Daclatasvir plus asunaprevir dual therapy for chronic HCV genotype 1b infection: results of Turkish early access program.

 Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. AIM: To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. MATERIAL AND METHODS: Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. RESULTS: Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. CONCLUSIONS: Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial.

BACKGROUND & AIMS: Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection. METHODS: This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000IU/ml were randomized to receive 12weeks of EBR/GZR 50mg/100mg once daily (n=129) or sofosbuvir (400mg once daily) plus PR (n=128). Primary efficacy objective was sustained virologic response 12weeks after the end of therapy (SVR12, HCV RNA <15IU/ml). The primary safety objective was the proportion of patients experiencing a tier 1 safety event. RESULTS: The majority of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6-15.3%). Because the lower bound of the 1-sided 1-sample exact test was greater than -10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference, 27.0% [95% CI, -35.5% to -19.6%; p<0.001]). CONCLUSIONS: EBR/GZR has a superior efficacy and safety profile in patients with HCV GT1 or 4 infection compared with SOF/PR. LAY SUMMARY: The combination of elbasvir/grazoprevir for 12weeks was highly effective in treating patients with chronic hepatitis C, genotypes 1 or 4 infection. This regimen was more effective than sofosbuvir/pegylated interferon/ribavirin for 12weeks, and was notably superior in patients regarded as difficult to treat, including those with previous treatment failure, cirrhosis, or a high baseline viral load. The combination of elbasvir/grazoprevir also demonstrated a superior safety and tolerability profile based on fewer serious adverse events, no serious drug-related adverse events, and no treatment discontinuations. CLINICAL TRIAL REGISTRATION: Clinical trials.gov Identifier: NCT02358044.

Nutritional habits in functional dyspepsia and its subgroups: a comparative study.

OBJECTIVE: Research data demonstrating nutritional habits of functional dyspepsia (FD) patients are very limited. This is the first study to evaluate nutritional habits in FD subgroups according to Rome III criteria. Our aim was to evaluate nutritional habits of FD patients and determine the food items that may provoke a dyspepsia symptom. METHODS: A total of 168 adults with FD and 135 healthy control subjects participated in the study. FD subjects were divided into epigastric pain syndrome (EP-FD), postprandial distress syndrome (PS-FD), mixed (MX-FD) subgroups according to Rome Criteria III. Subjects completed a questionnaire that included a short-form food frequency questionnaire. Furthermore, subjects were asked to list the food items that were causing a dyspepsia symptom. RESULTS: Functional dyspepsia subjects had a slightly higher BMI (26.1 ± 4.97 kg/m(2)) than control subjects (24.6 ± 4.08 kg/m(2)). The most common symptom triggering foods among all the FD groups were fried and fatty foods (27.1%), hot spices (26.4%), and carbonated drinks (21.8%). In FD subgroups, carbonated drinks were more likely to cause a symptom in PS-FD group (37.3%) than MX-FD (25.7%) and EP-FD (22.1%) groups. There was no difference in frequency of main meals and snacks among any of the groups. CONCLUSION: Fatty and spicy foods and carbonated drinks were the most common symptom triggering food items in FD group. In subgroups, carbonated drinks and legumes were more likely to cause a symptom in PS-FD. Removing these food items during the course of treatment might help alleviate the symptoms.

Long-term efficacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis.

BACKGROUND & AIMS: Data are limited on the efficacy and safety of tenofovir and entecavir when given for more than 1 year to patients with hepatitis B-related cirrhosis. We investigated the long-term safety and efficacy of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis, and compared results with those from lamivudine. METHODS: We performed a retrospective analysis of data from 227 adult patients with chronic HBV infection who were diagnosed with cirrhosis, beginning in 2005, at 18 centers throughout Turkey. There were 104 patients who had decompensated cirrhosis, and 197 patients were treatment naive before. Seventy-two patients received tenofovir (followed up for 21.4 ± 9.7 mo), 77 patients received entecavir (followed up for 24.0 ± 13.3 mo), and 74 patients received lamivudine (followed up for 36.5 ± 24.1 mo). We collected data on patient demographics and baseline characteristics. Laboratory test results, clinical outcomes, and drug-related adverse events were compared among groups. RESULTS: Levels of HBV DNA less than 400 copies/mL were achieved in 91.5%, 92.5%, and 77% of patients receiving tenofovir, entecavir, or lamivudine, respectively. Levels of alanine aminotransferase normalized in 86.8%, 92.1%, and 71.8% of patients who received tenofovir, entecavir, and lamivudine, respectively. Child-Turcotte-Pugh scores increased among 8.5% of patients who received tenofovir, 15.6% who received entecavir, and 27.4% who received lamivudine. Frequencies of complications from cirrhosis, including hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, and mortality, were similar among groups. Lamivudine had to be changed to another drug for 32.4% of the patients. CONCLUSIONS: Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection.

