[Show abstract][Hide abstract] ABSTRACT: Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long-term therapy may be required. We investigated whether adding-on peginterferon (PEG-IFN) to ETV therapy enhances serologic response rates. In this global investigator-initiated, open-label, multicentre randomized trial, HBeAg-positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5mg/day) and were randomized in a 1:1 ratio to either PEG-IFN add-on therapy (180µg/week) from week 24 to 48 (n=85), or to continue ETV monotherapy (n=90). Response was defined as HBeAg loss with HBV DNA <200 IU/mL at week 48. Responders discontinued ETV at week 72. All patients were followed until week 96. Response was achieved in 16/85 (19%) patients allocated to the add-on arm versus 9/90 (10%) in the monotherapy arm (p=0.095). Adjusted for HBV DNA levels prior to randomized therapy, PEG-IFN add-on was significantly associated with response (OR 4.8, 95%CI: 1.6 – 14.0, p=0.004). Eleven (13%) of add-on treated patients achieved disease remission after ETV cessation, versus 2/90 (2%) of patients treated with monotherapy (p=0.007), which was 79% (11/14) versus 25% (2/8) of those who discontinued ETV (p=0.014). At week 96, 22 (26%) patients assigned add-on versus 12 (13%) assigned monotherapy achieved HBeAg seroconversion (p=0.036). PEG-IFN add-on led to significantly more decline in HBsAg, HBeAg and HBV DNA (all p<0.001). Combination therapy was well-tolerated. Conclusion: Although the primary endpoint was not reached, 24 weeks of PEG-IFN add-on therapy led to a higher proportion of HBeAg response compared to ETV monotherapy. Add-on therapy resulted in more viral decline and appeared to prevent relapse after stopping ETV. Hence PEG-IFN add-on therapy may facilitate the discontinuation of nucleos(t)ide analogues. http://www.Clinicaltrials.gov number: NCT00877760. (Hepatology 2014;)
[Show abstract][Hide abstract] ABSTRACT: Although systemic lupus erythematosus (SLE) and autoimmune hepatitis (AIH) are distinct diseases, in clinical practice differentiation of one from other may be difficult. The aim of this study was to asses features of SLE in patients with diagnosis of AIH.Thirty patients [mean age: 52.4 ± 11.8 years; 23 (76.7 %) female] were included in the study. Seven (23.3 %) of the patients full filled 4 or more criteria for classification of SLE. None of the patients had muco-cutaneous lesions characteristic to SLE. Three patients had rheumatoid factor negative arthritis, and 2 patients had pericardial effusion. Four patients had significant thrombocytopenia (<100 × 10(3)/μL), and one of these patients had pancytopenia. None of the patients had hematuria, but 3 patients had proteinuria which did not affect renal function during the study period. One patient died due to pancytopenia-associated pulmonary infection. Among the treated patients with SLE features, 2/5 (40 %) achieved ALT normalization and 9/12 (75 %) of the remaining patients achieved ALT normalization (Fisher's exact test; p = 0.28) during the study period. Although the difference is non-significant, treatment response of AIH patients with SLE features seemed to be delayed and incomplete compared to other patients, but with the limited number of patients it is inconvenient to reach a definitive conclusion. Further studies are needed to identify role of features of SLE on treatment response in patients with AIH.
Rheumatology International 12/2012; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/Aims: To evaluate the indications, diagnostic yield, therapeutic interventions, complications and safety of double balloon enteroscopy (DBE) in clinical practice. Methodology: The medical records of the patients who underwent DBE at the Turkiye Yuksek Ihtisas Hospital between October 2007 and January 2010 were examined to note the demographic data, indications for the examination, results of previous non-invasive small bowel imaging and endoscopic procedures and the results of DBE including findings, endoscopic interventions, complications and pathological reports. Results: A total of 139 procedures were performed in 118 patients. DBE was performed 81 times through mouth and 26 times through anus and additionally both approaches were used 16 times in the same patients. Panenteroscopy was successfully performed in 13 of 16 patients (87.5%) in whom it was attempted. The most common indication was obscure gastrointestinal bleeding (28.8%). DBE had an overall diagnostic and/or therapeutic contribution in 63 (53.4%) patients. The main pathologies detected on DBE were polyps (12.7%), infammation (10.7%) and vascular lesions (3.4%). Complications were recognized in four cases (3.4%) but no major complication occured. Conclusions: Our retrospective analysis showed that DBE is a useful, safe and well-tolerated method with a diagnostic and therapeutic impact for the management of small bowel diseases.
