Jasmina Simonovic

Prevalence of hepatitis B virus MHR mutations and their correlation with genotypes and antiviral therapy in chronically infected patients in Serbia

Understanding the prevalence and diversity of HBsAg variants in a population is fundamental to assay design and planning vaccination programs. It has been shown that mutations within the S gene, caused by selection or natural variation, can lead to false‐negative results in assays for HBsAg, or have clinical implications, such as evading anti‐HBV immunoglobulin therapy or vaccine‐induced immunity. The region of HBsAg where most of these mutations occur is known as the major hydrophilic region (MHR). The aim of this study was to determine the prevalence and mutational patterns of MHR mutations in patients with chronic hepatitis B, and their correlation with patient characteristics, viral factors and antiviral therapy. The study comprised 164 plasma samples from patients with chronic hepatitis B, of which, 34.8% were on long‐term lamivudine monotherapy. Direct sequencing of part of the S/pol gene was used for identification of HBsAg mutations, HBV genotypes, subgenotypes and HBsAg subtypes. The overall frequency of MHR mutations was 22.6%, but it varied significantly between untreated and treated patients (16.8% vs. 33.3%). The most frequent substitution was at position 120 (9.1%) whereas the most common vaccine‐escape position, 145, was affected in 1.8% of isolates. The presence of MHR mutations was correlated with genotype D, subgenotype D3, and ayw2/ayw3 HBsAg subtypes and to older age (>40 years). It is concluded that natural viral variability present in a geographical region, duration of infection, and antiviral therapy are among the major factors associated with the occurrence of MHR mutations. J. Med. Virol. 82: 1160–1167, 2010.

The influence of single and combined IL28B polymorphisms on response to treatment of chronic hepatitis C

BACKGROUND Three single nucleotide polymorphisms (SNPs) near IL28B gene were shown to be highly predictive of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) infection. OBJECTIVES This study attempted to demonstrate the role of single and combined IL28B polymorphisms (rs8099917, rs12979860 and rs12980275) and other host and viral factors in predicting response to treatment, in Caucasian patients infected with HCV genotype 1. STUDY DESIGN The IL28B genotypes at 3 SNPs were determined in 106 patients who underwent standard 48-week therapy and out of which 55.7% achieved SVR. RESULTS Patients carrying genotypes CCrs12979860 or AArs12980275 were 3.5 and 3 times more likely to achieve SVR, respectively. Genotypes GGrs8099917 and TTrs12979860 were identified as predictors of treatment failure. The presence of IL28B profiles including at least one of the favourable genotypes was identified as the most important factor associated with SVR, followed by younger age and lower grade of histological activity. Of all patients who achieved SVR, 88.1% was carrying one of these IL28B profiles. The strongest PPV of single SNPs for achieving SVR was observed for CCrs12979860 (76.9%). The presence of GGrs8099917 showed the strongest NPV of 85.7%. The correlation of SNPs with other host and viral factors revealed association of TTrs8099917 and lower AST levels. CONCLUSIONS Results of this study confirm that all investigated IL28B polymorphisms are associated with treatment response and that presence of any of the favourable IL28B genotypes can be considered independent pretreatment determinant of the effectiveness of therapy.

Histopathology of chronic hepatitis C in relation to virus genotype

BACKGROUND/AIM The natural history of hepatitis C virus (HCV) infection is variable and the factors determining the course of the illness are unclear. There are geographical variations in the distribution of different HCV genotypes, and some of them are related to the specific infection routes. Regarding our country, the dominant genotype is genotype 1b. It is unclear and still remains a question whether the distinct histopathological manifestations are related to the particular genotypes of HCV. Thus, the aim of this study was to determine whether the distinct histopathological manifestations of HCV infection might be in relation to the individual virus genotype. METHODS In this study we examined 126 patients with chronic HCV infection regarding the histopathological features, demographic data, and virus genotype. The observed groups of patients were predominantly infected with HCV genotypes 1b and 3a. RESULTS In this study we found that the patients infected with HCV genotype 1b had more frequently moderate or severe necroinflammatory activity of the disease, significantly higher grading score as compared with other genotypes (p < 0.0001). A higher degree of fibrosis was, also, more common in the patients infected with genotype 1b of HCV as compared with other genotypes (p < 0.05). There were no significant correlations between the necroinflammatory activity of the disease and the stage of fibrosis in 1b, 4 and mixed genotypes. CONCLUSION The present data support the hypothesis that distinct genotypes of HCV are associated with the particular histopathological manifestation of the disease.

Chronic hepatitis C virus infection: Is there a correlation between HCV genotypes and the level of viremia?

INTRODUCTION Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. MATERIAL AND METHODS For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype 1b infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. RESULTS Patients infected by genotype 1b had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p < 0.05). Over 70% of patients infected by genotype 1b had more than 2 x 10(6) virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7 x 10(6) virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3 x 10(6) copies/ml; p < 0.05). CONCLUSION Our results are in concordance with the results of other authors reporting that genotype 1b is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype 1b infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems.

The importance of aminotransferases and platelets count in non-invasive evaluation stages of chronic hepatitis C

143 patients with chronic hepatitis C were investigated. The following two parameters were determined: the asparate to alanine aminotransferase ratio and the asparate aminotransferase to platelets count index. A liver biopsy was performed for every patient and stages of liver fibrosis were evaluated. Both parameters confirmed a positive correlation with liver fibrosis, which can be useful in predicting the progression of chronic hepatitis C.

Influence of depression on the quality of life in patients with chronic hepatitis C

INTRODUCTION Chronic hepatitis C reduces the quality of life in patients causing fatigue, loss of self-confidence, reduced working capacity, development of depression, emotional problems, and cognitive dysfunction. OBJECTIVE The aim of the study was to identify the presence of depression in patients with chronic hepatitis C, predicting factors for its expression, and the impact of depression on the quality of life in these patients. METHODS During the prospective study, we used the Hamilton depression scale to investigate the presence of depression, generic 36-Item Short Form Health Survey (SF-36) and Chronic Liver Diseases Questionnaire (CLDQ) to examine the quality of life in 100 patients with chronic hepatitis C, 30 patients with chronic hepatitis B, 30 patients with chronic liver disease nonviral aetiology and 50 healthy persons. RESULTS A significantly higher presence of depression, and cognitive dysfunction in patients with chronic hepatitis C were noted as compared to the healthy individuals (p=0.00). In relation to non-viral patients with chronic liver disease, depression was significantly less present (p=0.004). Depression was rare in younger patients. The largest number of patients with chronic hepatitis C was without depression. The presence of depression caused deterioration of the physical and mental components of the quality of life. Multivariate analysis showed that the most significant positive predictive factor for the presence of depression was married life (B=0.278; SE=0.094; p=0.004). CONCLUSION The presence of depression was more often in patients with chronic hepatitis C viral infection compared to healthy population and was correlated with decline in the quality of life. Depression is more pronounced in the elderly and intravenous drug addicts. The lowest depression is expected in patients who are not married.