubin levels caused by a biliary-venous fistula) in a 2½-year-old patient 4 months after partial left lateral segment living related liver transplantation. This case is unusual in that the fistula is the reversal of the more common venous-biliary fistula. The fistula developed after a percutaneous liver biopsy was performed.     

Coeliac disease and liver dysfunction

The spectrum and pathogenesis of liver dysfunction in coeliac disease (CD) is reviewed. CD and liver disease share common risk factors, and consequences of CD may cause liver dysfunction. Liver dysfunction should be sought in CD, and its aetiology explored when abnormalities persist after gluten exclusion. CD should be excluded in patients with unexplained liver dysfunction before being labelled "cryptogenic".     

Migration of Gelfoam to the gallbladder after liver biopsy

Liver biopsy is a common procedure, with an inherent risk of bleeding. There are different ways to help avoid hemorrhage, including biopsy through a transjugular venous route or embolization of the tract with liquid or solid materials. We describe an image-guided percutaneous core needle liver biopsy with tract embolization using thick Gelfoam slurry in a pediatric oncology patient. Imaging studies acquired after the biopsy indicated that the Gelfoam mixture had likely migrated to the gallbladder and common bile duct. We report this rare occurrence with its striking imaging in order to make those performing biopsies aware of this possibility.     

Early graft failure due to a veno-occlusive disease after a pediatric living donor liver transplantation

A 10-month-old boy with biliary atresia after Kasai procedure underwent a living donor liver transplantation (LDLT). Five days after the LDLT, high fever and increased ascites followed by poor bile drainage was accompanied by elevation of serum liver enzymes. Liver biopsy showed occlusion of the central veins by fibro-edematous endothelium and submassive necrosis of the parenchyma. Veno-occlusive disease (VOD) was suspected, and re-LDLT was urgently performed because of deterioration of hepatic failure. There are few cases of VOD after liver transplantation and this is the first one in an infant after LDLT.     

Reversible acute anuric kidney injury after surgical evacuation of perinephric hematomas as a complication of renal transplant biopsies

Percutaneous renal transplant biopsy is the gold standard investigation to diagnose the cause of renal allograft dysfunction. There are inherent risks to this investigation, despite the procedure becoming safer due to the increased utilization of ultrasound‐guided techniques. These biopsy risks can be increased when there is acute rejection present with a swollen transplanted kidney. Subcapsular hematomas are not uncommon after percutaneous renal transplant biopsies, but we describe two cases of post‐biopsy subcapsular hematoma which were associated with acute renal allograft dysfunction in pediatric renal transplant recipients who did not have acute rejection.     

The occurrence of intramitochondrial Ca2+ granules in valproate-induced liver injury

Two epileptic patients treated with anticonvulsants of valproic acid, phenobarbital, nitrazepam, and diphenylhydantoin developed anorexia, convulsions, and unconsciousness. The liver biopsy samples showed degenerated hepatocytes containing enlarged mitochondria with a distorted matrix. The matrix granules in the mitochondria were enlarged in size as compared with those of chronic hepatitis (Po = 0.0009). X-ray microanalysis has revealed the presence of calcium in large mitochondrial matrix granules. Both patients were thought to have valproic acid intoxication because they recovered quickly after the withdrawal of valproic acid.