Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS) is closely associated with an increased risk of cardiovascular disease. Fetuin-A is associated with MetS and NAFLD. We investigated the relationship of circulating fetuin-A level with markers of endothelial dysfunction and presence of carotid atherosclerosis in subjects with NAFLD. METHODS: The consecutive 115 patients with NAFLD and age-matched 74 healthy subjects were enrolled. Plasma levels of fetuin-A and markers of endothelial dysfunction [asymmetric dimethyl arginine (ADMA) and adiponectin] were measured by ELISA method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. Carotid artery intima-media thickness (cIMT) was assessed by high-resolution ultrasonography. RESULTS: Fetuin-A and ADMA were higher and, adiponectin was lower in NAFLD group than the control group (P = 0·004, P < 0·001 and P < 0·001, respectively). In addition, NAFLD group had greater cIMT measurements than the controls (P < 0·001). However, no difference was found for fetuin-A, ADMA, adiponectin and cIMT between two groups when the findings were adjusted according to the glucose, lipids and HOMA-IR index. In correlation analysis, fetuin-A was found to be positively correlated with triglyceride (r = 0·23, P = 0·001), HOMA-IR (r = 0·29, P < 0·001), ADMA (r = 0·24, P = 0·001), cIMT (r = 0·3, P = 0·003) and, negatively correlated with HDL-C (r = -0·17, P = 0·02) and adiponectin (r = -0·19, P = 0·01) levels. Multiple linear regression analysis showed that fetuin-A was independently associated with ADMA and cIMT levels. CONCLUSION: This study demonstrated for the first time that circulating fetuin-A in NAFLD is independently associated with endothelial dysfunction and subclinical atherosclerosis.

Association of plasma visfatin with hepatic and systemic inflammation in nonalcoholic fatty liver disease.

BACKGROUND: Visfatin is a proinflammatory and insulin-mimetic adipokine contributing to whole body glucose and lipid metabolism. Studies to date are conflicting regarding the relationship between visfatin and non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the relationship of circulating visfatin with NAFLD. MATERIAL AND METHODS: The study included 114 NAFLD patients and 60 healthy non-diabetic controls. Plasma visfatin, adiponectin, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels were measured by ELISA. High sensitive C-reactive protein (hsCRP) levels were measured by immunoturbidimetric fixed rate method. Insulin sensitivity determined by homeostasis model assessment (HOMA-IR) index. RESULTS: TNF-α, IL-6 and hsCRP levels were higher and, Adiponectin levels were lower in NAFLD group when compared to healthy controls (p < 0.001, for all). However, no difference was found regarding to visfatin levels between two groups. Different histologic subgroups of NAFLD had a significantly higher TNF-α, IL-6 and hsCRP, and lower adiponectin levels than those with controls (p < 0.001, for all). On the other hand, no statistically significant difference was found regarding to visfatin levels among different histologic groups. Visfatin was found to be negatively correlated with TNF-α (r = -0.236, p = 0.011) in NAFLD group. However, no association was found between visfatin and histological findings. CONCLUSION: Our findings show that plasma visfatin levels are not altered in the early stages of NAFLD. However, it is inversely associated with TNF-α. These findings suggest a role for visfatin in protection against liver injury in this widespread disease.

Efficacy of a modified sequential therapy including bismuth subcitrate as first-line therapy to eradicate Helicobacter pylori in a Turkish population.

