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Objectives: The incidence of HBV infections among the pregnant in Europe falls within the range of 1–7%, whereas it is 1.7–4.3% for HCV. The aim was to assess the course of pregnancy among women infected with HBV or HCV, and the condition of neonates in the fifth minute after the birth. Material and methods: The study included 157 pregnant individuals infected with HBV, 53 infected with HCV, and 330 healthy pregnant women. None of the women infected with HBV and HCV as well as from the control group were infected with HIV, and none of them took intoxicants. Results: Weight of neonates delivered by healthy women was higher as compared with children born by women infected with HBV or HCV (3.517 vs 3.347 and 3.366). The Apgar score of neonates delivered by women with HBV and HCV infections was lower as compared with the children born by healthy women (9.4 vs 9.3 vs 9.7; p < 0.05). Premature births occurred more often in HBV and HCV-infected women than in the control group (14.6% and 24.5% vs 6.96%; p < 0.05). Miscarriages were significantly more common among the patients with HCV infections as compared with the patients who were healthy (9.4% vs 1.8%; p < 0.05). In comparison with the healthy individuals, this group of patients experienced pruritus (10.5% vs 4.2%; p < 0.05), oedemas (9.4% vs 2.4%; p < 0.05), and hypertension (9.4% vs 1.5%; p < 0.05) more often. An increase in HBV loads was observed between the 6th and 28th–32nd week of pregnancy among the infected with HBV, and then, a decrease was observed in the 6th months after the delivery. Conclusions: The women infected with HBV without HBsAg (–) and the infected with HCV are subject to common incidence of premature births. Women infected with HCV often experience oedemas, hypertension, and pruritus.

Background: HBsAg is synthesized in the endoplasmic reticulum and is necessary for the formation of complete HBV particles. A decreased synthesis of this antigen leads to an intracellular inhibition of virus production. Methods: The study aimed to assess the incidence of HBsAg elimination among 1,290 patients who suffered from chronic HBV infection undergoing an antiviral treatment with nucleoside or nucleotide analogs (NAs). Furthermore, possible predictive factors for this elimination were analyzed. Results: A permanent HBsAg loss was confirmed in 3% of the patients, which was more frequent in men than in women (4.4% vs. 1.9%; P = 0.009). The HBsAg elimination occurred in 5% of HBeAg (+) patients and 2.8% of HBeAg (-) patients. The age of patients whose HBsAg was eliminated was higher than the age of the remaining patients (60 vs. 51 y/o). The effect of initially used pegylated interferon alfa (PEG-IFN) therapy on the HBsAg elimination was not observed. It occurred with the use of entecavir (ETV) and tenofovir (TDF); however, among patients treated with ETV, HBsAg was significantly more often eliminated in HBeAg (+) patients. Conclusions: The HBsAg elimination in patients undergoing antiviral treatment occurs more often in men, patients with positive HBeAg before treatment, individuals above 60 years, and patients treated with ETV.

BACKGROUND Autoimmune hepatitis (AIH) is a progressive inflammatory hepatopathy and an important cause of end-stage liver. The liver cells' destruction is reflected by increased activity of different enzymes in the serum. These enzymes include alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which play a significant role in the metabolism of many biological substances and exist mainly in the liver. In this study we investigated the activity of alcohol dehydrogenase and its isoenzymes and the total activity of ALDH in the sera of patients with autoimmune hepatitis. METHODS Serum samples were taken for routine biochemical investigation from 32 patients with autoimmune hepatitis and from 40 healthy subjects. Class I and II of ADH and ALDH activity was measured by the spectrofluorometric method. For measurement of class III ADH and total ADH activity we employed the photometric methods. RESULTS The activity of the class I ADH isoenzyme was significantly higher in the sera of patients with autoimmune hepatitis. The median activity of this isoenzyme in the patients group was approximately 63% (3.94 mU/L) higher than the control level (1.46 mU/L). For this reason, the total ADH activity was also significantly increased. The activities of other ADH isoenzymes and ALDH tested were unchanged. CONCLUSIONS The activity of total ADH and class I isoenzymes in the sera of patients with autoimmune hepatitis is increased, and it seems to be caused by the release of alcohol dehydrogenase from damaged liver cells.

