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Aim of the Study: This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy., Material and Methods: Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used., Results: Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic., Conclusions: Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions., Competing Interests: The writing of this paper was funded by AbbVie., (Copyright: © 2019 Clinical and Experimental Hepatology.)

Although chronic hepatitis C virus (HCV) infection affect 185 million people world-wide, pathomechanism of liver damage is still unclear. Electron microscopy can reveal liver injury in very early stage and help understanding the mechanisms that is crucial in the pathogenesis of chronic hepatitis C. We present the morphological changes in the liver of HCV infected 24-year-old female patient, using light and transmission electron microscopy. Examination by TEM revealed wide range of specific subcellular abnormalities in hepatocellular ultrastructure. The most common observed changes were ring-shaped nuclei with intranuclear inclusion, megamitochondria, and "membranous web" structures - the hallmark of RNA-viruses infection.

The Aim of the Study: Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016., Material and Methods: Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016., Results: The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients ( n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively. The sustained virologic response among 5646 G1 infected patients was the lowest with natural interferon α (7%, n = 70) or PegIFN (50%, n = 3779) with RBV, and improved in those receiving triple regimens of Peg-IFN + RBV combined with boceprevir (47%, n = 485), telaprevir (64%, n = 805), simeprevir (73%, n = 132) or sofosbuvir (70%, n = 23). The sustained virologic response with interferon-free regimens of sofosbuvir and RBV ( n = 7), sofosbuvir and simeprevir ( n = 53), and ledipasvir and sofosbuvir ( n = 64) achieved 86%, 89% and 94% respectively. The highest SVR of 98% was observed with ombitasvir/paritaprevir combined with dasabuvir ( n = 227). Patients infected with G3 ( n = 896) and G4 ( n = 220) received mostly Peg-IFN + RBV with SVR of 67% and 56% respectively. Interferon-free regimens were administered in 18 G3/G4 patients and all achieved an SVR. Sofosbuvir combined with Peg-IFN and RBV was administered to 33 patients with an SVR rate of 94%, and a similar rate was achieved among 13 G2 patients treated with interferon and RBV., Conclusions: We observed significant differences in efficacy of HCV regimens available in Poland at the turn of the interferon era. The data will be useful as a comparison for therapeutic options expected in the next few years.

The Aim of the Study: Was to assess current prevalence of hepatitis C virus (HCV) genotypes in Poland, including their geographic distribution and changes in a given period of time., Material and Methods: Data were collected with questionnaires from 29 Polish centers and included data of patients diagnosed with HCV infection between 1 January 2013 and 31 March 2016., Results: In total, data of 9800 patients were reported. The highest prevalence was estimated for genotype 1b (81.7%), followed by 3 (11.3%), 4 (3.5%), 1a (3.2%) and 2 (0.2%). Genotype 5 or 6 was reported in 6 patients only (0.1%). The highest prevalence of genotype 1 was observed in central (łódzkie, mazowieckie, świętokrzyskie), eastern (lubelskie) and southern (małopolskie, śląskie) Poland. The highest rate for genotype 3 was observed in south-western (dolnośląskie, lubuskie) and eastern (podlaskie, warmińsko-mazurskie and podkarpackie) Poland. Compared to historical data, we observed an increasing tendency of G1 prevalence from 72.0% in 2003 to 87.5% in 2016, which was accompanied by a decrease of G3 (17.9% vs. 9.1%) and G4 (9.0% vs. 3.1%)., Conclusions: Almost 85% of patients with HCV in Poland are infected with genotype 1 (almost exclusively subgenotype 1b), and its prevalence shows an increasing tendency, accompanied by a decrease of genotypes 3 and 4.

Background: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies., Aim: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions., Methods: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT., Results: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients., Conclusions: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting., (© 2016 John Wiley & Sons Ltd.)

