Hepatitis: Turkey

Tabak F, Mert A, Ozaras R, Biyikli M, Ozturk R, Ozbay G, Senturk H, Aktuglu Y. · Department of Clinical Bacteriology and Infectious Diseases, Cerrahpasa Medical Faculty, Istanbul University, Beylerbeyi 81210 Istanbul, Turkey. · J Clin Gastroenterol. · Pubmed #11960076 No free full text.

Abstract: Losartan, an angiotensin II receptor antagonist, is widely used for the treatment of hypertension. Clinical experience with this drug has demonstrated that it is safe. Losartan-induced hepatic toxicity is extremely rare. We report a case of severe hepatic toxicity and fibrosis caused by losartan use, and we review four previously reported cases. Drug-induced hepatic injury may be seen during the treatment of hypertension by losartan and the clinician should be aware of this toxicity, especially during the initial phase of treatment.

Andiran N, Sentürk GB, Bükülmez G. · Department of Pediatrics, Hacettepe University, Ihsan Dogramaci Children's Hospital, Ankara, Turkey. · Dermatology. · Pubmed #11834856 No free full text.

Abstract: An 11-month-old boy presented with Gianotti-Crosti syndrome. He had received measles and a third dose of hepatitis B vaccines 2 weeks before the onset of the eruption. There were no clinical symptoms of any viral infection at the presentation. Serological tests for common viral infections were negative. The combination of measles and hepatitis B vaccines was likely the relevant factor in the etiology.

Erensoy S. · Department of Microbiology and Clinical Microbiology, Ege University, 35100, Bornova, Izmir, Turkey. · J Clin Virol. · Pubmed #11397664 No free full text.

Abstract: BACKGROUND: Just after the identification and characterization of hepatitis C virus (HCV) in 1989, tests for the detection of HCV antibodies or HCV RNA in serum were developed. The enzyme-linked immunosorbent assays (ELISAs) and confirmatory/supplemental analytical antibody tests were improved in sensitivity and specificity with the development of further generations of these assays. Application of molecular tests for detecting, quantifying, and characterization of the infecting virus became very important in management of HCV infection. OBJECTIVE AND DESIGN: This review summarizes the assays developed for the diagnosis and management of HCV infection. Strategies for the diagnosis and monitoring with the advantages and disadvantages of the assays based on the setting and goal are discussed according to data in the literature and our experience. Results: Specific laboratory diagnostic tests for hepatitis C virus infection may be discussed under two titles: (i) Serological antibody tests which detect anti-HCV in serum or plasma; (ii) Molecular tests which detect HCV RNA genome, investigate viral load, and determine the characteristics of the genome. Strategies in different laboratory settings which screen populations with different HCV prevalences vary. CONCLUSIONS: Anti-HCV positive result in a low-risk setting such as blood banks should be confirmed with an analytical antibody test. Then a HCV RNA test should be performed on serum of the person with a positive or indeterminate confirmatory test result. On the contrary, anti-HCV positive test result in high-risk population or a situation where HCV infection is suspected, it is likely to be true positive and confirmation with HCV RNA test will be significant. Quantitative HCV RNA test and genotyping should be performed if therapy is considered.

Badur S, Akgün A. · Department of Microbiology, Division of Virology and Immunology, Istanbul University Medical School, Istanbul, Turkey. · J Clin Virol. · Pubmed #11397659 No free full text.

Abstract: Worldside viral hepatitis is still recognized as a major problem particularly in developing countries. During the past two decades there has been important progress in the field of viral hepatitis; the adaptation of molecular biology techniques to viral hepatitis has proven to be of great utility in the diagnosis of 'classical' hepatitis viruses, in monitoring during treatment, and also in learning more about the 'new' viruses. Here, the progress and pitfalls of serologic and molecular diagnosis techniques for viral hepatitis, unusual profiles and benefits of quantitative DNA/RNA tests will be discussed.

Ozturk M. · Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey. · Semin Liver Dis. · Pubmed #10518303 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is linked etiologically to viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]), chemical carcinogens (i.e., aflatoxins), and other environmental and host factors causing chronic liver injury. Some hepatoblastomas may be linked to inherited gene mutations, but adult hereditary HCC appears to be rare. HCCs display gross genomic alterations, including DNA rearrangements associated with HBV DNA integration, loss of heterozygosity, and, less importantly, chromosomal amplifications and loss of imprinting. Many genes with somatic mutations have now been identified in these tumors. Most frequently involved genes are tumor suppressor genes such as p53, M6P/IGF2R, beta-catenin, p16INK4A, and retinoblastoma genes. Most identified mutations are somatic, but germline mutations of p16INK4A, APC, and BRCA2 have also been reported. Oncogenic activation of several cellular genes such as cyclin D and cyclin A have been described in HCC, but the possible implication of candidate viral oncogenes (i.e., X protein of HBV) is still debated. A comprehensive analysis of all the genetic changes described for HCC demonstrates that at least four different growth regulatory pathways are altered in these tumors. However, each pathway appears to be implicated in a limited fraction of these tumors, suggesting that HCCs are genetically heterogenous neoplasms. This genetic heterogeneity correlates with the heterogeneity of etiologic factors implicated in HCC.

