Meral Akdogan

Early on‐treatment prediction of response to peginterferon alfa‐2a for HBeAg‐negative chronic hepatitis B using HBsAg and HBV DNA levels

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. (HEPATOLOGY 2010)

Endoscopic Application of Ankaferd Blood Stopper as a Novel Experimental Treatment Modality for Upper Gastrointestinal Bleeding: A Case Report

Endoscopic Application of Ankaferd Blood Stopper as a Novel Experimental Treatment Modality for Upper Gastrointestinal Bleeding: A Case Report

Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon

Summary.  Chronic delta hepatitis is the most severe form of chronic viral hepatitis for which interferon (IFN) is the only available treatment. In 39 patients (25 were treatment‐naïve, 14 had previously used IFN), efficacy of 1‐year treatment with IFN (9 MU, t.i.w.) or lamivudine (LAM; 100 mg, q.d.) alone was compared with IFN and LAM combination (2 months of LAM to be followed by combination treatment). IFN monotherapy was given only to treatment‐naïve patients. In both treatment‐naïve and previous IFN users, end of treatment virological and biochemical responses were similar with IFN–LAM combination and superior to LAM monotherapy (P < 0.05). Improvement in liver histology occurred more often with IFN ± LAM than with LAM alone (P < 0.05). In treatment‐naïve patients, combination treatment was not superior to IFN monotherapy. After treatment discontinuation, virological and biochemical response rates decreased in LAM and IFN combination and IFN monotherapy. On treatment virological response at month 6 of treatment predicted sustained virological response. The results of this study suggest that addition of LAM to IFN for the treatment of delta hepatitis is of no additional value and that both treatment modalities are superior to LAM monotherapy.

Ankaferd Blood Stopper as an effective adjunctive hemostatic agent for the management of life-threatening arterial bleeding of the digestive tract

latory failure, morbidity, and mortality are still important life-threatening prob- lems in this clinical setting. ABS may be useful as an adjunctive agent to mechan- ical intervention in cases of serious arte- rial bleeding. Neither any local adverse effect nor systemic toxicity was observed following the topical application of ABS.

Adding pegylated interferon to entecavir for hepatitis B e antigen–positive chronic hepatitis B: A multicenter randomized trial (ARES study)

Entecavir (ETV) is a potent inhibitor of hepatitis B viral replication, but long‐term therapy may be required. We investigated whether adding on pegylated interferon (Peg‐IFN) to ETV therapy enhances serological response rates. In this global investigator‐initiated, open‐label, multicenter, randomized trial, hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients with compensated liver disease started on ETV monotherapy (0.5 mg/day) and were randomized in a 1:1 ratio to either Peg‐IFN add‐on therapy (180 µg/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 of 85 (19%) patients allocated to the add‐on arm versus 9 of 90 (10%) in the monotherapy arm (P = 0.095). Adjusted for HBV DNA levels before randomized therapy, Peg‐IFN add‐on was significantly associated with response (odds ratio: 4.8; 95% confidence interval: 1.6‐14.0; P = 0.004). Eleven (13%) of the add‐on‐treated patients achieved disease remission after ETV cessation versus 2 of 90 (2%) of those treated with monotherapy (P = 0.007), which was 79% (11 of 14) versus 25% (2 of 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 hepatitis B surface antigen, 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 analogs. (Hepatology 2015;61:1512–1522)

A Randomized Trial of Peginterferon α-2a With or Without Ribavirin for HBeAg-Negative Chronic Hepatitis B

OBJECTIVES:Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients are at high risk of treatment relapse after any antiviral therapy. Combining peginterferon α-2a with ribavirin might improve sustained response rates.METHODS:Overall, 138 HBeAg-negative chronic hepatitis B patients were randomized to receive monotherapy (peginterferon α-2a 180 μg weekly plus placebo) or combination therapy (peginterferon α-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.RESULTS: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.CONCLUSIONS:Treatment with peginterferon α-2a resulted in a limited sustained response rate in HBeAg-negative chronic hepatitis B patients. Addition of ribavirin did not improve response to therapy.

Endoscopic topical application of Ankaferd Blood Stopper for neoplastic gastrointestinal bleeding: A retrospective analysis

AIM The aim of this study was to retrospectively assess the haemostatic efficacy of the endoscopic topical use of Ankaferd Blood Stopper (ABS) in the setting of neoplastic GI bleeding. METHODS The records of 10 patients with neoplastic GI bleeding (7 gastric, 3 rectal) were evaluated retrospectively. Written informed consent regarding the off-label use of ABS as a means of attaining haemostasis had been obtained from all of the patients prior to the procedure. In all patients, ABS was applied topically. Rates of bleeding control and post-procedural complications were documented. RESULTS Haemostasis was achieved in all patients within seconds of endoscopic application of ABS, with no immediate complications. Seven patients underwent subsequent cancer surgery after a bleeding-free post-procedural period. CONCLUSIONS ABS as a novel haemostatic agent could have a potential benefit in controlling bleeding from GI tumours. Prospective controlled studies are needed to help establish its efficacy, and perhaps offer a comparison to conventional haemostatic interventions.

Ankaferd Blood Stopper for controlling gastrointestinal bleeding due to distinct benign lesions refractory to conventional antihemorrhagic measures.

OBJECTIVE 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. METHODS 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. RESULTS Hemostasis with no immediate complications was achieved in all patients within seconds of endoscopic application of ABS. CONCLUSIONS 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.

Topical Ankaferd Blood Stopper Administration to Bleeding Gastrointestinal Carcinomas Decreases Tumor Vascularization

Topical Ankaferd Blood Stopper Administration to Bleeding Gastrointestinal Carcinomas Decreases Tumor Vascularization

Efficacy of interferon α‐2b and lamivudine combination treatment in comparison to interferon α‐2b alone in chronic delta hepatitis: A randomized trial

Background and Aim:  Delta hepatitis is characterized by rapidly progressive liver disease with adverse prognosis in most patients. Patients benefit from high doses and prolonged courses of interferon (IFN) therapy; however, lamivudine as a single agent has been disappointing. Data relating to the efficacy of IFN and lamivudine in combination is limited. The aim of this study was to test the efficacy of IFN‐α 2b and lamivudine combination treatment in comparison to IFN‐α 2b alone in patients with chronic delta hepatitis.