N. Chrysanthos

Hepatic Steatosis in Genotype 4 Chronic Hepatitis C Is Mainly Because of Metabolic Factors

BACKGROUND/AIM:Hepatic steatosis is considered to be mostly associated with viral factors in genotype 3 and metabolic factors in genotype 1 chronic hepatitis C, while there are rather few data for genotype 4. We determined the parameters associated with steatosis in 350 chronic hepatitis C patients, focusing on genotype 4.METHODS:Histological lesions were evaluated according to Ishaks classification and steatosis was semiquantitatively graded. Several patient characteristics on the biopsy day were also evaluated.RESULTS:Steatosis was present in 73% of patients without significant differences among genotypes. Moderate/severe steatosis was more frequent in genotype 3 than 4 (44% vs 26%, P = 0.025) and similar between genotype 4 and 1 patients. Moderate/severe steatosis was associated with body mass index (BMI) in genotype 4 (P = 0.023) and gamma-glutamyl-transpeptidase in genotype 3 patients (P = 0.044). In 150 nondiabetic patients with BMI ≤25 kg/m2, moderate/severe steatosis was present in 15, 40, and 11% of genotype 1, 3, and 4 patients, respectively, (P = 0.005) and was independently associated only with genotype 3. In multivariate analysis, steatosis grade or moderate/severe steatosis was independently associated with higher BMI, genotype 3, and lower cholesterol.CONCLUSIONS:Moderate or severe steatosis is significantly less frequent in genotype 4 than 3 chronic hepatitis C patients and similar between genotype 4 and 1. In nondiabetic, nonoverweight patients, moderate or severe steatosis is present in only 10–15% of genotype 4 or 1 compared with 40% of genotype 3 patients. Thus, hepatic steatosis in genotype 4 is mostly associated with metabolic factors, similar to those in genotype 1.

Serum apoptotic caspase activity as a marker of severity in HBeAg-negative chronic hepatitis B virus infection

Background and aim: In chronic hepatitis C and non-alcoholic fatty liver disease, apoptotic caspases are activated in liver, and serum caspase activity has been suggested as a sensitive marker of early liver injury. An investigation was carried out into whether the serum levels of caspase-generated fragments of cytokeratin-18 (CK-18) are associated with the severity of liver lesions in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection. Patients/methods: CK-18 fragment serum levels were determined in 115 treatment-naive, consecutive HBV patients and 30 healthy controls. Hepatic-expression of CK-18 fragments was evaluated by immunocytochemistry in chronic hepatitis B patients. Results: CK-18 fragment levels (U/l) were significantly lower in healthy controls (mean (SD), 154 (31)) than in 53 inactive carriers (172 (24), p = 0.003) and in 62 chronic hepatitis B patients (474 (488), p<0.001). The receiver operating characteristic curve showed excellent diagnostic accuracy (c-statistic: 0.87) for differentiating inactive carriers from chronic hepatitis B patients. A CK-18 fragment cut-off level of 240 U/l gave a sensitivity of 60%, and a specificity and positive predictive value of 100% for chronic hepatitis B diagnosis. CK-18 fragment levels were also lower in inactive carriers than in 16 chronic hepatitis B patients with transiently normal alanine aminotransferase (ALT; 327 (256), p = 0.001), offering good accuracy for such a differentiation (c-statistic: 0.78). In chronic hepatitis B patients, serum CK-18 fragments correlated positively with ALT/aspartate aminotransferase (AST), viraemia, grading score and their immunohistochemical hepatic expression, and negatively with platelet counts, but not with fibrosis or steatosis severity. Conclusions: Serum apoptotic caspase activity is strongly associated with the presence of liver injury in patients with HBeAg-negative chronic HBV infection. CK-18 fragment levels seem to be a very useful marker for differentiation between the inactive HBV carrier state and HBeAg-negative chronic hepatitis B, but not for estimation of the severity of liver histological lesions among HBeAg-negative chronic hepatitis B patients.