Background/aim Non-alcoholic liver disease (NAFLD) is one of the most common causes of chronic liver disease, and its prevalence and medical importance is increasing worldwide. Changes in enzyme activity in liver cells in various liver diseases are reflected by an increase in serum enzymatic activity. For example, alcohol dehydrogenase activity (ADH) and aldehyde dehydrogenase (ALDH), that occur in the liver in large quantities, correlate with disease severity during cirrhosis. In the current study, the activity of ADH isoenzymes and ALDH in the serum of patients with NAFLD was investigated. Materials and methods Serum samples were collected for routine biochemical studies from 55 patients with NAFLD patients and from 50 healthy individuals. Class I and II ADH and ALDH activity were measured by spectrofluorometric method. Photometric methods were used to measure ADH class III, IV and total ADH activity. Results Total ADH activity was significantly higher in non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) than in healthy individuals (44 and 48.5% activity, respectively). The median total activity of ADH was 1,164 mU/l in patients with NAFLD, 1,258 mU/l in NASH and 648 mU/l in the control group. The increase in ADH class I and II isoenzyme in serum of patients with NAFL and NASH was statistically significant. The activity of ADH I, ADH II, and total ADH significantly increased with increasing disease progression. Conclusion The activity of isozymes of class I and II alcohol dehydrogenase in patients with NAFLD is enhanced and appears to be due to the release of these isoenzymes from damaged hepatocytes.

Background & Aims: Recent reports suggest an involvement of Th17 responses in inflammatory and autoimmune reactions in alcoholic liver disease (ALD). Our study aimed to assess serum levels of Th17-interleukins in ALD with regard to the frequency of liver-specific autoantibodies and degree of liver damage.Methods: Ninety-five patients with ALD were enrolled. Serum concentrations of IL-17F, IL-17A, IL-22 were assessed by ELISA. The presence of autoantibodies AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, anti-desmin and anti-myosin in serum was assessed by immunoblotting, ANA antibodies were detected by ELISA. The results were analysed with regard to the degree of hepatic damage.Results: Serum IL-17F was significantly elevated in ALD patients compared to controls (p=0.03). There was a correlation between serum IL-17F and degree of liver failure evaluated by the MELD score (rs=0.23, p=0.03). Serum IL-22 also correlated with MELD score (rs=0.32, p=0.007) and CTP score (rs=0.28, p=0.02). Anti-F-actin antibodies were present in 19% and ANA-antibodies in 11% of the patients in the study group, and in no subjects in the control group. The prevalence of anti-F-actin autoantibodies was higher in subjects with more advanced liver diseases but also independently associated with IL-17A in the regression analysis. Furthermore, serum IL-22 in anti-F-actin(+)-patients was significantly higher compared to anti-F-actin(-)-patients (p=0.03).Conclusions: Elevation of serum IL-17A, IL-17F, IL-22 correlated with the progression of liver damage and also with presence of F-actin in ALD. Alcoholic liver disease may trigger autoimmunity and formation of autoantibodies, especially anti-F-actin, with possible engagement of Th17-related cytokines in this process.Abbreviations: AA: acetaldehyde; Abs: antibodies; AFP: α-fetoprotein; ALD: alcoholic liver disease; ALT: alanine aminotransferase; AMA-M2: antimitochondrial antibodies; ANA: antinuclear antibodies; ASMA: anti-smooth muscle antibodies; α-SMA: alpha smooth muscle actin; CTP Score: Child-Turcotte-Pugh Score; GAHS: Glasgow Alcoholic Hepatitis Score; GGT: γ-glutamyl transpeptidase; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; HSCs: hepatic stellate cells; IL-β1: interleukin β1; IL-6: interleukin 6; IL-17A: interleukin 17A; IL-17F: interleukin 17F; IL-22: interleukin 22; KCs: Kupffer cells; LC1: liver cytosol antigen type 1; LKM-1: liver kidney microsomal antigen; MA: malondialdehyde; MELD: Model of End-Stage Liver Disease; NASH: non-alcoholic steatoheptatitis; SLA/LP: soluble liver antigen/liver-pancreas; TGF-β: tumour growth factor β; TNF-α: tumour necrosis factor α.

