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Aim: The aim of this study is to assess the efficacy of an initial dose of ribavirin administered before a 48-week course of treatment with peg-IFN + ribavirin in treatment-naïve patients and in patients after previous failure of CHC treatment., Material and Methods: A total of 103 patients with chronic hepatitis C infected with genotype 1 HCV were qualified to the study. Study patients were randomised to receive one of two treatments: A- RBV for 4 weeks followed by combined therapy with peg-IFN alpha-2a +RBV for 48 weeks (n = 73), or B- combined therapy with peg-IFN alpha-2a +RBV for 48 weeks (n = 30)., Results: SVR 24 was observed in 44% patients in group A and in group 40% patients in group B (40%), p > 0.05. Comparing subgroups of the naive patients, it was found that the SVR24 value was higher in group A than group B (57% vs. 47%, p > 0.05). In the re-therapy subgroups, higher treatment response rates in patients not responding earlier was found in group A than group B (39% vs. 16%, p > 0.05)., Conclusion: No significant advantage was found in the use of a priming method over a standard regimen. However, it could be recommended in patients with a total lack of response to peg-IFN and ribavirin when no other therapeutic options are available.

HCV infection is a big problem worldwide. The virus is the main cause of chronic hepatitis and liver cirrhosis. The common treatment is based on a combination of pegylated IFN‑α and ribavirin. It leads to SVR in 40-52% of HCV-1-infected patients and more than 70% of HCV-2- or HCV-3-infected individuals. Unfortunately, this therapy is only partially effective, expensive and associated with numerous side effects. To improve the response, especially among individuals infected with genotype 1, which is the most resistant to standard therapy, new strategies are sought. In 2011 the US FDA licensed two agents, boceprevir and telaprevir, which are protease inhibitors. In the future triple therapy (pegIFN-α/RBV/protease inhibitor) may be the standard of care for patients infected with HCV-1. Polymorphisms in the regulatory region of the Il-28B gene (SNP rs12979860, SNP rs8099917) play a very important role in predicting treatment outcome. They are also associated with spontaneous recovery from HCV infection and explain the difference in response to standard therapy between the black and white races. Personalized therapy, which is defined as suitable treatment for the right patient, should become the main treatment strategy for HCV-infected individuals. It could be possible to make the therapy more effective and safe. Hepcidin is a hormone regulating iron metabolism. A low level of hepcidin leads to iron overload then to inflammation and liver fibrosis. It is observed in HCV-infected patients. Iron influence over HCV replication is not distinctly determined.

In 2011 the European Medicines Agency approved two new drugs (boceprevir and telaprevir) to treat patients with chronic hepatitis C or compensated liver cirrhosis infected with genotype 1 HCV. Their usage together with a standard therapy, ie. pegylated interferon alfa and ribavirin significantly increased the chance of sustained virologic response among both previously unsuccessfully treated and naïve patients. However, this involves a greater number of side effects that poorly monitored can be life threatening. To the known side effects of standard therapy joined new, such as dysguasia, anorectal symptoms. Both drugs can compromise cardiac complications, especially in predisposed patients. Furthermore there is also a greater risk of rash and serious skin reactions. New problem is the interaction between drugs and first generation protease inhibitors resulting from the inhibition of cytochrome p450, common to many drugs pathway.

Aim: This longitudinal non-interventional study aims to describe the demographics data disease characteristics and clinical management of a cross-sectional CHB patient population in Poland treated in regional medical centers., Material and Methods: [corrected] Between March 2008 and December 2010 we observed patients with HBV related liver disease from 5 medical centers in Poland, both sexes, > 18 years old. At baseline, we used a case report form to extract data from patient charts, comprising: sociodemographic data; disease characteristics, HBeAg/ antiHBeAg status, genotype HBV; co-morbidities; viral load, liver biopsy and ALT levels in previous 12 months; treatment history in previous 12 months; current CHB treatment; changes in disease characteristics and CHB management; time from diagnosis to the therapy and resource utilization and any reasons for termination of follow-up. Written informed consent was obtained from all participants, Results: The analysis population included 253 patients (94 treated and 159 non-treated at baseline) mostly male (69.1 vs. 56.6). Patients in treated group compared with untreated group were: significantly older (mean 42.6 vs. 37.5 years respectively, p < 0.001), observed longer since diagnosis(3.9 vs.2.9 years), with higher rate of HBeAg(+)(42.6% vs.5.1%), lower ALT activity, and higher VL HBV DNA PCR. Of the 53% of treated patients, the most frequently prescribed anti-HBV drugs were: Lamivudine (53%), Entecavir (23.7%), Pegylated IFN-alfa2a (23.7%), Adefovir (11.1%). During 24 months of follow-up in treated group 13(36.1%) patients underwent a treatment switch to another nucleosi(-ti)de analogue, in one (2.8%) patient another analogue was added, and in 25 (69.4%)patients the therapy was stopped. The proportion of all patients treated with monotherapy at the end of follow-up was 99.4%, unfortunately mostly with Lamivudine-49.3%., Summary: 1. Despite the several methodological limitations usually associated with this type of observation, the collected data does characterize the demographics of polish patients chronically infected with HBV well, provides some insights into the determinants of treatment initiation and the clinical management of patients in real-word settings. 2. These results indicate that in clinical practice in 5 medical non-academic centers in Poland, European guidelines regarding the qualification to HBV treatment were followed, but there were discrepancies between the initial treatment decisions in real-life current clinical practice and guideline recommendations

Predictors of effective chronic hepatitis B therapy were described in that article. The predictors are: ALT, HBV genotype, HBV DNA, qantification of HBsAg. New predictors as cccDNA and level of HBeAg were described too.

