The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort.

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC.

Primary pancreatic hydatid disease: A rare presentation of echinococcosis.

Hydatid disease is a zoonotic parasitic disease which rarely involves pancreas primarily. Diagnosis of pancreatic hydatid cyst is a challenge and operative skills are important to avoid spillage of cyst's content. A 19-year-old male patient was admitted to hospital with recurrent abdominal pain which was on epigastrium and left upper quadrant of abdomen. Pain was not associated with nausea, vomiting or fever. An abdominal computed tomography (CT) scan was ordered. As a result of abdominal CT scan, there was a cystic area in tail of pancreas with a diameter of 5.6 cm which includes septa and there was calcification on borders of the cyst. Possible diagnosis were either pancreatic hydatid disease, pancreatic cyst adenoma or cystadenocarcinoma or pseudocyst of autoimmune pancreatitis. Whole body positron emission tomography (PET-CT) scan showed no other cyst or lesion other than pancreatic cyst. Hydatid disease indirect hemagglutination test has been studied and it was positive. Imaging studies and laboratory results were suggested hydatid disease and laparoscopic distal pancreatectomy has been applied. Primary pancreatic hydatid disease should be in differential diagnosis when newly appearing pancreatic cyst has been diagnosed, especially in endemic areas. Appropriate surgical technique has to be applied to avoid dissemination of cyst's content.

The effect of sarcopenia and serum myokines on prognosis and survival in cirrhotic patients: a multicenter cross-sectional study.

OBJECTIVE: Sarcopenia is one of the most significant contributors to morbidity in patients with chronic liver disease. Serum myokines are potential biomarkers for detecting early sarcopenia. We aimed to investigate the relationship between serum myokines and cirrhosis-related mortality in the early stages of the disease. METHODS: In total, 262 patients and 50 healthy controls were enrolled in this study, which was designed as a multicenter cross-sectional study. At the beginning of the study, sarcopenia was defined by computed tomography scans using the third lumbar vertebra skeletal muscle index. Serum myostatin, irisin, and follistatin levels, nutritional status of the patients, and muscle strength as measured by the handgrip test were recorded. Cirrhosis-related mortality and overall survival were evaluated in the fourth year of the study as the second checkpoint of cross-sectional analysis. RESULTS: A total of 145 (55.3%) patients were diagnosed with sarcopenia. Multivariate analysis revealed that low BMI, high levels of myostatin, and decreased irisin levels were independent predictors of sarcopenia. While serum irisin level was the most predictive parameter in terms of 4th-year cirrhosis-related mortality in the CHILD A group, serum myostatin levels were found more indicative in the CHILD BC group regardless of sarcopenia status ( P < 0.001). CONCLUSION: Serum myostatin levels predict sarcopenia in all stages of cirrhosis. Serum irisin levels can also be used as a potential biomarker to predict both treatable sarcopenia and cirrhosis-related mortality in CHILD A patients.

The Efficiency of Fractional Anisotropy, Apparent Diffusion Coefficient, and Contrast Enhancement Index in Liver Fibrosis Staging.