Thrombotic risk factors and liver histologic lesions in non-alcoholic fatty liver disease

BACKGROUND/AIMS The pathogenetic mechanisms of development of non-alcoholic steatohepatitis (NASH) and fibrosis are not clear, although thrombosis of small intrahepatic veins has been suggested to trigger liver tissue remodelling and thrombotic risk factors have been associated with more advanced fibrosis in chronic viral hepatitis (CVH). We evaluated the prevalence of thrombotic risk factors (RFs) in non-alcoholic fatty liver disease (NAFLD) and their possible association with fatty liver or NASH. METHODS We included 60 patients with histologically documented NAFLD and a historical cohort of 90 patients with chronic hepatitis B (n=39) or C (n=51). Thrombophilic factors were evaluated on the day of the liver biopsy. RESULTS One or more thrombotic RFs were detected in 37% of NAFLD patients, and >or= 2 RFs were detected in 12% of NAFLD patients, being less frequently present than in CVH patients (37% and 68%, respectively; P <or= 0.001). Among NAFLD cases, one or more thrombotic RFs were significantly more frequently present in NASH than simple fatty liver (56% vs. 8%; odds ratio [OR]: 13.8, 2.8-67.4, P<0.001). In multivariate analysis, NASH was independently associated with moderate to severe steatosis (adjusted OR: 24.3; P=0.001) and the presence of one or more thrombotic RFs (adjusted OR: 38.7; P=0.002). Fibrosis stage was worse in NASH patients with than without thrombotic RFs (2.5+/-1.1 vs. 1.3+/-1.1; P=0.002). CONCLUSIONS Thrombotic RFs are frequently present in patients with NAFLD and are associated with NASH and more advanced fibrosis. Such an association may have significant clinical implications, even though it is not clear yet whether it represents a primary or secondary phenomenon.

[481] HBeAg-NEGATIVE CHRONIC HEPATITIS B (CHBe-) IN CHRONIC HBV PATIENTS WITH SERUM HBV-DNA LEVELS BELOW 2,000 lU/mL

G.V. Papatheodoridis’, E.K. Manesis’, S . Manolakopoulos2, J. Goulis3, N. Chrysanthosl, A. Bilalis2, S. Savvidou3, G. Katiri4, I. Delladetsima’, D. Tzourmakliotis2, A.J. Archimandritis’ . ‘2nd Department uflnternal Medicine, Athens Unioersity Medical School, Hippokration General Hospital, Athens; 2Departnzent o f Gastroenterology, Polyclinic General Hospital, Athens; 4th Department of Medicine, Aristotelian Univer~xit?, of Thewdoniki, Hippokrution General Hospital, Thessuloniki; ‘Department of Puthologj~, Hippokrution General Hospital, Athens; -5Department of Pathology, Luikon General Hospital, Athens, Greece E-mail: gepapath@med.uoa.gr

Small neuroendocrine tumor of the duodenal bulb: Endoscopic submucosal dissection, laparoscopic and endoscopic cooperative surgery or surgery?

Neuroendocrine neoplasms of the gastric tube are less common than adenocarcinomas. Topography includes stomach, small intestine, Vater ampulla, and gross intestine. They are graded as neuroendocrine tumors grade I and II (NETs GI and GII) and neuroendocrine carcinomas GIII based on Ki-67 index and mitotic count. [1] Endoscopic treatment for GI NETs ≤1 cm that does not extend beyond the submucosal layer and does not demonstrate lymph node metastasis is recommended. Tumors ≥2 cm, with lymph node metastasis, are indicated for surgical treatment. The treatment strategy for tumors between 10 and 20 mm in size remains controversial. [2] We present a rare case of a 60-year-old male patient with end-stage renal failure who underwent a screening pretransplantation endoscopic control. Colonoscopy had no pathological findings. Gastroscopy reveals an abnormal mucosa in the anterior upper part of the duodenal bulb that was described as a micronodular mucosa and a central nodule of 6 mm with erythematous mucosa. Histology of the micronodular mucosa reveals a heterotopic gastric mucosa and a small hyperplastic polyp. Biopsies from the nodule reveal a carcinoid tumor (NET GI). Immunohistochemistry: Positive chromogranin levels, low mitotic index (1/10 HPF), and Ki-67 index <1% [Figure 2]. Gastrin levels were normal and chromogranin levels were abnormal (314 ng/ml, ULN <120 ng/ml). Spiral tomography of the thorax and the abdomen were normal. Endoscopic submucosal dissection is indicated for small NETs (≤1 cm). Laparoscopic and endoscopic cooperative surgery is a novel method, but the experience is limited. Surgery is the best choice for large NETs (>2 cm) and those of the duodenal bulb with histological extensions and the lack of assessing depth invasion.