The standard of treatment of chronic hepatitis C is pegylated interferon and ribavirin. The improvement of sustained viral response rates is sufficient with new HCV specific inhibitors against the NS3/4A protease and the NS5B polymerase. First generation protease inhibitors will offer higher SVR for both naïve (70-80%) and treatment-experienced (40-50%) patients infected with HCV when added to standard pegylated interferon and ribavirin. Because of the high genetic heterogeneity of HCV and its rapid replication, monotherapy with directly acting antivirals agents poses a high risk for selection of resistance variants. Year 2011 should bring the approval of the first generation of protease inhibitors that will offer higher cure rates for genotype 1 HCV patients and open the door for eventual testing of interferon-free regiments.

Genetic heterogeneity is a characteristic feature of hepatitis C virus (HCV) and it reflects selection mechanisms affecting the virus. It is considered a major factor contributing the viral persistence and drug resistance. The following work presents the preliminary results of 5'UTR and E2/HVR1 genetic variation analysis and comparison in serum and peripheral blood mononuclear cells (PBMC) of 7 patients before and during the early phase of pegylated interferon alfa (PEG-IFN-alpha) and ribavirin therapy. Single strand conformational polymorphism (SSCP) analysis revealed genetic stability of 5'UTR in all but one patient who did not respond to treatment (SVR-), where new genetic variants appeared. E2/HVR1 genetic changes were characteristic in patients displaying treatment failure (SVR-) and usually reflected fluctuations in complexity and appearance of new genetic HCV variants. Genetic changes (reduction in complexity) were found in one of three sustained virological responders (SVR+ patients). Comparatory analysis of the HCV quasispecies present in serum and PBMC showed differences in at least one analysed region in all non-responders. Presented results suggest the independent forces driving genetic changes in analysed regions. They also point out the presence of genetic compartmentalization possibly having an impact on antiviral treatment result.

About 70% of HCV infection fail to resolve spontaneously and progress to chronic hepatitis C, eventually to cirrhosis and HCC. Many studies have demonstrated that clinical manifestation and the outcome of HCV infection are negatively influenced by a variety of cofactors and comorbidities. Moreover many of these cofactors often reduce the chance of achieving a sustained virological response (SVR) with only available combination therapy with pegylated interferon-alpha2 (PEG-IFN) and ribavirine (RBV). Dose modification of both currently licensed drugs for treatment of HCV infection and variations of treatment duration are the most discussed strategies to optimized the therapy, particulary in patients infected by genotype 1 HCV. Tailoring the duration of peginterferon/ribavirine therapy to HCV kinetics is useful to optimize the results of therapy.

The current standard of chronic hepatitis C therapy is the combined use of pegylated IFN-alpha 2a (PegIFN-alpha) and rybavirin (RBV). The new form of interferon, IFN-alpha 2b, was also introduced with no better results. Overall, the effectiveness of therapy with the use of the above scheme is not satisfactory. Thus the search for new therapeutic agents for hepatitis C is ongoing. These studies have the goal to find new preparations inhibiting the replication cycle of HCV. The new analogue of RBV, eg. tarybavirin was introduced, with lesser side effects, but the same effectiveness. The activity of new agents relies upon the inhibition of the most important enzymes of the HCV replication cycle: RNA polymerase, protease and helicase. Polymerase NS5 inhibitors are divided into nucleoside (R-7128) and nonnucleoside (ANA-598, GS 9190, VCH-759, VX-222). The intensive studies on the R-7128 analogue are ongoing. The effects of action of particular compounds in the I and II studies were summarized. The promised prodrug is nonnucleoside polymerase inhibitor, ANA-598 which when administrated to patients, gave 75% SVR. The combined administration of the newly described agents is the basis of specifically targeted antiviral therapies for HCV (STAT-C). These therapies allow to achieve better effectiveness of treatment, its shortening, the diminishment and limitation of side effects.

Unlabelled: The aim of the study was to compare 4 non-invasive biochemical scores of liver fibrosis (age/PLT; AST/ALT; APRI and FORNS) with results of hepatic biopsies classified according to Batts-Ludwig scale. The study included a total of 99 patients: 44 (44.4%) women with mean +/- SD age of 42 +/- 11.9 years and 55 (55.6%) men (43 +/- 12.2) treated for chronic hepatitis C., Results: Levels of several markers changed significantly after 3 months of treatment (with interferon alpha and ribavirin) comparing to values on admission to hospital: we observed statistically significant differences of ALT: 32.6 +/- 15.7 vs. 61.5 +/- 35.6 (U/l), p<0.001; AST: 34.1 +/- 11.1 vs. 48.2 +/- 26.5 (U/l), p<0.05 and total cholesterol concentration: 4.0 +/- 0.4 vs. 4.9 +/- 0.9 (mmol/l), p<0.01 in women; AST/ALT ratio in both men (0,8 +/- 0,3 vs. 0.69 +/- 0.25; p<0.05) and women (1.2 +/- 0.4 vs. 0.84 +/- 0.24; p<0.001) and age/PLT score: 0.4 +/- 0.3 vs. 0.28 +/- 0.12 (p<0.01) in men., Conclusions: Non-invasive biochemical scores: age/PLT, APRI and FORNS showed acceptable compliance with liver morphological status characterized in Batts-Ludwig scale as we observed significant differences between F0-F1 and F3-F4 groups. Age/PLT, APRI and FORNS seems to be helpful in prediction of early stage of liver fibrosis in patients with chronic hepatitis C. After 3 months of standard antiviral therapy (interferon alpha and ribavirin) we did not observe statistically significant differences in values of FORNS and APRI scores. Simultaneously, we noticed significant decrease in activity of aminotransferases and AST/ALT ratio recognized by clinicians as standard markers of inflammatory and necrosis processes.