Kose S, Gurkan A, Akman F, Kelesoglu M, Uner U. · Clinical Microbiology and Infectious Diseases Clinic, Izmir Tepecik Training and Research Hospital, Izmir, Turkey. · J Gastroenterol. · Pubmed #19277451 No free full text.

Abstract: PURPOSE: Hepatitis C virus (HCV) is prevalent in renal insufficient patients. The aim of the present study was to evaluate the efficacy and tolerability of pegylated interferon alpha-2a (peg-IFN-alpha-2a) among these patients. METHODS: Among 437 patients within total hemodialysis population in hemodialysis units, in total 83 patients (19.0%) were anti-HCV positive and of these 83 patients, 33 (39.7%) were HCV-RNA positive. Treatment was initiated in 33 patients who had chronic HCV infection. All patients were found to be HCV-RNA positive. During treatment, peg-IFN-alpha-2a (40 kDa), 135 microg/week was used on these 33 patients. RESULTS: Twenty-six (78.8%) of the 33 patients enrolled in the study completed the treatment. Two patients (6.0%) did not complete treatment because they had serious adverse events such as anemia and thrombocytopenia. At the onset of treatment, while all of 26 patients were HCV RNA positive, HCV RNA turned to negative in all 26 patients 3 months after treatment. CONCLUSIONS: At the end of the study, peg-IFN-alpha-2a treatment of patients with chronic hepatitis C on maintenance hemodialysis may improve prognosis and their quality of life.

Cil T, Altintas A, Pasa S, Bayan K, Ozekinci T, Isikdogan A. · Department of Medical Oncology, Internal Medicine, Dicle University, Diyarbakir, Turkey. · Leuk Lymphoma. · Pubmed #18464113 No free full text.

Abstract: Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.

Kilic ZM, Kuran S, Akdogan M, Cicek B, Oguz D, Odemis B, Sasmaz N. · Gastroenterology Department, Turkiye Yuksek Ihtisas Hospital, Suleymanbey Sok. 29/10, Maltepe, 06570, Ankara, Turkey. · Adv Ther. · Pubmed #18385953 No free full text.

Abstract: INTRODUCTION: In hepatitis B virus (HBV)-related liver cirrhosis, patients with HBV replication show a higher mortality rate than those without. We aimed to investigate the long-term effects of lamivudine on HBV DNA suppression, Child-Pugh score, and survival in patients with hepatitis Be antigen (HBeAg)-negative liver cirrhosis. METHODS: Sixty-eight patients (51 male, 17 female) diagnosed with HBV-positive liver cirrhosis, who were monitored by the hepatology and liver transplantation outpatient clinics of our hospital between June 1999 and May 2007, were included in the study. Lamivudine (100 mg/day) was administered orally. Follow-up visits were scheduled monthly during the first 3 months, and every 3 months thereafter. Complete blood count, haemostasis, biochemistry (aspartate aminotransferase [AST], alanine aminotransferase [ALT], amylase, urea, creatinine, total bilirubin, direct bilirubin, total protein, albumin), and alpha-foetoprotein were recorded every 3 months. HBV DNA levels, abdominal ultrasound and the Child-Pugh score were evaluated every 6 months. RESULTS: Sixty-eight patients (mean age, 52.05+/-12.6 years) were monitored for 49.51+/-18.51 months. Basal ALT, HBV DNA levels and Child-Pugh scores were 103.9+/-73.9 IU/ml, 4133+/-121,94 IU/ml, and 7.6+/-2.4, respectively. The ALT normalisation was 59.7% during the first year, 68.2% during the second year and 44.4% during the fifth year. There was a significant decrease in Child-Pugh scores in the first 3 follow-up years when compared with the baseline score (P<0.05). During the treatment, HBV DNA positivity and YMDD mutations were determined in 20 of 68 (29.4%) patients at 46+/-17.9 months. Nine patients (13.2%) developed hepatocellular carcinoma at 44.8+/-21.5 months. Thirteen patients (19.1%) died during the treatment due to liver failure or variceal bleeding. CONCLUSION: Lamivudine is beneficial in patients with HBeAg-negative liver cirrhosis in terms of improvement in liver function and enhancement of survival and quality of life. An HBV DNA suppressive effect and improvement in Child-Pugh score were seen especially in the first years. It is important to be aware of YMDD mutation early, as addition of new antivirals is necessary to overcome unwanted results of the mutation.