Background and aims: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) demonstrate an affinity towards lymphocytes B, stimulating the production of cryoglobulins. Deposits of cryoprecipitates contribute to glomerulonephritis and renal failure. The presence of cryoglobulins was investigated in the sera of HCV-monoinfected and HCV/HIV-coinfected individuals. Associations between types of cryoglobulins and HCV genotypes, viral load and renal function tests were also evaluated. Patients and methods: Seventy-seven patients were enrolled in this study. Forty-four were HCV infected and 33 were HCV/HIV coinfected. Cryoglobulins were detected in the sera by electrophoresis and immunofixation. Serum urea and creatinine concentration, glomerular filtration rate (GFR) and serum cystatin C concentration (CC) were analysed to evaluate renal function. The control group included 16 healthy individuals. Results: The occurrence of cryoglobulinaemia in HCV-monoinfected patients was 55%, whereas in HCV/HIV-coinfected patients it was 64%. Mixed cryoglobulinaemia type II was determined in 34%, whereas type III in 25%. The prevalence of cryoglobulinaemia was significantly higher in infection with HCV genotype 1 vs. genotype 3 (65 vs. 50%; P

BACKGROUND Hepatistis C virus (HCV) affects approximately 170 million people, and it is the leading cause of the chronic liver disease. The destruction of liver cells is reflected by an increase of different enzyme activities in the serum. These enzymes include alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which play a significant role in the metabolism of many biological substances and exist mainly in the liver. In this study we investigated the activity of alcohol dehydrogenase and its isoenzymes and the total activity of ALDH in the sera of patients with hepatitis C. METHODS Serum samples were taken for routine biochemical investigations from 50 patients with hepatitis C and from 50 healthy subjects. The activity of class I and II ADH isoenzymes and ALDH activity were measured by spectrofluorometric methods. For the measurement of total ADH activity and activity of class III and IV isoenzymes, the photometric methods were used. RESULTS The analysis of our results shows a statistically significant increase in the activity of ADH I and ADH II (2.5-fold and 2-fold, respectively). Activities of both classes of alcohol dehydrogenase isoenzymes have good correlation with alanine and aspartate aminotransferase. The observed increase in total alcohol dehydrogenase activity was not very high but confirmed the elevation of class I and II isoenzyme activity. CONCLUSIONS We can state that the activity of class I and II alcohol dehydrogenase isoenzymes in the sera of patients with hepatitis C is increased and it seems to be caused by the release of these isoenzymes from damaged liver cells.

Pigment epithelium-derived factor (PEDF) is an endogenous most potential angiogenic inhibitor and increased expression of PEDF in intestinal mucosa specimens was shown in the course of ulcerative colitis (UC). The aim of the present study was to evaluate serum concentration of pigment epithelium-derived growth factor, a potent anti-angiogenic factor and its possible association with vascular endothelial growth factor (VEGF) levels and disease activity.Concentrations of PEDF and VEGF were measured in sera of 33 patients (13 females and 20 males) with active UC.There was significant increase of serum PEDF (32.3+/-2.9 vs. 20.6+/-4.7 ng/mL, P0.05) as well as VEGF (326.4+/-58.1 vs. 110.9+/-15.7 pg/mL, P0.05) in UC patients compared to healthy controls. Serum PEDF showed strong, positive correlation with endoscopic score (r=0.622, P0.001), while such association was absent in respect to VEGF (r=0.05, P=0.77). In contrast serum VEGF decreased in severe UC comparing to patients with a mild course of disease, however the difference was not significant (274.9+/-64.9 vs. 360.4+/-103.4 pg/mL, P=0.53).Increase in serum PEDF during UC, especially in severe forms of disease suggests its involvement in UC pathogenesis.

We investigated the safety, efficacy, and impact of ribavirin and peginterferon dose reduction on complete early virologic response and sustained virologic response (SVR) to triple therapy with telaprevir in treatment-experienced patients with advanced liver fibrosis. Treatment was initiated for 211 patients who failed treatment with peginterferon and ribavirin, with bridging fibrosis (F3, n = 68) or cirrhosis (F4, n = 143), including 103 (49%) null-responders (NR), 30 (14%) partial responders (PR), and 78 (37%) relapsers (REL). Impaired liver function (ILF) platelets 60% of the total ribavirin dose (23% vs 44%, respectively) or 80% of the total ribavirin dose (33% vs 48%, respectively). A significant SVR24 decrease was noted subsequent to a total peginterferon dose reduction, both when comparing patients who received 60% of the total dose (NR: 0% vs 44%; REL: 33% vs 68%) and patients who received 80% of the total dose (NR: 17% vs 50%; REL: 46% vs 71%). Serious adverse events were observed in 31 patients (15%). Deaths occurred in 4 patients. All of the deceased subjects were cirrhotic members of the ILF (baseline serum albumin level

