CHaloska ivanova, Viktorija
Preferred name
CHaloska ivanova, Viktorija
Official Name
CHaloska ivanova, Viktorija
Main Affiliation
Email
viktorija.chaloska.ivanova@medf.ukim.edu.mk
45 results
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Item type:Publication, Clinical Significance of Quantitative HBs Antigen in the Prediction of Liver Fibrosis in Patients with Chronic Hepatitis B(Macedonian Academy of Sciences and Arts, 2018-07); ; ; - Some of the metrics are blocked by yourconsent settings
Item type:Publication, FOUR YEAR RESULTS OF CONSERVATIVE TREATMENT OF BENIGN STRICTURES OF THE ESOPHAGUS WITH SVARY GILLIARD TECHNIQUE OF BOUGIENAGE: CROSS-SECTIONAL STUDY REPRESENTING FIRST EXPERIENCES IN REPUBLIC OF MACEDONIA(Macedonian Academy of Sciences and Arts, 2018-01); ; ; - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Polymorphism IL 28B and response to therapy in chronic hepatitis C(2016); ; ; ; INTRODUCTION: Chronic hepatitis C is still a majgor cause for developing cirrhosis and hepatocellular carcinoma which often results in liver failure and thus in liver transplantation. According to the World Health Organisation 180 million people are infected worldwide and 3-4 million new infections per year were estimated (1). The current standard of care (SOC) for chronic HCV infection is a combination of pegylated interferon (PegINF -2a or PegINF -2b) plus body-weighted ribavirin (RBV) for the duration of 24 weeks or 48 weeks depending on the HCV viral genotypes (2). The primary goal of the treatment is HCV eradication, which is actally sustained viral response (SVR). The SVR is defined as undetectable HCV RNA in serum, 24 weeks after the completion of the antiviral treatment (3). However, only about 40-50% genotype 1 or 4 patients treated and 80% genotype 2 or 3 patients treated could respond completely and achive sustained virological response (4,5). Moreover, side effects from the therapy such as influenza-like symptoms, psychiatric symptoms and hematological abnormalities, could result in the dose reduction or even the premature discontinuation of the treatment (6). To avoid these potential adverse events in patients who do not benefit from the treatment and to reduce the cost of therapy, it is necessary to predict an individual’s response before at the early stage of the treatment. Virus-specific characteristic (viral load, genotype, viral variants as mutations of interferon sensitivity determining region- ISDR) may be responsible for virologic response but also clinical parametars (age, gender, BMI, fibrosis stage, liver enzymes) (7,8). Investigations on genetic determinants of chronic hepatis C established that a single nucleotide polymorphism (SNP) in the interleukin (IL)-28B gene promoter region affected the spontaneous and induced clearance of hepatitis C virus (9). Among 500 000 genetic variants which were analyzed genome-wide, a few associated with virologic response were identified, and showed variable frequency and importance across human ethnic groups (10). The mechanism by which SNPs influence the outcome of HCV infection and its treatment is not clear. It is suggested that regulation of the promoter region of IL28B in antiviral activity may also affect two other genes belonging to interferon (INF)- family encoded in this region (10, 11). INF- possess antiviral activities agains hepatitis C virus (12). The genome-wide associated studies (GWAS) showed that SNPs near IL28B gene (CC for rs12979860, TT for rs8099917 and AA for rs12980275) were associated significantly with treatment outcome in patient with chronic hepatitis C. However, about 50% of patients with a sustained virological response do not carry favorable IL28B alleles (13). The factors which increase the chance of a therapeutic response in these patient are not yet known. A detailed analysis if the course of therapy of chronic hepatitis C with pegylated INF and ribavirin in the presence of a hazardous IL28B allele might better delineate the clinical characteristics of the difficult-to-treat group of patients. The aim of the study was to evaluate the effects of IL28B polymorphism on response to treatment with peginterferon and ribavirin in patients with chronic hepatitis C. MATERIAL AND METHODS: Twenty-five adult Caucasians previous assessed with chronic hepatitis C due to HCV genotupe 1 and 3 were included in the study. The study protocol was approved by the institutional ethics committee and written informed consent was obtained from each study participant. Patients were treated with standard antiviral therapy with pegylated INF alfa and ribavirin. Pegylated interferon alfa 2a 180 μg was administered subcutaneously once a week. Body-weighted ribavirin was administered daily. The treatment duration was 48 weeks for patients with HCV genotype 1 and 24 weeks for patients infected with HCV genotype 3. SVR was used for the assessment of the antiviral