Claude Degott

Expression of cytokine-dependent immune adhesion molecules by hepatocytes and bile duct cells in chronic hepatitis C

BACKGROUND/AIMSnThe pathogenesis of liver cell injury in chronic hepatitis C is poorly understood. To test whether immune-mediated mechanisms might be involved in the pathogenesis of liver cell injury during infection by hepatitis C virus, the expression of cytokine-dependent immune molecules by hepatocytes and bile duct cells during chronic hepatitis C was studied.nnnMETHODSnIn 35 patients, expression of class I and II HLA antigens, intercellular adhesion molecule (ICAM) 1, and lymphocyte function antigen (LFA) 3 was studied by immunohistochemistry and scored by a semiquantitative grading system. Statistical analysis was performed using Spearmans test and t test.nnnRESULTSnClass I HLA antigens were induced on hepatocytes in 20 cases. In all cases, HLA-DR, ICAM-1, and/or LFA-3 were detected on hepatocytes in piecemeal necrosis and intralobular clusters. Bile duct cells expressed HLA-DR in 32 cases and ICAM-1 and LFA-3 in 14 cases. Expression levels of immune molecules on hepatocytes correlated with aminotransferase activity (P < 0.035), histological activity (P < 0.001), and score of necrosis (P < 0.01). ICAM-1 expression on hepatocytes was higher in patients with intraportal lymphoid nodules (P = 0.005). Expression levels of ICAM-1 and LFA-3 on bile ducts correlated with the severity of bile duct damage (P < 0.015).nnnCONCLUSIONSnThese results suggest the involvement of immune-mediated mechanisms in the pathogenesis of liver cell injury in chronic hepatitis C.

The ciliated hepatic foregut cyst, an unusual bronchiolar foregut malformation: A histological, histochemical, and immunohistochemical study of 7 cases

The ciliated hepatic foregut cyst is an unusual solitary cystic lesion of the liver. In a series of 7 cases of hepatic ciliated cysts, we performed a histological, histochemical, and immunohistochemical study to better define the histogenesis of this rare entity. The patients were 4 women and 3 men, aged 39 to 75 years. Four patients presented with abdominal pain. In 3 cases the cyst was discovered incidentally on ultrasonography. The cysts measured from 1 to 4 cm in diameter. Microscopically, the lining of the columnar epithelium was composed of ciliated cells and mucin secreting goblet cells. The wall was composed of bands of smooth-muscle fibers surrounded by an outer fibrous capsule. The goblet cells stained with PAS, alcian blue, and high-iron diamine. The immunohistochemical study showed that endocrine cells were present within the cyst epithelium, positive for chromogranin, synaptophysin, bombesin, and calcitonin, and negative for serotonin, somatostatin, glucagon, insulin, gastrin, and pancreatic polypeptide. In all the cases, immunoreactivity of some cells for CC10 strongly suggested the presence of Clara cells. Our study shows that the epithelium lining ciliated hepatic foregut cysts has histological, histochemical, and immunohistochemical features similar to those observed in the bronchiolar epithelium. This lesion is a developmental ventral foregut abnormality that could arise from a bronchiolar bud of the tracheobronchial diverticulum.

Tumeur à cellules géantes ostéoclastiques du pancréas

Resume Les tumeurs a cellules geantes osteoclastiques sont des tumeurs osseuses de l’adulte considerees comme benignes selon l’OMS mais localement agressives. Des tumeurs strictement identiques sont decrites dans le pancreas sans localisation osseuse concomitante. Nous rapportons l’observation d’une femme de 62 ans ayant une tumeur a cellules geantes osteoclastiques du pancreas gauche, sans contingent epithelial identifiable, dont le diagnostic n’a ete fait qu’apres exerese, et sans recidive avec un recul de 24 mois. Ces tumeurs pancreatiques sont exceptionnelles, d’histogenese imprecise et souvent confondues avec les carcinomes pleomorphes ou indifferencies pancreatiques avec composante a cellules geantes osteoclastiques, de pronostic tres sombre. Ces tumeurs pancreatiques a cellules geantes osteoclastiques se presentent comme de volumineuses formations kystiques. L’exerese chirurgicale complete assure dans certains cas une survie prolongee.

Chronic Non-A, Non-B, Non-C Hepatitis in French Blood Donors Assessed with HCV Third-generation Tests and Polymerase Chain Reaction

The livers of blood donors with increased serum aminotransferase levels were assessed histologically and were tested for antibodies to hepatitis C virus (anti-HCV) with a third-generation ELISA and RIBA and for serum HCV-RNA with polymerase chain reaction (PCR). Among 45 donors studied, 16 (35%) had chronic hepatitis. No evidence of HCV infection could be demonstrated by third-generation ELISA and RIBA or by PCR in 4 of them (25%). Since no known cause of chronic hepatitis was detected, and since there were no risk factors for parenterally acquired viral infection, the hypothesis that chronic hepatitis may be caused by a non-A, non-B, non-C virus must be considered.

Long-term Histologic Improvement and Persistent HCV Replication in Patients with Chronic Hepatitis C Having Responded to Recombinant Alpha Interferon

We assessed long-term outcome in 24 patients with chronic hepatitis C who responded to interferon-α in a previous study. All patients were followed up for 12 months and 16 patients were followed up for a further 41 ± 9 months. Within the 12 months after therapy, 16 patients (67%) relapsed and 8 patients had a sustained response. HCV-RNA remained detectable in the serum of 5 of 8 patients and in the liver of 1 of 3 patients with sustained response tested; 2 of them subsequently relapsed. Histologic assessment at 13 to 31 months after therapy showed a decrease of activity in most patients. In conclusion, despite biochemical remission induced by interferon therapy, HCV replication persists in many patients with a potential risk for late relapse. In contrast, some patients have no detectable HCV-RNA suggesting clearance of HCV. Long-term histologic improvement confirms the beneficial effect of interferon.