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are not satisfactory. Sequential therapy is an alternative method to overcome this problem. OBJECTIVES: The aim of this study was to assess efficacy of a modified sequential therapy with the addition of a bismuth preparation, as first-line treatment in the eradication of H. pylori infection. MATERIALS AND METHODS: One hundred and forty-two H. pylori-positive patients were included in the study. Patients were given a 14-day sequential therapy program consisting of pantoprazole, 40 mg (b.i.d. for 14 days); colloidal bismuth subcitrate, 300 mg 4 (two tablets before breakfast and dinner, for 14 days); amoxicillin, 1 g (b.i.d.for the first 7 days); tetracycline, 500 mg (q.i.d. for the second 7 days); and metronidazole, 500 mg (t.i.d. for the second 7 days). Eradication was tested by urea breath test (UBT) 6 weeks after completion of treatment. RESULTS: Of the 142 patients included, 131 completed the study. "Per-protocol" and "intention-to-treat" analyses revealed high eradication rates in this group (92.0-95% CI, 87.2-96.8%, and 81.0-95% CI, 74.5-87.4%, respectively). There was no relation to sex and age with this modified sequential therapy. Compliance was satisfactory (11 patients - four women and seven men were unavailable for follow-up), and side effects were minimal (six patients had to stop treatment - metronidazole-related facial swelling and numbness on the face and hands in two patients; tetracycline-related fever and epigastric pain and nausea and vomiting in two patients; and amoxicillin-related diarrhea and vaginal discharge in two patients). These side effects were reversible and resolved after the cessation of the related medication. CONCLUSIONS: This 14-day modified sequential treatment, including bismuth, achieves a significantly high eradication rates in patients with H. pylori infection, with five satisfactory patient compliance and minor side effects.

Circulating vaspin and its relationship with insulin sensitivity, adiponectin, and liver histology in subjects with non-alcoholic steatohepatitis.

OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is closely associated with components of metabolic syndrome. Vaspin is a novel adipocytokine that may link obesity, insulin resistance (IR), and type 2 diabetes mellitus. We aimed to investigate circulating vaspin levels in subjects with NASH and also to search for the association of vaspin with IR, adiponectin, and histological findings. MATERIAL AND METHODS: A total of 50 male patients with NASH and 30 healthy male controls were enrolled. Vaspin and adiponectin were measured with ELISA method. Insulin sensitivity determined by homeostasis model assessment (HOMA-IR) index. RESULTS: Plasma vaspin levels were higher and adiponectin levels were lower in NASH group compared with controls (p < 0.01 and p < 0.001, respectively). However, in multivariate analysis adjusted for glucose and lipid parameters, and HOMA-IR indexes, the difference in vaspin concentrations was disappeared. Nonetheless, the difference regarding the adiponectin levels remained significant between groups (p = 0.03). Vaspin was negatively correlated with low-density lipoprotein cholesterol (r = -0.32, p = 0.03) in subjects with NASH. CONCLUSIONS: This study indicates that circulating vaspin levels are not altered in male subjects with NASH. These results suggest that in the absence of metabolic risk factors, vaspin per se may not be involved in the pathogenesis of NASH.

Yttrium-90 (Y-90) resin microsphere therapy for patients with unresectable hepatocellular carcinoma. Identification of successful treatment response predictors and patient selection.

AIM: Selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 (Y-90) resin microspheres has been applied for hepatocellular carcinoma (HCC) lately. The aim of this study is to present our clinical experience of radiomicrosphere therapy in the treatment of unresectable HCC and determine the proper cases who could benefit from this therapy according to response results yielded by initial staging and control imaging modalities. METHODS: We administered 43 Y-90 microsphere therapy to 34 patients with unresectable HCC (twice in 9 patients). Patients with histopathologically confirmed HCC having a life expectancy of ≥3 months; Child A-B, Okuda stage 1-2 and BCLC stage A-B-C classifications were included in the study. The patients were divided into two groups: Group A consisted of 29 patients who responded to Y-90 therapy (complete response, partial response and stable disease), Group B 5 of non-responders (progressive disease). Predefined parameters were evaluated for response to SIRT and compared between two groups. RESULTS: We found a significant decrease in platelet and lymphocyte counts one month after therapy (p=0.02, p=0.01, respectively). On control imaging tests performed 3 months later, we observed complete response in 19% (n=6), partial response in 44% (n=15), stable disease in 25% (n=8) and progressive diease in 12% (n=5) of the patients. Mean overall survival (OS) was 19 (median value: 14) months. CONCLUSIONS: Y-90 microsphere therapy is a safe and effective treatment option for the patients with unresectable HCC without any serious side effect. Mean tumor dose delivery and lack of bilobar disease seem the best predictors for treatment success. KEY WORDS: Selective intraarterial Radionuclide therapy, Yttrium-90, hepatocellular carcinoma.

