chronic viral hepatitis c is one of the most serious chronic infections affecting 170 million people worldwide . in europe
the prevalence of hepatitis c virus ( hcv ) infection is also relatively high in latvia .
antibodies are found in 2.4% of the population , with hcv - rna prevalence of 1.7% of general population .
the outcome of hcv infection varies from spontaneous viral clearance , symptom free - hcv carrier state to chronic hepatitis , cirrhosis , and hepatocellular carcinoma .
some individuals have rapidly progressive liver disease while others remain in good health for many years .
there are a lot of factors such as viral kinetics , immune mechanisms , environmental factors , and patient - related factors which may be responsible for the various hcv - related outcomes .
risk factors for infection include intravenous and intranasal drug use , nonsterile tattooing , manicure and pedicure procedures , as well as virus transmission vertically from mother to child , and during sexual intercourse .
dialysis patients appear to be at increased risk of infection as do alcoholics [ 1 , 3 ] . in developing and transitional economy countries ,
the nosocomial transmission of new hepatitis c virus ( hcv ) infections is a major problem due to reuse of contaminated or inadequately sterilized syringes and needles used in medical , paramedical , and dental procedures ; an estimated 2.34.7 million new infections occur each year .
current standard of care treatment involves combination therapy with hopes of effective virus eradication resulting in a sustained virological response ( svr ) and thereby stopping the progression of disease . with the combination of pegylated alpha interferon and ribavirin ,
they induce inflammatory responses that can lead to tissue injury and serve as antiviral effectors as well .
cytokine synthesis is regulated by genetic mechanisms resulting in differences between individuals in their ability to produce cytokines .
this individual variability may be due to single - nucleotide polymorphisms within the coding regions of cytokine genes .
cytokine genes are polymorphic , and some of these variants modify the production of the specific cytokines thereby affecting the host immune response . in hcv infection , secretion of inappropriate amounts of cytokines may be associated with developments of chronic disease or resistance to interferon ( ifn ) treatment .
interleukin-28b ( il-28b ) , named also as interferon -3 , has been shown to be involved in the control of hcv infection , and the genetic polymorphism of the encoding il-28b gene may determine the clearance of hcv .
the il-28b gene on human chromosome 19q was discovered in 2003 , using the genomic screening process in which the entire human genome was scanned for putative genes [ 5 , 6 ] .
the aim of this study was to detect il-28b gene polymorphism in chronic hepatitis c patients in latvia and to analyze therapy results in patients with different il-28b gene polymorphisms .
this is the first study carried out in latvia , in the baltic states and likely in eastern europe for the detection of interleukin 28b gene polymorphism and how it impacts on hepatitis c treatment .
all chronic viral hepatitis c patients who came to infectology center of latvia for a hepatologist 's consultation were tested .
patients had to sign the informed patients ' consent prior to testing . in order to detect il-28b gene polymorphism  rs12979860 genotype frequency we used molecular biology methods : classical dna separation from blood samples by phenol , amplification by pcr , and standard sequencing by big dye ( applied biosystems ) .
142 patients were treated with the standard of care therapy - pegylated interferon in combination with ribavirin .
all patients were divided into 3 subgroups : cc , ct / tc , and tt .
different patient factors , laboratory tests , viral kinetics , and treatment response were analyzed . in terms of therapy result patients
responders achieved sustained virological response and were hcv - rna negative at the end of therapy and 24 weeks after stopping treatment .
nonresponders were hcv - rna positive at week 12 ( null responders ) , at the end of therapy ( partial responders ) or at week 24 after stopping therapy ( relapsers ) .
interrupters stopped therapy due to financial reason ( there is 75% drug reimbursement for chronic hepatitis c treatment , 25% of treatment expenses are covered by patient ) or due to unknown reason .
hcv - rna was measured using polymerase chain reaction ( pcr ) , amplicor , version 2.0 ; roche , usa . viral load for genotype 1 patients was measured at baseline and at week 12 on treatment .
liver biopsy was performed for 126 ( 88.7% ) patients , and morphological assessment was done using knodell 's hai index .
there were not statistically significant differences between groups with regard to fibrosis stage and hai index .
comparison between groups was performed using pearson chi - square test or fisher 's exact test .
study was approved by the independent ethics committee for clinical investigation of drugs and pharmaceutical products in latvia .
there were 53 patients ( 33% ) with cc genotype , 84 patients ( 53% ) with ct ( 83 patients ) or tc ( 1 patient ) genotype , and 22 patients ( 14% ) with tt genotype among chronic viral hepatitis c patients in latvia ( figure 1 ) .
142 patients were treated with the standard of care therapy - pegylated interferon in combination with ribavirin table 1 .
all included patients were caucasians , a majority of them male ( 59% ) and genotype 1 ( 61% ) patients .