Aim of the Study: To assess predictors of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) genotype 3 treated with standard therapy., Material and Methods: We retrospectively investigated data of 116 consecutive treatment-naïve patients chronically infected with HCV genotype 3, treated with pegylated interferon alpha (PegIFNα) and ribavirin (RBV) for 24 weeks. HCV RNA at week 4 (rapid virological response - RVR) and week 12 (early virological response - EVR) were measured in 85 and 105 patients respectively. Liver biopsy data were available for 103 patients. The variables were compared between patients with an SVR and those without., Results: Overall 70.7% of patients achieved an SVR. Pretreatment factors including younger age, mild liver fibrosis as well as normal values of gamma-glutamyl transferase (GGT) and platelet count were significantly associated with higher SVR rate in univariate analysis. In the multivariate analysis only baseline platelet count > 140 000/µl and normal GGT activity were correlated with higher SVR rate. At weeks 4 and 12 HCV RNA was undetectable in 34.1% and 84.8% of patients respectively. The SVR rate was significantly higher in patients with an RVR compared to those without ( p = 0.002). Only 2 patients with a rapid and early virological response did not achieve an SVR; both had negative pretreatment prognostic factors., Conclusions: In treatment-naïve patients with genotype 3 HCV infection, low baseline platelet count and elevated GGT activity were significantly associated with poor response to PegIFNα and RBV. Achieving a rapid and early virological response was associated with higher likelihood of an SVR.

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 <100,000/mm or albumin <35 g/L were present in 40 patients. The distribution of hepatitis C virus subtypes was: 1a, 1b, or 1, with undetermined subtype for 10 (5%), 187 (89%), and 14 (6%) patients, respectively. Treatment was started with peginterferon alpha-2a or alpha-2b, ribavirin, and telaprevir at standard doses.The overall SVR24 rate was 56% and was lower in cirrhotic patients (NR: 35%, PR: 40%, and REL: 63%, respectively) than in patients with bridging fibrosis (NR: 50%, PR: 75%, and REL: 75%, respectively). The lowest probability of SVR24 was in NRs with ILF (26%). The SVR24 rate significantly decreased in NRs receiving <60% vs >60% of the total ribavirin dose (23% vs 44%, respectively) or <80% vs >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% vs >60% of the total dose (NR: 0% vs 44%; REL: 33% vs 68%) and patients who received <80% vs >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 <35 g/L and/or platelet count <100,000/mm) group.Ribavirin dose reduction did not affect efficacy in REL but did in NR. Peginterferon dose reduction decreased the SVR24 rate for all groups, particularly in prior NR. ILF increased the risk of fatal complications with a low probability to achieve SVR24. One solution might be to provide wide and early access to novel, efficient, and safe interferon-free combinations to treatment-experienced patients, particularly those with liver cirrhosis.

Stanozolol is a 17α-alkylated synthetic anabolic steroid used illegally by bodybuilders. We present a 19-year-old man who was taking 50 mg of stanozolol intramuscularly, every other day for 2 months, to improve muscle mass. On admission, his bilirubin concentration was 44.34 mg/dl. The serum levels of liver enzymes were normal, with only alanine aminotransferase being slightly elevated. Liver biopsy revealed toxic hepatitis of minor grade with periportal fibrosis and intrahepatic cholestasis. Medical treatment of the patient was conservative. Despite the therapy the patient's general condition deteriorated - bilirubin level increased to 56.64 mg/dl, and INR rose to 1.7. Then we decided to administer low doses of hydrocortisone. As a result of the treatment, bilirubin concentration was 14.61 mg/dl after 2 weeks. Finally all hepatic enzymes returned to normal values 5 months after stanozolol was discontinued. This treatment appears to be safe and leads to a more rapid reduction of bilirubin., Competing Interests: Authors report no conflict of interest.

Background: Combination therapy with pegylated interferon, ribavirin and a first-generation NS3/4A protease inhibitor, telaprevir or boceprevir, is the new strategy for treatment of genotype 1 chronic hepatitis C virus infection. This combination improves therapeutic efficacy but it also increases the risk of adverse events., Objective: The aim of the study was to analyze frequency and severity of dermatological adverse events during protease inhibitor-based therapy and to evaluate the risk factors for their development., Patients and Methods: This is a retrospective study of 109 patients with genotype 1 chronic hepatitis C treated with boceprevir (n=33) or telaprevir (n=76) based triple therapy. A logistic regression for relationship between clinical, demographic and laboratory factors and cutaneous adverse events was performed., Results: Dermatological adverse events (skin rash, pruritus, anorectal paresthesia) occurred in both treatments (boceprevir and telaprevir) with similar frequency: 28% in telaprevir and 21% in boceprevir. In patients treated with telaprevir, men were more predisposed to develop skin rashes compared to women (OR 4,1 p=0,014) and age above 45 years was associated with occurrence of pruritus in men (OR 8,16 p=0,014). Being a female, coexistence of autoimmune thyroiditis and advanced liver fibrosis were independent factors predisposing to development of anorectal paresthesia (OR 4,13 p=0,041, OR 4,25 p=0,029, OR 4,54 p=0,018 respectively) in this group. In patients treated with boceprevir, coexistence of autoimmune thyroiditis predisposed to skin rashes (OR 10,22 p=0,017) and being a female predisposed to pruritus (OR11,2 p=0,033). The adverse events occurred after a mean time of 8,6 (range 1-24) weeks after initiation of therapy., Conclusions: In patients with chronic hepatitis C who received the triple therapy, the anorectal paresthesias were observed only in patients treated with telaprevir. The predisposing factors for this adverse event were: female gender and advanced liver fibrosis. The risk factors for other dermatological adverse were: 1) being a male over 45 years, for skin rashes and pruritus (for telaprevir), 2) coexistence of autoimmune thyroiditis for skin rashes (for boceprevir), 3) being a female, for pruritus (for boceprevir).