Betatrophin Levels Are Related to the Early Histological Findings in Nonalcoholic Fatty Liver Disease.

Betatrophin, a liver hormone, regulates glucose and lipid metabolism. We investigated the betatrophin levels in nonalcoholic fatty liver disease (NAFLD) and searched for any relationship with histological severity and metabolic parameters. Fifty males with NAFLD [Nonalcoholic Steatohepatitis (NASH) (n = 32); non-NASH (n = 18)] and 30 healthy controls were included. Plasma betatrophin was measured by ELISA method. Insulin sensitivity was assessed by HOMA-IR index. Histological features were scored by the semi quantitative classification and combined as the NAFLD activity score (NAS). Betatrophin levels in the non-NASH group were significantly higher than the controls. Betatrophin was positively correlated to the age, waist circumference, total cholesterol, triglycerides, LDL cholesterol, glucose, insulin, HOMA-IR index and gamma glutamyl transpeptidase levels, and negatively correlated to the steatosis and NAS. In the stepwise linear regression analysis, the triglyceride (ß = 0.457, p < 0.001), glucose (ß = 0.281, p = 0.02) and NAS (ß = -0.260, p = 0.03) were the independent determinants of betatrophin. Betatrophin levels are higher in the early stages of NAFLD and tend to decrease when the disease progresses. This could be an important preliminary mechanistic finding to explain the increased frequency of glucose intolerance during the course of NAFLD.

Levels of soluble CD40 ligand and P-Selectin in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of cardiovascular disease. We aimed to research whether the levels of soluble P-selectin (sP-selectin) and soluble CD40 ligand (sCD40L), markers of endothelial function, are altered in subjects with NAFLD having no confounding factors for atherosclerosis. sCD40L, sP-selectin, and high-sensitivity C-reactive protein (hsCRP) levels, and homeostasis model assessment of insulin resistance (HOMA-IR) indexes were measured in 50 NAFLD subjects and 30 healthy controls. sCD40L, sP-selectin, and hsCRP levels were not significantly different between two groups (P = 0.48, 0.51, and 0.34, respectively). Body mass index, waist circumference, and insulin levels and HOMA indexes were significantly higher in subjects with NAFLD (all P < 0.001). The present data show that sCD40L and sP-selectin may not contribute to the accelerated atherogenesis associated with this clinically relevant condition.

Elevated plasma levels of apelin in children with type 1 diabetes mellitus.

BACKGROUND: Apelin is a novel adipocytokine produced by white adipose tissue that binds the APJ receptor with high affinity. Insulin may have a role in regulation of apelin synthesis and secretion from the adipose tissue. OBJECTIVE: To investigate blood apelin concentrations in children with type 1 diabetes mellitus (T1DM) and display association of apelin with adiponectin, body mass index (BMI), lipids and insulin sensitivity. METHODS: Thirty patients with T1DM and 45 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, fasting plasma glucose, HbA1c and adiponectin levels. RESULTS: Plasma apelin and adiponectin levels were significantly higher in the diabetic group when compared to controls. No correlation was found between the apelin blood concentrations and adiponectin, BMI, lipids and insulin sensitivity. CONCLUSIONS: Children with T1DM have significantly increased circulating apelin levels when compared to healthy controls. However, no significant relation was found between the apelin and BMI, glucose, lipids and adiponectin levels, and also insulin sensitivity.

Plasma apelin and ADMA Levels in patients with essential hypertension.

