[IL28B CC genotype: a protective factor and predictor of the response to interferon treatment in chronic hepatitis C virus infection]. / IL28B CC genotípus: védo tényezo és az interferonválasz prediktora krónikus hepatitis-C-vírus infekcióban.

INTRODUCTION: In chronic hepatitis C-virus infection the possible role of gene variants encoding cytokines has become the focus of interest. AIM: The aim of the study was to investigate the effect of IL28B polymorphisms on the outcome of chronic hepatitis C-virus genotype 1 infection in the Hungarian population. In addition, the association between IL28B genotypes and the Th1/Th2 cytokine production of activated peripheral blood monocytes and lymphocytes was evaluated. METHOD: Total of 748 chronic hepatitis C-virus genotype 1 positive patients (365 males and 383 females, aged between 18 and 82 years; mean age, 54±10 years) were enrolled, of which 420 patients were treated with pegylated interferon plus ribavirin for 24-72 weeks. Of the 420 patients, 195 patients (46.4%) achieved sustained virological response. The IL28B rs12979860 polymorphism was determined using Custom Taqman SNP Genotyping Assays (Applied Biosystems, Life Technologies, Foster, CA, USA). For cytokine studies, tumour necrosis factor-α, interleukin-2, interferon-γ, interleukin-2 and interleukin-4 production by LPS-stimulated monocytes and PMA-ionomycine activated lymphocytes were measured from the supernatant of the cells obtained from 40 hepatitis C-virus infected patients, using FACS-CBA Becton Dickinson test. The cytokine levels were compared in patients with different (CC, CT, TT) IL28B genotypes. RESULTS: The IL28B rs12979860 CC genotype occurred in lower frequency in hepatitis C-virus infected patients than in healthy controls (26.1% vs 51.4%, OR 0.333, p<0.001). Patients carried the T allele with higher frequency than controls (73.9%, vs 48.6%, OR 3.003, p<0.001). Pegylated interferon plus ribavirin treated patients with the IL28B CC genotype achieved higher sustained virological response rate than those with the CT genotype (58.6% vs 40.8%, OR 2.057, p = 0.002), and those who carried the T allele (41.8%, OR1.976, p = 0.002). LPS-induced TLR-4 activation of monocytes resulted in higher tumour necrosis factor-α production in patients with the IL28B CC genotype compared to non-CC individuals (p<0.01). Similarly, increased tumour necrosis factor-α, interleukin-2 and interferon-γ production by lymphocytes was found in the IL28B CC carriers (p<0.01) CONCLUSIONS: The IL28B CC genotype exerts protective effect against chronic hepatitis C-virus infection and may be a pretreatment predictor of sustained virological response during interferon-based antiviral therapy. The IL28B CC polymorphism is associated with increased Th1 cytokine production of activated peripheral blood monocytes and lymphocytes, which may play a role in interferon-induced rapid immune control and sustained virological response of pegylated interferon plus ribavirin treated patients.

[Influence of weight reduction on the effectiveness of combined peginterferon and ribavirin treatment in chronic HCV hepatitis]. / A testsúlycsökkentés hatása a kombinált interferon-alfa-2a + ribavirin kezelésre adott válaszra idült HCV-hepatitisben.

UNLABELLED: Overweight/obesity is an independent negative predictive factor of steatosis in chronic hepatitis C virus infection. The nonresponse to combined peginterferon and ribavirin treatment in infection caused by genotype 1 is associated with the waist circumference, body mass index (BMI), diabetes, steatosis, and degree of fibrosis. The obesity is an independent negative predictive factor of inefficacy of antiviral treatment. CASE REPORT: The authors summarize the case of a 59-year-old obese (BMI = 46.47 kg/m 2 ) male patient with chronic HCV infection. The weight reduction--after two ineffective antiviral treatments--helped the biochemical and virological response to combined peginterferon-alpha-2a and ribavirin treatment. Between the combined peginterferon and ribavirin therapy, the patient was treated with amantadine and silymarin. DISCUSSION: The authors summarize the importance of steatosis and insulin resistance in chronic HCV hepatitis as well as review the impact of weight reduction and the improvement of insulin sensitivity. CONCLUSION: Body-weight reduction and hepatoprotective drugs might have increased the effectiveness of combined peginterferon and ribavirin treatment and thus the sustained virological response.

