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Öğe Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B(2015) Koklu, Seyfettin; Gulsen, Murat Taner; Tuna, Yasar; Koklu, Hayretdin; Yuksel, Osman; Demir, Mehmet; Guner, RahmetSummary Background Results are conflicting with respect to the renal effects of anti-viral agents used for hepatitis B virus infection. Aim To compare short and long-term renal effects in real-life settings and to determine risk factors for renal impairment during treatment. Methods 2221 treatment-naïve patients were enrolled. Among these, 895 (302 lamivudine, 27 telbivudine, 282 entecavir, 273 tenofovir and 11 adefovir initiated patients) had 'repeated measures' of creatinine (baseline, 1st, 6th, 12th and 24th month of treatment). Telbivudine and adefovir groups were excluded from further analysis because of the low number of patients. We calculated the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula at each time point. Hypophosphataemia was also recorded. Risk factors for renal impairment were analysed. Results Tenofovir caused a decline in GFR at each time point when compared to baseline levels. However, lamivudine and entecavir did not change GFR. GFR-shifting from ?90 to 60-89 mL/min/1.73 m2 was comparable among groups. The proportion of patients whose baseline creatinine increased more than 25% was comparable among all anti-virals. GFR showed a decline in patients who switched from entecavir to tenofovir. One patient with compensated cirrhosis needed to change from tenofovir because of renal safety. Seven and three patients developed transient hypophosphataemia in the tenofovir and lamivudine groups, respectively. Conclusions Although tenofovir caused a decline in GFR, differences between the anti-viral agents do not appear to be so impressive. In patients with and without renal risk factors at baseline, there is no impact of anti-virals, including tenofovir. © 2014 John Wiley & Sons Ltd.Öğe GASTROINTESTINAL STROMAL TUMOR IN TURCOT SYNDROME(Lippincott Williams & Wilkins, 2015) Bulus, Hakan; Tas, Adnan; Koklu, Seyfettin[Abstract Not Available]Öğe Lamivudine Treatment Failure Risks in Chronic Hepatitis B Patients with Low Viral Load(Karger, 2013) Koklu, Seyfettin; Gulsen, Murat Taner; Tuna, Yasar; Koklu, Hayretdin; Yuksel, Osman; Yilmaz, Bans; Karaca, CetinAim: 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 nave noncirrhotic adult patients with LVL (for HBeAg+ patients HBV DNA <10(9) copies/ml and for HBeAg patients 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/all 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. (C) 2013 S. Karger AG, BaselÖğe Long-term clinical outcomes of Entecavir and .tenofovir in hepatitis B cirrhosis(Wiley-Blackwell, 2012) Koklu, Seyfettin; Tuna, Yasar; Gulsen, Murat T.; Demir, Mehmet; Koksal, Aydin S.; Kockar, Muhammed C.; Aygun, Cem[Abstract Not Available]Öğe Long-term Efficacy and Safety of Lamivudine, Entecavir, and Tenofovir for Treatment of Hepatitis B Virus-Related Cirrhosis(Elsevier Science Inc, 2013) Koklu, Seyfettin; Tuna, Yasar; Gulsen, Murat Taner; Demir, Mehmet; Koksal, Aydin Seref; Kockar, Muhammet Cem; Aygun, CemBACKGROUND & 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.