Unlabelled: Available data on prevalence of HCV genotypes in Poland are insufficient. The aim of the study was the analysis of distribution of HCV genotypes in Poland over the period of recent 10 years regarding the age of patients and the regions of the country., Material and Methods: Analysis of HCV genotypes in Poland was carried out between 2003 and 2012, and included 14 651 patients from 22 centers where patients with chronic viral hepatitis C are diagnosed and treated. Genotypes were analyzed in age groups (< 20 years of age, 20-40 years of age, > 40 years of age) as well as in populations of HBV and HIV co-infections., Results: Genotype (G) 1 infection was demonstrated in 79.4%, G2 -0.1%, G3- 13.8%, G4- 4.9%, G6-0.09% and mixed infections in 1.6%. There was no infection with genotype 5. The highest prevalence of G1 was observed in the Łódzkie voivodship (89.2%) and the Slaskie voivodship (86.7%) while the lowest one in the Warmińsko-mazurskie (62.0%) and the Podlaskie voivodships (68.2%). Genotype 3 most commonly occurs in the Warmińsko-mazurskie (28.1%), and the Podlaskie voivodships (23.0%) and is least common in the Małopolskie (7.9%) and the Łódzkie voivodships (9.0%). Genotype 4 is more common in the Kujawsko-pomorskie (11.7%) and the Podlaskie voivodships (8.6%) and relatively less common in the Lubelskie (1.1%) and the Łódzkie voivodships (1.8%). Prevalence of G1 infection in 2003-2004 was 72% and increased up to 85.6% in 2011-2012, that was accompanied by decrease of G3 prevalence from 17% to 8% in this period. In HBV co-infected (n = 83), G1 infection was demonstrated in 85.5%, G3 - in 7.2%, G4 -4.8%, and mixed genotypes in 6%. Among HIV co-infected (n = 391), a much lower prevalence of G1 (33.0%) and a high of G3 (40.4%) as well as G4 (24.0%) were observed., Conclusions: There is a geographic variability of HCV genotypes prevalence in Poland. Increase of HCV G1 infections and decrease of G3 and G4 were observed in the last 10 years. Genotypes G3 and G4 occur more often in HCV/HIV co-infected than in HCV mono-infected patients.