[Successful elimination of hepatitis C virus after hepatic lobectomy in a patient with hepatocellular carcinoma]. / Hepatitis C-vírus sikeres eliminálása hepatocellularis carcinoma miatti lobectomiát követôen.

Hepatocellular carcinoma develops frequently after chronic hepatitis C and B virus infections. Hepatitis B virus has a direct, while hepatitis C virus an indirect role in hepatocarcinogenesis. THE AIM OF OUR WORK: To demonstrate a very unique and interesting case where after the elimination of early detected duplex hepatocellular carcinoma with a combined therapy of PEG-interferon and ribavirin, hepatitis C virus could be eliminated. CASE PRESENTATION: A 53-year-old male patient had chronic hepatitis C infection in his anamnesis. In 1995 histological examination confirmed cirrhosis in his liver. One year later he was non-responder for conventional interferon therapy. In 2002 CT examination confirmed a process with multiple plexus in the liver. With cytologic proof of hepatocellular carcinoma, a resection of the tumor by left-lobectomy of the liver was carried out. Four years after the operation a one-year PEG-interferon-alfa-2a and ribavirin combined therapy was instituted. The patient became virologically negative. CONCLUSION: In chronic liver diseases carcinoma can develop from multiple center at the same time. PEG-interferon and ribavirin combined therapy can be effective in chronic liver disease, as well as after resection of established hepatocellular carcinoma.

[Interferon in the treatment of viral hepatitis. The interferon was discovered 50 years ago]. / Interferon a vírushepatitis kezelésében. 50 éve fedezték fel az interferont.

The interferons are heterogenic glycoproteins which are produced on the effect of virus infection, as immune answer, by the living cells. They were discovered half a century ago. They have antineoplastic, antiviral and immunomodulator effect. The names of interferons used in the therapy are nominated with Greek letters. This nomination shows their origins: the interferon-alpha originates from leucocytes, the interferon-beta does from fibroblasts and the interferon-gamma is produced as immune interferon by lymphocytes. In human medicine both natural and recombinant interferons are applied. The connection of polyethyleneglycol to interferons ensures their sustained effect. Nowadays they are applied in the therapy of chronic hepatitis B or C as well as in oncology to inhibit the neoplasm progression.

IL28B and IL10R -1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort.

BACKGROUND: Previous studies have shown that single nucleotide polymorphisms (SNP) in IL28B and IL10R are associated with sustained virological response (SVR) in chronic hepatitis C patients treated with pegilated interferon plus ribavirin (P/R). The present study extends our earlier investigations on a large East-Central European cohort. The allele frequencies of IL28B and IL10R in genotype 1 HCV infection were compared with that of healthy controls for the purpose of examining the relationship between the polymorphisms and the SVR to P/R treatment. METHODS: A total of 748 chronic HCV1 infected patients (365 male, 383 female; 18-82 years) and 105 voluntary blood donors as controls were enrolled. Four hundred and twenty HCV patients were treated with P/R for 24-72 weeks, out of them 195 (46.4%) achieved SVR. The IL28 rs12979860 SNP was determined using Custom Taqman SNP Genotyping Assays. The IL10R -1087 (also known as IL10R -1082 (rs1800896) promoter region SNP was determined by RT-PCR and restriction fragment length polymorphism analysis. RESULTS: The IL28B CC genotype occurred with lower frequency in HCV patients than in controls (26.1% vs 51.4%, p<0.001). P/R treated patients with the IL28B CC genotype achieved higher SVR rate, as compared to patients with CT (58.6% vs 40.8%, p=0.002). The prevalence of IL10R -1087 GG genotype was lower in patients than in controls (31.8 % vs 52.2%, p<0.001). Among patients achieving SVR, the IL10R -1087 GG genotype occurred with higher frequency than the AA (32.0% vs 17.4%, p=0.013). The IL28B T allele plus IL10R A allele combination was found with higher prevalence in patients than in controls (52% vs 20.7%, p<0.001). The IL28B CC plus IL10R A allele combination occurred with higher frequency among patients with SVR than in non-responders (21.3% vs 12.8%, p=0.026). Both the IL28B CC plus IL10R GG and the IL28B CC plus IL10R A allele combinations occurred with lower frequency in patients than in controls. CONCLUSIONS: In our HCV1 patients, both the IL28B CC and IL10R GG genotypes are associated with clearance of HCV. Moreover, distinct IL28B and IL10R allele combinations appear to be protective against chronic HCV1 infection and predictors of response to P/R therapy.