According to WHO data the hepatitis C virus (HCV) has already infected 170 million people worldwide, and 750,000 of them in Poland what amounts some 1.4% of general country population. Currently used antiviral therapy with pegylated interferon alpha and ribavirin has only 50% effectiveness. Many new drugs and molecules, especially inhibiting viral replication, are studied in preclinical and clinical trials. However, still unknown HCV entry process can be a new, promising therapeutic target in chronic HCV infection.

Membranoproliferative glomerulonephritis is a typical manifestation of HCV infection, in most cases connected with cryoglobulinemia. Efficiacy of antiviral treatment with interferon and ribavirine in this group of patients is lower compared to the population without kidney disease. Another options of treatment are: use of rituximab (monoclonal antibody destroying lymphocytes B), low-antigen containing diet, plasmapheresis and immunosupressive treatment. Recommendations of antiviral treatment in HCV-infected patients with concomitant renal failure were presented.

The aim of our study was to assess efficacy and safety of antiviral treatment with natural interferon alpha in patients with thrombocytopenia during chronic HCV infection. The study group consisted of 14 patients infected with HCV genotype lb. There were 8 women and 6 men (mean age 50). 11 of these had compensated liver cirrhosis. Three patients had previous reIFN or PegIFN alpha therapy with severe adverse events and lack of sustained viral response (SVR). Sustained viral response was achieved in 4 patients. Only in one case therapy was discontinued due to symptomatic hemorrhagic purpura.

Unlabelled: The role of cellular immune response in pathogenesis of liver cell injury and course of chronic hepatitis C have been previously confirmed. The aim of this study was to determine the modification of T-lymphocyte subsets during pegylated interferon alpha (PegIFN) and ribavirin treatment and its correlation with response to the treatment., Material and Methods: The assessment of subsets of intrahepatic lymphocytes and peripheral blood lymphocytes was done in 62 patients with chronic hepatitis C using flow cytometry and immunohistochemical method., Results: Significant increase in peripheral blood CD4+ cells, was observed in week 12 of treatment in patients with both complete and partial response to therapy. There were no significant modifications in nonspecific CD8+ subsets, but after 12 week of treatment in patients with response to therapy, decrease or lack of HCV-specific CD8+ cells were observed. The assessment of subsets of intrahepatic lymphocytes revealed a significantly higher percentage of CD8+ cells in pretreatment liver biopsies from patients with sustained viral response., Conclusions: The results confirmed the impact of interferon alpha and ribavirin treatment on cellular response. Some immunological host factors should be considered in the early prognosis of successful treatment.

Unlabelled: The hepatitis C virus (HCV) infection course and efficacy of treatment may be depended on HLA antigens. The aim of the study is attempt to define dependence between the course of HCV infection and efficacy its treatment and HLA A antigens in children and youth., Patients and Methods: To the study included 61 patients (51 after treatment for HCV infection and 10 not treated). The average age was 13.77 years (range 5-18 years). Patients were divided to subgroups in depend on effect of the treatment: virusological and biochemical response. Antigens HLA A were molecularly typed on the low resolution method. To statistical analysis we applied the chi-square test., Results: We demonstrated no statistical significant dependences between HCV infection course and efficacy of its treatment children and youth HLA A antigens. However we observed following tendencies: antigens HLA A *01 and HLA A *02 can be related to unprofitable course of infection and unsuccessful antiviral therapy; HLA A *03 can be favorable prognostic factor for HCV infection course and response to treatment; HLA A *24 can be related to mild course of infection and profitable response to treatment; HLA A *11 can be favorable prognostic factor for course of infection; HLA A *30 can be profitable for efficacy of treatment and HLA A *25 can be disadvantage for it. Probably study performed with larger group of patients could gain dependencies statistical significant., Conclusions: It is possible that course if HCV infection and efficacy of antiviral treatment are depended on HLA A antigens.

Unlabelled: The aim of the study was an assessment of retherapy in children with chronic hepatitis C. Investigations were performed in 41 children divided on 2 groups (A and B). Children from group A were treated firstly with IFN monotherapy during 6 months and as retherapy they administered combined therapy with IFN alpha and ribavirin during 12 months. Patients from group B were firstly treated with combined IFN alpha and ribavirin therapy during 12 months and as retherapy with pegylated IFN and ribavirin. Sustained viral response achieved 44% of children (58% from group A and 33% from group B). ALT activity normalization was observed in 46% of treated children (53% from group A and 45% from group B). Prevalence of relapses in group A and B was 14% and 37% respectively. Among children who responded on treatment, baseline ALT activity was statistically significant higher in group A (p<0.05). The age of children from this group was statistically significant lower in comparison with children from group B (p<0.02). Mean leukocytes count after 3 months of treatment was statistically significant lower in children treated with pegylated IFN and ribavirin (p<0.02)., Conclusions: Retherapy of chronic hepatitis in children was effective and well tolerated. The high frequency of relapses seems to be a point of extending of retherapy.

Ribavirin, a guanosine analogue synthesized in 1970, possess activity against several RNA and DNA viruses. The addition of ribavirin to IFN-alpha in the treatment of chronic hepatitis C led to marked improvements in SVR rates. Now ribavirin plays an important role in combination with pegylated interferon during all stages of HCV therapy. Potential mechanisms for antiviral activity of ribavirin includes direct inhibition of HCV replication, inhibition of the enzyme inosine-monophosphate-dehydrogenase (IMPDH), immunomodulation and mutagenesis. Efficacy of ribavirin in hepatitis C combined therapy depends of appropriate ribavirin initial dose and maintaining the patient on this dose for as long as possible-until the end of therapy.