Background & Aims: Long-term treatment with entecavir resulted in durable virologic suppression and continued histologic improvement in nucleoside-naive chronic hepatitis B patients. Patients with advanced fibrosis or cirrhosis, who received long-term entecavir treatment, were evaluated for improvement in liver histology., Methods: The study included a subset of patients from phase III and long-term rollover studies, who received entecavir for at least 3 years, had advanced fibrosis or cirrhosis, and evaluable biopsies at baseline and after long-term treatment., Results: Ten patients had advanced fibrosis or cirrhosis at baseline (Ishak fibrosis score, ≥ 4). After approximately 6 years of cumulative entecavir therapy (range, 267-297 wk), all 10 patients showed improvement in liver histology and Ishak fibrosis score. The mean change from baseline in Ishak fibrosis and Knodell necroinflammatory scores were -2.2 and -7.6, respectively. A reduction in Ishak fibrosis score to 4 or less was observed for all 4 patients who had cirrhosis at baseline., Conclusions: Chronic hepatitis B patients with advanced fibrosis or cirrhosis demonstrated histologic improvement and reversal of fibrosis and cirrhosis after long-term treatment with entecavir., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: A phase 3 active-controlled study was conducted to assess the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of recombinant human albumin and interferon alfa-2b, in patients with chronic hepatitis C virus (HCV) genotype 2/3., Methods: In all, 933 patients were randomized to open-label subcutaneous treatment with pegylated interferon-alfa-2a (Peg-IFNalfa-2a) 180 μg/wk, or albIFN 900 or 1200 μg every 2 weeks for 24 weeks, each administered with oral ribavirin 800 mg/day. The primary end point of the study was sustained virologic response (SVR) (HCV-RNA level, <15 IU/mL at week 48). During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 μg to 900 μg, impacting 38% of this treatment arm., Results: By intention-to-treat analysis, SVR rates were 84.8% (95% confidence interval, 80.4%-88.6%), 79.8% (95% confidence interval, 74.9%-84.1%), and 80.0% (95% confidence interval, 75.1%-84.3%) with Peg-IFNalfa-2a, and albIFN 900 and 1200 μg, respectively. The primary hypothesis of noninferiority of SVR was established for albIFN 900 μg (P = .009) and 1200 μg (P = .006). Independent positive predictors of SVR by multivariate regression analysis were pretreatment HCV-RNA level less than 400,000 IU/mL, age younger than 45 years, body mass index less than 30 kg/m(2), genotype 2, normal γ-glutamyl transpeptidase and increased alanine aminotransferase levels at baseline, fibrosis stage F0-F2, no steatosis, and Asian geographic region (Peg-IFNalfa-2a only). The 3 treatment groups showed similar rates of serious (7%-8%) and severe (13%-16%) adverse events, and discontinuations owing to adverse events (3.6%-5.5%)., Conclusion: Albinterferon alfa-2b 900 μg every 2 weeks provides an alternative efficacious treatment option in patients with chronic HCV genotype 2 or 3., (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Adipocytokine profile seems to play a distinct role in the pathogenesis of chronic hepatitis C (CHC). Chemerin and vaspin are recently described adipocytokines with various suggested functions and potential to modulate inflammatory response and insulin resistance (IR). We assessed chemerin, vaspin and leptin serum concentration and studied their association with IR laboratory and morphological features in patients with hepatitis C. The study included 40 patients with hepatitis C and 20 healthy volunteers, similar in age and body mass index (43.6 +/- 11.6 vs 40.9 +/- 11.8 years and 25.0 +/- 4.1 vs 23.9 +/- 3.3 kg/m(2), respectively). Patients had to have a normal lipid profile, and diabetes was an exclusion criteria. Serum chemerin and leptin levels and IR were significantly higher in patients with hepatitis C when compared to the controls (P = 0.02, P = 0.02 and P = 0.02, respectively), whereas vaspin level was significantly decreased (P = 0.01). Serum chemerin was negatively associated with necro-inflammatory grade (r = (-0.49), P = 0.01). The lowest levels of serum chemerin were found in patients with moderate/severe inflammation (P = 0.03). Serum leptin tended to be up-regulated in patients with minimal inflammatory activity. Serum vaspin was higher, although not significantly, when fibrosis was more advanced. IR was positively associated with fibrosis stage (r = 0.33, P = 0.03). Serum chemerin and leptin were related to each other (r = 0.45, P = 0.02).Our findings support a complex interaction between the analysed adipokines and pathogenesis of inflammatory process in CHC. The role of chemerin and vaspin in pathogenesis of inflammatory response should be further investigated.

The drugs currently approved for treatment of HBV infections are: interferon alpha2a and alpha2b, pegylated interferon (PeglFN-al-pha2a) natural interferons and nucleos(t)ide analogues (NA): adefovir, entecavir, lamivudine, telbivudine (currently not available in Poland) and tenofovir. The following questions are described: the primary goal of antiviral treatment, criteria in therapeutic decision-making (including extrahepatic manifestations, compensated and decompensated cirrhosis of the liver), treatment failure (including: drug resistance), management of patients with HBV-positive markers, in whom chemotherapy or other immunosuppressive therapy is planned. In treatment-naive patients with chronic hepatitis B the first line therapy should be PeglFN-alpha2a monotherapy, and the first-line should be entecavir or tenofovir (highest potential for HBV replication suppression and high genetic barrier to resistance). In drug resistance the patient should be switched to another, preferably high-potency NA (entecavir or tenofovir) or start PeglFN-alpha2a therapy.

