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Öğe 96 weeks of pegylated-Interferon- alpha-2? plus tenofovir or placebo for the treatment of hepatitis delta: the HIDIT-2 study(Wiley-Blackwell, 2013) Wedemeyer, Heiner; Yurdaydin, Cihan; Ernst, Stefanie; Caruntu, Florin A.; Curescu, Manuela G.; Yalcin, Kendal; Akarca, Ulus S.[Abstract Not Available]Öğe Analysis of Virological, Histological and Clinical Features of Hepatitis Delta Virus Infection in Southeastern Turkey(Galenos Yayincilik, 2018) Yalcin, Mehmet Suat; Yalcin, KendalObjectives: The present study aims to investigate biochemical, virological and histological characteristics of hepatitis delta virus infection, which is a serious problem in our region, as well as its relationship with chronic hepatitis B virus (HBV) infection and cirrhosis. Materials and Methods: A total of 220 patients were included in the study. The patients were divided into three groups: group 1 included patients with hepatitis delta virus-related cirrhosis (DA cirrhosis), group 2 consisted of patients with chronic delta hepatitis (CHD) and group 3 composed of patients with chronic hepatitis B (CHB). Biochemical and virological parameters of the patients were analyzed. Patients with CHB and CHD underwent biopsy for histological examination. The results were compared among the three groups. Results: Seventy-five (34.09%) of the patients were women, 145 (65.90%) were males and their mean age was 38.04 years. There were 44 patients (20%) with delta hepatitis-associated cirrhosis, 86 patients with CHD (39.09%) and 90 patients with CHD (40.9%). HBV DNA level was significantly lower in patients with cirrhosis and chronic delta hepatitis than in patients with CHB (p<0.001) (p<0.001). Histology activity score and fibrosis stage were significantly higher in CHD than in CHB (p<0.001) (p<0.001). A significant correlation was determined between fibrosis stage and hepatitis delta virus RNA in CHD patients. There was also a significant correlation between necroinflammatory score and alanine aminotransferase in CHD (p=0.021). Conclusion: In Turkey, the age of onset of delta hepatitis is low and accordingly, related liver cirrhosis develops at a younger age. HBV DNA levels appear to be suppressed in patients with delta hepatitis as compared to patients with CHB. Histologically severe disease picture is seen in patients with delta hepatitis and delta hepatitis-positive cirrhotic patients.Öğe Anti-HDV immunoglobulin M testing in hepatitis delta revisited: correlations with disease activity and response to pegylated interferon-?2a treatment(Int Medical Press Ltd, 2012) Mederacke, Ingmar; Yurdaydin, Cihan; Dalekos, George N.; Bremer, Birgit; Erhardt, Andreas; Cakaloglu, Yilmaz; Yalcin, KendalBackground: The role of anti-HDV immunoglobulin M (IgM) testing in patients receiving pegylated interferon-alpha therapy for hepatitis delta is unknown. We performed anti-HDV IgM testing in a well defined cohort of HDVinfected patients who were treated with pegylated interferon-alpha 2a plus adefovir, or either drug alone. Methods: Sera from 33 HDV-RNA-positive patients from the international HIDIT-1 trial were available for anti-HDV IgM testing (ETI-DELTA-IGMK-2 assay, DiaSorin, Saluggia, Italy) before therapy, at treatment weeks 24 and 48, and at 24 weeks after the end of treatment. Results: Anti-HDV IgM tested positive in 31 out of the 33 patients (94%) prior to treatment. HDV IgM levels correlated with histological inflammatory activity (r= 0.51, P<0.01) and were higher in patients with alanine aminotransferase and gamma-glutamyl transpeptidase levels above the median (P<0.05). Quantitative anti-HDV IgM values declined in patients responding to antiviral therapy, however anti-HDV IgM remained positive after treatment in the majority of virological responders. Conclusions: We suggest that anti-HDV IgM testing might give additional useful information to determine disease activity in hepatitis delta and to predict treatment response to antiviral therapy with type I interferons. However, determination of anti-HDV IgM can not substitute HDV RNA testing, which remains the primary virological marker for response to therapy.Öğe Association between IL28B gene polymorphism (rs12979860) and sustained virological response in patients infected with hepatitis C virus Genotype 1(Wiley-Blackwell, 2012) Akkiz, Hikmet; Sezgin, Orhan; Altintas, Engin; Yalcin, Kendal; Ekin, Nazim; Uskudar, Oguz; Sandikci, Macit U.