Nayman Alpat S, Usluer G, Yavuz H, Doyuk Kartal E, Erben N, Bal C, Ozgunes I. · Eskisehir Osmangazi University Faculty of Medicine, Department of Clinical Microbiology and Infectious Diseases, Turkey. · J Chemother. · Pubmed #18343751 No free full text.

Abstract: Health-related quality of life (HRQoL) during therapy was found to be improved in patients treated with peginterferon alpha-2a compared to patients receiving interferon alpha-2a. This study aimed to assess the effect of different pegylated interferon therapies used in the treatment of patients with chronic hepatitis C on HRQoL.Forty chronic hepatitis C patients were enrolled. 22 patients were given a combination of peginterferon alpha-2a plus ribavirin and 18 patients received a combination of peginterferon alpha-2b plus ribavirin for 48 weeks. Patients completed a Short Form-36 (SF-36) questionnaire at the start of treatment and at week 12, week 24 and week 48 of treatment and week 24 posttreatment to evaluate HRQoL. In conclusion, the effect of both combination treatments on quality of life was similar.

Akman SA, Okcu SC, Halicioğlu O, Sutcuoglu S, Anil M, Kizilgunesler A, Bakiler AR. · Department of Pediatrics, Izmir Tepecik Training and Research Hospital, Izmir, Turkey. · Pediatr Int. · Pubmed #18045284 No free full text.

Abstract: BACKGROUND: Interferon (IFN)-alpha and lamivudine (LAM), a nucleoside analog, are frequently used drugs for the treatment of chronic hepatitis B (CHB), and their combined therapy has been shown to be effective. The purpose of the present study was to examine the therapeutic efficacy of sequential and simultaneous combination therapies of IFN-alpha and LAM in children with CHB. METHODS: A total of 45 children with CHB, whose antibody status was positive for hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), and HBV-DNA at least for 6 months; who had alanine aminotransferase (ALT) levels 1.5-fold higher than normal and hepatic activity index scores higher than 6, were allocated to two groups. The first group included 24 children who were given standard dose IFN-alpha (5 MU/m(2) s.c., thrice weekly) for 6 months, followed by LAM (4 mg/kg per day per oral, maximum 100 mg/day) for an additional 6 months (sequential therapy group). The second group included 21 children who were given IFN-alpha and LAM therapy simultaneously for 6 months and who continued with LAM alone for another 6 months (simultaneous therapy group). Partial response was defined as normalization of ALT and eradication of HBV-DNA. Complete response was defined as normalization of ALT, eradication of HBV-DNA and e seroconversion. Non-responders were defined as having positive HBV-DNA and abnormal ALT levels. Sustained response was defined as absence of HBsAg and presence of hepatitis B surface antibody (anti-HBs). RESULTS: The mean age of the sequential therapy group was 12.7 +/- 4.1 years, and 16 (66.7%) of the patients were male. The mean age of the simultaneous therapy group was 14.8 +/- 4.6 years, and 15 (71.4%) were male. In the first group, 13 patients (54.2%) were non-responders; partial response was observed in five patients (20.8%), and complete response was seen in six patients (25%). Despite the occurrence of e seroconversion, normalization of ALT was not achieved in one case. In the second group, which consisted of 21 patients, 11 subjects (52.4%) were non-responders; partial response was observed in one case (4.8%), and complete response was seen in seven (33.3%). Sustained response was found in two patients (9.5%). There were no significant differences between the groups (P > 0.05). CONCLUSION: When the therapeutic efficiency of two different treatment regimens applied for 1 year was evaluated in childhood CHB therapy, it was remarkable that there was a sustained response and a higher complete response in group 2, although there was no considerable difference between the therapy results of both groups.

Yurdaydin C, Bozkaya H, Karaaslan H, Onder FO, Erkan OE, Yalçin K, Değertekin H, Bozdayi AM, Uzunalimoğlu O. · Gastroenterology Section, University of Ankara Medical School, Turkey. · J Viral Hepat. · Pubmed #17927618 No free full text.

