The SOCS-1 -1478CA/del functional polymorphism (rs33989964) is associated with gastric cancer but is unrelated to overall survival.

BACKGROUND: In vitro studies have shown that the functional - 1478CA > del polymorphism (rs33989964) of the suppressor of cytokine signaling (SOCS)-1 gene is associated with an altered trascriptional activity. Here, we sought to examine the potential association of this polymorphism with the risk of gastric cancer (GC) and to analyze its prognostic impact on overall survival (OS). MATERIALS AND METHODS: The study cohort consisted of 74 Turkish patients with GC and 52 healthy controls. Genotyping of the SOCS-1 -1478CA > del polymorphism was carried out using restriction fragment length polymorphism analysis. RESULTS: After allowance of age and sex, multivariable logistic regression analysis revealed that the carriage of the del allele of the SOCS-1 -1478CA > del polymorphism was independently associated with an increased risk of GC (odds ratio = 6.78, 95% confidence interval = 3.24-10.99, P < 0.001). Kaplan-Meier analysis revealed no significant differences in OS for patients harboring at least one del allele of rs33989964 compared with CA/CA homozygotes (log-rank test, P = 0.17). CONCLUSION: While the SOCS-1 -1478CA > del polymorphism is significantly associated with the risk of GC in the Turkish population, it does not affect OS.

Mean platelet volume is an important predictor of hepatitis C but not hepatitis B liver damage.

BACKGROUND: The mean platelet volume (MPV) is the most commonly used measure of platelet size and is a potential marker of platelet reactivity. In this study, we aimed to explore the relationship between hepatic histopathology in viral hepatitis and MPV levels, which are associated with platelet count and activity. MATERIALS AND METHODS: We performed a retrospective case-control study of baseline histological and clinical parameters in chronic hepatitis B and C patients in our tertiary reference center between January 2005 and January 2011. Two hundred and five chronic hepatitis B patients and 133 chronic hepatitis C patients who underwent liver biopsy were included in the study. The patients were divided into two groups: Chronic hepatitis B and chronic hepatitis C and were additionally divided into groups of two according to histological activity index (HAI) and fibrosis scores obtained by liver biopsy results (according to the Ishak scoring system). The clinical characteristics of chronic viral hepatitis patients, including demographics, laboratory (especially MPV), and liver biopsy findings, were reviewed. RESULTS: One hundred and forty-three patients were male (69.1%), and the mean age was 41.9 ± 12.75 with an age range of 18-71 years in hepatitis B patients. In the classification made according to HAI, 181 patients were in the low activity group (88.3%) and 24 in the high activity group (11.7%). In the evaluation made according to fibrosis score, 169 patients were found to have early fibrosis (82.4%) and 36 were found to have advanced fibrosis (17.6%). In patients with hepatitis B, there was no statistically significant difference in terms of their MPV values between the two groups, separated according to their degree of activity and fibrosis. Sixty-three patients were male (47.3%), and the mean age was 50.03 ± 12.75 with an age range of 19-75 years. In the classification made according to HAI, 109 patients were in low activity group (81.9%) and 24 in high activity group (18.1%). In the evaluation made according to fibrosis score, 101 patients were found to have early fibrosis (75.9%) and 32 have advanced fibrosis (24.1%). There was a statistically significant difference between the activity and fibrosis groups of the hepatitis C patients (P = 0.04 and P = 0.02, respectively). CONCLUSION: MPV values are more reliable in hepatitis C patients than hepatitis B for predicting the advanced damage in liver histology. This finding might be useful for the detection of early fibrosis and also starting early treatment, which is important in hepatitis C.

The relation between liver histopathology and GGT levels in viral hepatitis: more important in hepatitis B.

