Effect of comedication on ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin therapy in chronic hepatitis C - a real-world study.

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.

Megamitochondria formation in hepatocytes of patient with chronic hepatitis C - a case report.

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.

Predictors of sustained virological response in patients with hepatitis C virus genotype 3 infection.

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.

Efficacy of HCV treatment in Poland at the turn of the interferon era - the EpiTer study.

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.

Prevalence of HCV genotypes in Poland - the EpiTer study.

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 (lódzkie, mazowieckie, swietokrzyskie), eastern (lubelskie) and southern (malopolskie, slaskie) Poland. The highest rate for genotype 3 was observed in south-western (dolnoslaskie, lubuskie) and eastern (podlaskie, warminsko-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.

Effect of Peginterferon or Ribavirin Dosing on Efficacy of Therapy With Telaprevir in Treatment-Experienced Patients With Chronic Hepatitis C and Advanced Liver Fibrosis: A Multicenter Cohort Study.

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.

Severe intrahepatic cholestasis and liver failure after stanozolol usage - case report and review of the literature.

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.

Dermatologic adverse events of protease inhibitor-based combination therapy in patients with chronic hepatitis C.

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).

Distribution of HCV genotypes in Poland.

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 Lódzkie voivodship (89.2%) and the Slaskie voivodship (86.7%) while the lowest one in the Warminsko-mazurskie (62.0%) and the Podlaskie voivodships (68.2%). Genotype 3 most commonly occurs in the Warminsko-mazurskie (28.1%), and the Podlaskie voivodships (23.0%) and is least common in the Malopolskie (7.9%) and the Lódzkie 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 Lódzkie 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.

Long-term treatment with entecavir induces reversal of advanced fibrosis or cirrhosis in patients with chronic hepatitis B.

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.

[Antiviral treatment of chronic B hepatitis; 2010 - therapeutic recommendations]. / Leczenie przeciwwirusowe przewleklego zapalenia watroby typu B--zalecenia terapeutyczne 2010.

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.

Albinterferon Alfa-2b was not inferior to pegylated interferon-α in a randomized trial of patients with chronic hepatitis C virus genotype 2 or 3.

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.

The cyclophilin inhibitor Debio 025 combined with PEG IFNalpha2a significantly reduces viral load in treatment-naïve hepatitis C patients.

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.

[Efficacy of combined antiviral therapy with interferon alfa and ribavirin in chronic hepatitis C patients with extrahepatic manifestations]. / Skutecznosc skojarzonego leczenia rekombinowanym interferonem alfa z rybawiryna chorych z przewleklym zapaleniem watroby typu C i obecnoscia zespolow pozawatrobowych.

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.

[Antiphospholipid antibodies with HCV infection. Innocent proteins or risk factor?]. / Przeciwciala antyfosfolipidowe w zakazeniu HCV. Niewinne bialka, czy czynnik ryzyka?

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.

[Assessment of the usefulness of combination of selected clinical and demographic parameters in prediction of the severity of liver fibrosis in patients with chronic hepatitis C]. / Ocena przydatnosci kombinacji wybranych parametrów kliniczno-demograficznych w przewidywaniu stopnia zaawansowania wlóknienia watroby u chorych z przewleklym zapaleniem watroby typu C.

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.

[The impact of coexisting diseases on the course of chronic hepatitis C]. / Wplyw chorób wspólistniejacych na przebieg przewleklego zapalenia watroby typu C.

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.