Is an 8-week regimen of glecaprevir/pibrentasvir sufficient for all hepatitis C virus infected patients in the real-world experience?

BACKGROUND AND AIMS: The revolution of the antiviral treatment of hepatitis C virus (HCV) infection resulting in higher effectiveness came with the introduction of direct-acting antivirals with pangenotypic regimens as a final touch. Among them, the combination of glecaprevir (GLE) and pibrentasvir (PIB) provides the opportunity for shortening therapy to 8 weeks in the majority of patients. Because of still insufficient evaluation of this regimen in the real-world experience, our study aimed to assess the efficacy and safety of 8-week GLE/PIB in chronic hepatitis C patients depending on liver fibrosis and genotype (GT). METHODS: The analysis included patients who received GLE/PIB for 8 weeks selected from the EpiTer-2 database, large retrospective national real-world study evaluating antiviral treatment in 12 584 individuals in 22 Polish hepatology centers. RESULTS: A total of 1034 patients with female predominance (52%) were enrolled in the analysis. The majority of them were treatment naïve (94%), presented liver fibrosis (F) of F0-F3 (92%), with the most common GT1b, followed by GT3. The overall sustained virologic response after exclusion of nonvirologic failures was achieved in 95.8% and 98%, respectively (P = 0.19). In multivariate logistic regression HCV GT-3 (beta = 0.07, P = 0.02) and HIV infection (beta = -0.14, P < 0.001) were independent predictors of nonresponse. CONCLUSIONS: We demonstrated high effectiveness of 8-week GLE/PIB treatment in a non-GT3 population irrespective of liver fibrosis stage. Comparable efficacy was achieved in non-cirrhotic patients regardless of the genotype, including GT3 HCV.

Real-world experience with Grazoprevir/Elbasvir in the treatment of previously "difficult to treat" patients infected with hepatitis C virus genotype 1 and 4.

BACKGROUND AND AIM: Grazoprevir/elbasvir (GZR/EBR) was approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 and 4 infected patients with or without compensated liver cirrhosis. The aim of this study was to assess GZR/EBR regimen in the real-world experience, particularly in previously "difficult-to-treat" patients with chronic kidney diseases, human immunodeficiency virus-coinfected, cirrhotics, and treatment-experienced. METHODS: The analysis included patients treated with GZR/EBR selected from 10 152 individuals from the EpiTer-2 database, large national real-world study evaluating antiviral treatment in 22 Polish hepatology centers between 2015 and 2018. Data were completed retrospectively and submitted online. RESULTS: A total of 1615 patients who started GZR/EBR therapy in 2017 and 2018 with a female predominance (54%) and median age of 54 years were analyzed. The majority were infected with GT1b (89%) and treatment naïve (81%). Liver cirrhosis was diagnosed in 19%, and 70% of patients had comorbidities, of which chronic renal disease was present in 7% and HIV-coinfection in 4%. Overall, a sustained virologic response (SVR) was achieved by 95% according to intent-to-treat (ITT) and 98% after exclusion of lost to follow up (modified ITT). No differences were found in cure rate between all included patients and subpopulations previously considered as difficult-to-treat. Majority of patients completed the treatment course as scheduled, adverse events were mostly mild and did not lead to therapy discontinuation. CONCLUSIONS: GZR/EBR treatment carried-out in patients infected with HCV genotype 1 and 4 demonstrated good tolerability and an excellent SVR rate with no effectiveness reduction in so called difficult-to-treat populations.

The efficacy of paritaprevir/ritonavir/ombitasvir+dasabuvir and ledipasvir/sofosbuvir is comparable in patients who failed interferon-based treatment with first generation protease inhibitors - a multicenter cohort study.