Serum nitric oxide levels in patients with benign and malignant biliary disease: a prospective single center study.

BACKGROUND: Despite advances in new diagnostic modalities, the differentiation of malignant from benign causes of biliary obstruction still remains difficult. The nitric oxide (NO) system is considered to be an important component in mediating cytokine activation of macrophages in inflammation. It also modulates tumorigenesis and regulates cell proliferation, angiogenesis, survival, and DNA repair. Although NO and its role in pancreatobiliary disorders has not been studied previously, the present study is designed to evaluate NO synthesis and metabolism in patients with biliary obstruction and to determine its usefulness in differentiating between benign and malignant causes of biliary obstruction. MATERIALS AND METHODS: Seventy-nine consecutive patients (60 malignant and 19 benign) with a history of biliary obstruction either with a benign or a malignant cause and 23 age-matched and sex-matched controls were included in this prospective study. NO metabolites, and conventional inflammation and tumor markers were determined. RESULTS: In patients with malignant biliary obstruction (MBO), serum NO metabolites were found to be significantly elevated (P<0.001). The receiver operating characteristic analysis showed that an NO level of 1.095 was the best cut-off value for predicting a malignant biliary stricture with a sensitivity of 78.3% and a specificity of 84.2% (area under the curve=0.821). Correlation analysis suggested that carbohydrate antigen 19-9 and carcinoembryonic antigen levels were correlated with NO levels for differentiating benign from malignant cause of biliary obstruction. CONCLUSIONS: Serum NO-associated tissue injury might be associated with the development of pancreatobiliary neoplasia by creating a local environment that is enriched with reactive oxygen species, cytokines, and other growth factors that may promote endothelial cell apoptosis. Moreover, serum NO levels may be used as an adjunctive marker to identify malignant causes of the obstructive jaundice.

Lamivudine treatment failure risks in chronic hepatitis B patients with low viral load.

AIM: To analyze the risk factors of lamivudine treatment failure (LTF) for the long-term use in patients with low viral load (LVL). MATERIAL AND METHODS: In this multicenter study, 548 antiviral naïve noncirrhotic adult patients with LVL (for HBeAg+ patients HBV DNA <10 9 copies/ml and for HBeAg­patients HBV DNA <10 7 copies/ml) were enrolled. As a control group, 46 lamivudine-initiated patients with high viral load (HVL) were included. Primary outcome was switching to or adding on another antiviral drug as a consequence of primary nonresponse, partial response, viral breakthrough or adverse events. Secondary outcomes included LTF rates at 1, 2, 3, 4 and 5 years and LTF-related viral and host factors. RESULTS: Among 594 patients, 294 had to change lamivudine at the follow-up. Primary nonresponse, partial response, viral breakthrough or adverse events frequencies were 6.8, 1.6, 64.5 and 0.1%, respectively. Five-year LTF rates were 61.3 and 84.2% in patients with LVL and HVL, respectively. Among patients with LVL, patients with <100,000 copies/ml and ≥ 100,000 copies/ ml had 54.8 and 67.3% LTF rates at the end of the 5th year, respectively. Logistic regression analysis of risk factors showed HBeAg+, hepatic activity index, HBV DNA, virological response at 6 months and duration of follow-up were independent predictors for LTF (p values were 0.001, 0.008, 0.003, 0.020 and 0.003, respectively). CONCLUSION: Similar to patients with HVL, first-line lamivudine therapy is not efficient for long-term use in patients with LVL. LTF risk is so high even in the absence of worse predictive factors.

Oral high-dose ankaferd administration effects on gastrointestinal system.