Abstract: High dose interferon treatment for 1 year is the only established treatment for chronic hepatitis D, but it is associated with a high relapse rate after treatment discontinuation. In this study, patients were treated with 10 MU interferon alpha 2b, thrice weekly for 2 years. Twenty-three patients were recruited and 15 completed the 2-year treatment and 6 months follow-up periods. Treatment response was assessed biochemically [normal alanine aminotransferase (ALT)], virologically (undetectable hepatitis D virus RNA) and histologically (at least 2 point decrease in the Knodell score) at the end of treatment (EOT) and at the end of follow-up. Out of 15 patients who finished the 2-year treatment period, seven patients (47%) had a biochemical response but only two (13%) had a normal ALT after follow-up. ALT decreased from the baseline value of 143.1 +/- 121.7 (mean +/- SD) to 39.7 +/- 20.6 (P < 0.01) at EOT. Virological response was observed in six patients at EOT and in two patients at follow-up. Two patients lost hepatitis B surface antigen. Of the 12 patients with paired liver biopsies, a histological improvement was observed in eight patients. Interferon treatment leads to a complete or partial response in a substantial number of patients but 2 years of treatment does not appear to increase sustained response rates over 1 year treatment.

Yilmaz Y, Dolar E, Ulukaya E, Akgoz S, Keskin M, Kiyici M, Aker S, Yilmaztepe A, Gurel S, Gulten M, Nak SG. · Uludag University Medical School, Department of Internal Medicine, Bursa 16059, Turkey. · World J Gastroenterol. · Pubmed #17352011 links to  free full text

Abstract: AIM: To investigate whether serum levels of two soluble forms of extracellular cytokeratin 18 (M30-antigen and M65-antigen) may differentiate nonalcoholic steatohepatitis (NASH) from simple steatosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 83 patients with suspected NAFLD and 49 healthy volunteers were investigated. Patients with suspected NAFLD were classified according to their liver histology into four groups: definitive NASH (n=45), borderline NASH (n=24), simple fatty liver (n=9), and normal tissue (n=5). Serum levels of caspase-3 generated cytokeratin-18 fragments (M30-antigen) and total cytokeratin-18 (M65-antigen) were determined by ELISA. RESULTS: Levels of M30-antigen and M65-antigen were significantly higher in patients with definitive NASH compared to the other groups. An abnormal value (> 121.60 IU/L) of M30-antigen yielded a 60.0% sensitivity and a 97.4% specificity for the diagnosis of NASH. Sensitivity and specificity of an abnormal M65-antigen level (> 243.82 IU/L) for the diagnosis of NASH were 68.9% and 81.6%, respectively. Among patients with NAFLD, M30-antigen and M65-antigen levels distinguished between advanced fibrosis and early-stage fibrosis with a sensitivity of 64.7% and 70.6%, and a specificity of 77.3% and 71.2%, respectively. CONCLUSION: Serum levels of M30-antigen and M65-antigen may be of clinical usefulness to identify patients with NASH. Further studies are mandatory to better assess the role of these apoptonecrotic biomarkers in NAFLD pathophysiology.

Kanra G, Kara A, Demiralp O, Contorni M, Hilbert AK, Spyr C, Viviani S. · Department of Pediatric Infectious Diseases, Medical Faculty, Hacettepe University, Ankara, Turkey. · Hum Vaccin. · Pubmed #17012890 No free full text.

Abstract: We assessed the safety and immunogenicity of a fully liquid, DTPw-HepB-Hib combination vaccine (Quinvaxem) in comparison with separately administered DTPw-Hib and hepatitis B vaccines. Infants participating in this open-label, randomized, phase II study received a primary vaccination course using a 2-3-4 month schedule. Blood samples were taken immediately prior to the first and one month after the third vaccination. Adverse events were assessed over a 7-day post-vaccination period using subject diaries. After completion of the primary vaccination course, 94.7% [95% CI: 89.8-97.7%] of infants receiving the combination vaccine achieved protective anti-HBs antibody titers (> or = 10 mIU/mL) with a mean 39-fold increase in GMTs in comparison with 99.3% [95% CI: 96.3-100%] seroprotection and a mean 29-fold GMT increase in the comparator group. Diphtheria, tetanus and Haemophilus influenzae type b (Hib) seroprotection rates and pertussis seroconversion rates were also similar between the two groups. There was no statistically significant difference in GMTs for diphtheria between the two groups, but significant differences were shown for tetanus, Hib, and pertussis with higher GMTs for each antigen observed in the comparator group. The combination vaccine was well tolerated, with fever (body temperature > or = 38 degrees C) being the most frequently reported adverse event in both the DTPw-HepB-Hib (12.5% [95% CI: 7.7-18.8%]) and comparator (12.6% [95% CI: 7.7-19.0%]) groups. This study demonstrated that the fully liquid DTPw-HepB-Hib combination vaccine has safety and immunogenicity profiles similar to the DTPw-Hib and hepatitis B vaccines when administered separately.

Yağci M, Yağci M, Acar K, Acar K, Sucak GT, Aki Z, Bozdayi G, Haznedar R. · Department of Haematology, Gazi Medical School, Ankara, Turkey. · Leuk Lymphoma. · Pubmed #16966273 No free full text.