BACKGROUND: According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs. ledipasvir/sofosbuvir±RBV (LSR) in PI-experienced patients in real-life setting. METHODS: Our analysis included patients registered in the nationwide, investigators initiated, multicentre EpiTer-2 database. Among 4530 patients registered, 335 with genotype 1 (93% 1b) were previously treated with IFN-based regimens with PIs: 127 with boceprevir (BOC), 208 with telaprevir (TVR). Patients with advanced fibrosis (F3/F4) were significantly predominant (BOC 28.4%/61.4%, TVR 18.8%/64.4%, respectively). Subjects were assigned to IFN-free retreatment as follows: BOC - 64 (50.4%) PrODR and 63 (49.6%) LSR; TVR- 103 (49.5%) PrODR and 105 (50.5%) LSR. RESULTS: SVR rates were comparable for particular groups: BOC → PrODR- 100%; BOC → LSR - 98%; TVR → PrODR - 97%; TVR → LSR - 96% (intent-to treat analysis-ITT) and BOC → PrODR→100%; BOC → LSR - 99%; TVR → PrODR - 99%; TVR → LSR - 98% (modified intent-to treat analysis-mITT). Both treatment regimens had a favourable safety profile. Adverse events (AEs) were generally mild or moderate in severity. Three deaths were reported. The treatment was stopped due to AEs in five patients (three treated with PrODR and two with LSR). CONCLUSION: Efficacy and safety of treatment with PrODR and LSR is comparable in BOC or TVR-experienced patients.

Epidemiology of hepatitis C virus infections in Lódzkie voivodeship / Epidemiologia zakazen HCV w województwie lódzkim

INTRODUCTION: Epidemiology of HCV subtypes plays an increasing role in treatment decision making in the era of direct acting antivirals. Data on incidence of HCV subtypes in Poland are sparse and equivocal. AIM OF THE STUDY: The aim of this study was to assess the distribution of HCV subtypes basing on data collected in Lodzkie province in 2015. MATERIALS AND METHODS: Patients with chronic hepatitis C were evaluated for antiviral treatment in one of the three infectious diseases departments in Lodzkie province in 2015 and had HCV genotype/subtype determined. The exclusion criteria were as follows: HBV and/or HIV coinfection and age under 18 years old. RESULTS: The study included 555 patients aged from 18 to 87 years. The rate of women was 52.8%, mean age was 47.4 years and treatment-experienced patients comprised 22.7% of study group. Genotypes 1, 3 and 4 were detected in 512 (92.25%), 34 (6.13%) and 7 (1.26%) patients, respectively. Subtype determination was performed in 464 patients infected with HCV genotype 1. The frequency of subtype 1a and 1b was 18.8% and 81%, respectively. Mean age in patients with HCV 1a infection was 28.6 years and was significantly lower than in patients infected with HCV 1b (52.5 years, p<0.05). A significant correlation between age and HCV subtype was observed. CONCLUSIONS: Prevalence of subtype 1a in patients with chronic hepatitis C in Lodzkie province is high, moreover, this subtype dominates in population of young adults (18-29 years).

Ribavirin priming has no beneficial effects for chronic hepatitis C patients.

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

Efficacy of 8- versus 12-week treatment with ledipasvir/sofosbuvir in chronic hepatitis C patients eligible for 8-week regimen in a real-world setting.

Introduction: Non-cirrhotic treatment-naive hepatitis C patients infected with genotype 1 can be treated with ledipasvir/sofosbuvir (LDV/SOF) for 8 weeks, but in practice this regimen is frequently extended up to 12 weeks at least in part due to insufficient real-world data supporting shortening of treatment. The aim of our study was to compare 8- and 12-week regimens' efficacy in patients eligible for 8-week therapy in a real-world setting. Material and methods: Data of HCV genotype 1 infected patients treated with LDV/SOF between 2015 and 2018 included in the EpiTer-2 database were analyzed with respect to patients' characteristics and length of treatment. Results: Among a total of 1718 patients treated with LDV/SOF, 679 were included in the analysis, 238 (35%) received 8-week regimen, whereas 441 were treated for 12 weeks although they fulfilled the criteria for a shorter course. The majority of patients were infected with genotype 1b (89%) and demonstrated minimal fibrosis (55%). The 12-week regimen was assigned significantly more frequently to patients with comorbidities, concomitant medications and advanced liver fibrosis. The sustained virologic response rate was similar after 8 (98%) and 12 (97%) weeks of therapy according to intent-to-treat analysis and reached 99% in both groups after exclusion of patients lost to follow-up. Conclusions: We confirmed high effectiveness regardless of treatment duration with LDV/SOF in non-cirrhotics infected with HCV genotype 1 eligible for the 8-week regimen according to the current label. This real-world study also demonstrated no need for addition of ribavirin (RBV) in this population and showed that shortening of treatment significantly improves the safety profile of LDV/SOF medication.

