Sustained Virological Response After Early Discontinuation of Hepatitis C Treatment.

To date, the effectiveness of direct-acting antivirals (DAAs) discontinued before 4 weeks has not been analysed in routine clinical practice. The study aimed to determine whether such a short therapy will enable achieving a sustained virological response under real-world experience. The study population of 97 patients who discontinued DAA therapy and had data enabling analysis of patient and disease characteristics, and assessment of treatment effectiveness was selected from 16,815 patients registered in the EpiTer-2 database. The most common reason for discontinuation was hepatic decompensation (20.6%) or the patient's personal decision (18.6%). Patients who discontinued treatment were significantly older, more frequently therapy-experienced, more likely to have cirrhosis, a history of decompensation and a Child-Pugh B or C classification than those who completed treatment. SVR was achieved by 93.5% of patients who discontinued treatment after 4 weeks, 60.9% if discontinued at 3 or 4 week and 33.3% at Week 1 or 2. Patients receiving pangenotypic but not genotype-specific treatment who discontinued after 4 weeks were as likely to achieve SVR as those who completed therapy. Patients who responded to treatment that lasted no longer than 2 weeks had a low baseline viral load (<400,000 IU/mL). Despite discontinuation of therapy after Week 4, the chances of SVR are high. Very early discontinuation does not preclude therapeutic success, especially in patients with low baseline viral load.

Direct-acting antivirals in women of reproductive age infected with hepatitis C virus.

Eliminating hepatitis C virus (HCV) infection in the population of women of reproductive age is important not only for the health of women themselves but also for the health of newborns. This study aimed to evaluate the implementation of this goal by analysing the effectiveness of contemporary therapy in a large cohort from everyday clinical practice along with identifying factors reducing therapeutic success. The analysed population consisted of 7861 patients, including 3388 women aged 15-49, treated in 2015-2022 in 26 hepatology centres. Data were collected retrospectively using a nationwide EpiTer-2 database. Females were significantly less often infected with HCV genotype 3 compared to males (11.2% vs. 15.7%) and less frequently showed comorbidities (40.5% vs. 44.2%) and comedications (37.2% vs. 45.2%). Hepatocellular carcinoma, liver transplantation, HIV and HBV coinfections were reported significantly less frequently in women. Regardless of the treatment type, females significantly more often reached sustained virologic response (98.8%) compared to males (96.8%). Regardless of gender, genotype 3 and cirrhosis were independent factors increasing the risk of treatment failure. Women more commonly reported adverse events, but death occurred significantly more frequently in men (0.3% vs. 0.1%), usually related to underlying advanced liver disease. We have demonstrated excellent effectiveness and safety profiles for treating HCV infection in women. This gives hope for the micro-elimination of HCV infections in women, translating into a reduced risk of severe disease in both women and their children.

The burden of infectious diseases throughout and after the COVID-19 pandemic (2020-2023) and Russo-Ukrainian war migration.

Understanding how the infectious disease burden was affected throughout the COVID-19 pandemic is pivotal to identifying potential hot spots and guiding future mitigation measures. Therefore, our study aimed to analyze the changes in the rate of new cases of Poland's most frequent infectious diseases during the entire COVID-19 pandemic and after the influx of war refugees from Ukraine. We performed a registry-based population-wide study in Poland to analyze the changes in the rate of 24 infectious disease cases from 2020 to 2023 and compared them to the prepandemic period (2016-2019). Data were collected from publicly archived datasets of the Epimeld database published by national epidemiological authority institutions. The rate of most of the studied diseases (66.6%) revealed significantly negative correlations with the rate of SARS-CoV-2 infections. For the majority of infectious diseases, it substantially decreased in 2020 (in case of 83%) and 2021 (63%), following which it mostly rebounded to the prepandemic levels and, in some cases, exceeded them in 2023 when the exceptionally high annual rates of new cases of scarlet fever, Streptococcus pneumoniae infections, HIV infections, syphilis, gonococcal infections, and tick-borne encephalitis were noted. The rate of Clostridioides difficile enterocolitis was two-fold higher than before the pandemic from 2021 onward. The rate of Legionnaires' disease in 2023 also exceeded the prepandemic threshold, although this was due to a local outbreak unrelated to lifted COVID-19 pandemic restrictions or migration of war refugees. The influx of war migrants from Ukraine could impact the epidemiology of sexually transmitted diseases. The present analysis indicates that continued efforts are needed to prevent COVID-19 from overwhelming healthcare systems again and decreasing the control over the burden of other infectious diseases. It also identifies the potential tipping points that require additional mitigation measures, which are also discussed in the paper, to avoid escalation in the future.

