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Despite one of the world's highest coronavirus-related death rates per capita, only 59% of Polish citizens decided to receive COVID-19 vaccine.[1] Such hesitancy toward vaccination has often been associated with a perception that the risk of being severely infected affects only very narrow group of individuals with certain risk factors and comorbidities.[2] Thus, educational efforts aimed at increasing the community knowledge on actual prevalence and impact of personal risk factors for severe COVID-19 are still warranted.[3] On the contrary, however, quantitative estimation of relative contributions of different host-related risk factors including comorbidities to the severe COVID-19 has still remained elusive.[4] Therefore, here we attempted not only to assess but also rather quantify to which extent well-known phenotypic and comorbid factors impact on the clinical severity of COVID-19. Heatmaps presenting the values of odds ratio for developing severe course of COVID-19 in man and woman based on age, sex, body mass index (BMI). Implementation of the web-based calculator estimating odds ratio of severe COVID-19 for unvaccinated individuals in a country with high coronavirus-related death toll. [Extracted from the article]

Background: Evaluation of the activity of the exudative form of age-related macular degeneration (AMD) during anti-vascular endothelial growth factor (anti-VEGF) therapy before and after administration of BNT162b2 (Pfizer/BioNTech) vaccination. Methods: The optical coherence tomography and best corrected visual acuity (BCVA) records of the two previous visits before the first dose of BNT162b2 (first pre-vaccination visit marked as “V-1”, the previous pre-vaccination “V-2”), and two subsequent visits after the second dose of vaccination (first visit after the second dose marked as “V1”, second visit after the second dose marked as “V2”) were collected for 63 eyes of 59 patients. Results: The difference in the average retinal thickness was observed between the last and each other checkpoint for the aflibercept group and in the overall outcome. The maximum thickness from the inner retinal surface to the inner border of RPE decreased during the observation; differences were observed comparing visits −2 and 1. Subretinal complex thickness decreased during follow-up, and the differences were observed between visits −2 and 2. There were no statistically significant differences in the BCVA and the occurrence of intraretinal cystoid fluid, serous PED, subretinal hyperreflective material, and retinal hemorrhage. Conclusion: In the present study, the activity of the exudative form of AMD did not deteriorate after the administration of the BNT162b2 vaccine. [ABSTRACT FROM AUTHOR]

Aim: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin (pegIFN/RBV), in treatment-naive hepatitis C virus (HCV) genotype (GT) 1-infected patients., Methods: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned (2:1) to daclatasvir vs telaprevir, stratified by IL28B rs12979860 host genotype (CC vs non-CC), cirrhosis status (compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype (GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus pegIFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus pegIFN/RBV; those without an extended rapid virologic response (eRVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of pegIFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus pegIFN/RBV followed by 12 (with eRVR) or 36 (no eRVR) wk of pegIFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12 (SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia (hemoglobin < 10 g/dL) and rash-related events, through week 12, were lower with daclatasvir + pegIFN/RBV than with telaprevir + pegIFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/mL, to investigate any link between NS5A polymorphisms associated with daclatasvir resistance and virologic outcome., Results: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups (6.0% and 8.2% in the GT1b and GT1a groups, respectively) than in the telaprevir groups (2.2% and 3.0%). Among GT1b-infected patients, daclatasvir plus pegIFN/RBV was noninferior to telaprevir plus pegIFN/RBV for SVR12 [85% (228/268) vs 81% (109/134); difference, 4.3% (95%CI: -3.3% to 11.9%)]. Anemia (hemoglobin < 10 g/dL) was significantly less frequent with daclatasvir than with telaprevir [difference, -29.1% (95%CI: -38.8% to -19.4%)]. Rash-related events were also less common with daclatasvir than with telaprevir, but the difference was not statistically significant. In GT1a-infected patients, SVR12 was 64.9% with daclatasvir and 69.7% with telaprevir. Among both daclatasvir and telaprevir treatment groups, across GT1b- or GT1a-infected patients, lower response rates were observed in patients with IL28B non-CC and cirrhosis - factors known to affect response to pegIFN/RBV. Consistent with these observations, a multivariate logistic regression analysis in GT1b-infected patients demonstrated that SVR12 was associated with IL28B host genotype (CC vs non-CC, P = 0.011) and cirrhosis status (absent vs present, P = 0.031). NS5A polymorphisms associated with daclatasvir resistance (at L28, R30, L31, or Y93) were observed in 17.3% of GT1b-infected patients at baseline; such variants did not appear to be absolute predictors of failure since 72.1% of these patients achieved SVR12 compared with 86.9% without these polymorphisms. Among GT1b-infected patients, treatment was completed by 85.4% (229/268) in the daclatasvir group, and by 85.1% (114/134) in the telaprevir group, and among GT1a-infected patients, by 67.2% (90/134) and 69.7% (46/66), respectively. Discontinuations (of all 3 agents) due to an AE were more frequent with telaprevir than with daclatasvir, whereas discontinuations due to lack of efficacy were more frequent with daclatasvir, due, in part, to differences in futility criteria., Conclusion: Daclatasvir plus pegIFN/RBV demonstrated noninferiority to telaprevir plus pegIFN/RBV for SVR12 and was well-tolerated in treatment-naive GT1b-infected patients, supporting the use of daclatasvir with other direct-acting antivirals.

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

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.

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.

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

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.

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

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

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

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