Chronic viral hepatitis B still remains serious diagnostic and therapeutic problem, that is mostly related to insufficient efficacy of available treatment options. This is the main reason of search for new recommendations and algorithms for optimizing procedures of patients selection and treatment. In this article we summarize informations collected from published recommendations of hepatologic scientific societies (EASL, AASLD, APASL) and independent groups of hepatologists, as well as therapeutic programs of Polish National Health Fund (NFZ). Principal criteria for patients selection include sera HBV-DNA concentration and alanine aminotransferase activity, but in some cases additional evaluation of histologic activity in liver biopsy can be necessary. Currently available medication used for HBV infection treatment are: adefovir, entecavir, lamivudine and pegylated interferon alfa 2a. The last two are most frequently prescribed in Poland, whereas use of adefovir and entecavir is limited due to lack of appropriate therapeutic programs covered by NFZ.

Unlabelled: Many articles concerning the hepatitis C virus (HCV) infection emphasize the role of cytokines Th1- and Th2-dependent. The aim of our study was to assess the changes in the concentration of cytokines (IL-2, IFN-gamma, IL-4, IL-10) determined by ELISA test in serum of HCV infected patients treated with interferon alpha (IFN-alpha) and ribavirine., Results: The cytokine levels in HCV patients (n = 40) were similar to levels observed in healthy volunteers (p > 0.05). During IFN-alpha and ribavirine therapy no statistically significant changes in cytokine levels were observed in patients who achieved sustained virological response (SVR) compared to unsuccessfully treated patients (p > 0.05)., Conclusions: 1. Serum is not useful compartment to determinate level of cytokines by ELISA method in chronic hepatitis C. 2. The measurement of cytokine levels using ELISA test was not confirmed to be useful in monitoring and assessment of the therapy results in HCV infected patients.

Over one million people all over the world die every year due to the complications of HBV infections. This problem is particularly important in Asia, Africa and in the West Pacific region where HBV infection is widely spread (from 5-20% up to 80% of all infected people in the world). In these regions HBV infections are transmitted mostly perinatally or during early childhood. In North America and in West Europe where after introducing anti-HBV vaccinations less than 2% of the population is affected, infections are usually transmitted by intravenous drug abuse, sexual intercourse, or much less frequently by blood transfusions. The immaturity of immune system in young children is responsible for the fact that nearly 90% of HBV infections acquired in infancy and 40-70% of HBV infections before the age of 3 years, result in chronic viral hepatitis. Therefore, the choice of an efficient and safe therapy is one of the most important problems. In this paper current data concerning indications for treatment and side-effects of interferon-alpha and lamivudine therapy in children with chronic viral hepatitis type B are presented.

The long-term outcomes showed a special place of IFN alfa-2a in therapy of chronic hepatitis B. Multivariate analysis revealed that patients who received 48 weeks treatment PegIFN-alfa-2a with reduction of serum ALT level and suppression of HBV-DNA replication will have a chance to keep this effect in the future. The results of long term follow-up showed that IFN alfa-2a improves prognosis in terms of reduction of progression to cirrhosis and hepatocellular carcinoma.

The current standard of care for the treatment of hepatitis C virus (HCV) infection is the combination of pegylated interferon and ribavirin. The interferon-based therapy is contraindicated in patients with HCV-associated thrombocytopenia. The pathogenesis of HCV-associated thrombocytopenia is still unclear. In this paper the main aspects of HCV-associated thrombocytopenia and alternative therapy with natural interferon (Alfaferone) are presented.

Despite the significant advances that have been made in the treatment of chronic hepatitis C the efficacy of treatment response seems to be unsatisfactory. Treatment failure concern above one half of treated patients. It is estimated that the number of non-responders will be systematically increased. For these reasons as treatment strategies in these patients there is a need to define optimal way to use new therapies as: extending of treatment duration, higher initial doses of administered medications, an increase of patients adherence, changing of kind of pegylated interferon or treatment combinations PEG IFN + RBV with other drugs, especially HCV-enzymes inhibitors. In the work the data of efficacy of retherapy with PEG IFN alfa-2a+RBV administered during 72 weeks were present. Retreatment with PEG IFN alpha-2a and RBV in patients who fail to achieve SVR in the treatment with PEG IFN alpha-2b+RBV revealed high early viral response, in patients with advanced liver histology too. In the future there are planned treatment of chronic hepatitis C with combined therapy with IFN, specific HCV-enzymes inhibitors and antiviral medications.

Unlabelled: Liver fibrosis is a result of disturbed balance between extracellular matrix protein synthesis and degradation. Growth factors may play the meaningful role in pathogenesis of fibrosis. The aim of the study was the assessment of VEGF role in pathogenesis of fibrosis associated with chronic hepatitis C (CHC) and evaluation of the influence of antiviral therapy on VEGF levels depending on treatment results., Material and Methods: Study group included 100 CHC patients with fibrosis (Scheuer: 1-4 points). Control group included 30 HCVAb-positive subjects with normal ALT, without fibrosis (Scheuer: 0 points). From all subjects blood samples were taken at the beginning of the study. From study group patients blood samples were also collected after the treatment with Rebetron., Results: There was no significant difference in VEGF levels between CHC group and control group. Significant negative correlation between VEGF levels and inflammatory activity (R = -0.40; p < 0.01) and fibrosis stage (R = -0.30; p < 0.05) was observed. After antiviral treatment significant elevation of VEGF occurred in responders (112.8 vs. 315.03 pg/ml; p < 0.05), but not in non-responders., Conclusions: 1. Progression of liver lesions is correlated with reduction of VEGF levels. 2. Good therapeutic effect is connected with the elevation of VEGF levels. 3. Angiogenesis stimulation by VEGF probably is an important element in regenerative processes accompanying fibrosis regression.