[Abstract Not Available]Öğe BASELINE ALT LEVELS BUT NOT HDV-RNA LEVELS ARE ASSOCIATED WITH RESPONSE TO PEGYLATED INTERFERON ALFA-2A TREATMENT OF DELTA HEPATITIS: DATA FROM THE HIDIT-1 TRIAL(John Wiley & Sons Inc, 2008) Wedemeyer, Heiner; Yurdaydin, Cihan; Zachou, Kalliopi; Erhardi, Annette; Cakaloglu, Yilmaz; Yalcin, Kendal; Gurel, Selim[Abstract Not Available]Öğe Brucellosis as a rare cause of granulomatous hepatitis with hepatic and bone marrow granulomas: A case report(Kare Publ, 2021) Yalcin, Kendal; Tuncel, Elif Tugba; Ucmak, Feyzullah; Bestas, RemziBrucellosis is a zoonotic infection that may involve the liver in a variety of ways, however, data on the histopathology of liver effects in brucellosis are limited. Brucellosis is generally characterized by a high fever, joint or back pain, and hepatosplenomegaly. This report illustrates a case of granulomatous hepatitis with granulomas in the liver and bone marrow in a patient who presented with non-specific symptoms, hepatomegaly, splenomegaly, digital clubbing, and laboratory signs of intrahepatic cholestasis. Granulomas were detected in the bone marrow and hepatic specimens. The diagnosis of brucellosis was based on the isolation of Brucella mellitensis in a blood culture and serum agglutination titers of 1:640. Treatment for brucellosis led to improved laboratory and clinical findings. Brucellosis should be considered in regions where it is endemic in cases of an elevated transaminase level and related clinical findings. Brucellosis should also be considered in the differential diagnosis of intrahepatic cholestasis and/ or granulomas in hepatic and bone marrow biopsies. This case report provides valuable histopathological features and detailed information of liver involvement in a case of brucellosis.Öğe THE BURDEN OF DELTA HEPATITIS PROJECTED USING A MATHEMATICAL MODEL IN A DELTA HEPATITIS ENDEMIC COUNTRY(John Wiley & Sons Inc, 2009) Toy, Mehlika; Onder, Fatih Oguz; Idilman, Ramazan; Bozkaya, Hakan; Degertekin, Halil; Yalcin, Kendal; Schalm, Solko W.[Abstract Not Available]Öğe C-Reactive Protein and Platelet-Lymphocyte Ratio as Potential Tumor Markers in Low-Alpha-Fetoprotein Hepatocellular Carcinoma(Karger, 2019) Suner, Asli; Carr, Brian I.; Akkiz, Hikmet; Karakulah, Gokhan; Uskudar, Oguz; Yalcin, Kendal; Kuran, SedefThe hepatocellular carcinoma (HCC) tumor marker alpha-fetoprotein (AFP) is only elevated in about half of the HCC patients, limiting its usefulness in following the effects of therapy or screening. New markers are needed. It has been previously noted that the inflammation markers C-reactive protein (CRP) and platelet-lymphocyte ratio (PLR) are prognostically important and may reflect HCC aggressiveness. We therefore examined these 2 markers in a low-AFP HCC cohort and found that for HCCs > 2 cm, both markers significantly rise with an increasing maximum tumor diameter (MTD). We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index value for each marker, and their area-under-the-curve values for each MTD group. Patients were dichotomized into 2 groups based on the CRP and PLR from the receiver-operating characteristic curve analysis. In the logistic regression models of the 4 different MTD patient groups, CRP and PLR levels were statistically significant to estimate MTD in univariate logistic regression models of MTD groups > 2 cm. CRP and PLR were then combined, and the combination was statistically significant to estimate MTD groups of 3-, 4-, and 5-cm cutoffs. CRP and PLR thus have potential as tumor markers for low-AFP HCC patients, and possibly for screening. (C) 2018 S. Karger AG, BaselÖğe Can response to pegylated interferon treatment in chronic delta hepatitis be predicted with on-treatment parameters?(Wiley-Blackwell, 2012) Onder, Fatih Oguz; Erhardt, Andreas; Idilman, Ramazan; Keskin, Onur; Dalekos, George N.; Yalcin, Kendal; Manns, Michael P.