Ultrastructure of hepatocyte mitochondria in nonalcoholic steatohepatitis in pediatric patients: usefulness of electron microscopy in the diagnosis of the disease

ME Sobaniec-Lotowska… - Official journal of the …, 2003 - journals.lww.com
ME Sobaniec-Lotowska, DM Lebensztejn
Official journal of the American College of Gastroenterology| ACG, 2003journals.lww.com
TO THE EDITOR: According to some reports, nonalcoholic steatohepatitis (NASH) in adults
as well as in children is an increasingly recognized disease of unknown pathogenesis, but
various theories have implicated free fatty acids (1–3). NASH is an important differential
diagnosis for asymptomatic patients with chronically elevated serum liver enzyme levels. It is
detected in 1.2–9% of patients who have liver biopsy (3). The main diagnostic criteria of
NASH are liver steatosis (mainly macrovesicular) accompanied by lobular inflammatory …
TO THE EDITOR: According to some reports, nonalcoholic steatohepatitis (NASH) in adults as well as in children is an increasingly recognized disease of unknown pathogenesis, but various theories have implicated free fatty acids (1–3). NASH is an important differential diagnosis for asymptomatic patients with chronically elevated serum liver enzyme levels. It is detected in 1.2–9% of patients who have liver biopsy (3). The main diagnostic criteria of NASH are liver steatosis (mainly macrovesicular) accompanied by lobular inflammatory infiltration with focal necrosis, with/without fibrosis in histological examination of liver biopsy, and lack of serological markers of hepatotropic viral infection or excessive alcohol intake. The histological features of the disease encompass a wide spectrum, from mild steatohepatitis to bridging fibrosis and cirrhosis (3–5). We present here the ultrastructure of hepatocyte mitochondria in liver tissue obtained through blind needle biopsies from five children (four boys aged 2, 3, 4, and 9 yr, and one girl aged 14 yr) with suspected nonalcoholic steatohepatitis. To date we have not known any report concerning mitochondrial morphology in NASH in pediatric patients, except for our preliminary work (6). Laboratory tests revealed increased serum transaminase activity in all of our patients and hypertriglyceridemia in the two oldest children. In differential diagnosis, infectious diseases of the liver (infection with hepatitis A, B, and C virus, cytomegalovirus, herpes simplex virus, Giardia lamblia, Toxoplasma gondii), metabolic disorders (cystic fibrosis, Wilson’s disease, galactosemia, fructosemia, tyrosynemia, α1-antitrypsin deficiency), autoimmune hepatitis, celiac disease, and diabetes were excluded in those children. In the histological findings of two patients, steatosis was of mixed type (macrovesicular steatosis with an associated microvesicular component), whereas macrovesicular type was present in three patients. All of the patients had lobular and portal inflammatory infiltrations, mostly of lymphocytic cells, associated with spotted foci of necrosis and fibrosis (slight and focal in two patients and more advanced in three). The morphological features of NASH were more severe in two children with steatosis of mixed type. For ultrastructural examinations, small fresh liver blocks (1 mm3) were fixed in solution containing 2% paraformaldehyde, 2.5% glutaraldehyde, and 0.1 mol/L cacodylate buffer, pH 7.4. The specimens were then postfixed in 2% OsO4. Subsequently, the material, after dehydration in ethanol and propylene oxide, was embedded in Epon 812. Ultrathin sections were double stained with uranyl acetate and lead citrate, and examined using an Opton 900 PC transmission electron microscope (Zeiss, Oberkochen, West Germany). Mitochondrial changes were determined by an electron microscopist who was blinded to the clinical information.
Lippincott Williams & Wilkins