BACKGROUND/AIMS: To investigate the relationship between gamma-glutamyl transpeptidase (GGT) levels and histopathological status determined by biopsy in patients with chronic hepatitis B and C. MATERIALS AND METHODS: Patients with chronic hepatitis B and C who were referred to the Uludag University Faculty of Medicine Gastroenterology outpatient clinic between January 2005-January 2011 and underwent liver biopsy were included in the study. Overall, 246 patients with hepatitis B and 151 patients with hepatitis C were enrolled. According to the evaluation based on the Ishak score, patients with a histological activity index (HAI) between 0-12 were defined as low activity, and those with an HAI between 13-18 were defined as high activity. In addition, patients with a fibrosis score of 0-2 were defined as low fibrosis, and those with a score between 3-6 were defined as high fibrosis; comparisons were made accordingly. RESULTS: In patients with hepatitis B, the mean GGT level was 38.86±42.4 (IU/L) in the low activity group and 60.44±44.4 (IU/L) in the high activity group (p<0.05). In hepatitis B patients, the mean GGT level was 26.89±14.83 (IU/L) in the low fibrosis group, whereas it was 65.60±59.7 (IU/L) in the high fibrosis group (p<0.001). There was no significant difference between HAI and fibrosis group with regard to GGT levels in the hepatitis C patients. CONCLUSION: In conclusion, it is proposed that in patients with chronic viral hepatitis, GGT levels can be taken into consideration to predict advanced histological liver damage, especially in patients with hepatitis B.

No association between the SOCS-1 -1478CA/del polymorphism and ulcerative colitis in Turkish subjects.

Suppressor of cytokine signaling (SOCS)-1 is an essential regulator of many cytokine signaling pathways, including those upregulated in the inflamed colonic mucosa of patients with ulcerative colitis. We sought to investigate whether the functional SOCS-1 -1478CA>del polymorphism is associated with UC susceptibility and its disease phenotype in a Turkish clinical sample. A total of 104 subjects were enrolled in a case-control study (52 UC cases and 52 controls). The SOCS-1 -1478CA>del polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The odds ratio of the del allele for UC relative to the CA allele was not significant (OR = 1.04, 95 % CI 0.59-1.82, P = 0.88). These results did not change after adjustment for age and sex in multivariable regression analysis (OR = 1.07, 95 % CI 0.42-1.69, P = 0.73). When the SOCS-1 -1478CA>del polymorphism was analyzed among UC patients according to continuous disease and non-continuous disease, the del allele was not associated with disease recurrence (OR = 1.56, 95 % CI 0.78-4.56, P = 0.83). Furthermore, when we divided UC patients into two groups according to a previous history of colectomy, we found no significant effect of the del allele (OR = 1.94, 95 % CI 0.55-5.61, P = 0.91). Taken together, these findings suggest that SOCS-1 -1478CA>del polymorphism does not contribute to UC susceptibility and its disease phenotype in Turkish subjects.

Noninvasive predictors for liver fibrosis in patients with nonalcoholic steatohepatitis.

AIM: To evaluate certain anthropometric, clinical and laboratory features indicating liver fibrosis in nonalcoholic steatohepatitis and to establish the noninvasive markers for liver fibrosis. METHODS: Eighty-one patients (40 male, 41 female) who were diagnosed with fatty liver by ultrasonographic examination and fulfilled the inclusion criteria participated in the study. Anamnesis, anthropometric, clinical and laboratory features of all cases were recorded and then liver biopsy was performed after obtaining patient consent. Steatosis, necroinflammation and liver fibrosis were examined according to age ≥ 45, gender, body mass index, central obesity, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 1, γ-glutamyltransferase (GGT)/ALT > 1, platelet count, insulin, c-peptide levels and the presence of hypertension, diabetes, hypertriglyceridemia and insulin resistance. RESULTS: Eighty-one patients with non-alcoholic steatohepatitis (NASH) enrolled in the study. 69 of 81 patients were diagnosed with NASH, 11 were diagnosed with simple fatty liver and 1 was diagnosed with cirrhosis. AST/ALT > 1, GGT/ALT > 11, high serum ferritin and fasting insulin levels, the presence of diabetes, hypertension, hypertriglyceridemia and insulin resistance seemed to enhance the severity of steatosis, necroinflammation and fibrosis but these results were not statistically significant. CONCLUSION: Liver steatosis and fibrosis can occur in individuals with normal weight. There was no significant concordance between severity of liver histology and the presence of predictors for liver fibrosis including metabolic risk factors.