In the study we described severe adverse events such as sepsis and bacterial endocarditis in the patient treated because of chronic hepatitis C (CHC). A case of 57 year old man with CHC, with recurring increased aminotransferases up to 100 IU/l; histological result of liver biopsy--G3, S2, HCV-RNA positive, genotype--HCV1b. The therapy with peginterferon alfa and ribavirin was introduced. The negative result of HCV RNA was obtained in 12th week of treatment. In the 7th month the patient was admitted to the hospital because of sepsis due to Escherichia coli, acute renal insufficiency and right orchitis. In spite of the treatment and general clinical improvement, the patient was still febrile. The bacterial endocarditis was found after number of diagnostic procedures. The treatment of endocarditis lasted 6 weeks in the hospital. During the hospitalization and 6 months after the HCV-RNA were performed with the negative results. The therapy of CHC with peginterteron and ribavirin is save in most cases however requires increased clinical surveillance, especially in the second half-year.

Unlabelled: The aim of the study was to estimate effectiveness and adverse events of alfaferone therapy in hepatitis B and/or C., Materials and Methods: 25 patients treated with alfaferone in Department of Infectious Diseases and Hepatology in Bydgoszcz were included into the study. That group contained 6 women, 8 men (age 19-68) and 11 children age 9-17. The natural interferon was applicated to 2 patients with acute hepatitis C, to 11 patients with chronic hepatitis C combined with ribavirine, to 10 with chronic hepatitis B and to 2 patients coinfected with HBV and HCV with ribavirin., Results: In 6 cases alfaferone was given as retherapy, to following 3 patients because of bad toleration of recombinant interferon alpha (INFalpha) the drug was switched to natural interferon. 16 patients were naive. Main adverse events were: flu like syndrome (9), psychiatric disorders (8), which in 2 cases were the cause of discontinuing therapy. Leucopenia (6) and thrombocytopenia (5) observed before treatment didn't get worse. Thrombocytopenia below of 50,000/ml wasn't contraindication for use of alfaferone. HCV viremia was undetected in one case with acute hepatitis C. SVR was reached in 5 patients with chronic hepatitis C. Two of these 5 patients had been unsuccessfully treated with INFalpha before. Seroconversion HBeAg/anti-HBe was observed in 1 patient and undetectable HBV in 3 cases. The therapeutic effect wasn't achieved in 2 patients coinfected with HBV and HCV., Conclusion: Alfaferone can be used in hepatitis B and/or C treatment in cases with leuco- and thrombocytopenia, as retherapy and as continuation of treatment with INFalpha when hematological complication appears. Therapeutic effectiveness was observed in hepatitis C.

Neuropsychiatric symptoms are commonly related to interferon alpha treatment. The paper summarises the current knowledge about their aetiology, course, and treatment. Interferon alpha is a cytokine with antiviral and antineoplasmatic activity. It is commonly used in the treatment of chronic hepatitis C and B, malignant melanoma, Kaposi sarcoma, renal cancers, and some haematological malignancies. Treatment with interferon alpha is associated with depressive symptoms, cognitive disturbances, chronic fatigue syndrome, dysphoria, anxiety symptoms, anorexia, mania and psychotic states. Up to a half of the patients need psychiatric consultations, 10-25% of them need psychiatric treatment. Neuropsychiatric symptoms are the results of direct affection of CNS by interferon and induced cytokines. They increase hypothalamic-pituitary-adrenal (HPA) activity, alter thyroid function and lead to a behavioural syndrome called 'sickness behaviour'. Moreover interferon induces the activity of 2, 3 indoloamine dioxygenase, the enzyme which converts tryptophan into kynurenine, leads to a reduced level of tryptophan, and thus to a reduced level of central serotonin and to an increased level of neurotoxic kynurenine metabolites. Interferon also affects central opioid receptors and changes dopaminergic and noradrenergic neurotransmission. Serotonin selective reuptake inhibitors (SSRI), other antidepressants i.e. nortriptyline, benzodiazepines, naltrexone, and neuroleptics (for maniac and psychotic states) are used to treat interferon associated psychiatric symptoms. Psychological therapy may also be useful, as well as psychoeducation and behavioural interventions.

Unlabelled: Targeted therapy with the use of imatinib mesylate is a recognized option for patients with chronic myeloid leukemia (CML) not eligible for allogeneic hematopoietic cell transplantation. We present results of a multicenter phase II study on the use of imatinib in chronic phase after failure to interferon-alpha (IFN-alpha). Sixty patients (27 female, 33 male), median age 46 (range, 21-64), were included with hematologic relapse (n= 11), hematologic refractoriness (n=4), cytogenetic relapse/ /+65resistance (n=40) or intolerance to IFN-alpha (n=5). The median time from CML diagnosis was 39 months (range, 4-132), the median time of IFN-alpha therapy equaled 23 months (range, 1-78). Imatinib mesylate was administered at a dose of 400 mg/day for 1 year. In patients who achieved major cytogenetic response (MCR) the therapy was continued until progression. Thirty-three (55%) patients achieved MCR after one year of treatment. At 4 years the cumulative incidence of complete cytogenetic response equaled 40% (95% CI, 29-56). Among 27 patients who did not achieve MCR at 12 moths, in 12 cases the study course was discontinued prematurely because of blast crisis (n=9), prolonged neutropenia (n=l), severe transaminases elevation (n=l) or incidental death not related to the study drug or disease (n=l). The probability of OS at 4 years equaled 82% (95% CI, 72-91) and was lower for patients with the disease duration >36 months and those with Sokal index > or =0.8. Among patients who achieved MCR, the probability of progression-free survival was 78% (95% CI, 69-85). Time to progression (cytogenetic, n=6; blast crisis, n=l) varied from 3-36 months., Conclusions: Imatinib mesylate is characterized by good tolerance and allows achieving cytogenetic response in more than half of late chronic phase CML patients with failure of interferon therapy. However, the progression rate is substantial, which raises concern regarding the curative potential of monotherapy with imatinib in this group of patients.