Objectives: Even though magnetic resonance imaging has been described as the most effective imaging method for the diagnosis of liver fibrosis, an accepted magnetic resonance imaging (MRI) technique is yet to be defined. The aim of this study is to determine the efficiency of MRI in the staging of liver fibrosis. Methods: Patients with chronic hepatitis B infection and had upper abdominal MRI with hepatocyte specific contrast agent were evaluated. Twenty-nine patients that had undergone liver biopsy were included in the study. ADC, FA, and signal intensity values of liver parenchyma were measured by two observers and contrast enhancement index (CEI) was calculated as well. Patients were grouped as early (A) and late fibrosis(B) according to Ishak grading system and then the correlations between the stage and MRI findings were analysed. The intraclass correlation coefficient was used to analyze the inter-rater agreements. ADC, FA, and CEI were compared with Student t-test between early and late fibrosis groups. Pearson's correlation was used to assess the correlation between ADC and FA values. Spearman correlation was used to evaluate the relationship between pathologic fibrosis grade and MRI parameters that were measured. Results: Twenty-two patients were staged as 1 and 2 (group A), seven patients were staged as 3 and above fibrosis(group B). Statistically, there was a strong, negative correlation between the FA values and the degree of fibrosis (r=-0.582, p=0.001). There was no correlation between the CEI and hepatocyte activity index (r=-0.88, p=0.655) and degree of fibrosis (r=0.0001, p=0.997). In terms of FA values, there was a statistically significant difference between two groups (group A=0.429 ± 0.06, group B=0.349 ± 0.06) (p=0.004). Conclusion: Correlation of FA values with fibrosis stage and significant difference in FA values between early-late stage fibrosis patients shows that diffusion tensor imaging can be a promising technique in the staging and follow-up of liver fibrosis.

A New Risk-Scoring System for Colorectal Cancer and Polyp Screening by Turkish Colorectal Cancer and Polyp Study Group.

BACKGROUND: Colorectal cancer is one of the most commonly diagnosed types of cancer worldwide. An early diagnosis and detection of colon cancer and polyp can reduce mortality and morbidity from colorectal cancer. Even though there are a variety of options in screen- ing tests, the question remains on which test is the most effective for the early detection of colorectal cancer. In this prospective study, we aimed to develop a simple, useful, effective, and reliable scoring system to detect colon polyp and colorectal cancer. METHODS: We enrolled 6508 subjects over the age of 18 from 16 centers, with colonoscopy screening. The age, smoking status, alcohol consumption, body mass index, polyp incidence, polyp size, number and localization, and pathologic findings were recorded. RESULTS: The age, male gender, obesity, smoking, and family history were found as independent risk factors for adenomatous polyp. We have developed a new scoring system which can be used for these factors. With a score of 4 or above, we found the following: sensitivity 81%, specificity 40%, positive predictive value 25.68%, and negative predictive value 89.84%, for adenomatous polyp detection; and sensitivity 96%, specificity 39%, positive predictive value 3.35%, negative predictive value 99.29%, for colorectal cancer detection. CONCLUSION: Even though the first colorectal cancer screening worldwide is generally performed for individuals over 50 years of age, we recommend that screening for colorectal cancer might begin for those under 50 years of age as well. Individuals with a score ≥ 4 must be included in the screening tests for colorectal cancer.

The effectiveness of small heterodimer partner and FGF 19 levels in prediction of perinatal morbidity in intrahepatic cholestasis of pregnancy.

Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules responsible for controlling serum bile acid levels. We designed this study for evaluating the effects of FGF 19 and SHP in intrahepatic cholestasis of pregnancy (ICP). Fifty-six pregnant women having ICP and 20 healthy pregnant women were included in the study. The patients were followed up until delivery in terms of pregnancy-related morbidity/mortality. Serum FGF 19 and SHP levels were determined by enzyme-linked immunosorbent assay (ELISA). Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group (p: .04, p: .003, respectively). In ROC analysis, SHP level above 1995 ng/L was found effective in predicting the need for neonatal intensive care unit (ICU) follow-up with 53.8% sensitivity and 77.8% specificity. High SHP levels were correlated with perinatal morbidity, mortality and neonatal ICU hospitalisation.Impact StatementWhat is already known on this subject? Itching, elevated serum transaminase and serum total bile acid (TBA) levels are the most important clinical and biochemical findings of intrahepatic cholestasis of pregnancy (ICP). Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules - responsible for controlling serum bile acid levels. ICP is associated with preterm labour, asphyxia, foetal distress, stillbirth and preeclampsia.What do the results of this study add? Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group. High SHP level was found effective in predicting the need for neonatal intensive care unit and showed a negative correlation with birth week and birth weight.What are the implications of these findings for clinical practice and/or further research? Checking SHP levels can help to predict perinatal mortality and morbidity. Treatments to be developed through the mechanism of action of FGF 19 and SHP can be promising in the treatment of ICP and other cholestatic liver diseases.