A case of torsion of the wandering spleen presenting as hypersplenism and gastric fundal varices.

Wandering spleen is the displacement of the spleen from its normal location due to the loss or weakening of ligaments that hold the spleen in the left upper quadrant. The possibility of torsion of the spleen is high due to the long and mobile nature of the vascular pedicle. Generally, cases are asymptomatic. Under conditions of delayed diagnosis, symptoms of splenomegaly, left portal hypertension, gastric fundal varices, and hypersplenism may present as a result of development of vascular congestion associated with chronic torsion. There are only a few cases in the literature reporting the association of wandering spleen and fundal varices. We report herein the case of a 55-year-old female who admitted to our clinic with complaints of fatigue and epigastric pain. She was determined to have gastric fundal varices and hypersplenism secondary to the development of left portal hypertension due to chronic splenic torsion.

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/ALT ratio do not seem to be reliable predictors for NASH. Despite numerous non-invasive biomarkers, all patients with fatty liver should undergo liver biopsy.

Elevated serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) in patients with nonalcoholic steatohepatitis and chronic hepatitis C.

BACKGROUND: Caspase-cleaved cytokeratin 18 (CK18-Asp396) is released from hepatocytes during apoptosis. Recent studies have indicated that serum levels of CK18-Asp396 could be a clinically useful biomarker of chronic liver disease. To shed more light on the rate of hepatocyte loss by apoptosis in chronic liver disease, serum levels of CK18-Asp396 were examined in patients with nonalcoholic steatohepatitis (NASH) and chronic hepatitis C. MATERIAL/METHODS: Apoptotic CK18-Asp396 levels were quantified in sera from 35 patients with nonalcoholic steatohepatitis (NASH), 21 patients with chronic hepatitis C (HCV), and 18 healthy controls. RESULTS: Analysis of serum CK18-Asp396 levels showed an increasing trend starting from healthy controls (median: 54.5 U/l), to HCV patients (80.1 U/l), to patients with NASH (144.1 U/l, Kruskall-Wallis test: P<0.001). Post hoc analyses revealed that CK18-Asp396 levels were significantly higher in the NASH patients than in both HCV patients (P=0.008) and healthy controls (P<0.001). Moreover, the levels were significantly higher in patients with HCV than in control individuals (P<0.05). In patients with chronic HCV infection there was a significant positive correlation between serum CK18-Asp396 levels and AST (r=0.442, P<0.05), the ultrasonographic grade of steatosis (r=0.446, P<0.05), and the histological steatosis score (r=0.759, P<0.001). CONCLUSIONS: Although subject to future confirmation, these pilot findings seem to indicate that serum levels of caspase-cleaved cytokeratin 18 (CK18-Asp396) are higher in patients with NASH than in those with chronic HCV infection. These data suggest that NASH patients have an increased hepatocyte loss by apoptosis compared with chronic hepatitis C patients.

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 female) who were diagnosed with fatty liver by ultrasonographic scan and fulfilled 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 nonalcoholic 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 without 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 >or= 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.

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.

Lymphocyte subsets and cytokines in ascitic fluid of decompensated cirrhotic patients with and without spontaneous ascites infection.

BACKGROUND AND AIM: Spontaneous ascites infection is a frequently encountered and important complication of decompensated liver cirrhosis. The immune system plays an important role in the development or eradication of this infection. A number of compositional and functional alterations in immune system cells have been demonstrated in cirrhotic patients; however, there is a lack of knowledge about this issue in ascitic infections. The aim of the present study was to evaluate lymphocyte subsets and levels of some ascitic and lymphocytic intracytoplasmic cytokines in decompensated cirrhotic patients with or without spontaneous ascites infection. METHODS: The study population consisted of 45 decompensated cirrhotic patients (32 men, 13 women) with different etiologies. Patients with ascitic polymorphonuclear leukocyte count > or =250/mm(3) and/or positive ascitic bacterial cultures were classified as the "infected group". Comparison was made between the infected and non-infected group for the following parameters: ascites leukocyte counts and differentiations; ascitic fluid protein; albumin levels and serum-ascites albumin gradients; flow cytometric detection of cell surface markers for ascitic T, B and natural killer lymphocytes; intracytoplasmic interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma; levels of ascitic IL-8, IL-10, IL-12 and TNF-alpha; and soluble Fas antigen and soluble Fas ligand. RESULTS: The CD4/CD8 ratio was significantly decreased and expression of T cell receptor-gammadelta was increased in the infected group. Furthermore, ascites TNF-alpha levels were also elevated in this group. Ascitic IL-8, IL-10, IL-12 and TNF-alpha levels were significantly higher in patients with positive ascitic bacterial culture. CONCLUSIONS: These results suggest that a cytotoxic, especially Th1, immune response predominates in ascites infections. It also demonstrates that TNF-alpha might be involved in the pathogenesis of ascites infections.

