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The Clinical Significance of Serum Apoptotic Cytokeratin 18 Neoepitope M30 (CK-18 M30) and Matrix Metalloproteinase 2 (MMP-2) Levels in Chronic Hepatitis B Patients with Cirrhosis.

Background Serum apoptotic cytokeratine 18 neoepitope M30 (CK-18 M30) and matrix metalloproteinase 2 (MMP-2) have been popular markers for detecting liver fibrosis in recent years. CK-18 is a major intermediate filament protein in liver cells and one of the most prominent substrates of caspases during hepatocyte apoptosis. MMP-2 plays an important role in tissue remodeling and repairing processes during physiological and pathological states. Objectives The objective of this study was to investigate the significance of CK-18 M30 and MMP-2 levels for clinical use in patients with chronic hepatitis B (CHB), as well as their sensitivity in determining cirrhotic patients. Patients and Methods This study included 189 CHB patients and 51 healthy controls. A modified Knodell scoring system was used to determine the fibrosis level in chronic hepatitis B patients. CK-18 M30 levels were determined with an M30-Apoptosense ELISA assay. MMP-2 levels were determined with the ELISA assay. Results The study group consisted of 132 (69.8%) males and 57 (30.2%) females, and the control group consisted of 25 males (49.0%) and 26 females (51%). Patients’ CK-18 M30 levels were higher than values of the control group (308 [1–762] vs. 168 [67–287], P=0.001). Serum MMP-2 levels were found to be statistically higher in the patient group with respect to the controls (3.0 [1.1–6.8] vs. 2.0 [1.2–3.4], P=0.001). The highest serum CK-18 M30 and MMP-2 levels were measured in patients with cirrhosis. Serum apoptotic CK-18 M30 levels positively correlated with advanced age, fibrosis stage, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P= 0.001, 0.033, 0.001, and 0.001, respectively). Serum MMP-2 levels positively correlated with fibrosis stage, serum ALT, and AST levels (P= 0.001, 0.001, and 0.001, respectively). Conclusions Our study indicated that CK-18 M30 and MMP-2 levels were higher in CHB patients compared to healthy controls and they were in association with significant hepatic fibrosis, especially cirrhosis.

Impaired thiol-disulphide balance in acute brucellosis

The objective of this study was to examine a novel profile: thiol-disulfide homeostasis in acute brucellosis. The study included 90 patients with acute brucellosis, and 27 healthy controls. Thiol-disulfide profile tests were analyzed by a recently developed method, and ceruloplasmin levels were determined. Native thiol levels were 256.72 ± 48.20 μmol/L in the acute brucellosis group and 461.13 ± 45.37 μmol/L in the healthy group, and total thiol levels were 298.58 ± 51.78 μmol/L in the acute brucellosis group and 504.83 ± 51.05 μmol/L in the healthy group (p < 0.001, for both). The disulfide/native thiol ratios and disulfide/total thiol ratios were significantly higher, and native thiol/total thiol ratios were significantly lower in patients with acute brucellosis than in the healthy controls (p < 0.001, for all ratios). There were either positive or negative relationships between ceruloplasmin levels and thiol-disulfide parameters. The thiol-disulfide homeostasis was impaired in acute brucellosis. The strong associations between thiol-disulfide parameters and a positive acute-phase reactant reflected the disruption of the balance between the antioxidant and oxidant systems. Since thiol groups act as anti-inflammatory mediators, the alteration in the thiol-disulfide homeostasis may be involved in brucellosis.

A retrospective controlled study of thiol disulfide homeostasis as a novel marker in Crimean Congo hemorrhagic fever

Objectives: Crimean Congo hemorrhagic fever (CCHF) is the second most common hemorrhagic fever worldwide. This study aimed to evaluate the oxidant–antioxidant balance of patients with CCHF by detecting dynamic thiol disulfide homeostasis (TDH), which is a novel oxidative stress marker, and other molecules, including paraoxonase (PON), arylesterase (ARES), ceruloplasmin (CLP), myeloperoxidase (MPO), and catalase. Methods: This retrospective, cross-sectional, controlled study, which involved patients with CCHF and healthy volunteers, measured dynamic TDH using a novel automated method developed by Erel. Results: We recruited 69 adult patients with CCHF (31 females, 38 males, median age 46 years). The case fatality rate was 1.49% (1/69). Increased disulfide/native thiol and disulfide/total thiol ratios, decreased total antioxidant status (TAS), and increased total oxidant status (TOS) were found in patients with CCHF. TAS, PON, and ARES values were found to be positively correlated with both native and total thiol levels, whereas TOS and CLP were negatively correlated with both, at a significant level. MPO activity was similar in both groups. Discussion: This is the first study in the literature to evaluate dynamic TDH in CCHF. TDH shifts to the oxidative side in patients with CCHF, leading to an increase in TOS.

Are bone morphogenetic protein-7 (BMP-7) serum levels correlated with development of hepatic fibrosis?