Serum fibrosis markers could aid in the prediction of factor for successful oral antiviral treatment in hepatitis C.

BACKGROUND: It has been demonstrated that there may be a relationship between liver fibrosis and serum biomarkers. The aim of this study was to investigate pre- and postoral antiviral therapy levels of these biomarkers and their relationship with other fibrotic parameters in hepatitis C virus (HCV) patients. METHODS: The study group comprised HCV patients who were treated with oral antiviral regimens. Prior to, and 8 months after the treatment, serum biomarkers, including transforming growth factor-ß (TGF-ß), chitinase-3-like protein 1 (YKL-40), collagen type IV, matrix metalloproteinases (MMPs) and hyaluronic acid levels, were examined and fibrosis-4 (Fib-4) and aspartate aminotransferase to platelet ratio index (APRI) scores were calculated at the same times. RESULTS: In total, 45 HCV patients (aged between 27 and 86 years) participated. Of these 20 (44.4%) were cirrhotic and 25 (55.6%) were noncirrhotic. The concentrations of YKL-40 (P = 0.01) and TGF-ß (P = 0.032) after treatment were significantly higher than the pretreatment values, whereas hyaluronic acid concentrations decreased after treatment (P = 0.001). Noncirrhotic patients had significantly higher (P = 0.03) YKL-40 levels prior to therapy compared to cirrhotic patients. Median MMP-2 concentrations were higher in men than in women (P = 0.001). Prior to treatment, TGF-ß, YKL-40 and collagen type IV levels were negatively correlated with Fib-4 scores, whereas only TGF-ß and YKL-40 concentrations were negatively correlated with APRI scores. CONCLUSION: YKL-40, TGF ß and hyaluronic acid may be markers for fibrotic change during oral therapy for HCV. In particular, TGF ß concentrations correlated with fibrotic indices. However, these results should be confirmed and validated by further research.

Liver and pancreas: 'Castor and Pollux' regarding the relationship between hepatic steatosis and pancreas exocrine insufficiency.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is found in 30-50% of diabetes mellitus (DM). Insulin resistance is triggering factor in both DM and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to investigate frequency of PEI in NAFLD, and relationship of fecal pancreatic elastase (PE) levels with liver histology and pancreatic fat. METHODS: Ninety-seven biopsy proven NAFLD patients and 50 controls were enrolled. Pancreas exocrine functions were measured by PE. Magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) was used to quantify fat. RESULTS: NAFLD patients had significantly lower PE levels than controls (297 [204-517] vs. 500 [298-678] µg/g, p < 0.01). PEI (PE < 200 µg/g) ratio of NAFLD patients (22.7%, n = 22) was higher than PEI ratio of controls (6%, n = 3) (p = 0.011). Among diabetic (n = 35) NAFLD patients, 9 (25.7%) exhibited PEI, compared to 13 (21%) of non-diabetics. There was no significant difference in patients with and without DM in terms of PEI (p = 0.592). Among NASH (n = 68) patients 16 (23.5%) exhibited PEI, compared to (20.7%) of non-NASH (p = 0.76). Multiple analysis revealed NAFLD as a predictor of PEI independent of age, sex and DM (OR = 4.892, p = 0,021). Mean pancreas MRI-PDFF was significantly higher in diabetics (13.7% ± 3.6% vs. 8.7% ± 5.1%, p = 0.001). There was no significant pancreas MRI-PDFF difference between NASH and non-NASH (P = 0.95). Mean pancreas MRI-PDFF was significantly higher in patients with PEI (13.7% ± 3.4% vs. 8.9% ± 5.2%, P < 0.01). CONCLUSION: This is the first study demonstrating the high frequency of PEI in NAFLD independent of DM. Moreover, increasing pancreatic steatosis appears to be associated with higher frequency of PEI in NAFLD.