Ursodeoxycholic acid and atorvastatin in the treatment of nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a serious disorder with the potential to gradually progress to cirrhosis. It is generally associated with obesity, diabetes and hyperlipidemia. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the effectiveness of atorvastatin and ursodeoxycholic acid (UDCA) in the treatment of NASH. METHODS: This prospective study included 44 adult patients (24 men, 20 women) with a mean age of 48.90+/-7.69 years and mean body mass index (BMI) of 29.40+/-3.82. Ten patients had a history of diabetes. Serological markers for viral hepatitis were negative in all patients and there was no history of alcohol or drug abuse. Patients who had autoimmune hepatitis were excluded from the study. Liver biopsy was performed before therapy to confirm the diagnosis. Among NASH patients, 17 normolipidemic cases received UDCA 13 to 15 mg/kg/day (group 1), while hyperlipidemic cases (n=27) received atorvastatin 10 mg/day (group 2) for six months. The BMI, serum lipids, liver function tests and liver density, assessed by computerized tomography, were evaluated before and after the treatment period. The BMI, serum aminotransferase levels, histological parameters (steatosis, inflammation, fibrosis scores) and liver densities were not statistically different between the groups at the beginning of therapy. RESULTS: The BMI, serum glucose, and triglyceride levels did not change in either group after the treatment period. In group 1, serum alanine aminotransferase (ALT) and gamma-glutamyl-transferase (GGT) levels reduced significantly, and in group 2, serum cholesterol, aspartate aminotransferase, ALT, alkaline phosphatase and GGT levels reduced significantly. Liver densities increased only in group 2, probably as a result of diminishing fat content of liver. The normalization of transaminases was also more prevalent in group 2. Liver steatosis was closely correlated with liver density, but inflammation and fibrosis were not. CONCLUSIONS: The use of atorvastatin in NASH patients with hyperlipidemia was found to be both effective and safe. The benefit of statin and UDCA therapy in normolipidemic patients with NASH requires confirmation with further placebo-controlled trials.

Fas antigen (CD95) expression and apoptosis in hepatocytes of patients with chronic viral hepatitis.

BACKGROUND: Apoptosis may be defined as programmed cell death. It is involved in the normal development and homeostasis of tissues in multicellular organisms. An increased or decreased rate of apoptosis may lead to a range of diseases. Fas antigen is a cell-surface receptor that induces apoptotic pathways when treated with Fas ligand or anti-Fas antibody. There is increasing evidence that apoptosis plays an important role in the immunopathogenesis of chronic viral hepatitis, in which the Fas antigen-Fas ligand pathway is particularly involved. METHODS: Fas antigen expression and apoptosis (apoptotic index) were assayed using flow cytometry in the hepatocytes of 27 patients with chronic viral hepatitis. Histopathological activity, scored by Knodell's histological activity index, other histopathological parameters, serum transaminase values and patient age were then compared with apoptotic index and Fas antigen expression. RESULTS: Apoptosis and Fas antigen expression in hepatocytes were correlated closely with histological activity (grade) of chronic viral hepatitis, but there were no correlations with histological stage, patient age or serum transaminase levels. CONCLUSION: Apoptosis and its triggering molecule, Fas antigen, induce mechanisms that appear to be associated with the pathogenesis of chronic viral hepatitis.