Is there still hope for the prophylactic hepatitis C vaccine? A review of different approaches.

Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating the development of an effective prophylactic vaccine. This review paper presents the current landscape of HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, and more modern, such as subunit protein, vectored, based on nucleic acids (DNA and mRNA) and virus-like particles. The concept of the HCV vaccine is first put in the context of viral genetic diversity and adaptive responses to HCV infection, an understanding of which is crucial in guiding the development of an effective vaccine against such a complex virus. Because ethical dimensions are also significant in vaccine research, development, and potential deployment, we also address them in this paper. The road to a safe and effective vaccine to prevent HCV infection remains bumpy due to the genetic variation of HCV and its ability to evade immune responses. The progress in cell-culture systems allowed for the production of an inactivated HCV vaccine candidate, which can induce cross-neutralizing antibodies in vitro, but whether this could prevent infection in humans is unknown. Subunit protein vaccine candidates that entered clinical trials elicited HCV-specific humoral and cellular responses, though it remains to be shown whether they translate into effective prevention of HCV infection or progression of infection to a chronic state. Such responses were also induced by a clinically tested vector-based vaccine candidate, which decreased the viral HCV load but did not prevent chronic HCV infection. These disappointments were not readily predicted from preclinical animal studies. The vaccine platforms employing virus-like particles, DNA, and mRNA provide opportunities for the HCV vaccine, but their potential in this context has yet to be shown. Ensuring the designed vaccine is based on conserved epitope(s) and elicits broadly neutralizing immune responses is also essential. Given failures in developing a prophylactic HCV vaccine, it is crucial to continue supporting national strategies, including funding for screening and treatment programs. However, these actions are likely insufficient to permanently control the HCV burden, encouraging further mobilization of significant resources for HCV vaccine research as a missing element in the elimination of viral hepatitis as a global public health.

The RdRp genotyping of SARS-CoV-2 isolated from patients with different clinical spectrum of COVID-19.

BACKGROUND: The evolution of SARS-CoV-2 has been observed from the very beginning of the fight against COVID-19, some mutations are indicators of potentially dangerous variants of the virus. However, there is no clear association between the genetic variants of SARS-CoV-2 and the severity of COVID-19. We aimed to analyze the genetic variability of RdRp in correlation with different courses of COVID-19. RESULTS: The prospective study included 77 samples of SARS-CoV-2 isolated from outpatients (1st degree of severity) and hospitalized patients (2nd, 3rd and 4th degree of severity). The retrospective analyses included 15,898,266 cases of SARS-CoV-2 genome sequences deposited in the GISAID repository. Single-nucleotide variants were identified based on the four sequenced amplified fragments of SARS-CoV-2. The analysis of the results was performed using appropriate statistical methods, with p < 0.05, considered statistically significant. Additionally, logistic regression analysis was performed to predict the strongest determinants of the observed relationships. The number of mutations was positively correlated with the severity of the COVID-19, and older male patients. We detected four mutations that significantly increased the risk of hospitalization of COVID-19 patients (14676C > T, 14697C > T, 15096 T > C, and 15279C > T), while the 15240C > T mutation was common among strains isolated from outpatients. The selected mutations were searched worldwide in the GISAID database, their presence was correlated with the severity of COVID-19. CONCLUSION: Identified mutations have the potential to be used to assess the increased risk of hospitalization in COVID-19 positive patients. Experimental studies and extensive epidemiological data are needed to investigate the association between individual mutations and the severity of COVID-19.

Optical Coherence Tomography Angiography Assessment of the Optic Nerve Head in Patients Hospitalized Due to COVID-19 Bilateral Pneumonia.