[Abstract Not Available]Öğe Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis(Makerere Univ, Fac Med, 2015) Yilmaz, Bulent; Koklu, Seyfettin; Buyukbayram, Huseyin; Yalcin, Kendal; Korkmaz, Ugur; Posul, Emrah; Can, GurayBackground: The effect of hepatitis B virus (HBV) infection on fatty liver disease is unclear.. Objectives: The aim of this study was to investigate the viral and host causes of fatty liver in chronic hepatitis B (CHB) patients. This study included 88 CHB patients of which 17 were not treated. Liver biopsy was performed in each patient. Group 1 included those with hepatic steatosis (n=28) and group 2 those without hepatic steatosis. The groups were compared in terms of age, body mass index (BMI), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), viral load, biochemical parameters and histological findings. Patients in group 1 were subdivided according to the degree of steatosis as follows: grade 1 (15 patients, 53.6%), grade 2 (6 patients, 21.4%), and grade 3 (7 patients, 25%). Results: In group 1 (n=28), mean age, BMI, cholesterol, and HOMA-IR were found to be significantly higher than in group 2 (n=60). There were no significant differences in the positivity of viral load, HbeAg, treatment, fibrosis and other laboratory parameters between the two groups. HOMA-IR was the only independent predictive factor of liver steatosis in patients with CHB in logistic regression analysis. Conclusion: Hepatic steatosis in CHB patients was associated with host metabolic factors.Öğe Development of hepatocellular carcinoma in patients with chronic hepatitis C who had sustained viral response following direct-acting antiviral therapy(Kare Publ, 2022) Ebik, Berat; Aygan, Mustafa; Tuncel, Elif Tugba; Kacmaz, Huseyin; Ekin, Nazim; Arpa, Medeni; Yalcin, KendalBackground and Aim: Several studies have suggested that treatment with direct-acting antivirals (DAAs) in patients with chronic hepatitis C virus (HCV) may be associated with an increased risk of developing hepatocellular carcinoma (HCC). We investigated the incidence and risk factors of HCC in HCV patients who achieved a sustained virologic response (SVR) following DAA therapies. Materials and Methods: The medical data of patients who were diagnosed with HCV and received DAA therapy in two tertiary centers in Turkey were retrospectively collected. Results: Among them, 75 patients (52.4%) were noncirrhotic and 68 patients (47.6%) were cirrhotic. The overall SVR rate was 97.2% (139/143). It was 100% in noncirrhotic and 94.1% in cirrhotic patients. HCC was developed in 5 (7.4%) patients, all of whom had baseline cirrhosis. The annual rate of HCC occurrence was 2.94%, and the 5-year cumulative incidence of HCC was 7.3%. The mean Child-Pugh score (CPS) and Model for End-Stage Liver Disease (MELD) score significantly decreased after DAA treatment (CPS 7.0 vs 5.9, p=0.001; MELD 10.8 vs 9.5, =-0.003). Conclusion: There was no significant increase in the rate of HCC in cirrhotic HCV patients treated with DAAs. This treatment led to a remarkably high SVR rate and lowered CPS and MELD scores in cirrhotic HCV patients.Öğe The Effects of Pegylated Interferon Alpha-2a and Alpha-2b Therapy on Chromosomal Aberrations and Mitotic Index in Patients with Chronic Hepatitis B(Ortadogu Ad Pres & Publ Co, 2012) Akbas, Halit; Yalcin, Kendal; Isi, Hilmi; Simsek, Selda; Atay, Ahmet Engin; Budak, TurgayObjective: We aimed to prospectively evaluate the effects of pegylated interferon alpha-2a and alpha-2b therapy on chromosomal aberrations and mitotic index in patients with chronic hepatitis B. Material and Methods: Fifty patients with chronic hepatitis B who underwent pegylated interferon alpha-2a or 2b therapy were evaluated for chromosomal aberrations and mitotic index before the treatment and at the end of 6 months of therapy. Results: Cytogenetic examinations revealed out that there was no significant difference between pre- and post-treatment frequencies of mitotic index and chromosomal aberrations. Conclusion: Interferon alpha-2a and alpha-2b therapy which is associated with common hematologic adverse effects has no significant cytogenetic effect.