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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.

SummaryBackground 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.

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.

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.

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.

Purpose To assess the prevalence and predictive factors of extrahepatic manifestation (EM) in patients with chronic hepatitis C (CHC) infection in Poland. Material and Methods 340 consecutive patients (mean age: 42 years) with untreated CHC were studied between 2000 and 2006. The HCV infection was defined by positive serology and serum HCV RNA. The inflammation grade and fibrosis stage were assessed according to Ishak. Demographic, laboratory and liver biopsy data were collected. The patients with liver cirrhosis, concomitant HBV or HIV infection, autoimmune liver diseases and alcohol abusers were excluded from the analysis. Results 210 patients with CHC (61.7%) presented at least 1 extrahepatic manifestation, including mixed cryoglobulinemia (37.1%), thrombocytopenia (27.6%), thyroid autoimmunity (16.2%), dermatological disorders (4.1%) and type 2 diabetes (4.1%). Other EM such as the sicca syndrome, nephropathy, polyneuropathy and B-cell lymphoma were observed in single cases. In multivariate analysis lower platelet count was found as a predictive factor of EM in patients with CHC. Conclusions The majority of patients with CHC, living in Poland, have EM, of which cryoglobulinemia, thrombocytopenia, thyroid autoimmunity, dermatological disorders and type 2 diabetes are most common. Through the multivariate analysis the lower platelet predicts extrahepatic manifestations associated with chronic hepatitis C.

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

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.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.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.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.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).

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.

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.

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 (p0.001). 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).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.

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).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.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.

to investigate the relationship between coexisting diseases (CD) and the progress of liver disease in chronic hepatitis C (CHC).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.Multivariate analysis revealed that CD is independently associated with AF (adjusted OR = 3.4; p0.0001). 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 (p0.0001).Patients with CD are at relatively high risk of AF and simultaneously, notable part of them presents contraindications to antiviral treatment.

The aim of the study was both to evaluate the natural outcome of acute hepatitis C (AHC), in this factors influencing chronicity of HCV, and to assess results of antiviral therapy in acute phase of disease.Seventy-seven pts with diagnosis of AHC (all HCVRNA-positive, in this 44 anti-HCV-positive at entry) were seen. Sixty-four of them (F/M: 33/31; mean age: 45.4y +/- 16.0) were non-treated (NT pts) with IFN during 6-months follow-up and thirteen patients (F/M: 5/8; mean age: 36.6ys +/- 11.9) were treated (T pts) with IFN. Antiviral therapy was started within 2 to 18 (median 10) weeks after the onset of AHC including seven pts with IFN alpha-2b at 5MU thrice weekly (TIW) and one pt with IFN-alpha-2a at 6MU TIW for 24 weeks, three pts with combined (Rebetron) therapy according to HCV genotype (1F/3a for 24 weeks and 2M/1b for 48 weeks) and two pts with PEG-Intron for one month followed by Intron at 3MU TIW for 20 weeks.64.1% of NT pts developed chronic hepatitis. In multivariate logistic regression analysis age40y, nonicteric course and medical procedures as route of infection were independently and significantly associated with chronicity. Ten of the thirteen (77%) treated pts presented sustained response (SR) at the end of follow-up. Only one seronegative pt no responded to the therapy. The others 12 pts (all seropositive) presented rapid normalisation of ALT levels. However, 3 of them developed breakthrough between 12 and 20 week of therapy and ribavirin was added with beneficial effect. At the end of treatment point, all seropositive patients showed biochemical and virological response but two (with breakthrough history) of them relapsed.Seropositive, nonicteric patients with acute hepatitis C should be treated as soon as possible and pegylated-IFN for 24 weeks seems to be currently the best choice. Combination therapy with PEG and ribavirin could be proposed to the patients who failed to monotherapy. The beneficial effect of AHC therapy is indicative for necessity of creating conditions for diagnosed AHC more frequent than hitherto.

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.

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.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.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.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.

We presented the results of treatment in patients with AHC and compared these findings with natural outcome of AHC in untreated patients.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.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.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).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.

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.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.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.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.

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.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 RLFor = 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.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 p0.0001). 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.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.

Patients with on-going HBV viral replication often present with clinical features of active chronic hepatitis. Until the recent introduction of nucleoside analogues, interferon-alpha was the only approved drug for these patients. One of the former drugs, lamivudine, has been shown in clinical trials in the US and Asia to effectively inhibit the viral polymerase of HBV. Our study was undertaken to assess the efficacy and safety of lamivudine therapy in Polish patients with chronic hepatitis B.Forty-five patients with chronic hepatitis B (HBeAg positive, anti-e negative, HBV-DNA positive by hybridization assay) were enrolled in the study. The patients received 100mg of lamivudine orally, once daily for 12 months. They returned for routine clinical and laboratory control every two weeks during the first months of treatment, and later at 3-month intervals while receiving lamivudine.At the end of treatment, serum HBeAg was not detected in 21 patients (48.8%), and anti-HBe appeared in the serum of 19 patients. 37.2% of the patients in the study group showed sustained suppression of serum HBV DNA at the end of treatment. Lamivudine therapy was well tolerated, with the rate of occurrence of adverse events similar to that observed in other clinical studies.12-month lamivudine therapy in this Polish population of patients with chronic hepatitis B induced a high rate of HBeAg seroconversion, accompanied by reduction of HBV-DNA and the normalization of alanine aminotransferase activities.