INTRODUCTION Bone morphogenetic protein-7 (BMP-7) is a key protein in organogenesis and liver development. The protein has been studied in the context of liver fibrosis and regeneration. The aim of the present study was to explore any possible association between fibrosis levels (as revealed by liver biopsy) and serum BMP-7 levels. METHODOLOGY A total of 189 patients with chronic hepatitis B and 51 healthy controls were enrolled in the study. RESULTS The study group contained 120 (63.5%) males and 69 (36.5%) females, and the control group contained 25 males (49.0%) and 26 females (51%). In general, serum BMP-7 values of patients were higher than those of controls (p = 0.001). Serum BMP-7 values of patients with liver fibrosis of stages 1, 2, 3, or 4 were higher than control values (all p values = 0.01), but the serum BMP-7 levels of patients with stage 5 fibrosis were similar to that of controls. Associations between fibrosis stage and the serum levels of BMP-7, ALT, HBVDNA, platelets, and albumin were all statistically significant (p = 0.001). The AUROC for the BMP-7 level in advanced stage fibrosis was found to be 0.23. The data were analyzed using the binary logistic regression analysis (backward stepwise method) and BMP-7, HBVDNA, and platelet levels were found to be risk factors associated with fibrosis (p values 0.031, 0.040, and 0.001, respectively). CONCLUSIONS BMP-7 may play anti-inflammatory and anti-fibrogenic roles in the pathogenesis of chronic hepatitis B infection.

Is serum high-mobility group box 1 (HMGB-1) level correlated with liver fibrosis in chronic hepatitis B?

Background: High-mobility group box 1 (HMGB1), identified as an alarmin molecule, was shown to have a role in virus-triggered liver injury. We aimed to evaluate the association between serum levels of HMGB1 and liver fibrosis. Method: This cross-sectional case-control study included 189 chronic hepatitis B (CHB) patients and 51 healthy controls. All patients underwent liver biopsy and modified Knodell scoring system used to determine the fibrosis level in CHB patients. Serum HMGB1 levels were determined with enzyme-linked immunosorbent assay (ELISA). Results: Mean serum HMGB1 levels of patients (58.1 ± 54.7) were found to be higher than those of the control group (7.1 ± 4.3) (P = .001). HMGB1 levels of patients with advanced-stage fibrosis (stage 4 and 5) were detected to be higher than those of patients with early-stage fibrosis (stage 1–3). However, this difference was not statistically significant (P > .05). Albumin levels of fibrosis 3 and 4 patients were lower than fibrosis 1 and 2 patients. ALT, HBV DNA, and AFP levels of fibrosis 5 patients were significantly higher than fibrosis 1 and 2 patients, and their platelet and albumin levels are lower than fibrosis 1 and 2 patients (P < .001). In a logistic regression model, fibrosis levels were correlated with ALT values and inversely correlated with albumin levels. Conclusion: In this study, we demonstrated that serum HMGB1 levels increase in the early course of liver injury and this increase is not correlated with severity of the liver damage.

Evaluation of the Relation Between Hepatic Fibrosis and Basic Laboratory Parameters in Patients With Chronic Hepatitis B Fibrosis and Basic Laboratory Parameters

Background: The hepatitis B virus is an important healthcare problem. According to current clinical practice, a liver biopsy is required for the diagnosis and treatment of chronic liver disease. However, a liver biopsy is an invasive, inconvenient procedure, which requires an expert pathologist opinion. Therefore requirement of biochemical tests, which are considered to indicate hepatic fibrosis and may be repeated easily, increases gradually today. Objectives: This study evaluated the correlation between hepatic fibrosis and routine laboratory values in patients with chronic hepatitis B. Patients and Methods: The files of 456 patients with CHB (chronic hepatitis B) who were referred to the infectious diseases and clinical microbiology clinic between January 2009 and March 2012 were screened retrospectively. Liver biopsy samples were examined according to Ishak scoring. Laboratory parameters and histopathology reports were recorded, and correlations between the fibrosis grade and laboratory parameters were analyzed. Results: There were 320 male and 136 female patients, with a mean age 36.7 ± 12.1 years. According to liver biopsy results, a low fibrosis score (stage 0-2) was detected in 281 patients (61.6%), and a high fibrosis score (stage 3-5) was detected in 175 patients (38.4%). Patients with a high fibrosis score had significantly higher ALT (alanine amino transferase), AST (aspartate aminotransferase), and HBV-DNA values and a significantly lower platelet count compared with those with a low fibrosis score (P = 0.001, 0.001, 0.025, and 0.001, respectively). A positive correlation was detected between the fibrosis score and age, BMI, HAI, ALT, and AST values, and a negative correlation was detected between the fibrosis score and albumin and platelet counts. In the regression analysis performed to evaluate the factors associated with high-stage fibrosis, fibrosis was determined to be associated with thrombosis, ALT, and gender. The results of the regression analysis demonstrated that the risk of fibrosis was 4.6 fold higher in men. Conclusions: According to the results obtained in our study, advanced age, higher BMI, AST, ALT, and HBV-DNA levels, and low albumin and platelet levels are correlated with advanced fibrosis in patients with CHB.