Introduction The changes of enzyme activity in the hepatocytes in the course of different liver diseases are reflected by increase of the corresponding enzyme activity in the plasma. For example, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) correlate with the severity of the condition during cirrhosis. In this study we measured the activity of ADH isoenzymes and ALDH in the sera of patients with hepatitis C. Material and methods Serum samples were taken from 60 patients suffering from viral hepatitis C and from 66 control subjects. Total ADH activity and class III and IV isoenzymes were measured by the photometric method and ALDH activity, ADH I and II by the fluorometric method. Results The ADH activity was significantly higher in patients with hepatitis C than in healthy (p < 0.001). The total activity of ADH was 1284 mU/l in patients, and 745 mU/l (controls). The activity of isoenzymes classes ADH I and ADH II in the hepatitis C group increased respectively 55% (4.24 vs. 1.88 mU/l; p < 0.001) and 47% (26.63 vs. 14.11 mU/l; p < 0.001) in the comparison to the control. There was significant increase in the activity of ADH I isoenzyme (4.96 vs. 3.81 mU/l; p < 0.001) and ADH total (1833 vs. 1105 mU/l; p < 0.001) in patients with high viral load in comparison to patients with low viral load. Conclusions The activity of class I and II ADH isoenzymes in the sera of patients with hepatitis C is increased, and it seems to be caused by the release of these isoenzymes from damaged liver cells.

Cryoglobulinemic syndrome refers to a systemic inflammatory process that involves small and medium-sized vessels accompanied by multi-organ damage. The aim of the present study was to determine the incidence of cryoglobulinemia among patients infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HCV/HIV co-infection, as well as evaluation of cryoglobulinemia type. The association was evaluated between cryoglobulinemia and clinical symptoms, selected biochemical measures of liver and kidney function, virologic measures, as well as histopathological changes in the liver. One hundred and forty-one patients were enrolled (59 HCV mono-infected, 48 HIV mono-infected, and 34 HCV/HIV co-infected). Cryoglobulinemia was nearly five times less frequent among HIV mono-infected patients (10%) than HCV mono-infected (53%) and HCV/HIV co-infected patients (59%). Cryoglobulinemia was more frequent in patients infected with genotype 1 HCV than genotype 3 (63% vs. 46%, p=0.12). There was a lower incidence of cryoglobulinemia in HIV mono-infected patients treated with antiretroviral drugs (p=0.04). Cryoglobulinemia correlated with ALT activity (p=0.01) and HIV viral load (p0.001). Symptoms were significantly more frequent among cryoglobulinemic patients than those without cryoglobulinemia (38% vs. 9%, p0.001). The most common symptoms related to cryoglobulinemia, regardless of cryoglobulinemia type, were fatigue (38%), arthralgia (20%), polineuropathy (18%), and skin lesions (14%). In conclusion, HCV mono-infection and HCV/HIV co-infection, regardless of HCV genotype, are potent stimulators of cryoglobulinemia, with its symptomatic form occurring in about 40% of cases. Effective antiretroviral therapy seems to be protective against cryoglobulinemia development in HIV mono-infected patients.

Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) coinfections can affect mechanisms of programmed cell death and therefore influence acquired immunodeficiency syndrome (AIDS) development as well as the course of chronic hepatitis C. The aim of the study was to assess soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in HIV- and HCV-coinfected patients and, moreover, to establish their relationships with HIV viral load, CD4+ T lymphocyte count, as well as liver function tests. Seventy-eight patients were included in the study, among them 30 coinfected with HIV and HCV, 10 infected only with HIV, and 38 infected only with HCV. HIV infection was confirmed by means of Western blot analysis; HIV viral load was measured by RTPCR; and CD3+, CD4+, and CD8+ T lymphocyte counts were established by means of flow cytometry. HCV infection was confirmed through HCV RNA isolation, using RT-PCR. sFas and sFasL concentrations were measured in duplicate by ELISA. The mean CD4+ T lymphocyte count decreased in HIV- and HCV-coinfected patients versus HIV-infected individuals (429 versus 279/ml). sFasL protein was detectable principally in HIV-infected individuals without HCV infection (90%), whereas in those with HCV infection it occurred only in 11% of cases. The highest sFas concentration was observed in HCV-infected patients (25.9 ng/ml) as well as in HIV- and HCV-coinfected individuals (20.3 ng/ml). This concentration was negatively proportional to sFasL prevalence. The results of our study suggest that HCV infection in HIV-positive individuals may suppress processes of programmed cell death. There was no correlation between sFas, sFasL, and HIV-1 viral load. On the other hand, sFas concentration and the presence of sFasL were related to CD4+ T lymphocyte count.