Real-world efficacy and safety of Ledipasvir + Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience.

BACKGROUND/AIMS: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population. MATERIAL AND METHODS: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)±ribavirin (RBV) orombitasvir/paritaprevir/ritonavir±dasabuvir (PrOD)±RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed. RESULTS: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90±54.60 U/L to 17.00±14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51±4.54 to 7.32±3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0±16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%). CONCLUSION: LDV/SOF or PrOD±RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.

Changes in Liver Tissue Trace Element Concentrations During Hepatitis B Viral Infection Treatment.

Approximately 350-400 million people in the world have Hbs Ag (hepatitis B virus surface antigen) positivity. In the international guidelines, the permanent suppression of replication in chronic hepatitis B virus (HBV) infection therapy is reported as the primary therapeutic goal. Trace elements play a key role in liver diseases. The aim of our study is to determine some trace element concentrations in the liver during HBV treatment periods. The measurement of 11 trace elements (manganese, lead, nickel, chromium, cadmium, iron, copper, zinc, silver, cobalt, and aluminum) was carried out by the method of inductively coupled plasma mass spectrometry in liver biopsy materials (before starting treatment and at the sixth month of the treatment period). There was an increase in zinc and copper concentrations in liver materials at the sixth month of treatment compared to the pre-treatment values (the median zinc value was 48.05 µg/g before treatment and 74.9 µg/g at 6 months after initial treatment, p = 0.035; median copper was 2.82 µg/g before treatment and 5.31 µg/g after 6 months, p = 0.002). General estimations indicated that zinc (p = 0.002), iron (p = 0.0244), copper (p = 0.0003), and aluminum (p = 0.0239) values may be effective in HAI (histological activity index) changes. Only iron levels could be at a very low level effective on the changes caused by fibrosis (p = 0.0002). Liver tissue zinc and copper levels increased in parallel with the improvement of inflammation in antiviral-treated HBV patients. In addition, the levels of zinc and copper in the liver tissue can be useful markers for liver tissue damage detection.

Value of Cystatin C-Based e-GFR Measurements to Predict Long-Term Tenofovir Nephrotoxicity in Patients With Hepatitis B.

BACKGROUND: Cystatin C is a genuine marker for detecting minor reductions in estimated glomerular filtration rate (e-GFR). STUDY QUESTION: We aimed to investigate the efficiency of cystatin C levels in predicting nephrotoxicity due to antiviral therapy in patients with chronic hepatitis B virus infection. STUDY DESIGN: Seventy-six naive hepatitis B virus patients and 44 controls were enrolled in this prospective cohort study. MEASURES AND OUTCOMES: Serum cystatin C, phosphate and creatinine levels, and urinary albumin/creatinine ratios of all patients were measured at baseline, 3rd, 12th, and 24th months. Nephrotoxicity was determined according to the amount of change in creatinine level at the fourth year of treatment compared with baseline ([INCREMENT]Cr0-4). RESULTS: Mean age was 36.1 ± 9.2 years and 40 (52.2%) of patients were women. There was no significant difference between baseline values of tenofovir disoproxil fumarate and entecavir groups. Although the creatinine level at the fourth year of treatment was statistically nonsignificant compared with baseline in the entecavir group, it was significantly higher in the fourth year of tenofovir treatment compared with baseline (0.95 ± 0.27 mg/dL vs. 0.76 ± 0.16 mg/dL, P = 0.002). While the increase in [INCREMENT]Cr0-4 was ≥0.2 mg/dL in 43.2% of patients in the tenofovir group, this rate was 18.8% in the entecavir group. Diagnostic accuracy in identifying decreased renal function as area under the curve (AUC) was high for baseline serum cystatin C level; furthermore, the highest AUC was calculated for cystatin C plus creatinine-based e-GFR equation (AUC: 0.81, P < 0.001). CONCLUSIONS: Long-term tenofovir disoproxil fumarate nephrotoxicity can be predicted by serum cystatin C plus creatinine-based e-GFR measured before treatment.