Among "patients difficult to treat" there are infected with genotypes 1,4 HCV, patients with liver cirrhosis, blacks, immunocompromised, hemodialyzed and non-responders to previous treatment. Multicenter, randomized trials were confirmed lower sustained virologic response (SVR) in patients infected with genotype 1 HCV. To improve the response longer therapy during 72 weeks was suggested. In genotype 4 HCV infected relationship of therapeutic efficacy with patients ethnicity was shown. The standard of HCV therapy in HIV infected patients is combined therapy with pegylated interferon and ribavirin. This therapy depends of the advance of HIV infection and administered antiretroviral therapy. Pharmacokinetic examination of safety and tolerability of pegylated interferon in patients with renal insufficiency was revealed the base to administering it in these patients. Controversial in this group is administering of ribavirin. Relationships between body weight, body mass index, obesity, liver steatosis, insulin resistance and therapeutic response in patients with chronic hepatitius C are analyzed. Trials assessed the efficacy of retherapy with pegylated interferon and ribavirin patients, who non responded to previous therapy revealed positive results.

Despite of significant progress in the treatment of chronic hepatitis C after introduction of combination therapy with pegylated form of interferon-a with ribavirin, still overall response rate in HCV genotype-1 infected has been modest. Several teams has been working on modification of therapeutic methods. Optimization of the results is realized by individualization of therapy taking under consideration some known virological and host features. The main trends are following: settlement of optimal period of treatment of infected with HCV genotype-1, applying interferon-induction therapy for non-responders and relapsers at the course of previous treatment, as well as prolongation of therapy-period, and ribavirin-dose increasing. Very important is also looking for optimal predictive-viral parameters in early course of disease.

Fatty liver disease is one of most frequently diagnosed hepatopathies while detailed examination of potential causes of liver enzymes abnormalities is done. Despite its isolated nosology fatty liver disease often co-exists with other liver pathologies or - more often - it is their natural consequence. Liver steatosis is also more often found in primary hepatotropic viral infections. However, it's more prevalent among HCV (hepatitis C virus) infected persons than in those HBV (hepatitis B virus) infected. It is described in 30-70% routinely pursued liver biopsies in HCV infected individuals. Hitherto, there were many analyses concerning clinical and prognostic implications pursued of HCV influence upon inflammatory and fibrotic process of the liver. This article is an up-to-date review of current clinical and therapeutic implications of hepatosteatosis supported by referent study results.

Among patients with chronic hepatitis B 30% there are HbeAg negative. In Europe the most of these patients are infected with genotype D HBV and live on The Mediterrane Basen. Molecular investigations were revealed presence of mutant HBV infection in this group of patients. The most common type of mutationts there are "precore stop codon" and dual mutation "basal core promoter". In clinical trials was revealed that treatment with interferon-alfa decreases staging, esspecially in treatment responders. On the base of the results of multicenter, randomized trial it was revealed that biochemical treatment response assessed as ALT activity normalisation was higer in patients receiving pegylated interferon. Similar in these groups of patients virologic response measured as HBV viral load <20.000 copies/ml was higher. Pegylated interferon seems to be the first drug for treatment of chronic hepatitis B.

Early virologic response (EVR) depending on various hepatic fibrosis was analyzed at 12 week of pegylated interferon alfa-2b (Pegintron, 12 KD) with ribavirin treatment among chronic hepatitis C patients (pts) infected with genotype non 2/3. The A group composed 29 pts. They were of staging 0 and grading 1. The group B composed 47 pts of staging 1, C 33 pts of staging 2, D 35 pts of staging 3 and 4. Liver biopsies were analyzed according to the Scheuer's and Knodell's scores. Early virologic response (ERV) was defined as decrease of VL >2 log or undetectable HCV RNA. Viral load (VL) was determined with HCV RNA Assay and CA HCV Monitor Test (Roche Diagn. Sys.). The EVR rates for the A, B, C, D groups were as follow: 86,2% (25/29), 80,9% (38/47), 75,8% (25/33) and 60% (15/25), respectively.

Unlabelled: The aim of study was to report the preliminary results and complications of HCV infection treatment after liver transplantation., Material: Six patients after liver transplantation (one after combine liver and kidney) had been qualified to treatment with pegylated interferon and ribavirin., Results: In four patients the therapy was discontinued due to severe side effects (anaemia, cholestasis, sepsis, acute rejection). In two patients the normalization of biochemical parameters of liver function was achived after treatment., Conclusion: HCV treatement in solid organ recipients should be individualised.

The current standard therapy in terms of treatment efficacy is the combination of peginterferon and ribavirin. Many factors affects response to this therapy: viral factors, host factors, factors related to therapy. The overall sustained virological response (SVR) is only 50%-61% among patients infected with genotype 1,4, following 48 weeks therapy and 78%-88% among patients infected with genotype 2,3, following 24 weeks therapy. Because there are some differences between the two brands of peginterferon clinicians are awaiting more information regarding the most effective anti-viral schedule for naive patients with chronic hepatitis C, particulary with genotype 1,4. IDEAL is the current ongoing trial comparing the effectiveness of these two form peginterferons approved for the treatment of chronic hepatitis C.