BACKGROUND AND AIMS: Ankaferd Blood Stopper (ABS) is a herbal extract obtained from five different plants. It has a therapeutic potential for the management of external hemorrhage and controlling gastrointestinal bleeding. However, ABS's effects are not unknown on gastrointestinal systems. The aim of this study was to assess the effect of short- and long-term systemic exposure and gastrointestinal safety following the oral administration of high-dose ABS in rats. METHODS: Eighteen healthy adult male rats were included into the study. The rats were divided into 4 groups: group A was fed with high dose ABS (2ml/Kg) for one week, group B for one month, group C for three months and group D's diet did not contain any ABS. On termination of the ABS treatment, the gastrointestinal system from the esophagus to the anus and the liver were surgically removed and histological investigated. RESULTS: During the study period, there was no mortality; signs of intoxication in any of the studied groups. No gastrointestinal tissue fibrosis, dysplasia, or metaplasia was detectable in any of the groups. The stomach had a normal morphology in all groups. However, the other gastrointestinal tract sections showed mucosal inflammation, goblet cell decrements, and intra-epithelial lymphocyte infiltration. The most common changes were mucosal inflammation in all rats in group B and C. Frequency of inflammation was greater in groups B and C in comparison to group A (P= 0.001). Loss of goblet cell and intra-epithelial lymphocyte infiltration were not significantly different between groups A and B (P=0.308 and P=0.189, respectively). However, there was significantly higher intra-epithelial lymphocyte infiltration in group C than in group A (P=0.04). Histopathological examination of the liver showed no inflammation, fibrosis, bile duct destruction or proliferation in any of the groups. However, each groups revealed vascular dilatation and erythrocyte accumulation at the sinusoidal structures of the liver. CONCLUSIONS: ABS seems to be a safe agent and it can be used for hemorrhage originated from gastric lesions. Further work needs to be done to establish whether ABS leads to be used to stop gastrointestinal bleeding.

Clinical trial: transcutaneous interferential electrical stimulation in individuals with irritable bowel syndrome - a prospective double-blind randomized study.

BACKGROUND: The exact etiology of irritable bowel syndrome (IBS) remains unclear. Curative treatment is not available and current treatment modalities are mainly directed against the predominant symptoms. There are a few studies reporting the beneficial effects of transcutaneous electrical stimulation in patients with chronic constipation, gastroparesis, and functional dyspepsia. AIM: To investigate whether transcutaneous electrical stimulation is an effective procedure in IBS patients. METHODS: IBS patients were randomly placed in vacuum interferential current (IFC) and placebo groups. Both treatments consisted of 12 sessions administered over 4 weeks. Symptoms due to IBS were documented via questionnaires, including the IBS Global Assessment of Improvement Scale, numeric rating scales, visual analogue scale, and IBS Quality of Life Scale at the beginning of, end of, and 1 month after the treatment. RESULTS: Patients in the therapy (29 cases) and placebo (29 cases) groups were homogeneous with respect to demographic data and gastrointestinal system symptoms. When compared to the beginning scores, severity of abdominal discomfort, bloating, and abdominal distension and rumbling improved significantly in either interference or placebo groups at both the end of treatment and 1 month after treatment. In the IFC group, severity of symptoms continued to decrease significantly at 1 month after treatment when compared to scores at just the end of treatment, whereas in the placebo group severity of these symptoms did not change significantly on numeric severity scales. Also, the visual analogue scale of the first month after treatment continued to decrease significantly when compared to the level at the end of treatment in the IFC group. Total quality score increased significantly in the IFC group. CONCLUSIONS: Vacuum IFC therapy can significantly improve symptoms and quality of life in patients with IBS. It may represent a novel treatment modality for drug-refractory IBS patients.

Factors affecting the success of endoscopic bougia dilatation of radiation-induced esophageal stricture.