HCV Genotype Has No Influence on the Incidence of Diabetes-EpiTer Multicentre Study.

HCV infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, one finds more and more extrahepatic manifestations of HCV infection, including its possible influence on the development of diabetes. In the presented work, one finds the frequency analysis of the incidence of diabetes among 2898 HCV infected patients treated in Poland, and the assessment of their relevance to the HCV genotype and the progression of fibrosis. The results indicate that the hepatitis C infection seems to be a risk factor for diabetes in persons with more advanced liver fibrosis, for older people, and for the male gender. Thus, one found no differences regarding the frequency of its incidence depending on HCV genotype, including genotype 3.

Hepatitis C Infection as a Risk Factor for Hypertension and Cardiovascular Diseases: An EpiTer Multicenter Study.

Hepatitis C infection is one of the main reasons for liver cirrhosis and hepatocellular carcinoma. In recent years, more and more is being heard about extrahepatic manifestations of the hepatitis C infection including its possible influence on the development of hypertension and cardiovascular diseases. In the given work, the frequency analysis of the incidence of hypertension and cardiovascular diseases among 2898 HCV-infected patients treated in Poland and the assessment of their relevance to the HCV genotype and the progression of liver fibrosis can be found. The prevalence of hypertension in the group of analyzed patients was 39% and was significantly associated with old age (OR = 1.08 (1.07-1.08)) and female sex, as well as the progression of liver fibrosis (OR = 1.54 (1.29-1.85)). Hypertension was found in 47.6% of patients with F4 fibrosis, 42.1% of patients with F3 fibrosis, and 25% of patients with F1 fibrosis. The incidence of cardiovascular disease in the studied group of patients was as follows: all incidents, 131 (4.52%); including ischemic heart disease 104, (3.95%); stroke, 2 (0.07%); atherosclerosis, 21 (0.72%); and aneurysms, 4 (0.14%). The obtained results prove that the prevalence of cardiovascular diseases is significantly associated with the advanced age of patients and the progression of liver fibrosis. The relevance of sex and the HCV genotype to the prevalence frequency of cardiovascular diseases in the study group has not been proven. This being the case, no differences in the frequency of their incidence depending on the HCV genotype, including genotype 3, was found. Hepatitis C infection as a non-classical risk factor for cardiovascular disease and hypertension does require further studying.

[Polish multicenter study on safety and efficacy of adefovir dipivoxil in the treatment of lamivudine resistant chronic hepatitis B in adults (HEP 2008)]. / Wieloosrodkowe badanie bezpieczenstwa i skutecznosci preparatu dipiwoksyl adefowiru w leczeniu przewleklego wirusowego zapalenia watroby typu B u doroslych z opornoscia na lamiwudyne (HEP 2008).

Initiated in April 2008 Polish multicenter study HEP2008 aimed clinical data concerning safety and efficacy of adefovir dipivoxil (ADV, Hepsera, Gilead Sciences) in adult chronically infected HBV with lamivudine (LAM) resistance after earliest treatment. We examined 38 men (70.4%) and 16 women (29.6%) with chronic hepatitis B in age 23-81 (average 53) mostly HBeAg positive (70.4%). Majority of patients received earlier LAM (72%), but others additional entekawir and\ or pegylated interferon. Average time from discovering infection HBV was 95 +/- 77 (10-307) months. Majority of patients received monotherapy ADV, but physicians decided at 12 (22%) persons about continuation of LAM therapy. Median HBV DNA level decreased from a baseline value 6.73 +/- 1.71 (1.8-9.0) to 3.25 log10 copies/mL. At least HBV DNA drop 1 log10 and 2 log10 get 78.8 and 60.6% in 24 week, 84.8 and 69.7% in 48 week. HBV DNA reduction below level 300 and 50 copies/mL it observed in 15.2 and 6.1% in 24 week, 39.4 and 30.3% in 48 week. Patients with undetectable Mean ALT activity dropped significantly and were below limit norm at 24 week in 40%, and at 48 week in 58% of patients. Patients treated ADV and LAM reached great reduction of ALT activity but was no influence on HBV DNA reduction. Results of research have confirmed efficiency and safety 48-week's therapy ADV in patients with LAM resistance.