34 patients ( 74% ) in cc genotype subgroup achieved svr versus 50 patients ( 52% ) in non - cc subgroup41 patient in ct / tc and 9 patients in tt subgroups .
there were 4 patients ( 8.7% ) nonresponders in cc subgroup ( all were relapsers : 3 of them with hcv genotype 1 , 1 patient 
hcv genotype 2 ) versus 35 patients ( 36.5% ) in non - cc subgroups ( 7 patients null responders , hcv genotype 1 , 13 patients partial responders : 11 patients hcv genotype 1 , 2 patients hcv genotype 3 , and 15 patients relapsers , hcv genotype 1 ) ; the differences were statistically significant , p = 0.002 , pearson chi - square test ( figure 2 ) .  
there was statistically significant difference also in patients with genotype 1 hcv infection  svr which was achieved in 16 patients ( 16/19 , 84% ) in cc subgroup versus 30 patients ( 30/63 , 47.6% ) in non - cc subgroups , p = 0.007 , fisher 's exact test ( table 2 ) .
the last two decades have seen major advances in hcv treatment options and patient management .
however , the standard of care treatment ( peg interferon plus ribavirin ) is effective in less than half of chronically infected hcv genotype 1 treatment nave patients , regardless of the type or dose of peg interferon used [ 810 ] .
there are many factors influencing therapy result ; sometimes it is hard to understand which of them is the most essential . during recent years
there are publications of interleukin 28b gene polymorphism as a strong predictor of svr in patients treated with pegylated interferon and ribavirin . according to thompson et al .
data , published in 2010 , il-28b gene polymorphism between caucasians is distributed as follows : cc 37% , ct 51% , and tt 12% . in latvia majority of people are caucasians .
these results are similar to our data : cc33% , ct 53% , and tt 14% .
svr rates achieved in thompson 's study are 69% of patients in cc group , 33% in ct group , and 27% in tt group . in our study
this difference is probably because of different patient profile : we included all genotype patients ( 61% were 1st genotype ) , but in thompson 's study there were only 1st genotype patients included , and it is already known that svr rates are better in patients with 2nd and 3rd genotypes .
have published data in cemed where cc genotype in hcv patients was noted with significantly lower frequency than in healthy controls ( 79/281 , 28.11% versus 54/104 , 51.92% ) , suggesting a protective role of this variant .
also patients treated with pegylated interferon and ribavirin with cc genotype achieved svr at significantly higher rates , than those with tt genotype ( 25/46 , 54.34% versus 7/24 , 29.16% ) . if we analyze only hcv genotype 1 patients , our data shows slightly better results in comparison with thompson and par studies . in cc subgroup
svr was achieved in 69% ( thompson ) , 54.34% ( par ) , and 84% in our study .
in addition , in our study we analyzed other different treatment efficacy factors , including number of missed treatment doses .
we have to stress that chronic viral hepatitis c patients are paying 25% of treatment costs themselves in latvia , and 75% is covered by sick fund .
actually they are highly motivated to use assigned medicine . in terms of the higher svr on cc genotype patients from the study cohort when compared with thompson et al . '
2010 study , this cohort had younger patients with lower bmi 's , but with higher advanced fibrosis and steatosis rate . besides that , fibrosis stage was higher in nonresponders group , in comparison to responders group , p = 0.029 , mann - whitney u - test .
these factors influence svr rates in hepatitis c patients and could have played a role as well in the difference from virologic responses .
our study is the first study in latvia and baltics done on interleukin b28 gene polymorphism with findings similar to other studies involving caucasian patients .
while the most prevalent genotype of il-28b in latvia is ct , the most favorable response to treatment and svr is seen in genotype cc patients .
 
 introduction . with the standard treatment of chronic hepatitis c , sustained virological response ( svr ) can be achieved only in half of all patients . 
 interleukin-28b appears to be involved in the control of hcv infection , and the genetic polymorphism of the encoding il-28b gene may determine the efficacy of clearance of hcv . 
 the aim of this paper was to detect il-28b gene polymorphism in latvia and to analyze therapy results . 
 this is the first study on il-28b gene polymorphism in latvia . 
 
 material and methods . 
 there were 159 chronic viral hepatitis c patients included in the study . in order to detect il-28b gene polymorphism , we used molecular biology techniques and methods : classical dna separation , amplification by pcr , and standard sequencing 
 . genotype was defined as cc , ct , tc , or tt type . 
 142 patients were treated with the standard of care treatment . 
 results were analyzed according to il-28b polymorphism . 
 results . 
 there were 53 patients ( 33% ) with cc genotype , 84 patients ( 53% ) with ct / tc genotype , and 22 patients ( 14% ) with tt genotype . 
 34 patients ( 74% ) in cc genotype subgroup achieved svr versus 50 patients ( 52% ) in non - cc subgroups . in patients with genotype 1 , 
 svr was achieved in 16 patients ( 84% ) in cc subgroup versus 30 patients ( 47.6% ) in non - cc subgroups , p = 0.007 . 
 conclusions . 
 the most common genotype of il28b in latvia is ct / tc , with an incidence of 53% . 
 patients with cc genotype achieved svr more often than ct or tt subgroups . 
 il28b gene polymorphism therefore is a strong predictor of treatment result . 
1. Introduction
2. Material and Methods
3. Results and Discussion
4. Conclusions