Unlabelled: The aim of our study was to investigate the immunogenicity of hepatitis B vaccine in a group of patients suffering from chronic heaptitis C. Thirthy seven patients with chronic hepatitis C (anti-HCV+, HCV-RNA+, histological findings) were selected. Only those patients without serological markers for HBV infection (HBsAg (-), anti-HBcT(-), anti-HBs (-)) were vaccinated the hepatitis B vaccine. The recombinant vaccine (Engerix-B SKB 20 microg) was used according to a 0, 1,2 month regime. The vaccinees were divided into two groups. Group A-12 patients with HCV infection, were treated with interferon alpha 2b during vaccination. Group B-25 patients did not recive the interferon. The seroconversion rates and the concentrations of anti-HBs were taken at month 1, 2 and 3 after the first injection., Results: Patients suffering from chronic hepatitis C react much less favorably to the hepatitis B vaccine than healthy subjects. Administration of the hepatitis B vaccine coupled with interferon-alpha treatment resulted in statistically significant improvement of the immunological response to the vaccine.

Genetic material of HCV consists of single-strained RNA. Generation of HCV mutants insensitive to the immune system activity and resistant to used medications seem to be a consequence of HCV genetic variability, unusual replication potential and selection pressure of the host organism. During only one day 10(12) of viral particles may be formed, many of which contain mutations. Selection pressure put by the immune system and used medications lead to the selection of new HCV variants insensitive to therapeutics. The aim of the study is to draw attention (by means of discussing the structure and replication of HCV) to therapeutical problems of chronic hepatitis C consisting of the biology of the virus. Clinical and laboratory factors dependent on the patient (e.g. biochemical, histopathological, genotype) were omitted.

Unlabelled: THE AIM OF THE STUDY was to evaluate prospectively serum hyaluronic acid (HA) and laminin (LAM) concentration in children with chronic hepatitis B (chB) during lamivudine treatment., Material and Methods: The observation was carried out on 40 children (29 boys and 11 girls), aged 4-17 yrs with biopsy proven chB who were nonresponders to previous IFN alpha therapy. Lamivudine was given in the dose of 3-4mg/kg/day up to 100 mg/day. The concentration of HA and LAM were measured with EIA technique in serum (CORGENIX and TAKARA kits respectively) before and after 12 months of therapy., Results: After 12 months of therapy mean serum concentration of HA and LAM were lower then before treatment (20.3 +/- 13.3 vs 26.1 +/- 18.2 ng/ml, p=0.0112; 430 +/- 93 vs 455 +/- 161 ng/ml, p=NS respectively). The decrease of HA concentration was observed in subgroups of both responders and nonresponders (21.9 +/- 10.9 vs 26.1 +/- 10.6, p=NS; 20.1 +/- 13.7 vs 26.1 +/- 19.0, p=0.01 resp.)., Conclusion: The decrease of HA and LAM serum concentration may suggest that lamivudine treatment inhibits liver fibrosis. Further studies with liver morphology evaluation are needed to confirm antifibrotic effect of lamivudine in children with chB.

We present history of 16-year-old boy, HBsAg carrier, treated with interferon alpha at the age of 6 because of hepatitis B (HBeAg/antyHBe seroconversion). In August 2002--admitted to Department of Pediatric Oncology due to pancytopenia--diagnosis of severe aplastic anaemia was made (bone marrow cellularity--10%). We found no relative donor for hematopoietic cells transplantation and started immunosuppresive therapy (ATG, G-CSF, methyloprednisolon, cyclosporin). Haematologic parameters were improving. At day +60 he was admitted to our Department due to the increase in aminotransferases and cyclosporin activity. He was treated with cefuroxim, acyclovir and drugs improving liver cell function, cyclosporin was stopped. Presence of HBV DNA in serum confirmed HBV reactivation--a boy received lamivudine and cyclosporin again (as a maintenance therapy of aplastic anaemia). Aminotransferase activity and haematological parameters returned to normal. This case indicates the possibility of HBV reactivation in the course of immunosuppressive therapy (e.g. after antithymocytic globulin and cyclosporin) for aplastic anaemia.

Unlabelled: Changes of lipid metabolism are often observed in patients (pts) with chronic viral hepatitis during interferon therapy. Many studies show changes in blood lipids including increase of triglycerides level, decrease of total cholesterol as well as HDL lipoprotein levels. This study was an attempt to widen our knowledge about additional factors responsible for changes in lipid metabolism of pts with chronic viral hepatitis during interferon therapy. The aim of this study was to assess the changes of total cholesterol, triglycerides and LDL-, HDL-lipoproteins levels in blood serum in comparison to: activity of hepatic inflammation, degrees of fibrosis, type of hepatotropic viruses and response to antiviral treatment., Material and Methods: In the group of 53 pts (18 female, 35 male), age 16-61 years old with chronic hepatitis B (13 pts) and chronic hepatitis C (40 pts) treated with interferon alpha we examined the cholesterol, HDL, LDL-lipoproteins and TG levels in blood serum at the beginning of therapy and in the sixth month. Changes of lipids values at the beginning and in the sixth month of therapy were assessed in respect to: necro-inflammatory changes of the liver in histopathological examination, degrees of fibrosis, obesity, loss of the weight during IFN therapy, response to treatment, type of hepatotropic viruses (HBV, HCV), sex and age., Results and Conclusions: During sixth month of interferon therapy there was significant decrease of total cholesterol level (before treatment 4.1 +/- 1.0, after treatment 3.8 +/- 0.9, p < 0.05) and HDL-lipoproteins level (before treatment 1.3 +/- 0.35, after treatment 1.1 +/- 0.35, p < 0.05). Increase of TG level was not statistically significant. The necro-inflammatory changes in the liver correlated with the values of TG level. Low activity of hepatic inflammation correlated with the increased TG level at sixth month of therapy. There was not observed effect of any other factors on the lipid metabolism.