Abstract: Chemotherapy-induced hepatitis B virus (HBV) reactivation is a serious problem in chronic HBV carriers with hematologic malignancies. In 12 patients with hematologic malignancies, we performed a prospective study to determine the effectiveness of nucleoside analogues in the pre-emptive therapy of chemotherapy-induced HBV reactivation. HBV reactivation occurred in seven patients (58.3%) whereas five of the seven patients (71%) responded to nucleoside analogue therapy. HBV reactivation-related acute liver failure and death was not observed in the present study. All five patients with chronic lymphocytic leukemia (CLL) experienced chemotherapy-induced HBV reactivation regardless of the chemotherapy regimen. Therefore, we suggest that CLL carries a significant risk of chemotherapy-induced HBV reactivation. The pre-emptive therapy of chemotherapy-induced HBV reactivation appears to be safe, based on the results of this pilot study. Pre-emptive therapy enables the definition of high-risk patients who cannot be identified by primary prophylaxis.

Yilmaz A, Akcam M, Gelen T, Artan R. · Pediatric Gastroenterology, Akdeniz University, Pediatri Anabilim Dali, Arapsuyu, Antalya 07059, Turkey. · Eur J Pediatr. · Pubmed #16944240 No free full text.

Abstract: Chronic hepatitis B virus infection is among the most common causes of chronic liver disease in children. The aim of this study was to document prospectively our experiences related to lamivudine and high-dose interferon-alpha2a combination in naïve, e antigen positive, chronic hepatitis B virus infection treatment in children. Thirty-three children diagnosed as naïve, immunoactive chronic hepatitis B were treated with lamivudine (3 mg/kg/day) and interferon-alpha2a (10 MU/m2, thrice weekly). Initially, lamivudine was initiated three months before interferon-alpha for induction, and after June 2002, both drugs were started simultaneously. After interferon-alpha was stopped, lamivudine alone was continued for six months. HBeAg seroconversion with the normalization of serum ALT was achieved at the end of treatment and at the end of follow-up for 20/33 patients. Initial mean alanine aminotransferase, 142.9 IU/L, decreased to a mean value of 31.4. End-treatment response and sustained response rates were 66.7% (14/21) and 50% (6/12), respectively, in patients that underwent lamivudine induction before interferon-alpha and in patients that began to receive the two drugs simultaneously (p=0.4). Flu-like syndrome and anorexia were the most common complaints. As our conclusions, we propose that interferon-alpha2a plus lamivudine combination therapy is highly successful and safe in children suffering from chronic hepatitis B. Lamivudine induction before interferon does not seem to be necessary.

Bolukbas C, Bolukbas FF, Kendir T, Akbayir N, Ince AT, Abut E, Horoz M, Dalay AR, Sokmen MH, Ovunc O. · Department of Internal Medicine, Division of Gastroenterology, Harran University, Sanliurfa, and Gastroenterology Clinic, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey. · Dig Dis Sci. · Pubmed #16944009 No free full text.

Abstract: In this study, the effect of lamivudine therapy on viral suppression, Child-Pugh score, and survival was assessed in patients with decompensated cirrhosis due to precore mutant hepatitis B virus and the results were compared with those for nonreplicative cirrhotic patients. Twenty-three replicative patients who received lamivudine and 15 nonreplicative patients were included and followed up for an average of 23.7+/-13.4 months. At baseline, there were no significant differences between the groups with regard to clinical and biochemical parameters or Child-Pugh scores, except for serum alanine aminotransferase levels (P<0.05) and quantitative hepatitis B virus DNA measurements (P<0.001). Compared to baseline, there was no significant difference in Child-Pugh score in the lamivudine group at the last visit (P=0.202), whereas a marked increase was observed in nonreplicative patients (P=0.002). Mortality rates in the lamivudine and nonreplicative groups were 17.43% and 13.3%, respectively (P=0.556), and there was no difference in survival analysis (P=0.809). Lamivudine therapy stabilizing clinical situation in decompensated cirrhotics with precore mutation makes the natural history of the disease equal with nonreplicative decompensated cirrhotics or even provides some advantages over them.