Role of Bismuth in the Eradication of Helicobacter pylori.

Bismuth salts exert their activity within the upper gastrointestinal tract through action of luminal bismuth. Bismuth exerts direct bactericidal effect on Helicobacter pylori by different ways: forms complexes in the bacterial wall and periplasmic space, inhibits different enzymes, ATP synthesis, and adherence of the bacteria to the gastric mucosa. Bismuth also helps ulcer healing by acting as a barrier to the aggressive factors and increasing mucosal protective factors such as prostaglandin, epidermal growth factor, and bicarbonate secretion. To date, no resistance to bismuth has been reported. Also synergism between bismuth salts and antibiotics was present. It was shown that metronidazole and clarithromycin resistant H. pylori strains become susceptible if they are administered together with bismuth. Bismuth-containing quadruple therapy was recommended both by the Second Asia-Pacific Consensus Guidelines and by the Maastricht IV/Florence Consensus Report as an alternative first choice regimen to standard triple therapy, in areas with low clarithromycin resistance, and it is recommended as the first-line therapeutic option in areas with a high prevalence of clarithromycin resistance. Greater than 90% eradication success can be obtained by bismuth-containing quadruple therapy. Choosing bismuth as an indispensable part of first-line therapy is logical as both metronidazole and clarithromycin resistances can be overcome by adding bismuth to the regimen.

Etiopathogenesis, Prevention, and Treatment of Thromboembolism in Inflammatory Bowel Disease.

The close relationship between inflammation and thrombosis affects the progression and severity of inflammatory bowel disease (IBD). The prevalence of venous thromboembolism (VTE) varies between 1% and 7% among patients with IBD. The VTE risk in patients with IBD is at least 3 times higher than that in the normal general population. The absolute risk is very high during hospitalization, active disease, and surgery. The IBD-related VTE occurs at younger ages and recurs more frequently. The development of thrombosis in IBD is due to the interaction of many hereditary and acquired risk factors. Each patient diagnosed with IBD should be evaluated for a personal and family history of thrombosis and for prothrombotic drug use. Although procoagulant factors are increased during the natural course of inflammation, natural anticoagulants and fibrinolytic activity are decreased. Although IBD is accepted as a prothrombotic condition, there is no treatment that can remove this risk from daily practice. Patient training is required to control important factors, such as long-term immobilization and smoking. Oral contraceptives and hormone replacement therapy should be avoided. Inducing permanent disease remission must be the key approach for the prevention of thrombosis. Low-molecular-weight heparin (LMWH) is the basis of prophylactic treatment, which reduces the thrombosis risk by 50%. Prophylaxis with LMWH should be administered to all patients with IBD hospitalized due to disease attack or surgery. Long-term or even life-long anticoagulation therapy should be planned if there is insufficient disease control, recurrent VTE attacks, positive thrombophilia tests, or thrombosis in vital veins.

Insulin Resistance as a Novel Risk Factor for Post-ERCP Pancreatitis: A Pilot Study.

BACKGROUND AND AIMS: The relationship between insulin resistance and post-ERCP pancreatitis (PEP) is not known. We aimed to determine the relation between pre-ERCP insulin resistance and risk of PEP, and to evaluate the relationship of insulin resistance with well-established risk factors for PEP. METHODS: Consecutive patients who underwent ERCP with the diagnosis of choledocolithiasis between January and December 2013 were enrolled in this prospective study. Pre-procedural insulin resistance state and other risk factors were evaluated according to PEP development. RESULTS: Pancreatitis developed in 16 (11.3 %) of 141 ERCP procedure. Homeostasis model assessment of insulin resistance (HOMA-IR) levels was found statistically significantly higher in patients who developed PEP than the ones who did not (3.37 ± 0.8 vs. 2.38 ± 1.4, p < 0.001). Common bile duct (CBD) diameter of the patients developing PEP was found significantly lower than the non-PEP group (10.1 ± 4 vs. 13.4 ± 4.5 mm, p = 0.01). Mean procedure time was 33.5 min in PEP group and 27.9 min in non-PEP group (p = 0.006). HOMA-IR (OR 2.39), procedure time (OR 1.15), and CBD diameter (OR 0.82) were independent predictors of PEP development. CONCLUSIONS: The presence of insulin resistance is an important risk factor for PEP, and these data can be used as a considerable clue to predict the risk of PEP before ERCP and to decrease related morbidity.