CD40 receptor is activated by ligand CD40L (CD154) which is synthesized in inflammation by NK cells, monocytes and lymphocytes B. TRAF proteins are activated in cells by CD40 stimulation and next they stimulate different enzymatic pathways. High concentrations of CD40L stimulate CD40, and consequently STAT enzyme system inhibits the expression ofnonstructural proteins ofHCV NS3 and NS5A and E2 core in infected human hepatocytes. PURPOSE. The aim of the study was to evaluate the concentration of soluble components of the complex: sCD40 and sCD40L in the serum of patients infected with HCV and HCV/HIV-1 co-infected. The effect ofHCV genotype, HIV and HCV viral load and rs12979860 polymorphism on serum sCD40 and sCD40L was established among the patients. The influence of the number of CD3+, CD4+ and CD8+ on the concentrations of sCD40 and sCD40L was evaluated in the HIV-1 infected group MATERIALS AND METHODS. Serum concentrations of sCD40 and sCD40L were determined using ELISA in 68 HCV infected patients including 39 HCV monoinfected and 29 HCV/HIV-1 co-infected. RESULTS. Serum concentration of sCD40 and sCD40L was significantly higher in HCV and HCV/HIV coinfected patients compared to healthy subjects (25.7 and 23.2 v. 8.5 pg/ml and 12.7 and 7.3 v. 0.79 ng/ml). The concentration of sCD40L in patients with genotype CC rs12979860 was significantly higher compared to patients with Non-CC genotypes (11.8 v. 7.6 ng/ml, p0.018). CONCLUSIONS. High levels of sCD40 and sCD40L were detected among patients with chronic HCV and HCV/ HIV-1 infection The high concentration of sCD40L correlates with CC rs12979860 genotype.

Lamivudine (LMV) is still the most commonly used nucleoside analogue in majority of the world. Its administration rapidly leads to resistance associated with mutations in HBV polymerase. THE AIM of the study was to assess the prevalence, nature and the time of LMV resistant variants appearence during a long term therapy.Study was carried out among 175 chronic hepatitis B patients treated with LMV. HBsAg, HBeAg as well as anti-HBe antibodies were detected by enzyme immunosorbent assay and HBV-DNA quantification was performed by RT-PCR. Mutations in HBV polymerase gen were detected by PCR using specific primers and direct sequencing. Liver biopsies were performed in 138 patients to evaluate grading and staging of chronic hepatitis by Scheuer's classification.Mean pre-treatment viral load was comparable among HBeAg-positive and negative patients (4.24 x 10(8) vs. 1.26 x 10(8) IU/ml). Mutations in HBV polymerase gen were detected in 96 patients. After 5 years of LMV therapy the prevalence of mutations was 51.9% in HBeAg-positive and 56.1% in HBeAg-negative. The most common mutations were observed at position 180, followed by 204, 202, and 169 of HBV polymerase gen. After average treatment period of 25 months in HBeAg-positive and 35 months in HBeAg-negative additional mutation 204 was observed in 81% and 77% respectively.Large majority of patients develop point mutations at positions 180 and 204 of HBV polymerase gene after 2 years of treatment with LMV. These mutations limit the efficacy of LMV but also yield cross-resistance with entecavir.

CC genotype of SNP rs 12979860 promotes spontaneous HCV clearance in monoinfected patients. The aim of this analysis was evaluation of impact of rs12979860 polymorphism on HIV or HCV viral load, CD3, CD4 and CD8 count as well as HCV clearance among HCV/HIV coinfected patients.The study included 41 consecutive HCV/HIV coinfected patients. HIV RNA, HCV RNA, HCV genotype and rs12979860 polymorphism sequence as well as CD3, CD4 and CD8 cells count were analyzed in all patients.CC genotype rs12979860 was identified in 16 from 41 patients. During at least 4 years follow-up, five genotype CC patients (31%) became HCV RNA undetectable, that was not a case in CT and TT patients. No statistical differences in HIV viral load and the number of CD3, CD4 and CD8 related to rs12979860 polymorphism were observed. The baseline level of HCV RNA in patients with CC genotype was significantly lower compared to patients with non-CC genotypes (88546 +/- 74181 vs. 726021 +/- 30709 IU/mL).CC genotype related to SNP rs 12979860 can affect the lower level of HCV viral load compared to patients with CT and TT genotypes and promotes spontaneous clearance of HCV RNA in HCV/HIV coinfected patients.