treatment effectiveness. SVR is defined by undetectable viral RNA 24 weeks after the end of treatment. Finaly eighteen patients were analysed, because two premature discontinuated the treatment and for five there are no available data for SVR. Sample od peripheral blood were collected from each patient enrolled in the study for HCV quatntification and IL28B polymorphism genotyping. Reverse transcriptase-polymerase chain reaction assay for HCV quantification was done with One-tube real time PCR HCV amplification with lower detection limit 70 IU/ml. Polymorphisms rs12979860 (C>T) and rs8099917 (T>G) in gene IL28B were genotyed by PCR. Each polymorphism assay contained one pair of primers and one pair of probes, and each allele of the polymorphisms was labeled. For statistical analysis mean and standard deviation were used for parametric variables. Considering the small sample difference test (percentage of structure) was used to determinate the genetic predictors of the SVR. A p<0.05 was consideded statistically significant. RESULTS: The study population included 9 genotype 1 and 9 genotype 3 HCV infected patients. Their median age was 31.4±4.4 years and 88.88% were males. SVR were achived in 83.3% patients. The distribution of the frequencies od rs12979860 genotypes in the analyzed sample was: 10 (55.55%) patients with CC genotype and 8 (44.44%) patients with CT genotype. The distribution of the frequencies od rs8099917 genotypes was: 15 (83.33%) patients with TT genotype and 3 (16.66%) patients with TG genotype. The difference test showed that difference in persentage which is registered between SVR in CC and CT is not statistically significant (p=0,6714). There is no association in achievement SVR in CC and non-CC genotypes of rs12979860. There also no significance in achieving SVR in patients with TT genotype of rs8099917 and in patients with TG genotypes (p=0.3961). Futhermore there was no association with the achivment od SVR as compared with genotype (p=0.0579). DISCUSION: In this study, no significant difference was found in the response to treatment and allele proportions of SNPs rs12979860 and rs8099917 possibly due to the small size of the sample. The study of Silva Conde et al. confirmed similar effect of IL28B polymorphism on SVR in infected HCV patients (14). In another study from Norway and Denmark involving genotype 3 HCV-infected patients, RVR was achived by a significantly greater number of patients who had CC and TT genotypes at rs 12979860 and rs8099917, respectively, but these genotypes showed no association with SVR (15). Consistent to our findings were results of the study of Sarrazin et al.which present no significant association of SNPa rs8099917 with virologic treatment response (16). Investigation of a comparable number of genotype 2/3 infected patients in study by Rauch et al. also showed no correlation between the rs8099917 genotype and virologic response to pegylated interferon/ribavirin combination therapy (17). In contrast, the GWAS identified that homozygosis for C allele of rs12979860 and homozygosis for the T allele of rs8099917 were favorable genotypes of the IL28B gene polymorphisms which predicted the SVR in patients with chronic hepatitis C treated with peginterferon and ribavirin (18,19). The distribution of frequencies of rs12979860 genotypes in our study group was : CC 55.55% and CT in 44.44% . The distribution of frequencies of rs8099917 genotypes in our study sample was TT 83.33% and TG 16.66%. Sticchi et al. reported distribution of rs8099917 genotypes TT in 55%, TG in 40% and GG in 5% of the study participants (20). Results of other studies reported bigger percentage of CT than CC for distribution of the frequencies of rs12979860 (21.22). However, about 50% of patients with a sustained virological response do not carry favorable IL28B alleles (13). The factors which increase the chance of a therapeutic response in these patient are not yet known. Other factors, such as HCV genotype, viral-load, ethnicity should be used together with IL28B genotype as predictors of response on antiviral therapy. CONCLUSION: We did not find a significant association of SNPs rs12979860 and rs8099917 with SVR thus disagreeing with studies that found an association between genotype CC (rs12979860) and SVR in individuals with genotype 1, 2 and 3 as well as between genotype TT (rs 8099917) and SVR in individuals with genotype 3. Our study is limited by its sample size. And possibly results due to this fact. Nevertheless genotyping of this polymorphism on a large HCV population will aid clinical decision making for both current standard care and potentially for the integration of other agents in future, providing an opportunity for clinicians to individualize treatment regimens for hepatitis C patients. - Some of the metrics are blocked by yourconsent settings