[Show abstract][Hide abstract] ABSTRACT: Chronic hepatitis B (CHB) infection is a serious public health problem due to its potential liver disease sequelae and highly expensive medical costs such as the need for liver transplantation. The aim of this study was to quantify the burden of active CHB in terms of mortality and morbidity, the eligibility of antiviral treatment and to assess various treatment scenarios and possible salvage combinations for cost-effectiveness.
A population cohort from a large data base of chronic hepatitis B patients was constructed and stratified according to 10-year age groups, the prevalence of HBsAg, HBV DNA level, ALT level, HBeAg status and the presence of cirrhosis. An age-specific Markov model for disease progression and cost-effectiveness analysis was constructed and calibrated for the specific population setting.
Of about 3.2 million estimated HBsAg carriers, 25% are eligible for treatment. If the active cohort remains untreated, 31% will die due to liver related complications. Within a 20-year period, 11% will have developed decompensated cirrhosis, 12% liver cancer and 6% will need liver transplantation. Quality adjusted life years (QALYs) for the no treatment scenario ranged from 9.3 to 14.0. For scenarios with antiviral treatment, QALYs ranged from 9.9 to 14.5 for lamivudine, 13.0-17.5 for salvage therapy, and 16.6-19.0 for the third generation drugs entecavir and tenofovir.
In a country with considerable amount of active CHB patients, monotherapy with a highly potent third generation drug has the most health-gain, and is cost-effective in both HBeAg-positive and negative in all stages of liver disease.
The European Journal of Health Economics 07/2012; 13(5):663-76. · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) has poor long-term prognosis so we need new diagnostic techniques and markers to detect HCC in the early phases. The aim of this study was to analyze the levels of serum mean platelet volume in HCC.
The clinical data of 230 subjects with normal, chronic hepatitis, cirrhosis and HCC were retrospectively analyzed at our hospital between January 2009 and December 2009. The levels of MPV were determined in patients with liver disease and compared between patient groups and with healthy persons.
Serum MPV levels were significantly increased compared to the patients with chronic hepatitis, cirrhosis, and the control group (p<0.01). The cut-off value for MPV for the detection of HCC in cirrhotic patients was calculated as ≥9.2fl using ROC analysis [Sensitivity: 68.3%, specificity: 62.1%, AUC: 0.676 (0.580-0.773), p<0.001]. Additionally, serum MPV levels show higher sensitivity for diagnosis of HCC than AFP. An AFP of more than 7.4IU/mL and an MPV of ≥9.2fl, both put together, had a specificity of 95.2%, while when used separately, they have a sensitivity of 87.5%.
MPV may be a potential or adjunctive marker of HCC in patients with chronic liver disease.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND OBJECTIVE: Non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin have antiaggregant properties and patients with pancreaticobiliary disease commonly use these drugs. We prospectively investigated whether aspirin and NSAIDs are associated with endoscopic sphincterotomy related hemorrhage. METHODS: Three hundred and eight patients who underwent sphincterotomy were sequentially recruited into this prospective case-control study. Pre-endoscopic assessment included a complete blood count, coagulation studies and a detailed drug history after sphincterotomy patients were followed up for bleeding. Cases and controls were compared for patient and procedure-related risk factors of post-endoscopic sphincterotomy bleeding. RESULTS: Hemorrhage occured in 74 (24%) patients. Eight (2.6%) were clinically significant and five (1.6%) were severe. Amongst cases with hemorrhage, 17.6% were on NSAIDs and 14.9% on aspirin; 27.4% of controls took NSAIDs, and 9.8% aspirin (P>0.05). Aspirin use in patients with significant (12.5%) or severe hemorrhage (20%) was not different from the controls (P>0.05) and none of them had NSAIDs prior to sphincterotomy. Based on univariate analysis, coagulopathy and comorbidity were risk factors for significant post-sphincterotomy hemorrhage and coagulopathy was the only independent parameter (odds ratio=22.72, 95% CI [4.25; 125]). CONCLUSION: Aspirin and NSAIDs do not increase the risk of post-sphincterotomy hemorrhage and they can be safely used before the procedure.