Background and objectives: We aimed to investigate changes in the radial peripapillary capillary (RPC) network using optical coherence tomography angiography (OCTA) in patients who recovered from coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study of patients hospitalized due to COVID-19 bilateral pneumonia between March and May 2021. The control group included healthy individuals matched for age and sex. Two months after discharge, the patients underwent ophthalmological examination, including optical coherence tomography (OCT) imaging. The RPC network and retinal nerve fiber layer (RNFL) of the optic disc (RNFL optic disc) were automatically evaluated and compared between the study groups. Additionally, the RPC parameters were compared between the men and women in the COVID-19 group, and correlations between the RPC and RNFL optic disc parameters were assessed. Results: A total of 63 patients (120 eyes) with bilateral pneumonia caused by severe acute respiratory syndrome coronavirus 2 infection were examined. No ophthalmic symptoms were reported by the patients. No significant differences were observed in the RPC parameters between the patients from the COVID-19 group and the 43 healthy controls. Moreover, the RPC parameters did not differ between the men and women in the COVID-19 group. A positive correlation was found between the RPC and RNFL optic disc parameters in the COVID-19 patients (p < 0.001). Conclusions: No changes in the RPC network were observed among the patients with COVID-19 bilateral pneumonia in the early period after hospital discharge. However, a longer follow-up is needed to monitor COVID-19-related changes in the microvasculature of the optic nerve head.

Overview of autoantibodies in COVID-19 convalescents.

Accumulating evidence shows that SARS-CoV-2 can potentially trigger autoimmune processes, which can be responsible for the long-term consequences of COVID-19. Therefore, this paper aims to review the autoantibodies reported in COVID-19 convalescents. Six main groups were distinguished: (i) autoantibodies against components of the immune system, (ii) autoantibodies against components of the cardiovascular system, (iii) thyroid autoantibodies, (iv) autoantibodies specific for rheumatoid diseases, (v) antibodies against G-protein coupled receptors, and (vi) other autoantibodies. The evidence reviewed here clearly highlights that SARS-CoV-2 infection may induce humoral autoimmune responses. However, the available studies share number of limitations, such as: (1) the sole presence of autoantibodies does not necessarily implicate the clinically-relevant risks, (2) functional investigations were rarely performed and it is often unknown whether observed autoantibodies are pathogenic, (3) the control seroprevalence, in healthy, noninfected individuals was often not reported; thus it is sometimes unknown whether the detected autoantibodies are the result of SARS-CoV-2 infection or the accidental post-COVID-19 detection, (4) the presence of autoantibodies was rarely correlated with symptoms of the post-COVID-19 syndrome, (5) the size of the studied groups were often small, (6) the studies focused predominantly on adult populations, (7) age- and sex-related differences in seroprevalence of autoantibodies were rarely explored, (8) genetic predispositions that may be involved in generation of autoantibodies during SARS-CoV-2 infections were not investigated, and (9) the autoimmune reactions following infection with SARS-CoV-2 variants that vary in the clinical course of infection remain unexplored. Further longitudinal studies are advocated to assess the link between identified autoantibodies and particular clinical outcomes in COVID-19 convalescents.

Short-term exposure to ambient air pollution and COVID-19 severity during SARS-CoV-2 Delta and Omicron waves: A multicenter study.

Air pollution may affect the clinical course of respiratory diseases, including COVID-19. This study aimed to evaluate the relationship between exposure of adult patients to mean 24 h levels of particulate matter sized <10 µm (PM10 ) and <2.5 µm (PM2.5 ) and benzo(a)pyrene (B(a)P) during a week before their hospitalization due to SARS-CoV-2 infection and symptomatology, hyperinflammation, coagulopathy, the clinical course of disease, and outcome. The analyses were conducted during two pandemic waves: (i) dominated by highly pathogenic Delta variant (n = 1440) and (ii) clinically less-severe Omicron (n = 785), while the analyzed associations were adjusted for patient's age, BMI, gender, and comorbidities. The exposure to mean 24 h B(a)P exceeding the limits was associated with increased odds of fever and fatigue as early COVID-19 symptoms, hyperinflammation due to serum C-reactive protein >200 mg/L and interleukin-6 >100 pg/mL, coagulopathy due to  d-dimer >2 mg/L and fatal outcome. Elevated PM10 and PM2. 5 levels were associated with higher odds of respiratory symptoms, procalcitonin >0.25 ng/mL and interleukin >100 pg/mL, lower oxygen saturation, need for oxygen support, and death. The significant relationships between exposure to air pollutants and the course and outcomes of COVID-19 were observed during both pandemic waves. Short-term exposure to elevated PM and B(a)P levels can be associated with a worse clinical course of COVID-19 in patients requiring hospitalization and, ultimately, contribute to the health burden caused by SARS-CoV-2 variants of higher and lower clinical significance.