Both apelin and asymetric dymethyl arginine (ADMA) regulate blood pressures. Low apelin and high ADMA levels have been reported in several cardiometabolic disorders. However, there is no data about ADMA and apelin levels in essential hypertension and any relationship between them. We investigated a group of newly diagnosed and untreated 30 young hypertensive men and 30 healthy controls. Apelin levels were significantly lower and the ADMA levels were significantly higher in the patients (p = 0.04 for both). Both ADMA and apelin were related to the systolic blood pressures (SBP) (beta = -0.393, p = 0.003; beta = 0.285, p = 0.03, respectively). Future studies are necessary in order to clearly define the role of ADMA and apelin in the pathogenesis of essential hypertension.

The COVID-19 pandemic: Clinical practice advice for gastroenterologists, hepatologists, and liver transplant specialists.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel acute infectious disease that has rapidly reached staggering pandemic proportions. This review addresses gastroenterologists, hepatologists, liver transplant (LT) specialists, and health-care professionals working in the field of liver diseases and liver transplantation. It has been written based on a limited number of publications, recommendations of national and international liver and organ transplantation societies, and experiences of patients with COVID-19 around the world. The purpose of this review is to provide information addressing questions and concerns about COVID-19, to reveal the effects of the novel disease on patients with chronic liver disease and LT recipients, and to share information about ways in which this pandemic will affect clinical practices. We, the Turkish Association for the Study of the Liver (TASL), would like to remind you that this text is actually not a practical guide. It is imperative to act according to the standards set by health-care institutions and the Ministry of Health, Republic of Turkey.

The effect of iNOS inhibitors and hyperbaric oxygen treatment in a rat model of experimental colitis.

AIM: Our aim was to investigate the effectiveness of aminoguanidine (AMG), an inducible nitric oxide synthase inhibitor, and hyperbaric oxygen (HBO) treatment in an experimental colitis model. METHODS: We induced colitis in rats. In the control group, we applied 2 ml serum physiologic intraperitoneally for 7 days. In the HBO group, 100% oxygen at 2.4 atm pressure was applied for 7 days. In the AMG group, 100 mg/kg AMG was applied intraperitoneally for 7 days. In the HBO + AMG group, HBO and AMG were applied, respectively. At the end of 7 days, rats were sacrificed and the distal 10 cm part of colon was examined macro- and microscopically. RESULTS: Severity of colitis and NO activities were reduced by AMG, HBO, and HBO + AMG application. There was histologically significant improvement, especially in the HBO + AMG group. CONCLUSIONS: Both HBO and AMG were significantly effective in preventing weight loss, reducing NO activities, and severity of colitis, when comparing HBO and AMG separately.

Yttrium-90 (Y-90) Resin Microsphere Therapy for Patients with Unresectable Hepatocellular Carcinoma: a Single-Center Experience.

BACKGROUND/AIM: Selective intraarterial radionuclide therapy (SIRT) with yttrium-90 (Y-90) resin microspheres presently has successful results in primary or metastatic inoperable liver tumors. This procedure, which is also known as radioembolisation, delivers high doses of radiation selectively to hepatic tumors while minimum healthy liver exposure. The aim of this study was to present our clinical experience of radiomicrosphere therapy for the treatment of patients with unresectable hepatocellular carcinoma (HCC). METHODS: We performed 40 Y-90 microsphere therapies in 28 patients (5 females, 23 males; mean age ± SD 48 ± 8) with HCC during the period from April 2008 through December 2016. Pretreatment Tc-99m microaggregated albumin (MAA) scintigraphy was performed to all patients in order to detect eligibility for SIRT. All patients had pre- and post-biochemical tests (hemogram and serologic tests) and imaging methods (CT or MRI or PET/CT) at regular intervals to detect any possible complication and determine response rates. RESULTS: The mean shunting to the lungs on MAA scan was 6.5% and the mean ± SD administered dose of Y-90 was 1.55 ± 0.32 GBq in all patients. The estimated doses to the target tumors, normal liver parenchyma and lungs were 105.7 ± 55.3, 25.5 ± 8.2 and 5.8 ± 1.7 Gy, respectively. No significant complication was observed during or early after (first week) the treatment procedure and it was well tolerated by all the patients. Only one patient developed a treatment-related gastroduodenal ulcer 3 weeks after the treatment. In control imaging tests (MRI or FDG PET/CT) performed 2.5 months after the treatment, we observed complete response in 2 (7%) patients, partial response in 10 (36%) patients, stable disease in 5 (18%) patients and progressive disease in 11 (39%) patients. CONCLUSION: According to our clinical experience, we can conclude that Y-90 microsphere therapy is a safe and effective treatment option for the patients with unresectable HCC without any serious side effects.