Gastroentérologie Clinique et Biologique 06/2012; · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peginterferon (PEG-IFN) is considered as a first-line treatment option for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We aimed to evaluate the long-term response to PEG-IFN in HBeAg-negative patients.
All patients enrolled in the PARC study who completed the treatment phase were eligible for this long-term follow-up (LTFU) study. Patients received PEG-IFN α-2a (180 μg weekly) ± ribavirin (1000-1200 mg daily) for 48 weeks and had at least one additional LTFU visit after the initial follow-up period of 24 weeks (mean duration 2.1 ± 0.2 years). Retreated patients were considered nonresponders.
Of 117 patients who completed the treatment phase, 79 (68%) were included in this LTFU study. Among 19 patients with a combined response at 24 weeks after treatment [initial responders; hepatitis B virus DNA<10 000 copies/ml (<1714 IU/ml) and normal alanine aminotransferase], 12 (63%) sustained this response through LTFU. Three additional patients showed such a response at LTFU, resulting in a total of 15 (19%) combined responders at LTFU. A marked decrease in the serum hepatitis B surface antigen (HBsAg) levels was observed in initial responders, resulting in HBsAg clearance in 26% of the patients (6% of all LTFU participants).
About one-third of HBeAg-negative patients with a response to PEG-IFN at 24 weeks after treatment subsequently had a relapse during 2 years of follow-up. Despite the limited overall efficacy of PEG-IFN, patients responding to PEG-IFN treatment showed a marked decrease in serum HBsAg, resulting in a high rate of HBsAg clearance, which indicates the need for predictors of response to PEG-IFN in HBeAg-negative disease.
European journal of gastroenterology & hepatology 06/2012; 24(9):1012-9. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to retrospectively analyze all the polyps of patients undergoing endoscopic polypectomy or forceps biopsy according to their types, frequency, localization, number and gender distribution.
Data from patients who underwent upper endoscopy in the Türkiye Yüksek Ihtisas Postgraduate Research Hospital between March 2007 and November 2009 were analyzed retrospectively. Forceps biopsy or polypectomy were performed for all polypoid lesions that were identified during the endoscopy.
In the study period, 14,935 patients underwent 18,522 upper endoscopies. After excluding cirrhotic patients, and patients with a history of prior gastrectomy, chronic gastritis and edema or congestion, the remaining 124 (0.83%) patients with gastric polyps were included in the study. Histopathologically, the most frequently diagnosed polyps were hyperplastic polyps (55.6%). Fundic gland polyps (9.7%), foveolar hyperplasia (8.1%) and inflammatory polyps (7.3%) were also frequent. Adenocarcinoma was more frequently seen in males, whereas hyperplastic polyps and carcinoid tumors were found more often in females, and this difference was statistically significant (p<0.009).
Results of the present study indicate that hyperplastic polyps make up the largest group. Although there is widespread PPI use, no increases in the frequency of fundic gland polyps were observed. However, increases in the ratio of carcinoid tumors suggest a suspicion of tumor development with PPI use.
[Show abstract][Hide abstract] ABSTRACT: Gastric variceal bleeding is a common problem in patients with cirrhosis and despite early endoscopic and/or pharmacological therapy, variceal bleeding cannot be controlled or recurs early in about 10 to 20% of patients with considerable morbidity and mortality rates. For this reason, effective control of active bleeding varices is of great importance for the prevention of late complications. Although endoscopic band ligation and sclerotherapy are the choice of endoscopic treatment modalities with various grades of success, limited data is available for the use of Ankaferd Blood Stopper (ABS) for the controlling of variceal bleeding due to gastric varices. We herein present a unique case of gastric variceal bleeding despite cyanoacrilate injection, which was successfully controlled with topical ABS application.