Karaoglan M, Demirci F, Coskun Y, Karaoglan I, Bayraktaroglu Z, Okan V, Karsligil T. · State Pediatrics Hospital of Gaziantep, Gaziantep, Turkey. · J Natl Med Assoc. · Pubmed #16708498 links to  free full text

Abstract: PURPOSE: The aim of this study is to investigate the effects of HBsAg vaccine and levamisole on virological indicators in naive patients suffering from chronic hepatitis B (CHB) and in healthy carriers of hepatitis B. METHOD: Vaccination and treatment with levamisole were applied to 93 minor patients in total, 43 of them inactive CHB carriers and 50 patients suffering from CHB. RESULTS: 15 (30%) of 50 patients who had high ALT values in the beginning of the study had normal values after treatment. In nine (12%) patients, posttreatment ALT values were higher than pretreatment values, and six (10%) patients showed HBV-DNA loss. In spite of the presence of 50 (54%) HBeAg-positive patients before treatment, 17 (34%) patients proved to be HBeAg-negative after treatment. HBeAg sero-conversion was seen in 10 (20%) cases. In two (2%) patients, HBsAg sero-conversion occurred. CONCLUSION: It was found that treatment with levamisole and vaccine had positive effects on CHB patients and healthy carriers with respect to HBV DNA loss, HBeAg sero-conversion and ALT normalization. The viral load increases and ALT increases that occurred in certain cases were thought to be related to the early immune response. It was determined that combined levamisole and vaccine therapy had no additional positive effect.

Artan R, Akcam M, Yilmaz A, Kocacik D. · Akdeniz University Faculty of Medicine Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Antalya, Turkey. · J Chemother. · Pubmed #16433196 No free full text.

Abstract: We assessed the effectiveness of interferon (IFN) monotherapy in thalassemic or hemodialysis patients with chronic hepatitis C viral (HCV) infection. Ten thalassemic and four hemodialysis patients were included in the study. Chronic HCV was confirmed with both serum HCV-RNA and liver histopathology. IFN alpha-2a was administered three times a week for 24-48 weeks, at a dose of 5 MU/m2 (maximum 6 million units). Sustained response was defined as negative HCV-RNA at least 24 weeks after termination of the treatment. All patients completed the study. Eight of 10 thalassemic (80%) and one of four hemodialysis patients (25%) showed a sustained response. IFN monotherapy proved to be an effective treatment, especially in thalassemic patients with chronic HCV. IFN monotherapy seems reasonable for patients with thalassemia and chronic hepatitis C virus in whom ribavirin cannot be used.

Sertoz RY, Erensoy S, Pas S, Akarca US, Ozgenc F, Yamazhan T, Ozacar T, Niesters HG. · Department of Clinical Microbiology, Ege University Medical Faculty, Turkey. · J Chemother. · Pubmed #16323440 No free full text.

Abstract: The aim of this study was to compare direct sequence analysis of partial HBV pol gene and Inno-LiPA HBV DR in serum samples of 120 chronic hepatitis B patients sent to the Clinical Microbiology Laboratory of Ege University Hospital because of lamivudine resistance. Sequence analysis was performed on ABI Prism 310 Genetic Analyzer. Comparison of Inno-LiPA and sequence results obtained by double-blind evaluation showed full agreement (both at rt180 and rt204) in 58.8% of samples. Visually rechecking of the electropherograms increased this rate to 68.3% Codon based rates are 81.7% and 75.8% at rt180 and rt204 respectively. LiPA detected variants in additional 12 (10%) samples, but missed one variant sample (both rt180 and rt204) and one sample was indeterminate due to poor probe binding. LiPA allows determination of mixed variants and seems to be more sensitive and simple for routine testing even though sequence analysis is still the gold standard for detecting new variants.

Gunsar F, Akarca US, Ersoz G, Kobak AC, Karasu Z, Yuce G, Ilter T, Batur Y. · Ege University Medical School Gastroenterology, Izmir, Turkey. · Antivir Ther. · Pubmed #16218171 No free full text.

Abstract: The only beneficial agent for the treatment of chronic delta hepatitis (CDH) is interferon (IFN). However, there is no consensus on the best dosage or duration of IFN therapy. As ribavirin (RBV) increases the sustained response when added to IFN in chronic hepatitis C, probably because of its immunomodulatory effect, we aimed to investigate the efficacy of 2-year IFN treatment and whether RBV had any additive effect to IFN in CDH. METHODS: Patients (n = 31) with CDH were randomized with a 1:2 ratio as 10 patients (3 females/7 males, age 39 +/- 9) receiving IFN monotherapy (9 MU IFN-alpha2a three times weekly) and 21 patients (8 females/13 males, age 38 +/- 11) receiving IFN plus RBV for 2 years (IFN at the same dosage and RBV at 1000-1200 mg/day). Alanine transferase normalization and hepatitis delta virus (HDV) RNA negativity at the end of treatment and at the end of the follow-up period (at least 6 months following 2-year treatment) were primary endpoints of the study. In addition, virological response and biochemical response were determined separately. RESULTS: Eight of 31 patients (25%) had cirrhosis in liver biopsies. Six patients from the IFN monotherapy group and 12 patients from the combination group had biochemical response. Five patients from the IFN monotherapy group and 11 patients from the combination group had virological response at the end of therapy. Two patients from the IFN group and five patients from the combination group had sustained biochemical response at the end of the follow-up period. Hepatitis B virus (HBV) activations with HBV DNA positivity were observed in two patients (one from the IFN monotherapy group, one from the combination group). Two patients (20%) in the IFN group and five patients (23.5%) in IFN plus RBV group remained as virological responders at the end of the follow-up period (P > 0.05). None of the patients with liver cirrhosis were responsive at the end of the follow-up period. CONCLUSION: Almost 20% of the patients with CDH were responsive to 2-year IFN treatment at the end of the follow-up period and no additional effect of RBV was observed. Patients with advanced liver disease failed to respond to treatment.