Unlabelled: The anti-hepatitis C virus (HCV) effect and safety of three different oral doses of the cyclophilin inhibitor Debio 025 in combination with pegylated interferon-alpha2a (PEG IFN-alpha2a) were investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase II study in treatment-naïve patients with chronic hepatitis C. Doses of 200, 600, and 1,000 mg/day Debio 025 in combination with PEG IFN-alpha2a 180 microg/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 microg/week PEG IFN-alpha2a. In patients with genotypes 1 and 4, the 600- and 1,000-mg combination treatments induced a continuous decay in viral load that reached -4.61 +/- 1.88 and -4.75 +/- 2.19 log(10) IU/mL at week 4, respectively. In patients with genotypes 2 and 3, HCV RNA levels at week 4 were reduced by -5.91 +/- 1.11 and -5.89 +/- 0.43 log(10) IU/mL, respectively, with the same treatment regimens. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with PEG IFN-alpha2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1,000 mg/day)., Conclusion: These results confirm that Debio 025 has a potent activity and an additive effect on HCV RNA reduction in genotype 1 and 4 patients at 600 and 1,000 mg/day when combined with PEG IFN-alpha2a.

The aim of the study was to assess the efficacy and safety of treatment with interferon alpha and ribavirin in patients with chronic hepatitis C and extrahepatic manifestations as well as to determine prognostic factors of therapy effectiveness. 179 consecutive naive patients with chronic hepatitis C treated with interferon alpha and ribavirin were studied. 120 patients (67%) presented extrahepatic manifestations. The most frequent were cryoglobulinaemia, thrombocytopenia and thyroid gland pathology. Efficacy of antiviral treatment was lower (SVR 33.3% vs. 52.5%, p=0.013) and frequency of adverse events higher in patients with chronic hepatitis C and extrahepatic manifestations in comparison to those without extrahepatic pathology. Younger age, shorter duration of HCV infection and less advanced liver fibrosis were prognostic factors of better response to antiviral therapy in group of patients with chronic hepatitis C and extrahepatic manifestations.

Infection with hepatitis C virus (HCV) may be associated with a wide spectrum of immunological abnormalities. HCV tends to induce nonspecific autoimmune reactions, as demonstrated by the high prevalence of various autoantibodies, including antiphospholipid antibodies (aPL). The aPL antibodies (lupus anticoagulant and anticardiolipin antibodies) are a heterogeneous family of immunoglobulins reactive with complexes of phospholipids and plasma proteins (cofactors). The most important of these protein cofactors are beta2-glycoprotein (beta2-GPI) and prothrombin. The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by arterial or venous thrombosis, recurrent fetal losses in association with the presence of antiphospholipid (aPL) antibodies. Increased prevalence of aPL antibodies in several bacterial, parasitic, and viral infections have been reported. Most of the published data agree that anticardiolipin antibodies are frequently found in patients with chronic HCV infection, but they do not appear to be of clinical importance. Some studies, however, have found an increased incidence of thrombotic disorders in patients with chronic hepatitis C virus (HCV) who manifest aPL positivity. More prospective, long-term studies are required in order to address whether HCV is involved or not in the etiopathogenesis of APS.

Objective: To create a simple diagnostic index I for noninvasive distinguish between mild and significant liver fibrosis (stages 0-2 versus 3-6 according to Ishak's criteria) among patients with chronic hepatitis C (CHC)., Patients and Methods: Consecutive interferon-naive 572 CHC patients (F/M: 246/326; median age: 43 years). The I index was created on the data from training group (341 patients diagnosed in 1995-2000 years) and its discriminative value was then assessed separately in training group, validation group (231 patients diagnosed in 2001-2003 years) and entire group using among other things the AUROC measure., Results: The I index is based on information about patient's age, alcohol abuse, AST activity and platelet counts. The AUROC measures were 0.875 [95% CI (0.833-0.916)], 0.926 [95% CI (0.889-0.962)] and 0.890 [95% CI(0.860-0.921)] for training, validation and entire group, respectively. The I values corresponding to at least 95% of sensitivity (observed in about 40% of all patients) could excluded the stage 0-2 with accuracy close to 100%. Based on I values corresponding to at least 95% of specificity (observed in about 17% of all patients) the presence of stage 3-6 could be confirmed with accuracy of about 70%. The I index possesses the statistically significant ability to distinguish between mild and significant fibrosis and seems to be useful in monitoring of non-treated patient with mild fibrosis.