The relationship between blood urea nitrogen levels and metabolic, biochemical, and histopathologic findings of nondiabetic, nonhypertensive patients with nonalcoholic fatty liver disease.

BACKGROUND/AIM: Nonalcoholic fatty liver disease (NAFLD) is known as the most common cause of chronic liver disease. It is accepted that the leading cause of death in patients with NAFLD is from coronary events. Blood urea nitrogen (BUN) was used as a prognostic indicator for cardiovascular disease. We aimed to investigate the relationship between BUN levels and metabolic, biochemical, and histopathologic findings of nondiabetic patients with NAFLD. MATERIALS AND METHODS: A total of 195 male patients with biopsy proven NAFLD and 82 healthy controls with normal liver and renal function tests and normal abdominal ultrasonography were enrolled in the study. BUN levels were reviewed retrospectively. RESULTS: The mean BUN levels of patients and controls were 13.07 (11.3-15.41) and 13.31 (10.97-15.87) mg/dL respectively. Patients were grouped as simple steatosis (n = 33, 16.9%), borderline nonalcoholic steatohepatitis (n = 64, 32.8%), and nonalcoholic steatohepatitis (n = 98, 50.3%), and the BUN levels of the histologic subgroups were 13.14 ± 2.89, 14.34 ± 3.04, and 13.71 ± 3.21 mg/dL, respectively. We could not find any differences between the patient group and control group with respect to BUN levels. CONCLUSION: Our findings showed that there was no relationship between BUN levels and metabolic, biochemical, and histopathologic findings of patients with NAFLD. Further investigations, including in patients with late stages of NAFLD, are required.

The relationship of circulating fetuin-a with liver histology and biomarkers of systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Fetuin-A, a glycoprotein with anti-inflammatory properties, plays an important role in counter-regulating inflammatory responses. It has also been associated with insulin resistance and metabolic syndrome. We aimed to investigate circulating concentrations of fetuin-A and its possible association with hepatic and systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease (NAFLD). PATIENTS AND METHODS: We included 105 nondiabetic male subjects with NAFLD [nonalcoholic steatohepatitis (NASH, n = 86) and simple steatosis (SS, n = 19)]. Plasma levels of fetuin-A and markers of inflammation [high-sensitive C reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and adiponectin] were measured by enzyme-linked immunosorbent assay method. Insulin sensitivity was determined by homeostasis model assessment of insulin resistance (HOMA-IR) index. RESULTS: Fetuin-A was negatively correlated with age (r = -0.27, P = 0.006), however there was no association between fetuin-A and body mass index, waist circumference (WC), glucose, insulin, HOMA-IR, lipid parameters, and inflammatory markers. In addition, no significant association was observed between fetuin-A and histological findings including liver fibrosis. CONCLUSION: This study demonstrated that plasma fetuin-A levels are not correlated with the hepatic histology and systemic markers of inflammation in nondiabetic subjects with NAFLD. Our data also suggested that age is significantly associated with fetuin-A in this clinically relevant condition.