M.C. Diaz

Recurrence of Bile Salt Export Pump Deficiency after Liver Transplantation

Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic liver transplantation for severe BSEP deficiency had post-transplantation episodes of cholestatic dysfunction that mimicked the original disease. Remission of all episodes was achieved by intensifying the immunosuppressive regimen. The phenotypic recurrence of the disease correlated with the presence of circulating high-titer antibodies against BSEP that inhibit transport by BSEP in vitro. When administered to rats, these antibodies targeted the bile canaliculi and impaired bile acid secretion.

A High Index of Suspicion: The Key to an Early Diagnosis of Wilson's Disease in Childhood

BACKGROUND To study the clinical features of Wilsons disease in childhood. METHODS Retrospective review of the clinical, laboratory, and histologic features and prognosis of Wilsons disease in 26 Spanish children. RESULTS The first medical visit, at age 9.8+/-3.4 years (range, 4-16 years), was prompted by liver dysfunction detected accidentally (61%), symptoms of liver disease (27%), family screening (8%), and extrapyramidal symptoms and personality changes (4%). There were laboratory data of hepatic failure in 27%. All copper metabolism test results (total serum copper, 24-hour urine excretion, serum ceruloplasmin) were abnormal in 62%, two in 27%, and one in 11%. All patients in whom extrahepatic involvement was found at diagnosis had severe liver disease. Histologic findings were portal fibrosis with steatosis (29%), cirrhosis (21%), portal fibrosis (17%), chronic active hepatitis (17%), and minimal changes or normality (17%). Penicillamine was administered to all but one patient. Four children underwent liver transplantation, three of them having received penicillamine for 12, 45, and 70 days. Three other patients recovered from liver failure after 1 year of treatment with penicillamine. After a follow-up of 4.5+/-3.3 years, all the children survived. Penicillamine caused severe toxicity in one patient. CONCLUSIONS Wilsons disease in childhood is generally detected by maintaining a high suspicion of liver disease in patients who have no or nonspecific hepatic symptoms. Kayser-Fleischer ring is rare in childhood. Drug therapy is effective and well tolerated, even in some cases of hepatic insufficiency.

Unusual Viruslike Particles in Chronic Non-A, Non-B Hepatitis in Childhood

Liver biopsies from 16 children with clinical and pathologic evidence of chronic hepatitis have been examined by electron microscopy for cytoplasmic and nuclear changes. Parallel studies by radioimmunoassay on sera from the same patients support the diagnosis of all these cases as non-A, non-B hepatitis (NANB). Ultrathin sections of the liver biopsies demonstrated in one case intranuclear hepatitis B virus-like core particles, 25 nm diameter. In a second biopsy from the same patient, the corelike particles could still be observed. This finding could be used either to support the thesis that a NANB virus is a member of the hepadnavirus group or to reflect the existence of seronegative cases of chronic HBV infection. Furthermore, we have observed in some mononuclear cells from the inflammatory infiltrate of a portal tract, some structures that resemble virus budding. There is a striking similarity between the morphology of these particles (which are enveloped and possess projections) and the ultrastructure of retrovirus.