Objective: to investigate the relationship between coexisting diseases (CD) and the progress of liver disease in chronic hepatitis C (CHC)., Patients and Methods: 557 consecutive pts (F/M: 262/295; median age: 42 years) with untreated CHC. CD were defined as a chronic diseases requiring treatment at least 12-months before liver biopsy. HBsAg- and/or HIV-positive as well as alcohol abusers and intravenous drug abusers were excluded from analysis. The significant progress of liver disease was described in the terms of advanced fibrosis (AF), defined as stage 3-6 according to Ishak's system. The relationship between CD and AF was assessed in multivariate analysis simultaneously taking into account the following variables: age, gender, route of transmission, liver steatosis and overweight., Results: Multivariate analysis revealed that CD is independently associated with AF (adjusted OR = 3.4; p < 0.0001). Similar relationship is observed for age over 40 years as well as HCV infection as a result of medical procedures. The contraindications to antiviral treatment were observed in 18.7% pts with CD and only 1.1% pts without CD (p < 0.0001)., Conclusions: Patients with CD are at relatively high risk of AF and simultaneously, notable part of them presents contraindications to antiviral treatment.

Unlabelled: We evaluated the efficacy and safety of peginterferon alfa-2a [40KD] (Peg-IFNalpha-2a) plus ribavirin in patients with chronic hepatitis C in an open-label programme in a routine clinical setting in Poland. Patients received Peg-IFNalpha-2a 180mg/week plus ribavirin 800-1200 mg/d for 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV RNA (<50IU/mL) at the end of follow-up (week 72). 466 adults were enrolled. Most patients (87.3%) had genotype 1 infection. 440 subjects (94,4%) completed treatment. The overall SVR rate was 55.7%. A higher SVR rate was obtained in treatment-naïve patients (58.7%) than in relapsers (47.8%; p=0,048). SVR rates in genotype 1 and non-1 patients were 51.1% and 88.5%, respectively (p<0.001). There were significant higher SVR rates in patients with lower baseline fibrosis (p=0,01). There were no differences in SVRs by gender or viral load. Hemoglobin, leukocyte and neutrophil levels decreased significantly during treatment, but returned to baseline after the end of treatment. ALT levels decreased significantly during treatment in patients with and without an SVR. 38.4% of patients experienced adverse events like neutropenia, anemia, thrombocytopenia, and other. There was one death (severe thrombocytopenia)., Conclusions: The overall SVR achieved in this predominantly genotype 1 population was 55.7%. SVR rates were significantly higher in treatment-naïve patients, those with non-1 genotypes, and in patients with lower baseline fibrosis scores.

Background: Since 2002, blood donors in Poland have been tested not only for hepatitis C virus antibodies (anti-HCV) but also for HCV RNA or HCV core antigen. This screening program identifies asymptomatic, recently infected individuals with no anti-HCV (in the "window period"). The aim of this study was to compare HCV genotype and subtype distribution in window-period (wp) donors, anti-HCV-positive donors, and chronic hepatitis C (CHC) patients., Study Design and Methods: A total of 2.37 million donors were investigated for HCV RNA, and 340,000 for HCV core antigen. HCV genotypes and subtypes were investigated in 50 HCV RNA-positive, anti-HCV-negative donors; in 70 anti-HCV-positive donors; and in 170 CHC patients. Re-questioning of wp donors for probable risk factors was introduced., Results: HCV RNA was detected in 50 donors of 2.71 million (1:54,200) anti-HCV-negative blood donations. Of these 50 donors, 36 percent exhibited Subtype 1b, whereas Subtypes 3a and 4c/d were identified in 40 and 14 percent, respectively. In anti-HCV-positive donors and CHC patients, the frequency of Subtype 1b was significantly higher (75.7 and 85.3%, respectively); in both groups the lower frequency of Subtypes 3a (14.3 and 10.6%, respectively) and 4c/d (4.3 and 1.2%, respectively) was found. The probable source of infection was identified in 9 wp donors., Conclusions: The frequency of wp donors is 18.5 per 1 million. The unexpected high frequency of Genotype 4 and Subtype 3a and the low frequency of Subtype 1b was observed in wp donors compared to anti-HCV-positive individuals. Additional epidemiologic questioning introduced after HCV RNA detection may help to identify infection source.