Safety of therapies using ustekinumab in patients with psoriasis who have had hepatitis B virus infection.

Biological therapies used in psoriasis treatment pose a risk of reactivation of hepatitis B virus (HBV) infection. This risk occurs not only in patients with HB surface antigen (HBsAg) (+) but also in patients with past or occult HBV infection (with negative HBsAg, positive HB core antibodies (HBcAb), and positive HBV deoxyribonucleic acid [DNA]). Ustekinumab (UST) is a biologic agent acts by blocking the IL-12/23 pathway. Thus, hindering this response may lead to HBV reactivation. UST therapy is associated with mild HBV-r risk; however, there is insufficient data to confirm that hypothesis. Herein, we present observations on the safety of UST therapy in patients with psoriasis and serologically proved past HBV infection. One-hundred and six consecutive patients with moderate to severe psoriasis treated with biological therapy between May 2013 and January 2020 were retrospectively analyzed. Out of 106 patients, there were five who reported having past HBV. Those five patients were tested for the presence of HBsAg, HBcAb, HBsAb as well as HBV DNA at baseline and at the end of the follow-up period. HBV reactivation was defined as changing of "undetectable" to "detectable" viremia. All five patients were treated with UST. Five patients in our cohort group were found to have resolved HBV infection: HBsAg (-), HBcAb (+), and HBV DNA (-); 4/5 were HBsAb (+) and 1/5 HBsAb (-). None of the patients experienced an increase in their liver function tests values and no signs of hepatitis or HBV reactivation were observed at any point during the study. All the patients were HBsAg and HBV DNA negative at the end of the follow-up period. The average treatment time was 82.4 (28, 96) weeks. The average follow-up time was 75.2 (31, 176) weeks. Based on the available literature and the results from our observations, UST therapy seems to be a safe option for patients with resolved HBV infection.

Is elimination of HCV in 2030 realistic in Central Europe.

According to the recent data presented by Central-European HCV experts, the estimated prevalence of HCV is between 0.2% and 1.7% in certain countries in this region. There are no financial limitations to access to treatment in most countries. Patients in these countries have access to at least one pangenotypic regimen. The most common barriers to the elimination of HCV in Central Europe are a lack of established national screening programmes and limited political commitment to the elimination of HCV. Covid-19 has significantly affected the number of patients who have been diagnosed and treated, thus, delaying the potential elimination of HCV. These data suggest that the elimination of HCV elimination projected by WHO before 2030 will not be possible in the Central Europe.

Real-world effectiveness and safety of direct-acting antivirals in patients with cirrhosis and history of hepatic decompensation: Epi-Ter2 Study.

BACKGROUND AND AIMS: The aim of this study was to assess the real-life effectiveness and safety of direct acting antivirals (DAAs) in patients with cirrhosis and history of hepatic decompensation compared to those with compensated cirrhosis. METHOD: Data of patients treated with DAAs and included in the EpiTer-2 database (N = 10 152) were collected retrospectively. The primary endpoint was sustained viral response (SVR) at 12 weeks posttreatment. Patients were also evaluated in terms of liver-related adverse events and treatment modification/discontinuation. RESULTS: The overall SVR rate was 91.4% in the intent to treat (ITT) analysis and 95.2% in the per-protocol (PP) analysis (P < .001). Patients with decompensated cirrhosis had lower SVR rates compared to those with compensated cirrhosis in ITT analysis (86.4% vs 92.0%, P < .001), while not in PP analysis (92.9% vs 95.5%, P > .05). Adverse events (AE) occurred 45.6% and 29.3% of patients with decompensated and compensated cirrhosis (P < .001). Patients with decompensated cirrhosis were at higher risk of death (5.4% vs 0.9%; P < .0001) or liver decompensation (21.5% vs 1.3%; P < .0001). Treatment with protease inhibitors was not associated with hepatic decompensation (P = .3). Only 82.6% of patients with decompensated cirrhosis completed DAA treatment (vs 92.8% in compensated cirrhotics; P < .0001). CONCLUSION: Despite higher frequency of AE and treatment modifications, once completed, DAAs yield comparable results for patients with decompensated and compensated cirrhosis. High rate of serious adverse events in patients with advanced liver disease treated with PI may not be related to the detrimental effect of the medications, but rather to the disease itself.

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.

Viral respiratory infections and air pollution: A review focused on research in Poland.