Autoantigens are present in normal cells and tissues. However, in physiological conditions autoantigens pose no danger due to the phenomenon of immunologic tolerance. The loss of immunologic tolerance and following autoagression could result from the structure changes of autoantigens as an effect of the activity of chemical factors, such as acetaldehyde, which is metabolite of ethanol. The aim of the study was to evaluate of occurrence of autoantibodies in patients with alcoholic liver disease.Ninety-five patients with chronic alcoholic liver disease and 16 healthy controls were enrolled in this study. The presence of autoantibodies against liver proteins were assessed. The occurrence of studied autoantibodies was evaluated with regard to the degree of liver damage. Inclusion criteria were: age over 21 yrs, at least 3-yrs history of alcoholic liver disease, HBV and HCV-negativity, absence of autoimmunological diseases. The presence of autoantibodies AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, desmin and miozin in serum was assessed by immunoblotting method and ANA by ELISA.Autoantibodies were demonstrated in sera of 33% of patients. Single isolated autoantibodies were present in 24% of patients, whereas 9% of patients have several autoantibodies. The most prevalent were anti-F-actin (19%) and antinuclear antibodies (11%). Occurrence of anti-F-actin antibodies increased with degree of liver damage.Concluding these results suggest that alcohol may contribute to the activation of autoimmune processes, and particularly against contractile filaments of cells for which F-actin antibodies are produced.

Research on new antivirals drugs applied in the treatment of chronically HCV infected indicate that even the most perfect therapeutic molecules do not guarantee 100% efficacy. Since the beginning of the history of HCV infection treatment clinicians looked for predictors of treatment efficacy. Numerous studies confirm the high probability of cure in patients who cleared HCVinfectional 4 and 12 weeks of therapy. However despite of viral factors, recent research demonstrated predictive role of some host dependent factors. The most important role seems to play genetic factors including polymorphism rs12979860, as well as chemokins including first of all CXCL10 (IP-10). Very interesting seems to be also results of studies on association between vitamine D concentration and treatment efficacy. However in the future the most important predictive factor remain probably early on-treatment viral response.

Background & Aims Cytochrome c (CYC) and M30-neoepitope of cytokeratin-18 (M30-CK18) are involved at different levels in apoptotic pathways. We aimed to evaluate an association between serum CYC, M30-CK18 and disease activity as well response to therapy in chronic hepatitis C (CHC). Methods Seventy CHC patients were enrolled in this study. Forty five of them completed pegylated interferon plus ribavirin therapy. Histopathological evaluation of hepatic inflammatory activity and fibrosis, as well as blood liver function tests, was performed. Serum concentrations of M30-CK18 and CYC were measured by ELISA. Results Median serum concentration of M30-CK18 was higher in CHC patients [283 U/L] vs. control [113 U/L] (P = 0.0003) and was associated with inflammatory activity and liver fibrosis (P

Infection with human cytomegaly virus (CMV) may lead to liver damage in immunocompromised individuals. Chronic hepatitis C is featured by impairment of innate and specific immunity as well apoptotic cell death. The aim of the study was to assess to frequency of CMV infection in patients with chronic hepatitis C. The influence of CMV infection on parameters of full blood count and early virologic response to the treatment were evaluated. Materials and methods. One hundred twenty three patients with chronic hepatitis C were enrolled in the study. Infection with CMV was diagnosed through the detection of CMV DNA in sera by means of RT-PCR method. The starters used in the study were specific for pp65 gene of CMV. Results. Active CMV replication was observed in 18/123 individuals (14.6%). Majority of them (16/18) have low level of CMV viraemia. There were no apparent correlations between HCV and CMV viral loads. Hemoglobin concentration, erythrocytes, leucocytes and platelet count, absolute neutrophil count and activity of alanine transaminase was similar in HCV and HCV/CMV-infected patients. Active CMV infection did not influence inflammatory activity and fibrosis in liver tissue. The early virologic response to anti-HCV therapy was independent of CMV infection. Conclusions. Active CMV infection affects over 14% of studied population of patients with chronic hepatitis C. Coinfection with CMV has not influence on the laboratory biochemical parameters and injury of liver tissue. Moreover, it does not affect the efficacy of anti-HCV treatment.