Transfusion Transmitted Virüs (TTV) Prevalansı İnaktif Hepatit B Taşıyıcılarında Hemodiyalizden Etkileniyor Mu

Objective: Inthisstudy, it was aimed to determine the prevalence of Transfusion Transmitted Virus (TTV) virus in inactivated hepatitis B carriers with and without hemodialysis treatment. Materials and Methods: This study was conducted on 50 inactive hepatitis B patients treated with hemodialysis and 40 inactive hepatitis B patients with normal renal function. Anti-TTV IGG was studied with ELISA kit from serum samples taken from patients. Data were evaluated by Chi-square test. Results: Anti-TTV IGG positivity was detected in 39 (78%) of 50 hemodialysis patients while Anti-TTV IGG positivity was detected in 8 (20%) of 40 inactivated hepatitis B patients without hemodialysis. This difference was statistically significant (p=0.001). Conclusion: We think that standard measures for cleaning, disinfection and infection control should be applied more carefully in these units in order to prevent transmission of hepatitis viruses because of the high TTV seropositivity in hemodialysis patients.

SERUM LEVELS OF ANNEXIN A2 AS A CANDIDATE BIOMARKER FOR HEPATIC FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B

Background: Hepatologists have studied serologic markers of liver injury for decades. Annexins are a prominent group of such markers and annexin A2 (AnxA2) is one of the best characterized annexins. AnxA2 inhibits HBV polymerase among other functions. Its expression is up-regulated in regenerative hepatocytes. Objectives: To determine if serum AnxA2 level has a role in estimating liver damage in chronic HBV infection and investigate whether AnxA2 levels correlate with hepatic fibrosis. Patients and Methods: This study included 173 patients with chronic hepatitis B (CHB) and 51 healthy controls. Liver fibrosis was graded histologically on liver biopsy samples. Blood samples were taken from patients during biopsy and serum AnxA2 levels were measured with ELISA. Results: In a group of adult patients with CHB, AnxA2 values were far higher than those of the control group (P = 0.001). When we assessed AnxA2 levels based on fibrosis stages, serum AnxA2 levels of patients with early stage fibrosis (stages 1 - 3) were significantly higher than those of patients with advanced stage fibrosis (stages 4 - 5; P = 0.001). Conclusions: AnxA2 is a useful biomarker for early stage fibrosis in patients with CHB.

Evaluation of 48-week response of treatment-naive chronic hepatitis B patients to 0.5 mg/day entecavir

AIM The hepatitis B virus (HBV) is an important healthcare problem. Chronic hepatitis B infection may present with a wide range of manifestations from inactive carrier state to cirrhosis and hepatocellular cancer. Therefore, treatment is very important in chronic hepatitis B. In this study, the treatment results of 199 chronic hepatitis B patients taking entecavir 0.5 mg/day for 48 weeks were evaluated. MATERIALS AND METHODS This study retrospectively evaluated data of 199 treatment-naive chronic hepatitis B patients who were treated with entecavir. RESULTS Of the 199 treatment-naive chronic hepatitis B patients, 141 (70.9%) were males and 58 (29.1%) were females, and mean age of the whole group was 37.5 ± 12.1 years. HBeAg was positive in 91 (45.7%) and antiHBe was positive in 108 (54.3%) patients. Mean HBV DNA value was 666,449,365.5 ± 2,759,013,996.9 IU/mL, mean ALT value was 112.1 ± 95.7 U/L, and mean AST value was 95.3 _ 71.2 U/L. At week 24 of the treatment, HBV DNA levels were below 50 IU/mL in 56% of the HBeAg-positive and 76% of the HBeAg-negative patients. At week 48 of the treatment, HBV DNA levels were below 50 IU/mL in 79% of the HBeAg-positive and 87% of the HBeAg- negative patients. At week 24, ALT had normalized in 72% of the HBeAg-positive and 79% of the HBeAg-negative patients. At week 48, ALT had normalized in 89% of the HBeAg-positive and 88% of the HBeAg-negative patients. AntiHBe seroconversion was seen in 2 of 91 patients (2.2%), but the loss of HBsAg was never observed. CONCLUSION The 48-week entecavir treatment at a dose of 0.5 mg/day was shown to be effective both for HBeAg-positive and negative patients.

Seropositivity of Delta Hepatitis in HBsAg Positive Patients in Adıyaman Province

ABS TRACT Objective: This study was planned to detect incidence of delta virus in Adıyaman because the city is in Southeastern region of Turkey where no previous study was performed on this topic. Materials and Methods: Total 462 patients whom 112 chronic hepatitis B patients and 350 inactive hepatitis B carriers who admitted to the hospital between January 2010 and June 2012 were retrospectively evaluated. Results: Anti-HDV positivity was detected in 15 of 462 patients (3.1%). HDV-RNA positivity was detected in 8 of these 15 patients. Conclusion: Anti-HDV positivity rate in Adıyaman was lower than respective data in our country. (Viral Hepatitis Journal 2012; 19(1): 8-10)