Factors influencing the failure of interferon-free therapy for chronic hepatitis C: Data from the Polish EpiTer-2 cohort study.

BACKGROUND: The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients. AIM: To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting. METHODS: The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis. RESULTS: During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy. CONCLUSION: In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR.

Sofosbuvir/velpatasvir in treatment-experienced HCV-infected patients - short report.

AIM OF THE STUDY: The aim of this overview was to evaluate the efficacy of sofosbuvir/velpatasvir (SOF/VEL) combination in a real-life setting, with particular regard to treatment-experienced individuals. MATERIAL AND METHODS: Seventy-five consecutive patients who were treated with SOF/VEL, completed the 12-week follow-up and had sustained virologic response (SVR) evaluated were included in the analysis. Out of them, 60 (80%) patients were treatment-naïve and 15 (20%) were treatment-experienced. RESULTS: SVR rates reached 89.4% (66/75) in the whole study group and were comparable irrespective of the fibrosis stage or HCV genotype. However, a significant difference in treatment efficacy between treatment-naïve and treatment-experienced individuals was observed, with SVR rates of 98.3% (59/60) and 46.7% (7/15), respectively (p < 0.0001). CONCLUSIONS: Further studies including large real-life cohorts of treatment-experienced patients treated with SOF/VEL are warranted to elucidate the real efficacy of this regimen as a retreatment option.

Comparative effectiveness of 8 versus 12 weeks of Ombitasvir/Paritaprevir/ritonavir and Dasabuvir in treatment-naïve patients infected with HCV genotype 1b with non-advanced hepatic fibrosis.

PURPOSE: Since 2017 treatment-naïve patients infected with genotype 1b of hepatitis C virus and minimal or moderate fibrosis can be treated with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir (OPrD) for 8 weeks according to updated Summary of Product Characteristics. The aim of our study was to assess the comparative efficacy of 8 and 12-weeks therapy with OPrD in large cohort of patients eligible for 8 weeks regimen treated in real-world setting. MATERIALS AND METHODS: We analysed data of 3067 HCV genotype 1b infected patients treated with OPrD between 2015 and 2017. Final analysis included patients with none, minimal or moderate fibrosis (F0-F2). RESULTS: A total of 771 patients were enrolled in the study, including 197 (26%) treated for 8-weeks and 574 patients fulfilling criteria for 8-weeks but assigned to 12-weeks regimen. Majority of patients had no or minimal fibrosis (F0-F1). Longer treatment duration was more often administered in patients with moderate fibrosis, comorbidities, concomitant medications. SVR was achieved in 186 (94%) patients treated for 8 weeks and 558 (97%) for 12 weeks (p = 0.07). After exclusion of lost to follow-up patients, sustained virological response (SVR) rate reached 95% and 99%, respectively (p = 0.01). We were not able to identify factors associated with non-response. CONCLUSIONS: This real-word experience study confirmed similar, high effectiveness of 8 and 12-weeks regimens of OPrD in genotype 1b HCV infected patients with non-advanced fibrosis. Despite of reduced SVR rate after 8-weeks regimen, there is no need to extend therapy to 12-weeks in vast majority of such patients and no need to add ribavirin.

Low risk of HBV reactivation in a large European cohort of HCV/HBV coinfected patients treated with DAA.