Serum ST2 in inflammatory bowel disease: a potential biomarker for disease activity.

ST2, a specific ligand of interleukin 33, was described as a biomarker protein of inflammatory processes and overexpression of ST2 in ulcerative colitis (UC) was shown previously. We aimed to investigate the potential relationship of serum ST2 levels with the clinical, endoscopic and histopathological activity scores in UC and Crohn's disease (CD). Serum ST2 levels were determined in 143 patients with inflammatory bowel disease (IBD) (83 UC and 60 CD), in 50 healthy controls (HC), and in 32 patients with irritable bowel syndrome (IBS). Serum ST2 levels were elevated in IBD (56.8 (41.9-87.2) pg/mL) compared to HC and IBS (30.7 (20.2-54.3), p<0.001 and 39.9 (25.9-68.7) pg/mL, p=0.002, respectively). No significant difference was found between UC (54.2 (41.3-93.0) pg/mL) and CD (63.8 (42.7-88.4) pg/mL) and between IBS and HC. Serum ST2 levels were significantly increased in active UC compared to inactive UC (72.5 (44.1-99.5) vs 40.0 (34.7-51.6) pg/mL, p<0.001) and in active CD in comparison with inactive CD (63.8 (42.7-88.4) vs 48.4 (29.6-56.9) pg/mL, p=0.036). Patients with CD showing fistulizing behavior had significantly higher ST2 levels compared to patients with inflammatory and stricturing CD (p<0.001). Clinical activity scores of patients with UC and CD were correlated with serum ST2 levels (r=0.692, p<0.001 and r=0.242, p=0.043, respectively). Serum ST2 levels showed stepwise increases with the increasing histopathological scores of patients with UC and CD (p<0.001 for both). The present study highlights significant associations between ST2 and IBD presence and activity and demonstrates elevated serum ST2 levels in patients with active CD as a novel finding.

Chemerin: a new biomarker to predict postendoscopic retrograde cholangiopancreatography pancreatitis.

INTRODUCTION: Individuals with increased visceral adiposity are considered to be more sensitive and more prone to severe acute pancreatitis because of the inflammatory microenvironment they have. We hypothesized that insulin resistance, adipokines, and proinflammatory cytokines that markedly affect the course of pancreatitis can contribute toward development of postendoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP) and aimed to investigate the association between PEP risk and preprocedural serum vaspin, chemerin, tumor necrosis factor α, interleukin-6 (IL-6) levels, and homeostasis model assessment of insulin resistance. PATIENTS AND METHODS: Eighty-two patients with a diagnosis of choledocholithiasis and 30 controls were enrolled. Preprocedural chemerin, vaspin, IL-6, and well-known PEP risk factors were compared between PEP and non-PEP groups. RESULTS: The mean age of the patients was 56.3±14.4 years; 52 patients were women. Adipocytokine levels, BMIs, and waist circumferences of the patient group were found to be higher than those of the controls. Total cannulation success and the mean procedure time were 82.9% and 28.7±8.8 min, respectively. PEP developed in 12 (14.6%) patients. Chemerin levels in the PEP group were higher than those in the non-PEP group (580.2±172.5 vs. 392.2±168.2 ng/ml, P<0.01). Insulin resistance was higher in the PEP group than the non-PEP group (P=0.001), but there was no significant difference between PEP and non-PEP groups in terms of preprocedural vaspin, tumor necrosis factor α, IL-6, and C-reactive protein levels. According to logistic regression analysis, increased chemerin levels, homeostasis model assessment of insulin resistance 2.5 or greater, and pancreatic duct cannulation were found to be independent risk factors for PEP [odds ratio (OR)=1.006, P=0.006; OR=4.57, P=0.05; OR=6.54, P=0.02]. CONCLUSION: Elevated serum chemerin levels and insulin resistance are independent risk factors of PEP development.