AIMS: The purpose of this retrospective study was to assess clinical outcomes of endoscopic bougie dilation of esophageal strictures after radiation therapy for head and neck cancer, and to assess the risk factors which affect the treatment success. METHODS: Thirty-one patients with esophageal stricture due to radiation therapy were treated with endoscopic bougie dilation. The following parameters were evaluated; age, gender, primary site of the tumor, initial treatment of the tumor, prescribed dose of radiation, the time to onset of esophageal stricture after radiation therapy, grade of esophageal stricture according to clinical and endoscopic findings, number of dilatations, recurrence of esophageal stricture, and the result of the therapy. RESULTS: The average follow-up was 26 months with a range of 1-84 months. Successful endoscopic bougie dilation was achieved in 26 of 31 patients. The median time to onset of esophageal stricture after radiation therapy was significantly shorter in patients who did not respond to endoscopic bougie dilation. CONCLUSION: Endoscopic bougie dilation is a safe and effective procedure for the management of radiation-induced esophageal stricture. Time to onset of esophageal stricture is the most important factor for the treatment success. In addition, the total prescribed dosage of radiation has minimal effects on the result of endoscopic bougie dilation.

A novel appetite peptide, nesfatin-1 in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver pathology worldwide and is strongly associated with obesity and insulin-resistance and food intake. Nesfatin-1 is a new peptide that controls appetite and food intake. The objective of this research was to examine the serum concentrations of nesfatin-1 in NAFLD. MATERIAL AND METHODS: Thirty NAFLD patients who had elevated liver enzymes and 40 age- and sex-matched healthy subjects were included in this study. NAFLD was diagnosed and graded with the findings of liver ultrasound scan. Nesfatin-1 concentrations were measured using an ELISA method and the relationship between nesfatin-1 and metabolic parameters were investigated. The subjects were divided into two groups according to their body mass index (≥ 30 and < 30) and nesfatin-1 concentrations were examined between both groups. RESULTS: Serum nesfatin-1 concentrations in NAFLD patients were lower than healthy controls (0.26 ± 0.14 ng/ml, 0.38 ± 0.18 ng/ml, respectively, and p = 0.008). We found a negative correlation between nesfatin-1 and fasting glucose and body mass index. In obese subjects, serum nesfatin-1 concentrations were significantly lower when compared with non-obese subjects (0.26 ± 0.12 ng/ml, 0.37 ± 0.19 ng/ml, respectively; p = 0.014). In addition, we showed that nesfatin-1 concentrations in subjects with insulin resistance were significantly lower in comparison with insulin-sensitive ones (0.27 ± 0.17 ng/ml, 0.38 ± 0.17 ng/ml, respectively; p = 0.015). CONCLUSION: Our study has shown that nesfatin-1 concentrations were reduced in NAFLD. The results of this study indicate that nesfatin-1 may have a significant role in NAFLD.

Evaluation of serum TWEAK concentration in patients with acute pancreatitis.

BACKGROUND AND AIM: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor super family of structurally-related cytokines. The aim of this study was to determine the diagnostic and prognostic role of serum TWEAK concentration in patients with acute pancreatitis. METHODS: Twenty four patients with acute pancreatitis and 24 consecutive healthy age- and sex-matched control subjects were included in the study. The serum concentrations of TWEAK were measured at admission and then at remission. The average time between admission and remission was 7-10 days. RESULTS: At admission, TWEAK concentration was significantly lower in patients with acute pancreatitis compared to control subjects (p < 0.001). Serum TWEAK concentrations were elevated after the remission period, however the differences were not statistically significant. In addition, serum TWEAK concentration showed a significant, inverse correlation with amylase, lipase, CRP, AST, fibrinogen, LDH and a positive correlation with calcium, albumin and platelet count. CONCLUSIONS: Patients with acute pancreatitis have lower serum TWEAK concentration than healthy subjects. These results suggest that serum TWEAK concentration could be a potential biomarker of acute pancreatitis.

Recurrent pyogenic cholangitis in a case with congenital biliary anomaly.

Recurrent pyogenic cholangitis is endemic to South-east Asia but has been very rarely reported from natives of other parts of the world. A 43-years-old woman was presented with sepsis that had a history of recurrent epigastric pain and fever attacks. Her liver tests were unremarkable suggesting any hepatobiliary diseases. Recurrent pyogenic cholangitis and congenital extrahepatic biliary anomaly have been diagnosed after serial diagnostic and therapeutic procedures including endoscopic retrograde cholangiography, MR-cholangiography, percutaneous transhepatic cholangiography and finally left hepatectomy. She was cured completely following surgical treatment.

Adipokine levels in the course of mild biliary pancreatitis.