Öğe Five years follow-up of 96 weeks peginterferon plus tenofovir disoproxil fumarate in hepatitis D(Elsevier, 2023) Anastasiou, Olympia Aevdoxia; Caruntu, Florin Alexandru; Curescu, Manuela Gabriela; Yalcin, Kendal; Akarca, Ulus S.; Gurel, Selim; Zeuzem, Stefan[Abstract Not Available]Öğe Gaucher's Disease Presenting with Massive Hepatic Fibrosis and Skeletal Abnormalities: A Case Report with Review of the Literature(Ortadogu Ad Pres & Publ Co, 2011) Yalcin, Kendal; Ucmak, Feyzullah; Bestas, Remzi; Unal, Hakan Umit; Necmioglu, Serdar; Mizrak, BulentThe case presented in this manuscript is a 32-year-old female referred to our clinic with massive hepatosplenomegaly, thrombocytopenia, anemia and avascular necrosis at the head of right femur. Gaucher's disease was diagnosed upon observation of specific blood cells in bone marrow and liver. Homozygote N370S mutation was established in the Gaucher's mutation screening. Glycocerebrosidase enzyme level of the patient was quite low (0.66 nmol/hour/mg). Additionally, histological examination of the liver revealed massive hepatic fibrosis without any clinically significant signs of cirrhosis or portal hypertension. Other significant signs of the patient were severe skeletal involvement with stage V/c avascular necrosis of the femoral head and Erlenmeyer flask paralysis. Glycocerebrosidase enzyme replacement therapy was initiated at 60 units/kg after the diagnosis was established. The case presented here is a female patient with signs of hepatic, bone marrow and skeletal system involvement. This rare non-neuropathic type 1 Gaucher's case with massive hepatic fibrosis and pathogonomic skeletal signs has been evaluated in the light of literature.Öğe Implications of HBsAg, HBcAg and HDAg Immunohistochemistry in Course and Treatment of Chronic Delta Hepatitis (CDH)(Wiley-Blackwell, 2012) Kabacam, Gokhan; Wedemeyer, Heiner; Heidrich, Benjamin; Yalcin, Kendal; Onder, Fatih Oguz; Dienes, Hans P.; Manns, Michael P.[Abstract Not Available]Öğe Latest updates on chronic delta hepatitis(Marmara Univ, Fac Medicine, 2016) Yalcin, Kendal; Tuncel, Elif Tugba; Gunduz, FeyzaThe hepatitis D virus was shown for the first time in 1977 by Rizzetto and friends. The HDV genome and the cloning of sequence were made in 1986. HDV is the first animal virus with circular RNA genome which is seen only in plant viruses. HDV is an RNA virus with the known smallest viral genome in animal viruses. It is classified as Deltavirus genius depending on the type of virus by ICTV in 1996. HDV is classified as the sole example of delta virus in this genus. Chronic delta hepatitis is the least common form of chronic viral hepatitis due to hepatotropic viruses. In contrast, the virus is highly pathogenic and can cause serious consequences. Today, prevalance of delta hepatitis has been shown to decrease. However, the delta hepatitis continues to be an important health problem in some parts of the world. In our country, especially in Eastern and Southeastern Anatolia, hepatitis D is a serious and important health problem and still maintains its importance as a health problem. In Turkey, still there is a significant number of patients with HDV infection despite a documented decrease in HDV infection. The recommended treatment for chronic HDV infection in the current guidelines is the treatment with peginterferon alfa given once a week for 48 weeks. Treatment is indicated for patients who has compensated disease with active infection. In patients with advanced form of disease, the expected benefits of the peginterferon must be well balanced against the potential side effects and low response rate. An oral antiviral can be recommended in patients who has high levels of serum HBV DNA. In contrast, the control of HBV infecion does not seem to change the natural history of HDV related disease.Öğe A novel non-invasive fibrosis score based on cytokines and clinical parameters for the use in chronic hepatitis delta(Wiley-Blackwell, 2013) Heidrich, Benjamin; Wranke, Anika; Yurdaydin, Cihan; Stift, Judith; Caruntu, Florin A.; Curescu, Manuela G.; Yalcin, Kendal[Abstract Not Available]Öğe A one step real time PCR method for the quantification of hepatitis delta virus RNA using an external armored RNA standard and intrinsic internal control(Elsevier Science Bv, 2014) Karatayli, Ersin; Altunoglu, Yasemin Celik; Karatayli, Senem Ceren; Alagoz, S. Gokce K.; Cinar, Kubilay; Yalcin, Kendal; Idilman, RamazanBackground: Hepatitis delta virus (HDV) RNA viral load measurement is critical in diagnosis and monitoring the response to antiviral treatment. Objectives: Our aim is to design a real time PCR method for accurate quantitation of HDV RNA in clinical specimens using an armored RNA as external standard, and an intrinsic internal control. Study design: A plasmid bearing delta antigen region of genotype I HDV genome was used to develop an armored RNA. Serial dilutions of the armored HDV RNA standard with 10(12) copy/mL