First Week HCV RNA Level Under the Pegylated Interferon and Ribavirin Treatment Predicts Sustained Virological Response.

This study was planned to investigate whether the decrease in the hepatitis C virus (HCV) RNA levels at the first week of combined pegylated interferon and ribavirin treatment of naive genotype 1 patients with HCV was predicting sustained virologic response (SVR). Fifty-two patients were enrolled into the study. HCV RNA levels were measured at the baseline, first, fourth, and 12th weeks of treatment. Thirty-four patients achieved SVR, which basal, first week, and fourth week HCV RNA levels were log 5.57, log 3.65, and log 1.92, respectively. Eighteen patients could not achieve SVR, which basal, first week, and fourth week HCV RNA levels were log 6.22, log 5.45, and log 3.84, respectively (P < 0.05). Patients were distributed in 2 groups according to the amount of decrease in HCV RNA levels at the first week as less or more than 1.5 log. There were 20 patients with ≥1.5 log decrease in the HCV RNA levels at the first week. They were named as patients with very rapid virologic response (VRVR). All patients (100%) with VRVR were achieved SVR. In only 14 (44%) of the 32 patients without VRVR, SVR was achieved. In 16 (84%) of the 19 patients with rapid virologic response and 33 (79%) of the 42 patients with early virologic response, SVR was achieved. A ≥1.5 log decrease (VRVR) in HCV RNA levels of patients with HCV at the first week of combined pegylated interferon and ribavirin treatment predicts SVR very strongly.

Effect of Entecavir and Tenofovir Treatment on Noninvasive Fibrosis Scores: Which One Is Better?

Liver biopsy is the best method for detecting fibrosis grade of the liver in chronic hepatitis B. However, the invasiveness of liver biopsy complicates its routine use in follow-up of treatment. We planned to determine the usage of fibrosis predicting noninvasive scores in the follow-up of the treatment of patients with chronic hepatitis B treated with entecavir or tenofovir. Two hundred twenty-eight patients with hepatitis B with liver biopsy were included in the study. Fibrosis grade was determined by Ishak score. The laboratory data at months 0, 12, and 24 during treatment were collected and noninvasive fibrosis scores (aspartate aminotransferase to alanine aminotransferase ratio [AAR], aspartate aminotransferase to platelet ratio index [APRI], fibrosis index based on the 4 factors [FIB-4] and red cell distribution width to platelet ratio [RPR]) were calculated. Statistically significant increase in all scores and decrease in platelet count were observed as the fibrosis level increased. For differentiation of patients with fibrosis ≥grade 2, the highest sensitivity and specificity rates were shown by APRI score (sensitivity 67%, specificity 69%, and cutoff ≥0.5). FIB-4 was the most successful score for differentiation of patients with fibrosis ≥grade 3 (sensitivity 83%, specificity 74%, and cutoff ≥1.45). A significant decrease in all noninvasive fibrosis scores was observed at months 12 and 24 during treatment with both entecavir and tenofovir (P < 0.001). Among these, only the improvement in APRI score was found better in entecavir group with statistical significance (P < 0.05). APRI score was effective in demonstrating early-stage fibrosis. FIB-4, RPR, and platelet count were better in demonstrating advanced fibrosis. Although noninvasive scores cannot replace liver biopsy for diagnosis, they can be used for monitoring the response to treatment.