HCV infection is a common cause of cryoglobulinaemia, characterized by existence of antibodies that show reversible precipitation at low temperatures. Deposition of cryoglobulines in glomerular vessels tends to induce development of membranous, or less commonly, mesangial glomerulonephritis with renal insufficiency as final consequence. Objective was investigating the existence of cryoglobulinaemia, its types and relation with renal impairment in patients chronically infected with hepatitis C virus.The research included 36 patients (9 women and 27 men) chronically infected with hepatitis C virus at the average age 38 years. Existence and types of cryoglobulines in serum were measured using electrophoresis and then immunofixation on cryogel by the method of Bence Jones (Sebia, France). Renal functioning was estimated with reference to serum urea and creatinine concentrations, glomerular filtration rate (GFR) and serum cystatin C concentration with immunoenzymatic method.Cryoglobulinaemia was significantly more common among patients infected with genotype 1 than 3 (71% vs. 39%; p0.05). Types II and III of cryoglobulinaemia existed in equal frequency. The most common heavy chains were gamma immunoglobulins (42%) and the light ones--kappa (54%). Urea and creatinine concentration were normal in all patients. Three patients diagnosed with cryoglobulinaemia and infected with genotype 1 had abnormal GFR. There was dependency between cryoglobulinaemia and elevated cystatin C concentration (R=0.4; p0.013).

Liver failure is decadent stage of its severe damage, in which, processes of detoxication, carbohydrate and lipid metabolism, nitrogen balance and synthesis of high-energy compounds are significantly diminished or even totally blocked. Moreover, these incorrect metabolic pathways as well as oxygen deficiency in hepatocytes are implicated in the pathogenesis of endocrine system diseases. The different endocrinal dysfunctions make worse patient's prognosis.

Nonspecific immunology response and apoptotic pathways play the important role in development of chronic hepatitis C. HCV stimulates synthesis of many cytokines, mainly proinflammatory. In these processes, the activation of Thl and Th2 lymphocytes has a particular significance. Stronger activation of Th1 lymphocytes has an influence on dysregulation of cytokines' synthesis, affecting also the protraction of HCV infection. Cognition of HCV influence on the regulation of nonspecific immunology response and apoptotic pathways could bring nearer the comprehension of chronic hepatitis C development and indicate new treatment's directions.

To evaluate the effect of antiviral treatment on plasma levels of transforming growth factor-beta1 (TGF-beta1), metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in patients with chronic hepatitis C.TGF-beta1, MMP-1, and TIMP-1 plasma concentrations were measured by an enzyme immunoassay in 28 patients, during 48 wk of treatment with pegylated interferon-alpha 2b (PEG-IFN-alpha2b) plus ribavirin (RBV) and after 24 wk of follow-up. Patients were divided into two groups: responders (R) and non-responders (NR) related to achieved sustained virologic response. Normal values were evaluated in plasma samples of 13 healthy volunteers.Baseline plasma concentrations of TGF-beta1 and TIMP-1 (30.9+/-3.7 and 1 506+/-61 ng/mL respectively) measured in all subjects significantly exceeded the normal values (TGF-beta1: 18.3+/-1.6 ng/mL and TIMP-1: 1 102+/-67 ng/mL). In contrast, pretreatment MMP-1 mean level (6.5+/-0.9 ng/mL) was significantly lower than normal values (11.9+/-0.9 ng/mL). Response to the treatment was observed in 12 patients (43%). TGF-beta1 mean concentration measured during the treatment phase decreased to the control level in both groups. However at wk 72, values of NR patients increased and became significantly higher than in R group. TIMP-1 concentrations in R group decreased during the treatment to the level similar to normal. In NR group, TIMP-1 remained significantly elevated during treatment and follow-up phase and significant difference between both groups was demonstrated at wk 48 and 72. MMP-1 levels were significantly decreased in both groups at baseline. Treatment caused rise of its concentration only in the R group, whereas values in NR group remained on the level similar to baseline. Statistically significant difference between groups was noted at wk 48 and 72.These findings support the usefulness of TGF-beta1, TIMP-1, and MMP-1 in the management of chronic hepatitis C. Elevated TIMP-1 and low MMP-1 plasma concentrations during antiviral therapy may indicate medication failure.