Gastroentérologie Clinique et Biologique 08/2011; 36(1):e9-11. · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ectopic varices (EcV) accounting for 1-5% of all varices in portal hypertension are composed of dilated portosystemic collaterals located in unusual sites instead of the most known gastroesophageal region. The difficulty in localization of bleeding is a great burden on the management of these patients. Herein, we present patients with EcV as well as with portal hypertension and recurrent intestinal bleeding. The sites of EcV were identified with computed tomographic angiography, after a series of inconclusive endoscopies, and moreover a selective celiac arteriographic examination of one of the patients.
European journal of gastroenterology & hepatology 07/2011; 23(7):620-2. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare estimated remnant liver volume (ERLV) ratios among the major main portal vein (MPV) variants.
Eighty-five potential donors underwent multidetector CT examination. Arterial, portal and hepatic venous phase images were obtained. CT volumetric measurements were performed by using summation-of-area method. MPV variants were classified into three groups. In type 1 (group 1), the MPV branches into the right portal vein (RPV) and the left portal vein (LPV). In type 2 (group 2), the MPV trifurcates into the right anterior portal vein (RAPV), right posterior portal vein (RPPV) and LPV. In type 3 (group 3), the RPPV arises from the MPV as a first branch, and the RAPV emerges directly from the LPV.
No differences were observed between groups 1 and 2 with respect to ERLV ratios. However, significant differences were discovered between groups 1 and 3 and between groups 2 and 3 (p<0.001 and p<0.05, respectively).
The ERLV proportions in the donors with a type 3 MPV variation were significantly lower than those in the donors with type 1 and type 2 MPV variations and six (31.6%) donors in group 3 presented an ERLV percentage below 30% of the total liver volume.
European journal of radiology 02/2011; 81(3):478-83. · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the safety and efficacy of the endoscopic injection therapy with combined cyanoacrylate and lipiodol for bleeding gastric fundal varices.
The medical records of cirrhotic and non-cirrhotic patients who underwent at least one episode of endoscopic application of N-butyl-2-cyanoacrylate-lipiodol mixture for gastric varices at our gastroenterology clinic between October 2004 and January 2010 were reviewed. The technique comprised the dilution of 0.5 mL of cyanoacrylate with 0.5 mL of lipiodol and repeating intravariceal injections of 1.0 mL each until hemostasis was achieved.
A total of 66 patients (41 male and 25 female) with gastric varices underwent 86 endoscopic injections of cyanoacrylate for hemostasis. Overall 38 patients (57.6%) had active bleeding during the endoscopic procedure, while the remaining 28 (42.4%) underwent cyanoacrylate under elective conditions. In one patient (1.5%) hemostasis could not be achieved, prompting referral for emergency surgery. The median number of sessions was one (range 1-3). Eleven patients (16.6%) rebled during a median follow-up period of 6.02 months (0.1-62.4 months). There was no bleeding-related death. One patient developed splenic infarction a day after N-butyl-2-cyanoacrylate injection.
Endoscopic injection therapy combining cyanoacrylate and lipiodol is effective for bleeding gastric fundal varices.