Plasma Pentraxin 3 Differentiates Nonalcoholic Steatohepatitis (NASH) from Non-NASH.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a variety of histopathological findings ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which can only be differentiated by liver biopsy. There is yet no unique biomarker found to discriminate NASH from simple steatosis.We aimed to investigate the relationship of plasma pentraxin 3 (PTX3) and its main stimulant tumor necrosis factor alpha (TNF-α) with the degree of liver damage in NAFLD. METHODS: Plasma PTX3 and TNF-α levels were measured in 70 patients with histologically verified NAFLD (56 with NASH, 14 with non-NASH) and 12 controls. RESULTS: PTX3 and TNF-α levels were found significantly higher in the NAFLD group than in the control group (4.1 ± 2.3 vs. 1.3 ± 0.8 ng/mL, P < 0.001, and 7.6 ± 4.1 vs. 3.3 ± 1.3 pg/mL, P < 0.001 respectively) and in biopsy proven NASH subgroup than non-NASH subgroup (4.6 ± 2.2 vs. 2.2 ± 1.7 ng/mL, P = 0.001, and 8.3 ± 4.3 vs. 4.6 ± 1.6 pg/mL, P = 0.001 respectively). To discriminate NASH from non-NASH PTX3 had 91.1% sensitivity and 71.4% specificity at the cutoff value of 2.45 ng/mL. Plasma PTX3 levels showed correlation with NAFLD activity score, fibrosis stage and steatosis grade (r = 0.659, P < 0.001; r = 0.354, P < 0.01; and r = 0.455, P < 0.001, respectively). CONCLUSION: This study demonstrated markedly higher PTX3 levels in NAFLD patients compared with controls, and in biopsy proven NASH patients compared with non-NASH ones. Thus, in this cohort we showed that plasma PTX3 may be a promising biomarker for the presence of NASH.

The Relationship of Serum Hemojuvelin and Hepcidin Levels with Iron Overload in Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Mild iron overload is frequently reported in patients with nonalcoholic fatty liver disease (NAFLD). Hepcidin is the master iron-regulatory peptide and hemojuvelin (HJV) is the key regulator of iron-dependent secretion of hepcidin. The aims of this study were to evaluate serum HJV and hepcidin levels in patients with biopsy-proven NAFLD with and without hepatic iron overload, and to identify potential associations of HJV and hepcidin with the clinical characteristics of the patients enrolled. METHODS: Serum levels of HJV and hepcidin were measured in 66 NAFLD patients with (n=12) and without (n=54) iron overload, and controls (n=35) by enzyme-linked immunosorbent assay. Hemojuvelin and hepcidin levels were assessed in relation to clinical characteristics and liver histologic evaluation of the participants. RESULTS: Significantly lower serum HJV (281.1 [239.2-353.6] vs. 584.8 [440.3-661] ng/ml, p<0.001) and similar serum hepcidin levels (60.5+/-31.1 vs. 55.8+/-11.9 ng/ml, p=0.285) were found in NAFLD patients when compared to controls. Iron-overloaded NAFLD patients had significantly lower HJV (249.9 [187.6-296.3] vs. 292.9 [243-435] ng/ml, p=0.032) and significantly higher hepcidin (78.4+/-35.5 vs. 56.5+/-28.9ng/ml, p=0.027) levels than NAFLD patients without iron overload. Fibrosis stage was significantly higher in iron overloaded NAFLD group (p<0.001). Ferritin levels correlated significantly both with HOMA-IR (r=0.368, p=0.002) and fibrosis stage (r=0.571, p<0.001). CONCLUSIONS: Our findings suggest that HJV levels are low in NAFLD and even lower in iron overloaded NAFLD, while hepcidin levels are higher in NAFLD with iron overload. The gradually decreased HJV and increased hepcidin concentrations in our patients most likely reflect the physiological response to iron accumulation in the liver.