were used as standards for quantitation. A primer-probe set derived from HDAg region was used in one step EZ RT PCR kit chemistry which uses rTth enzyme allowing reverse transcription and polymerization in the same tube. The kit also uses the advantage of uracil-N-glycosylase (UNG) enzyme treatment to prevent PCR contamination. Results: The established assay has a dynamic range of 10(2)-10(11) copy/mL with a PCR efficiency of 96.9%. Detection limit was 858 +/- 32 copy/mL with 95% confidence interval. Intra-and inter-assay variabilities were low for high, medium and low levels of viremia. Incorporation of freely circulating GAPDH in serum into the assay as an intrinsic internal control prevented false negative results and failures in PCR amplifications due to inhibitors, inefficient extraction procedures or enzymatic reactions. Conclusion: In conclusion, this study defines a novel assay for sensitive and reliable quantification of HDV RNA using an armored HDV RNA as a standard and GAPDH in plasma or serum as an intrinsic internal control in a single tube. (c) 2014 Elsevier B.V. All rights reserved.Öğe p53 CODON 72 POLYMORPHISM ASSOCIATED WITH HEPATITIS B(John Wiley & Sons Inc, 2009) Akbas, Halit; Isi, Hilmi; Yalcin, Kendal; Tekes, Selahallin; Simsek, Selda; Budak, Turgay[Abstract Not Available]Öğe Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial(Elsevier Sci Ltd, 2019) Wedemeyer, Heiner; Yurdaydin, Cihan; Hardtke, Svenja; Caruntu, Florin Alexandru; Curescu, Manuela G.; Yalcin, Kendal; Akarca, Ulus S.Background Hepatitis D is the most severe form of chronic viral hepatitis. Treatment guidelines recommend 1 year of peginterferon alfa, which is effective in 25-30% of patients only. Whether prolonged therapy with peginterferon alfa-2a for 96 weeks and combination therapy with tenofovir disoproxil fumarate (TDF) would increase hepatitis D virus (HDV) RNA suppression is unknown. We aimed to explore whether prolonged treatment of HDV with 96 weeks of peginterferon would increase HDV RNA response rates and reduces post-treatment relapses. Methods We did two parallel, investigator-initiated, multicentre, double-blind randomised, controlled trials at 14 study sites in Germany, Greece, Romania, and Turkey. Patients with chronic HDV infection and compensated liver disease who were aged 18 years or older were eligible for inclusion. All patients were HBsAg positive for at least 7 months, anti-HDV positive for at least 3 months, and HDV-RNA positive at the local laboratory at the screening visit. Patients were ineligible if alanine aminotransferase levels were higher than ten times above the upper limit of normal and if platelet counts were lower than 90 000 per mu L, or if they had received interferon therapy or treatment with a nucleoside and nucleotide analogue within the preceding 6 months. Patients were randomly assigned by blinded stratified block randomisation (1:1) to receive 180 mu g of peginterferon alfa-2a weekly plus either TDF (300 mg once daily) or placebo for 96 weeks. The primary endpoint was the percentage of patients with undetectable HDV RNA at the end of treatment assessed by intention to treat. The trials are registered as NCT00932971 and NCT01088659. Findings Between June 24, 2009, and Feb 28, 2011, we randomly assigned 59 HDV RNA-positive patients to receive peginterferon alfa-2a plus TDF and 61 to receive peginterferon alfa-2a plus placebo, including 48 (40%) patients with cirrhosis to the two treatment groups (23 in the peginterferon alfa-2a plus TDF group and 25 in the peginterferon alfa-2a plus placebo group). The primary endpoint was achieved in 28 (48%) of 59 patients in the peginterferon alfa-2a plus TDF group and in 20 (33%) of 61 patients in the peginterferon alfa-2a plus placebo group (odds ratio 1.84, 95% CI 0.86-3.91, p=0.12). We recorded 944 adverse events (459 in the peginterferon alfa-2a plus TDF group and 485 in the peginterferon alfa-2a plus placebo group). The most common adverse events were haematological, behavioural (eg, fatigue), musculoskeletal, influenza-like syndromes, and psychiatric complaints. Interpretation Addition of TDF resulted in no significant improvement in HDV RNA response rates at the end of treatment. These findings highlight that alternative treatment options are needed for hepatitis D. Copyright (c) 2019 Elsevier Ltd. All rights reserved.