150 adult patients were assigned pegylated interferon alpha-2b (once weekly 1.5 microg/kg) plus ribavirin (800-1200 mg depending on bodyweight). The treatment lasted 52 weeks and was completed by 139 persons (92.7%). Because of adverse events the treatment was interrupted in 7 persons, 4 other persons resigned. Periodical reduction of pegylated interferon doses was necessary in 19% and the reduction of ribavirin in 21% of patients. Six months after the completion of treatment HCV-RNA was negative in 82 (59%) patients. Neither hepatitis C virus genotype, nor viremia was marked in the study. The negative correlation between the degree of fibrosis in the liver tissue and the results of sustained virological response was stated. Degree of inflammation at liver tissue, sex, age over and less than 40 years did not correlate with the final virological results. The recurrence of infection happened at 7% of the treated persons (negative HCV-RNA directly after the treatment--positive 6 months after the completion). During the treatment period, and comparison with the results obtained before its implementation, statistically significantly decreased: hemoglobin concentration, the number of leukocytes, granulocytes and thrombocytes. They returned to the referential values half a year after the completion of treatment. The activity of enzymes (AIAT, AspAT, GGTP) was decreasing statistically significantly since the first weeks of the treatment till the end and remained significantly lower after 6 months. In both sexes statistically significant reduction of bodyweight was stated, while it increased during the six months after the completion of treatment. Adverse events, which mostly were mild and were not the cause of interruption of treatment, were numerous and occurred at different frequency, in the range from over 50% (flu-like) to 0.7%.

Background: The natural history of chronic hepatitis C (CHC) is characterized by gradual progression of hepatic fibrosis, which can lead to cirrhosis. The aim of our study is to examine the influence of ineffective antiviral therapy on progress of the liver disease in CHC patients., Material/methods: Seventy-seven treated and non-treated CHC patients with two liver biopsies: baseline (BLB) and control (CLB) performed at least 12 months after treatment and at least 18 months from BLB in non-treated patients were studied. Twenty-eight CHC patients (age: 40.3 +/- 9.2 yrs; 22M), non-responding to interferon therapy (all with pretreatment fibrosis), were compared with non-treated patients divided into subgroups NT1 (21 patients [age: 45.1 +/- 11.2 yrs; 10M] with fibrosis in BLB) and NT2 (28 patients [age: 34.7 +/- 12.6; 17M] without fibrosis in BLB). The baseline clinical data between study groups as well as activity grade and fibrosis staging scores of the paired biopsy samples were compared., Results: All three groups were comparable in terms of mean duration of the disease and interval between biopsies. There were no significant differences of clinical features in T and NT1 groups. In CLB, the patients from NT1 group presented non-significant worsening of staging and grading and in NT2 group a slight but statistically significant increase in grading was observed. In contrast, the treated patients had a slight, but significant improvement in liver histology., Conclusions: Antiviral treatment stopped the progression of liver disease in CHC despite the lack of biochemical and virological response. In non-treated patients a slight tendency to worsening of morphological parameters was observed.

Background: Combined interferon-alpha (IFN) plus ribavirin therapy is recommended as first-line regimen treatment of chronic hepatitis C (CHC) patients. The aim of the study was to evaluate the selected clinical factors in the prediction of response to IFN with ribavirin for initial therapy and retreatment of CHC., Patients and Methods: Ninety eight consecutive CHC patients who completed the combined IFN with ribavirin therapy (24 or 48 weeks), including 79 naive patients (age: 41.0 +/- 10.9 yrs; 51M; NAIVE group) and 19 nonsustained responders to prior IFN monotherapy (age: 40.8 +/- 10.2 yrs; 10M; RETHERAPY group). Sustained Response (SR) was defined as persistent normalization of ALT and loss of serum HCV-RNA 6 months after the end of treatment; all other patients were defined as nonresponders (NR). Age, gender, pretreatment histology (assessed according to Ishak's scoring system) and baseline ALT, gamma-GTP and iron serum levels were compared in SR and NR patients, separately in NAIVE and RETHERAPY groups., Results: The baseline clinical characteristics of NAIVE and RETHERAPY group did not differ significantly. 28 of 79 (35.4%) NAIVE patients and 9 of 19 (47.4%) RE-THERAPY patients achieved SR to the therapy. NAIVE sustained responders presented significantly lower staging scores and gamma-GTP levels in comparison with nonresponders. Multivariate logistic regression analysis showed that only fibrotic score lower than 3 was independently (p = 0.04) associated with SR. In RETHERAPY group, only female gender was positively correlated with SR. The other analyzed parameters did not significantly differ between responders and nonresponders., Conclusions: The results of the present study suggest that sustained response to combined therapy in naive CHC patients is associated with absence or minimal hepatic fibrosis prior to the therapy. Among retherapy patients, females are more likely to achieve sustained response, irrespective of fibrosis stage.