OBJECTIVES: Obesity markedly increases the risk of severe acute pancreatitis (AP). Several adipokines have been ascribed a role as a predictor of clinical severity in AP. Therefore, the aim of this study was to investigate a possible relationship between leptin and adiponectin and mild biliary AP. METHODS: We included 24 consecutive patients with mild biliary AP and 24 consecutive healthy age- and sex-matched controls. Clinical severity was classified by the Ranson score. ELISA was used to assess leptin and adiponectin levels on admission and in remission. Complete blood cell counts and other laboratory tests were also performed at baseline and in remission. RESULTS: Leptin, adiponectin, insulin and HOMA-IR measurements showed no difference in pancreatitis patients both on admission and in remission compared to the control group. No difference was found in leptin, insulin or HOMA-IR levels in the course of pancreatitis. However, adiponectin levels were higher in remission compared to admission. CONCLUSIONS: Increased adiponectin levels in remission may be an indication of improvement in this condition. Further studies are needed to determine whether adiponectin provides protection from AP.

Visfatin levels in nonalcoholic fatty liver disease.

PURPOSE: Recently, role of adipokin in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has been suggested. Among adipokins, role of leptin and adiponectin is rather well known; however, there are only a few data concerning visfatin. MATERIAL AND METHODS: NAFLD is confirmed in 30 patients by ultrasonography. As a control group, patients without fatty liver or other liver diseases were included. Viral hepatitis, metabolic liver diseases, and autoimmune hepatitis and consumption of alcohol were excluded in all patients. Fasting serum level of visfatin was determined by ELISA method. RESULTS: Serum visfatin concentration in the NAFLD group (14.7 ± 8.1 ng/ml) was significantly higher than in controls (9.4 ± 1.6 ng/ml) (P < 0.001). There were no correlations between visfatin and anthropometric parameters, transaminases, lipids, and homeostasis model assessment-estimated insulin resistance (HOMA-IR). CONCLUSION: Serum visfatin concentration increases in patients with NAFLD.

Amantadine in non-responder patients with chronic hepatitis C: a randomized prospective study.

BACKGROUND/AIMS: The management of non-responders (NR) represents the most challenging of all aspects in the care of patients with chronic hepatitis C (CHC). The purpose of the study was to evaluate the efficacy of amantadine. METHODOLOGY: Fourty- three patients with CHC who did not respond to prior combination therapy [IFNα-2a plus ribavirin for 48 weeks] were enrolled into the study. The first group (n=21) was administered pegylated IFN-α2a (180 mcg/week) plus ribavirin (1000-1200 mg/day) and amantadine (200mg/day) for 48 weeks. After discontinuation of therapy, patients were followed-up for an additional 24 weeks. The second group (n=22) received only amantadine (200mg/day) daily for at least 24 weeks (mean 96 weeks) and starting from the 24th week, HCV-RNA was assessed every 12 weeks without discontinuation of therapy. RESULTS: Mean ALT levels before treatment were 115.30 units in the first and 107.73 units in the second group whereas they were 48.38 and 54.76 units, respectively, after the treatment (p<0.001 for both). Sustained viral response rate for the first group at the 72nd week was 52.3% (11/21) (p<0.025). Among patients receiving amantadine, 1 patient became HCV-RNA negative at the 24th and 3 patients at the 48th week (response rate at week 48 was 18.2%), 1 patient at the second year and 1 patient at the fourth year of the treatment (p=0.031). CONCLUSIONS: Amantadine has a potential anti-inflammatory activity that can be a safe alternative for NR-CHC subjects to combination therapy.

An unusual cause of unilateral hydronephrosis: invasive colonic amebiasis.

A 62-year-old man was admitted to our hospital with complaints of abdominal pain and rectal bleeding. Although the colonoscopic examination was highly suggestive of a carcinoma, the histopathological examinations were consistent with chronic inflammation. CT examination revealed a solid lesion from cecum to the ascending colon with right urethral invasion. Percutaneous right nephrostomy was performed for grade 2-3 hydronephrosis. Three days after hospitalization, ileus developed and right hemicolectomy was performed. During surgery we observed that the lesion had invaded the middle part of ureter. So the middle part of ureter was removed with side-to-side urethral anastomosis and 6F double-J catheter was placed. The histopathological findings of resected specimen were consistent with ameboma. Reviewing the literature unilateral hydronephrosis due to colonic amebiasis has not been reported.