Journal of Digestive Diseases 10/2010; 11(5):284-90. · 1.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Peginterferon alfa-2a results in a sustained response (SR) in a minority of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). This study investigated the role of early on-treatment serum hepatitis B surface antigen (HBsAg) levels in the prediction of SR in HBeAg-negative patients receiving peginterferon alfa-2a. HBsAg (Architect from Abbott) was quantified at the baseline and during treatment (weeks 4, 8, 12, 24, 36, and 48) and follow-up (weeks 60 and 72) in the sera from 107 patients who participated in an international multicenter trial (peginterferon alfa-2a, n = 53, versus peginterferon alfa-2a and ribavirin, n = 54). Overall, 24 patients (22%) achieved SR [serum hepatitis B virus (HBV) DNA level < 10,000 copies/mL and normal alanine aminotransferase levels at week 72]. Baseline characteristics were comparable between sustained responders and nonresponders. From week 8 onward, serum HBsAg levels markedly decreased in sustained responders, whereas only a modest decline was observed in nonresponders. However, HBsAg declines alone were of limited value in the prediction of SR [area under the receiver operating characteristic curve (AUC) at weeks 4, 8, and 12 = 0.59, 0.56, and 0.69, respectively]. Combining the declines in HBsAg and HBV DNA allowed the best prediction of SR (AUC at week 12 = 0.74). None of the 20 patients (20% of the study population) in whom a decrease in serum HBsAg levels was absent and whose HBV DNA levels declined less than 2 log copies/mL exhibited an SR (negative predictive value = 100%). Conclusion: At week 12 of peginterferon alfa-2a treatment for HBeAg-negative CHB, a solid stopping rule was established with a combination of declines in serum HBV DNA and HBsAg levels from the baseline. Quantitative serum HBsAg in combination with HBV DNA enables on-treatment adjustments of peginterferon therapy for HBeAg-negative CHB.
[Show abstract][Hide abstract] ABSTRACT: To assess the hemostatic efficacy of the Ankaferd Blood Stopper (ABS, Ankaferd Health Products Ltd, Turkey) hemostatic agent for controlling gastrointestinal bleeding associated with various benign lesions refractory to conventional antihemorrhagic measures.
The records of all patients who underwent upper and lower endoscopy procedures at the Turkiye Yuksek Ihtisas Teaching and Research Hospital (Ankara, Turkey) between April 2008 and June 2009 were reviewed. Patients in whom ABS was used as a primary or adjuvant hemostatic agent were included in the study. Rates of bleeding control and postprocedural complications were documented.
Hemostasis with no immediate complications was achieved in all patients within seconds of endoscopic application of ABS.
ABS may have a role as a primary treatment or as an adjuvant to conventional modalities used to control gastrointestinal bleeding. Prospective controlled studies are needed to help establish its efficacy and, perhaps, offer a comparison with conventional hemostatic interventions.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 06/2010; 24(6):380-4. · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients are at high risk of treatment relapse after any antiviral therapy. Combining peginterferon alpha-2a with ribavirin might improve sustained response rates.
Overall, 138 HBeAg-negative chronic hepatitis B patients were randomized to receive monotherapy (peginterferon alpha-2a 180 microg weekly plus placebo) or combination therapy (peginterferon alpha-2a weekly plus ribavirin 1,000 or 1,200 mg daily, depending on body weight) for 48 weeks. Post-treatment follow-up lasted 24 weeks. Analyses were based on the modified intention-to-treat population after exclusion of five patients.
At the end of follow-up, 14 (20%) of 69 patients assigned to monotherapy and 10 (16%) of 64 assigned to combination therapy had a combined response (hepatitis B virus (HBV) DNA <10,000 copies/ml (<1,714 IU/ml) and a normal alanine aminotransferase level, P=0.49). At the end of treatment, more patients had a combined response (25 (36%) vs. 26 (41%) in the monotherapy and combination therapy group, respectively, P=0.60), but subsequently relapsed during follow-up. Serum HBV DNA and hepatitis B surface antigen (HBsAg) levels decreased during treatment (mean change at week 48 compared with baseline -3.9 vs. -2.6 log copies/ml, P<0.001 and -0.56 vs. -0.34 log IU/ml, P=0.23, respectively). HBV DNA levels relapsed after treatment discontinuation; HBsAg remained at end-of-treatment levels. In general, combination therapy was well tolerated, although it was associated with a higher risk of anemia and neutropenia.
Treatment with peginterferon alpha-2a resulted in a limited sustained response rate in HBeAg-negative chronic hepatitis B patients. Addition of ribavirin did not improve response to therapy.
The American Journal of Gastroenterology 05/2010; 105(8):1762-9. · 9.21 Impact Factor