OBJECTIVES: The aim of the study was to analyze the prevalence and clinical characteristics of HCV/HBV coinfection and to evaluate the rate of HBV-reactivation during anti-HCV therapy in a large real-world study. METHODS: Analyzed population consisted of 10,152 chronic hepatitis C patients treated with DAA between 2015 and 2019 in a nationwide study. Prior to the DAA all subjects had HBsAg and 60% anti-HBc testing. RESULTS: 111 of 10,152 patients (1.1%) had detectable HBsAg and 1239 of 6139 (20.2%) anti-HBcAb. The prevalence of occult hepatitis B was 0.48%. HCV/HBV patients were younger with a higher proportion of males, HIV-coinfected, and advanced fibrosis. They were less often diagnosed with diabetes but more often with chronic kidney disease. In HBsAg(+) subjects with baseline HBV-DNA available 6/102 (5.9%) HBV-reactivations during or after DAA therapy were observed, and in two (1.9%) significant hepatic flares were noted. In HBsAg(-)/anti-HBc(+) group 2 (0.16%) reactivations were observed only in patients undergoing immunosuppressive therapy. DISCUSSION: Data from a large European cohort suggest a relatively low risk of HBV-reactivation during DAA-therapy for HCV infection in HBsAg(+) patients. In HBsAg(-)/anti-HBc(+) HBV-reactivation seems to be limited to subjects with immunodeficiency. Importantly, previous exposure to HBV and occult hepatitis B is present in a significant proportion of HCV-infected.

Comparison of (99m)Tc-HEPIDA and (99m)Tc-MBrIDA from the standpoint of hepatic clearance determination-- preliminary communication.

BACKGROUND. In order to evaluate the functional capacity of the liver by means of clearance determination, the derivative of iminodiacetic acid ((99m)Tc-HEPIDA) has been used in recent decades. Because of recent problems with manufacturing and delivery of (99m)Tc-HEPIDA, an investigation was undertaken with the aim of testing whether a more widely available (99m)Tc-MBrIDA could be used for clearance determination and whether hepatic clearance measured with the use of this compound provides a similarly useful test of hepatic function. MATERIAL AND METHODS. Comparative investigations were performed in 73 patients of both sexes. The state of the efficiency of liver parenchyma was determined based on seven widely used biochemical tests, i.e. levels of: bilirubin, albumin, and gamma globulin; activity of AST, ALT, GGTP, and prothrombin index. The clearances of both radiopharmaceuticals, (99m)Tc-HEPIDA and (99m)Tc-MBrIDA, were determined by means of multisample technique. The results of determination were correlated among themselves and with the results of biochemical tests. The set of results of all estimations allowed a factorial analysis to be performed to find a common factor and to compute the values of factor loadings in particular tests. RESULTS. Obvious correlation between plasma and hepatic clearances of both radiopharmaceuticals was obtained and between plasma clearance of (99m)Tc-MBrIDA and hepatic clearance of (99m)Tc-HEPIDA. Correlation coefficients of (99m)Tc-MBrIDA clearance and the biochemical test results attained somewhat lower values than for (99m)Tc-HEPIDA clearance. Similarly, values of chi(2) test of independence of (99m)Tc-MBrIDA clearances and test results were also less close than for (99m)Tc-HEPIDA clearances. Factorial analysis showed that common factor loading is greatest for hepatic clearance of (99m)Tc-HEPIDA; the values of two loadings of (99m)Tc-MBrIDA clearances are very close, but somewhat lower than those for (99m)Tc-HEPIDA. CONCLUSIONS. From the performed investigations it is possible to conclude that (99m)Tc-MBrIDA clearances may be used for the evaluation of liver parenchyma performance, even if the results may not be as certain as those obtained using (99m)Tc-HEPIDA.

Is Interferon-Based Treatment of Viral Hepatitis C Genotype 3 Infection Still of Value in the Era of Direct-Acting Antivirals?

The aim of the study is to analyze treatments available for patients infected with genotype (G) 3 hepatitis C virus (HCV) in Poland at the beginning of the interferon (IFN)-free era and evaluate the efficacy and safety of different therapeutic options administered in a real-world setting. We analyzed data of 198 patients who started antiviral therapy after July 1, 2015, and completed it before December 31, 2016; 57.6% of them had liver cirrhosis and 46% were treatment experienced. Fifty percent of patients were assigned to sofosbuvir (SOF)+pegylated IFN alfa (PegIFNa)+ribavirin (RBV), 9% to PegIFNa+RBV, 36% received SOF+RBV, and 5% SOF+daclatasvir (DCV)±RBV. Cirrhotic patients were assigned more frequently to IFN-free regimens. Overall, a sustained virological response was achieved by 84.3% of patients in intent-to-treat (ITT) analysis and 87% in modified ITT analysis. For SOF+PegIFNa+RBV and SOF+DCV±RBV regimens, the sustained virologic response (SVR) rate reached at least 90%, whereas the two other therapeutic options demonstrated efficacy <80%. The SVR rate in noncirrhotics was higher than in cirrhotics, irrespective of regimen. Adverse events were documented in 52.5%, with the most common being weakness/fatigue and anemia. We confirmed effectiveness and safety of the SOF-based treatment in a real-world cohort of patients with chronic HCV G3 infection. Most notably, we demonstrated good tolerability and high efficacy of the SOF+PegIFNa+RBV regimen.