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Item type:Publication, Insulin resistance in patients with chronic hepatitis C(Македонско лекарско друштво = Macedonian Medical Association, 2016); ; ; ; Introduction: Insulin resistance is the most common extrahepatic manifestation associated with hepatitis C virus, which leads to developing more pronounced fibrosis and liver steatosis. The aim of the study was to assess the prevalence of insulin resistance in non-diabetic, treatment naive patients with chronic hepatitis C and to analyze the relation of insulin resistance with genotype, viral load, gender, age, laboratory parameters, inflammatory and fibrotic changes in the liver, body mass index (BMI) and the presence of steatosis. Material and methods: In this cross sectional study, 224 patients with hepatitis C viral infection were included. The patients were divided into two groups. The first group was with no insulin resistance and the second one with present insulin resistance. They were compared in terms of genotype, viral load, gender, age, inflammatory and fibrotic changes in the liver, BMI and liver steatosis. Results: Insulin resistance was present in 45.5% of patients. The following factors were associated with insulin resistance: age (p = 0.0022), inflammatory and fibrotic changes in the liver (p = 0.001, p = 0.006, respectively), steatosis (p = 0.015) and transaminase activities (for AST, p = 0,002, for ALT, p = 0.001). Conclusion: In the Republic of Macedonia, high percentage of 45.5% among non-diabetic and treatment naïve patients with chronic viral hepatitis C, had insulin resistance. Insulin resistance was more prevalent in older patients, in those with more pronounced inflammatory and fibrotic changes in the liver, in patients with steatosis and in those with higher transaminase activity. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Management of an adolescent with familial adenomatous polyposis: report of a case(2019); ; ; ; Ana Karadzova Dzambaz - Some of the metrics are blocked by yourconsent settings
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Item type:Publication, MODEL FOR END-STAGE LIVER DISEASE (MELD) IN STRATIFIACATION OF IN HOSPITAL PATIENTS WITH TERMINAL LIVER DISEASE(2012); ; ; Syardelova KINTRODUCTION: Liver cirrhosis is end stage of liver disease where liver transplantation is the only curative treatment. MELD score system is relatively newer system (the last ten years) used as assesment tool for liver disease severity as well as for creating of liver transplantation priority lists. In the contrary of already used system - Child-Turcotte-Pugh, where posibility for subjective assesment of variables as ascites and encephalopathy is existing, this system avoids such posibility. MELD includes another very important variable – renal function assesment as serious prognostic factor. Well-defined formula calculating natural logarithms of bilrubin, creatinin and international normalized ratio (INR) of prothrombin time determined MELD-'s set of points. The aim of this study is to stratify in hospital patients in Clinic of Gastroenterohepatology, Skopje with terminal liver disease using MELD scoring system and easy recognize the real need for transplantation in these patients. MATERIAL AND METHODS: This retrospective study is analyzing medical discharge summary among 192 patients hospitalized at our clinic in the period from 01.01.2011 to 31.12.2011 with diagnosis of liver cirrhosis, who have all the necessary parameters available to calculate the MELD score (patients with the same diagnosis without the necessary parameters were excluded from the study). Patients were aged between 20 and 90 years (average age 55.7 years) with predominance of males (147 males and 45 females). They were analyzed in accordance to cirrhosis etiology, indication for hospitalization, MELD score and the risk of lethal outcome. Descriptive statistics to analyze data was used. RESULTS: Total of 192 patients are analyzed, 76.6% are male, while 23.4% are women. From the etiological point of view the alcohol as cause of cirrhosis dominates in 73 patients (38%), followed by HBV infection in 49 patients (25.5%), undefined etiology has in 24 patients (12.5%), mixed etiology of ethyl and viral origin of hepatitis B in 11 patients (6%), HCV infection in 9 patients (4.7%), immunogenic etiology in 8 patients (4.1%), portal vein thrombosis in 4 patients (2.1%), secondary biliary cirrhosis in 4 patients (2.1%), alcohol and HCV infection in 3 patients (1.5%), mixed HBV and HCV infection in 2 patients (1%), primary biliary cirrhosis in 2 patients (1%), Wilson disease in 2 patients (1%) and nonalcoholic steatohepatitis as a cause of cirrhosis in 1 patient (0.5%). The most common reason for hospitalization is variceal bleeding in 51 patients (26.6%), followed by refractory ascites in 35 patients (18.2%), jaundice in 31 patients (16.1%), portal encephalopathy in 29 patients (15.1%), diagnostic differentiation (liver biopsy) in 28 patients (14.6%), and hepato-renal syndrome in 14 patients (7.3%). In accordance to the MELD score, patients are divided into 5 groups regarding to calculated percentage of three month mortality. Average MELD score for all 192 patients is 15. Under this scoring system 4 patients (2.1%) belong to the group with highest risk (71.3% is the rate of mortality within three months), 14 patients (7.3%) in group having 52.6% mortality rate within three months, 31 patients (16%) belong to a group with 19.6% mortality rate, and the remaining patients in the group with 6% mortality rate (69 patients - 36%) and the group with the lowest mortality of 1.9% (74 patients - 39.5%). The outcome of 20 from 192 patients analyzed was lethal. The reason for this outcome was hepato-renal syndrome in 11 patients (55%), variceal bleeding in 7 patients (35%) and in 2 patients (10%) hepatic coma. DISCUSSION: Liver cirrhosis as an indication for hospitalization is often seen in our daily practice. Especially common reason for hospitalization is the occurrence of complications of cirrhosis (variceal bleeding, refractory ascites, jaundice, portal encephalopathy or hepato-renal syndrome), which caused lethal outcome in some patients. According to our analysis, a significant percentage of patients (39/192 or 25.4%) with MELD score> 20, belong to the group with high short-term risk of lethal outcome (3 months mortality rate). Those patients in developed countries would find themselves on a priority list for liver transplantation. Our commitment (such as internal disease specialists and surgeons) should be to enable these patients equal access to treatment as in those patients with terminal liver failure in developed countries. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, КВАНТИТАТИВНО ОДРЕДУВАЊЕ НА КАЛПРОТЕКТИН ВО АСЦИТ КАЈ ПАЦИЕНТИ СО СПОНТАН БАКТЕРИСКИ ПЕРИТОНИТИС ПРЕД И ПО АНТИБИОТКСИОТ ТРЕТМАН(SHMSHM / AAMD, 2019); ; ; ; Вовед. Спонтаниот бактериски перитонитис (СБП) кај пациентите со црнодробна цироза е новонастаната,спонтана бактериска инфекција на стерилна асцитна течност, во отсуство на интраабдоминални извори на инфекција или малигнитет. Најсензитивен показател за поставување на дијагнозата е кога бројот на полиморфонуклерани клетки (ПМНК) е ≥250 во 1 мл асцитна течност (рачното микроскопско или автоматизирано пребројување) и/или кога во микробиолошката култура биде изолиран еден бактериски вид. Цели Целите на нашата пилот студија беше да се одреди концентрацијата на калпротектин во асцит кај пациентите со СБП и не-СБП со BÜHLMANN Quantum Blue®Reader, дали има сигнификантна разлика меѓу просечните вредности на Turcotte-Pugh II и MELD скорот кај пациентите со СБП и не-СБП и да се одреди концентрацијата на калпротектин кај пациенти со СБП пред и по антибиотскиот третман. Материјали и методи. Во оваа проспективно-аналитичко-опсерваториска пилот студија беа вклучени 30 пациенти со црнодробна цироза и асцит, поделени во две групи, СБП и не-СБП. Квантитативното мерење на калпротектин во асцит се вршеше со тестот Quantum Blue Calprotectin Ascites (LF-ASC25). Собраните податоци се обработија со помош на статистичкиот програм SPSS 23 за Windows. Резултати и дискусија: Во нашата студија просечната вредност на калпротектин кај пациенти со СБП беше 1.4 μg/mL Најниската вредност на калпротектин во испитуваната група беше регистрирана кај еден пациент со вредност од 0.61 μg/mL, додека највисока вредност од 1.81μg/mL кај четири пациенти. Резултатите покажаа повисоки вредности на калпротектин во асцит кај пациенти со алкохолна болест на црниот дроб во споредба со останататите етиологии. Рефракторен асцит се регистрира кај 60,0% од испитаниците а само кај еден пациент (6,7%) се регистрира klepsiella pneumonie во микробиолошката анализа на асцитот. Нодамна објавентие студии презентираа слични вредности на калпротектин во асцит како и нашата студија. Според Child-Turcotte-PughII класификација сите пациенти од испитуваната група беа класа C, додека просечната вредност на MELD скорот изнесуваше 23,9±6,2. Контролниот број на ПМНК кај сите испитаниците во испитуваната група беше < 200 во 1 мл асцитна течност, додека просечната вредност на клапротектин во асцтот беше 0.69μg / mL и укажа на добар одговор на иницијалниот антибиотски третман, со исклучок на четворица пациенти со концентрација на калпротектин во асцит поголема од 1,39 μg /l , и индиректно покажа дека најверојатно станува збор за лажно негативен број на ПМНК. Двајца пациенти со виско ниво на калпротектин во асцит и покрај конвенционалнитот третман за СБП настапи смртен исход во тек на двенеделна хоспитализација. Високото ниво на калпротектинво асцит по седудневен антибиотски третман е лош прогностички знак за двенеделно преживување. - Some of the metrics are blocked by yourconsent settings
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