Soluble forms of extracellular cytokeratin 18 may differentiate simple steatosis from nonalcoholic steatohepatitis

AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n = 45), borderline NASH (n = 24), simple fatty liver (n = 9), and normal tissue (n = 5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA. RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively. CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.

Liver histology according to the presence of metabolic syndrome in nonalcoholic fatty liver disease cases

AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (40 male,41 fe-male) who were diagnosed with fatty liver by ultraso-nographic scan and fulfi lled the inclusion criteria. First anamnesis,anthropometric,clinical,laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification. RESULTS:Sixty-nine of the 81 patients had nonalco-holic steatohepatitis (NASH),11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation. Comparisons were made between two groups of NASH patients,those with and without metabolic syndrome. We did not detect statistically significant differences in liver histology between NASH patients with and wit-hout metabolic syndrome. CONCLUSION:NASH can progress without metabolic risk factors or the presence of metabolic syndrome.

Evaluation of leukocyte esterase and nitrite strip tests to detect spontaneous bacterial peritonitis in cirrhotic patients

AIM： To investigate the diagnostic efficacy of leukocyte esterase and nitrite reagent strips for bedside diagnosis of spontaneous bacterial peritonitis （SBP）. METHODS： A total of 63 consecutive patients with cirrhotic ascites （38 male, 25 female） tested between April 2005 and July 2006 were included in the study. Bedside reagent strip testing was performed on ascitic fluid and the results compared to manual cell counting and ascitic fluid culture. SBP was defined as having a polymorphonuclear ascites count of ≥ 250/mm^3. RESULTS： Fifteen samples showed SBP. The sensitivity, specificity, positive and negative predictive values of the leukocyte esterase reagent strips were; 93%, 100%, 100%, and 98%, respectively. The sensitivity, specificity, positive and negative predictive value of the nitrite reagent strips were 13%, 93%, 40%, and 77%, respectively. The combination of leukocyte esterase and nitrite reagents strips did not yield statistically significant effects on diagnostic accuracy. CONCLUSION： Leukocyte esterase reagent strips may provide a rapid, bedside diagnostic test for SBP.

Clinical outcomes of lung metastasectomy in patients with colorectal cancer

AIM： To investigate prognostic factors of survival fol- lowing curative, non-palliative surgical removal of lung metastases secondary to colorectal cancer （CRC）.

Non-alcoholic steatohepatitis with normal aminotransferase values

AIM： To investigate the aspects of liver histology in patients with non-alcoholic steatohepatitis （NASH） who had normal aminotransferase levels. METHODS： Thirty-four patients diagnosed with liver steatosis by ultrasonographic examination participated in the study. We compared all non- alcoholic fatty liver disease and NASH cases, according to aminotransferase level, aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio and presence of metabolic syndrome. RESULTS： Sixteen of 25 patients with high aminotransferase levels were diagnosed with NASH and nine with simple fatty liver according to liver histology. Among the nine patients with normal aminotransferase levels, seven had NASH and two had simple fatty liver. The patients with normal and high liver enzyme levels had almost the same prevalence of NASH and metabolic syndrome. Liver histology did not reveal any difference according to aminotransferase levels and AST/ALT ratio. CONCLUSION： Aminotransferase levels and AST/AIT ratio do not seem to be reliable predictors for NASH. Despite numerous non-invasive biomarkers, all patients with fatty liver should undergo liver biopsy.

Clinical significance of activity of ALT enzyme in patients with hepatitis C virus

AIM: To investigate serum alanine aminotransferase (ALT) levels in relation to the clinical,biochemical,ultrasonographic and histological characteristics of patients with hepatitis C virus. METHODS: Duration of disease,HCV-RNA,liver steatosis,and the hepatitis activity index (HAI) were correlated with serum ALT in 36 patients with HCV. ALT values were also investigated in 16 control subjects without any liver diseases. RESULTS: In bivariate analyses,ALT levels correlated with duration of HCV infection (P < 0.01),HCV-RNA (P < 0.05),and the HAI (P < 0.01). Among the components of the HAI,ALT concentrations were significantly associated with periportal bridging/necrosis (P < 0.01) and fibrosis (P < 0.05). In multivariate analysis,periportal bridging/ necrosis (β = 0.508; P < 0.01),duration of HCV infection (β = 0.413; P < 0.01),and HCV-RNA (β = 0.253; P < 0.05) were independently associated with ALT activity. The normal ALT activity for men and women was < 23 IU/L and < 22 IU/L,respectively. CONCLUSION: In patients with HCV,alterations in the liver tissue as reflected by ALT elevation are mainly associated with periportal bridging/necrosis,viral load and duration of disease. A cut-off value < 23 IU/L distinguished with high diagnostic accuracy healthy controls from patients with HCV.

Biomarkers for noninvasive biochemical diagnosis of nonalcoholic steatohepatitis:Tools or decorations?

In light of the growing epidemics of nonalcoholic fatty liver disease(NAFLD),identification and validation of the novel biochemical surrogate markers for nonalcoholic steatohepatitis(NASH)are paramount to reduce the necessity for liver biopsy.The availability of such markers has tremendous potential to radically alter the management strategies of NAFLD patients and to monitor the disease activity.Although current biomarkers do not entirely fulfill the many requirements for the identification of patients with NASH,they should not discourage our quest,but remind us that we need to cognize the challenges ahead.