The 1H MR spectroscopy (1H MRS) creates possibility of non-invasive study of morphological changes 1H MRS and metabolic disturbance of the liver. The aim of study was estimated of 1H MRS in investigation of liver metabolic changes, with special regard of lipids in patients with HCV and HIV/HCV infection.Research was moved among patients with HCV infection and in HCV/ HIV co infection. 1H MRS of the liver was moved with use of system Picker, Eclipse 1.5 T. Investigation were executed with use of tube of whole body, with use of sequence PRESS 35 (TE 35 ms, TR 1500 ms, nex 192). Suppression of water was made of MOIST method. Voxel about sizes 3x3x3 (27 cm3) were located in right piece of liver on basis of paintings T2- dependence in front and transverse planes.In group of HCV patients without HIV infection were observed over 6 x increase proportion of PME/TL (0.112; p = 0.001) and 2 x increase of Glx/TL (0.042; p = 0.02) in refer to control group. In patients with HCV and HIV infection were observed significance increase of Glu/ TL - 328%, Glx/TL - 458% and PME/TL 728% in comparison to control group. The patients with only HCV infection were statistical significance decrease of TL level in comparison to control group (43.2 +/- 9.4 v. 74.1 +/- 12.2; p = 0.09). The patients with HCV and HIV infection, level of TL was lowered in refer patients with only HCV infection (20.7 +/- 5.6; p0.05).Proton magnetic resonance spectroscopy of the liver is useful diagnostic method in detecting of parenchyma liver damage and to make up supplement of histology diagnosis.

IFN-alpha maybe stimulate to synthesis of autoantibodies which damaging of myelin sheath at peripheral neurons. We report the patient, man, with hepatitis C infection who was treated with peginterferon alfa-2a by one month and next with peginterferon alfa-2b by 3 months in combination with ribavirin. We observed paresis of hands and legs in fourth months of treatment. This patient's dust of difficulty with walking. In EMG investigation was detected demyelin damage of sensor motor nerves. These changes were on whole length or in distal part of neuron. It is qualified hard whether cause of peripheral polineuropathy: interferon's or pegylated part. The finished of antiviral treatments as well as use of steroids in therapy were reason of fast improvement of patients.

AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. Patients after kidney transplantation and patients with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney-transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P

AIM: To estimate the amount of apoptosis among healthy HBsAg carriers, patients with chronic HBV infection treated with lamivudine and patients with chronic HCV infection treated with interferon alpha and ribavirin. Activity of apoptosis was evaluated by serum sFas/sFasL concentration measurement. Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied. METHODS: Eighty-six persons were included into study: 34 healthy HBsAg carriers, 33 patients with chronic HBV infection and 19 patients with chronic HCV infection. Serum levels of sFas/sFasL were measured by ELISA assay. HBV-DNA and HCV-RNA were measured by RT-PCR assay. Levels of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection. HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment. RESULTS: Twenty-four (71%) healthy HBsAg carriers showed HBV-DNA over 105/mL, which was comparable to the patients with chronic hepatitis B. Independently from HBV-DNA levels, the concentration of sFas among healthy HBsAg carriers was comparable to healthy persons. Among patients with chronic hepatitis B and C, the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy persons. In chronic hepatitis B patients the concentration of sFas was decreased during lamivudine treatment. Among chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment. sFasL was not detected in control group. Furthermore sFasL occurred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients. CONCLUSION: There are no correlations between apoptosis and HBV-DNA levels. However ther is an association between apoptosis and activity of inflammation in patients with chronic HBV infection. Apoptosis can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α.

To evaluate the activity of apoptosis in liver tissue and explore its possible association with hepatic necroinflammation and fibrosis as well as serum hepatitis C virus (HCV) load.The studied population included 50 chronic hepatitis C patients (20 women and 30 men, aged 18-66 years). HCV-RNA quantification was performed by two-step real-time quantitative RT-PCR method using the TaqMan technology (reagents of Applera Corporation firm, USA). The morphology of liver tissue was assessed descriptively and scored (necroinflammatory activity and fibrosis). The early apoptosis activity in liver tissue was examined by ssDNA apoptosis ELISA kit, (Chemicon, Germany).The correlation between apoptosis and fibrosis in liver tissue was observed. High intensification of apoptosis was proportional to the increase of fibrosis (ssDNA: 16.65 x 10(-5) microug/g; 12.71 x 10(-5) microg/g), however, this difference was not statistically significant (P0.05). Activity of apoptosis in the liver tissue, expressed by ssDNA concentration did not depend on hepatic necroinflammatory changes, HCV-RNA viral load, ALT, and AST activity as well as prothrombin time and INR index.Fibrosis in the tissue is closely associated with early apoptosis in HCV-infected patients.

AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C. METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6 mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series. RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P