Diagnostic value of optimised real-time sonoelastography in the assessment of liver fibrosis in chronic hepatitis B and C.

AIM: To optimise the method of real-time elastography (RTE) in the assessment of liver fibrosis using an in-house prepared method for elastogram analysis, as well as a semiquantitative analysis based on newly introduced parameters. MATERIAL AND METHODS: Sonoelastography was performed in 94 patients with various degrees of liver fibrosis and also in 25 healthy volunteers. As a reference method for diagnostic efficacy of sonoelastography-based parameters used for the assessment of fibrosis degree in patients with chronic B and C hepatitis, a liver biopsy was used. Patient's elastograms were analysed using in-house prepared software, Pixel Count, calculating two semiquantitative parameters: mean stiffness fraction (MSF%) and intrinsic stiffness ratio (ISR). RESULTS: Statistically significant differences between distributions of the above presented parameters for different degrees of liver fibrosis were revealed. Indices of diagnostic efficacy for detection of significant liver fibrosis (F ≥ 2) using MSF% amounted to: sensitivity - 76%, specificity - 87% and ISR: 81% and 87%, respectively. Sensitivity of both parameters in detection of cirrhosis (F = 4) was equal to 88% and specificity amounted to: for MSF% - 84% and ISR - 86%. Interobserver reproducibility determined for both of the above parameters was high, intraclass correlation coefficients (ICC) were 0.91 for MSF% and 0.93 for ISR. CONCLUSIONS: Real-time elastography applied in this study, using in-house prepared Pixel Count software, provided good reproducibility and diagnostic efficacy, especially specificity, in the assessment of liver fibrosis degree.

Efficacy and direct costs of chronic hepatitis C treatment with first generation NS3/4A protease inhibitors in a real life population.

INTRODUCTION: Recent years have brought a significant advance in chronic hepatitis C (CHC) treatment that includes development of direct acting antivirals (DAA). Two of them, boceprevir (BOC) and telaprevir (TVR), were first approved for treatment of patients infected with CHC genotype 1 in combination with pegylated interferon (P) and ribavirin (R). Our aim was to evaluate the efficacy and direct costs of BOC/PR and TVR/PR in a real life population. MATERIAL AND METHODS: The study included adult patients qualified for the CHC Therapeutic Programme treated with TVR/PR or BOC/PR. Treatment was continued for 24 or 48 weeks. Sustained virological response, treatment discontinuation due to adverse events and lack of virological response rates were compared. RESULTS: A total of 243 adult patients with CHC were included. TVR/PR and BOC/PR were administered in respectively 122 and 121 patients. Thirty-two patients (13%) were treatment-naïve, whereas liver cirrhosis/advanced fibrosis was observed in 138 patients (56.7%). Overall, 43.6% of patients achieved a sustained virologic response (SVR). In the BOC/PR group the SVR rate was significantly lower than in the TVR/PR group (33.1% vs. 54.1%; p = 0.00094). Lack of response to therapy was observed in 41.3% and 12.3% of patients receiving BOC and TVR, respectively (p < 0.00001). The direct cost of achieving SVR in one patient was 285 450 PLN with BOC and 185 757 PLN with TVR. CONCLUSIONS: The very low treatment efficacy may be the result of inclusion criteria that allowed treatment of patients with advanced liver fibrosis/liver cirrhosis or previous treatment failure. Telaprevir seems to be significantly more potent against hepatitis C virus, with similar safety and tolerance.

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.