Hepatitis C virus (HCV) is an extremely dangerous human pathogen. It is widespread all over the world and often leads to the development of chronic hepatitis C (CHC), which can eventually result in cirrhosis a hepatocellular carcinoma. The efficiency of the current applied methods of treatment of HCV infection remains unsatisfactory. The main course of development of CHC and of therapeutic problems is the genetic polymorphism of HCV. The conducted analysis of the structure of the virus' population permits are conclude that the degree of diversity it presents is a crucial agent in the prediction of the outcome of IFN and ribavirin therapy.

The aim of the study was to evaluate the efficacy of interferon alpha (IFNalpha)-2b in combination with oral ribavirin for treatment of chronic hepatitis C in relation to age, sex, liver enzymes activity as well as to grading and staging of liver disease in histologic examination. There were 154 adult patients assigned for the retrospective analysis including 69 females and 85 males of 16 to 70 years of age (mean age 43.3 +/- 12 years) treated with IFNalpha and ribavirin for 24 or 48 weeks. Sustained virological response was achieved in 66 patients (42.9%) and sustained biochemical response rate was 44%. Sustained response correlated with younger age, lower baseline AST, GT and ALP activities as well as with lower staging of liver disease. Combination treatment with interferon and ribavirin was significantly more effective in patient under 40 years of age and in patients without cirrhosis. Sex, baseline ALT activity and histological grading of liver disease did not differ between sustained responders and non-responders. Sustained virological response on combination therapy was achieved in 5 out of 7 previous monotherapy relapsers (71.4%) whereas only 5 patients out of 22 monotherapy non-responders benefited from combination therapy (22.7%). In conclusion, efficacy of combination therapy with IFNalpha and ribavirin in patients with liver cirrhosis is less effective and should be considered in chosen situations, especially in younger patients. Normal ALT activity should not be an exclusion criterion to therapy. Combination retherapy in previous monotherapy non-responders seems to be ineffective whereas in monotherapy relapsers good sustained response can be achieved.

Neuroendocrine tumors of the gastroenteropancreatic (GEP) system are rare neoplasms, characterized by their capacity to synthesize, store, and release hormonal products and biogenic amines. Because of their low incidence, limited data about clinical outcomes and prognostic variables are available. They can present clinical symptoms caused by the products secreted, tumor mass or metastases. Assessment of specific or nonspecific tumor markers offers high sensitivity in establishing diagnosis and can also have prognostic significance. Imaging modalities include endoscopic ultrasonography, computerized tomography, magnetic resonance imaging, and in particular, scintigraphy with somatostatin analogs. The radical treatment of GEP tumors is tumor surgery, but this is rarely possible. Somatostatin analogs have been the treatment of choice in symptomatic patients with GEP tumors. In poorly differentiated tumors or in selected cases of advanced or rapidly growing disease, interferon alpha, chemotherapy, and/or radio-metabolic treatment with radiolabeled somatostatin analogs can be performed. Symptomatic therapy is also helpful.

The prevalence of hepatitis C virus (HCV) infection in dialyzed patients (pts) with end stage renal disease (ESRD) is higher than that of the general population. Generally it is thought that the course of hepatitis C is milder then in pts with normal renal function, but there is no agreement about natural history of HCV infection in dialyzed. Immunosuppressive therapy after renal transplantation (RTx) worsens the prognosis for pts with HCV infection. Additionally, actually available anti-HCV treatment is contraindicated after RTx due to the high risk of the graft rejection. That is the reason why antiviral therapy should be given before RTx and indications for treatment should be wider (treatment of HCV infection not only of hepatitis). The biggest number of papers addressed to anti-HCV treatment in dialyzed pts considers monotherapy with standard interferon. One out of two pegylated interferons was approved for dialyzed pts--but up to date there is no data about efficacy and safety of this compound in this group of pts. The use of ribavirin in ESRD pts is contraindicated due to the high risk of anemia.

Objective: The aim of our study was to assess: (1) whether seroconversion to IgG anti-HBs, induced by IFN-alpha therapy in children with chronic active hepatitis B, is maintained 4-10 years after treatment; and (2) whether HBV-DNA is present in circulation despite the synthesis of anti-HBs., Methods: Serum samples were collected from 38 patients and serological markers of HBV were determined in each of them. HBV-DNA was determined by PCR in anti-HBs positive sera. Serum samples obtained from 19 subjects with a complete spontaneous seroconversion after acute HBV served as controls., Results: Four to 10 years after therapy, anti-HBs were present in ca. 97.4% patients with GMT value of 775 IU/L vs 127 IU/L found in controls. HBsAg was found in 2/38 subjects. In 13 out of 37 patients (35.1%) free and/or bound HBV-DNA was present., Conclusions: This study showed that seroconversion induced by IFN-alpha may not be a sustained phenomenon. HBV-DNA may persist for a long time after therapy despite the anti-HBs synthesis.

PEGInterferon and ribavirin combination therapy is a gold standard in hepatitis C treatment. However it is not efficacious in all cases. Therefore, many studies are conducted to identifying additional drugs and therapeutic regimens, which might be more affordable. The progress in development of HCV culture systems (e.g.replicon) is crucial for successful therapeutic intervention in viral life-cycle (viral NS5B polymerase and NS3/4A protease inhibitors, antisense nucleotides, ribozymes, siRNA). Other classes of immunomodulatory/antiviral agents and new interferon formulation have also been considered for IFN-based therapy also. On the other hand immunomodulatory pathways are attractive target for novel anti-HCV therapy. Combination therapy targeting different aspects will be probably in the future successful option in hepatitis C treatment.