Background: We presented the results of treatment in patients with AHC and compared these findings with natural outcome of AHC in untreated patients., Material/methods: Ten treated AHC patients (5F/5M, mean age: 35.5 yrs; all HCV-RNA-positive including 9 anti-HCV-positive). Antiviral treatment was started within 3 to 18 (median 9) weeks after the onset of acute hepatitis including eight patients with monotherapy of IFN and two patients with combined (IFN + ribavirin) therapy., Control Group: Fifty consecutive untreated AHC patients (26F/24M, mean age: 40.8 yrs; all HCV-RNA-positive, including 29 anti-HCV-positive) without contraindications to treatment with IFN., Results: Only one treated patient presented no response and the other 9 patients presented rapid normalization of serum ALT levels in 4th-6th week of the therapy. In two patients, ALT increased in the course of therapy and after adding ribavirin the treatment was continued up to 48 weeks in total. At the end of treatment point, nine patients showed biochemical and virological response, but one relapsed both in biochemical and virological respect and virological relapse was observed in another one. Finally, sustained response was observed in 7 of 10 (70%) of treated compared with 22 of 50 (44%) untreated patients (p = n.s.). The beneficial effect of antiviral treatment was observed among patients with early anti-HCV seroconversion: 7 of 9 treated patients recovered persistently compared with 8 of 29 untreated (p = 0.021)., Conclusions: The antiviral therapy in AHC seems to be effective and should be widely used, especially for individuals with early anti-HCV seroconversion. Ribavirin seems to be helpful for patients, who have not responded to interferon monotherapy.

Aim: To assess the rate of liver fibrosis (RLF) among previously untreated patients with chronic hepatitis C (CHC) and to identify predictors of rapid progression to cirrhosis in this group., Patients and Methods: Medical records of 337 consecutive patients with biopsy proven CHC (anti-HCV and HCVRNA positive; F/M: 153/184; mean age at biopsy: 43 +/- 14 years) and with known probable age at infection have been analysed. There were no intravenous drug users among the patients. HBsAg--and HIV-positive subjects as well as those with other concomitant liver disease were excluded from the analysis. The RLF was defined as the ratio between fibrosis stage (scored 0-6 units [U] according to Ishak's criteria, with 6 representing established cirrhosis) and the duration of HCV infection (in years). The RLF was analysed in relation to the age at infection, sex, route of transmission, alcohol abuse, past HBV infection, acute hepatitis history, HCV genotype and hepatic steatosis. Based on published data, a patient with RLF > or = 0.3 U/yr (cirrhosis up to 20 years after HCV infection) was arbitrarily defined as a rapid progressor. Both uni- and multivariate statistical analyses were performed., Results: The mean RLF was 0.14 +/- 0.17 U/yr (range 0-0.83) and the expected mean duration from infection to cirrhosis was 43 years. In multivariate analysis the only independent factors associated with an increase in RLF were the older age at infection and alcohol abuse (both with p < 0.0001). 58 [17.2%] patients were rapid progressors and the same factors as mentioned above have been independent predictors of cirrhosis up to 20 years after infection. There were as much as 55.5% of rapid progressors among alcohol abusers infected in the age over 30 and only 1.9% among non-alcoholic patients infected in the age up to 30 years., Conclusions: Our study showed that natural course of CHC in Poland is similar to other regions of the world. HCV-related liver disease progression is accelerated among alcohol abusers and infected in older age. In contrast, risk of cirrhosis seems to be minimal among non-alcoholic patients infected before the age of 30.

Adult giant cell hepatitis (AGCH) is a rare event and only about 100 cases have been reported within the last 20 years. The AGCH has been observed in association with viral infection, drug reactions or autoimmune disorders but in many cases its etiology remains unclear. AGCH manifests clinically as severe form of hepatitis histologically characterized by diffuse giant cell transformation of hepatocytes. We report the case of a 39-yr-old man with acute community-acquired hepatitis without previous pathology of the liver. Laboratory data revealed slight hypergammaglobulinemia and high titer of anti-smooth-muscle antibody with negative serology of hepatotropic viruses and absence of other known causes of hepatitis. Preliminary diagnosis of autoimmune hepatitis was established, additionally confirmed by excellent clinical and biochemical improvement during corticosteroid treatment. A liver biopsy showed the typical findings of panlobular syncytial giant cell hepatitis and positive HCV-RNA both in serum and liver. The above verified the diagnosis of acute type C hepatitis manifested histologically as adult giant cell hepatitis. After three months of treatment we withdrew corticosteroids as spontaneous clearance of HCV occurred and the lack of autoantibodies in serum as well as significant improvement of liver histology was ascertained. Within 30 months of the follow-up we have not observed biochemical and immunological abnormalities and control liver biopsy has shown no signs of hepatitis.