Karabay O, Tamer A, Tahtaci M, Vardi S, Celebi H. · Department of Clinical Microbiology and Infectious Diseases, Izzet Baysal University School of Medicine, Bolu, Turkey. · J Microbiol Immunol Infect. · Pubmed #16118673 links to  free full text

Abstract: Results comparing the effectiveness of lamivudine used as monotherapy or in combination with interferon-alpha (IFN-alpha) in the treatment of chronic hepatitis B are not conclusive. This study compared the effects of IFN-alpha alone or in combination with lamivudine for the treatment of hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B. Participation of patients in the IFN-alpha monotherapy and combination groups was randomized to a 1:1 ratio. Twenty seven HBeAg-negative patients with chronic hepatitis B received IFN-alpha (13 patients) at 9 million units 3 times weekly for 24 weeks or IFN-alpha at 9 million units 3 times weekly for 24 weeks plus lamivudine 100 mg/day (14 patients) daily for 1 year. Hepatitis B virus (HBV) DNA was measured quantitatively by real-time polymerase chain reaction at 0, 6, 12 and 18 months after the start of treatment. Sustained virologic response was defined as non-detectable serum HBV DNA 72 weeks after starting treatment. Sustained biochemical response was defined as normalization of alanine aminotransferase (ALT) values 72 weeks after starting treatment. The baseline characteristics of the 2 treatment groups were similar with respect to age, gender, ALT, HBV DNA levels and histologic diagnosis. Sustained biochemical responses were found at week 72 in 7 patients in each group (54% with IFN-alpha monotherapy and 50% with combination therapy) [p>0.05]. Sustained virologic responses were found at week 72 in 5 patients (38%) in the monotherapy and 7 patients (50%) in the combination therapy group (p>0.05). Combination therapy was not superior to IFN-alpha alone for the treatment of chronic hepatitis B. Combination treatment was associated with some disadvantages, such as additional cost. Lamivudine, on the other hand, may be more suitable for patients with cirrhosis, non-responders to IFN-alpha or in cases with contraindication for IFN-alpha.

Ertekin V, Selimoğlu MA, Orbak Z. · Department of Pediatric Gastroenterology, Atatürk University, Faculty of Medicine, Erzurum, Turkey. · Eur J Gastroenterol Hepatol. · Pubmed #15879728 No free full text.

Abstract: BACKGROUND AND AIM: Although the most common major toxicity of lamivudine has been pancreatitis, there is no report investigating possible impaired pancreatic functions, including glucose intolerance due to lamivudine therapy. The aim of this study was to evaluate the effects of lamivudine on the glucose metabolism in children. METHOD: Twenty-three children were included: eight patients were treated with lamivudine, others with both lamivudine and interferon-alpha. An oral glucose tolerance test (OGTT) was performed before the treatment, and after 6 and 12 months. RESULTS: After 6 and 12 months of the treatment four (18.4%) and eight (34.8%) patients had impaired OGTT, respectively. We did not find any relationship between impaired OGTT and age, gender, elevated amylase, abdominal pain and the mode of therapy (P>0.05). While mean glucose value after 2 h was higher than that of baseline, mean insulin concentrations and area under the curve values were not different (P<0.0001, P>0.05, and P>0.05, respectively). CONCLUSION: This is the first report demonstrating that lamivudine may impair the OGTT. Since at least 8.7% of our patients had persistently impaired OGTTs during the first year of the therapy, it may be reasonable to screen children before lamivudine therapy is started.

Bozkaya H, Yurdaydin C, Idilman R, Tüzün A, Cinar K, Erkan O, Bozdayi AM, Erden E, Uzun Y, Cetinkaya H, Uzunalimoglu O. · Department of Gastroenterology, Ankara University School of Medicine, Cebeci, Ankara-Turkey. · Antivir Ther. · Pubmed #15865226 No free full text.

Abstract: BACKGROUND: Our aim was to determine the short-term natural course of viraemia and the response to lamivudine treatment in HBeAg-negative chronic hepatitis B patients with a persistently low hepatitis B virus (HBV)-DNA level. METHODS: A total of 55 patients were included. Group 1 consisted of 37 patients with low-level viraemia and high serum alanine aminotransferase (ALT) levels and further randomized to two groups: group 1a (n=19) patients received 1 year of lamivudine therapy and group 1b (n=18) patients were untreated controls. Group 2 consisted of 18 inactive carriers who were followed as controls of untreated low viraemic chronic hepatitis B patients. HBV DNA was longitudinally determined by real-time polymerase chain reaction assay. RESULTS: A female predominance in group 2 was observed while males were predominant in group 1. Mean age and baseline HBV-DNA levels did not differ between group 1 and 2 patients while group 1 patients had a higher histological score (P<0.01). Of group 1a patients, 44% had complete ALT normalization at end of treatment, whereas 21% untreated group 1b patients had normal ALT at the end of the follow-up. No change in histological activity was observed in group 1a patients at the end of treatment. HBV-DNA levels did not significantly change from baseline to end-of-treatment/observation period in patient groups. The viraemia course was not different across the groups. CONCLUSIONS: Low viraemic HBeAg-negative patients with high ALT present with minimal/mild histological activity. Inactive carriers cannot be differentiated from low viraemic patients with high ALT based on HBV DNA determination. Although lamivudine treatment can be effective in some cases, observation rather than a prompt treatment attempt seems to be more logical because of mild histological changes and low response rate to treatment in these patients.

Yurdaydin C, Bozkaya H, Cetinkaya H, Sahin T, Karaoğuz D, Törüner M, Erkan O, Heper AO, Erden E, Bozdayi AM, Uzunalimoğlu O. · Department of Gastroenterology, Pathology and the Hepatology Institute, University of Ankara Medical School, Ankara, Turkey. · J Viral Hepat. · Pubmed #15850466 No free full text.

Abstract: To determine whether combination treatment of HBeAg(-) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(-), HBV DNA-positive chronic hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or lamivudine-interferon (9 MU, t.i.w.) in combination. In the combination arm, 2 months of lamivudine treatment preceded 10 months of combination treatment. Biochemical, virologic and histologic responses were assessed at the end of treatment, after six and a median 27 months of drug-free follow-up (short- and long-term follow-up, respectively). Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by real-time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of treatment was investigated with a line probe assay. Both treatment regimes led to a median 2 log decline in HBV DNA levels. Virologic end of treatment responses were 90 and 92% with mono- and combination treatment, respectively. Corresponding virologic responses at short- and long-term follow-up were 59 and 54%, and 27 and 25%, respectively. Patients having a baseline HBV DNA value > or =200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level <200 pg/mL (P = 0.041). YMDD mutants were observed in 53% of patients receiving lamivudine compared with 24% of patients receiving the combination regime (P = 0.017). In conclusion, efficacy of combination treatment is similar to lamivudine monotherapy. However, combination treatment decreases the development of YMDD mutant strains compared with lamivudine monotherapy.

Sunbul M, Leblebicioglu H. · Department of Infectious Diseases and Clinical Microbiology, Ondokuz Mayis University, Medical School, Samsun, Turkey. · World J Gastroenterol. · Pubmed #15800989 links to  free full text

Abstract: AIM: Hepatitis B virus (HBV) strains isolated worldwide has been classified into eight genomic groups deduced from genome comparisons and designated as genotypes A to H. We aimed to investigate prevalence of HBV genotypes and subtypes in Turkey. METHODS: A total of 88 chronic hepatitis B (CHB) patients from 15 hospitals throughout the country were included. Patients who were HBsAg positive in serum at least for 6 mo, who had HBV-DNA in serum and elevation of ALT levels more than two times upper limit of normal, and who had percutaneous liver biopsy within 6 mo were included. Genotyping of HBV was done by restriction fragment length polymorphism (RFLP). The patients received subcutaneous 9 MU interferon-alpha 2a thrice a week for a period of 6 mo. RESULTS: Genotype D was detected in 78 of 88 (88.7%) patients, however, genotyping failed in two patients (2.3%), while no product was obtained in eight (9.0%) patients. Regarding subtypes, D2 was more prevalent (67 patients between 78% and 85.9%) followed by subtype D2+deletion (seven patients of 78 or 8.9%), subtype D1 (three patients of 78% or 3.9%) and subtype D3 (one patient of 78% or 1.3%). Thirty-three patients (37.5%) were HBeAg positive compared to 55 (62.5%) anti-HBe positive patients. The endpoint for the viral response of HBeAg positive patients was 27.2%, while it was found 52.7% in HBeAg negative patients (P<0.05). Long-term persistent viral response was 29.5% for all patients. CONCLUSION: This multi-center study indicates that the predominant genotype with CHB patients in Turkey like in other Mediterranean countries is genotype D.