The COVID-19 pandemic has reinforced an interest in the relationship between air pollution and respiratory viral infections, indicating that their burden can be increased under poor air quality. This paper reviews the pathways through which air pollutants can enhance susceptibility to such infections and aggravate their clinical course and outcome. It also summarizes the research exploring the links between various viral infections and exposure to solid and gaseous pollution in Poland, a region characterized by poor air quality, especially during a heating season. The majority of studies focused on concentrations of particulate matter (PM; 86.7%); the other pollutants, i.e., BaP, benzene, CO, NOx, O3, and SO2, were studied less often and sometimes only in the context of a particular infection type. Most research concerned COVID-19, showing that elevated levels of PM and NO2 correlated with higher morbidity and mortality, while increased PM2.5 and benzo[a]pyrene levels were related to worse clinical course and outcome in hospitalized, regardless of age and dominant SARS-CoV-2 variant. PM10 and PM2.5 levels were also associated with the incidence of influenza-like illness and, along with NO2 concentrations, with a higher rate of children's hospitalizations due to lower respiratory tract RSV infections. Higher levels of air pollutants also increased hospitalization due to bronchitis (PM, NOx, and O3) and emergency department admission due to viral croup (PM10, PM2.5, NOx, CO, and benzene). Although the conducted studies imply only correlations and have other limitations, as discussed in the present paper, it appears that improving air quality through reducing combustion processes in energy production in Poland should be perceived as a part of multilayered protection measures against respiratory viral infections, decreasing the healthcare costs of COVID-19, lower tract RSV infections, influenza, and other respiratory viral diseases prevalent between autumn and early spring, in addition to other health and climate benefits.

Hepatitis B virus coinfection in patients treated for chronic hepatitis C: clinical characteristics, risk of reactivation with long-term follow-up, and effectiveness of antiviral therapy.

INTRODUCTION: Hepatitis B virus (HBV) and hepatitis C virus (HCV) share a similar transmission route, which increases coinfection odds and worsens clinical outcomes. OBJECTIVES: Our aim was to investigate coinfected patients undergoing HCV treatment with direct-acting antivirals (DAAs) to understand their characteristics, risk of HBV reactivation, and effectiveness of the therapy. PATIENTS AND METHODS: Our study comprehensively analyzed 1118 patients with chronic HCV infection, divided into 3 subgroups based on their HBV status. RESULTS: We documented that 0.7% of the analyzed population was positive for hepatitis B virus surface antigen (HBsAg), while 14.3% had evidence of a past HBV infection. The patients without HBV coinfection were less burdened with comorbidities, and were mostly treatment-naive, while the individuals suffering from coinfection were younger and more likely to have a history of a previous therapy. Infection with HCV genotype 3 was more common among the HBsAg-positive patients than in the other studied groups. Response to DAA therapy was comparable between the groups, and most patients completed the course of treatment as planned. Only 3 cases of HBV reactivation were observed, all of which achieved sustained virologic response after DAA therapy. Two were women on immunosuppressants with antihepatitis B core positive antibodies, and the third patient was an HBsAgpositive man. These patients remained in long-term follow-up. CONCLUSIONS: Neither the presence of HBV markers nor HBV reactivation during DAA treatment reduced effectiveness of the therapy. Our findings are important for future recommendations and guidelines on managing HBV/HCV coinfection.

Trends of Hepatitis A Virus Infection in Poland: Assessing the Potential Impact of the COVID-19 Pandemic and War in Ukraine.

Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis, which is preventable by vaccination. This study analyzed trends of HAV infections in Poland according to socio-demographic features in the years 2009-2022 and assessed the potential impact of the COVID-19 pandemic (2020-2023) and the migration of war refugees from Ukraine (since February 2022). In 2009-2022, 7115 new cases of HAV infection were diagnosed in Poland, especially among men (66.4%) and in urban areas (77.4%). Infections among men were most common at the age of 25-34 (median rate 0.43 per 105) and in women aged 15-24 (median rate 0.39 per 105). Analysis of the 14-year frequency of HAV infections exhibited three trends, regardless of gender, age, and residence. The infections revealed a downward trend in 2009-2014, increased significantly in 2014-2018, and decreased again after 2018. A particularly rapid increase in HAV infections occurred between March 2017 and February 2018 (median rate 0.79 per 105). The high level of new infections persisted until the beginning of the COVID-19 pandemic, at which point it dropped significantly but did not reach the level recorded before March 2017. During the Omicron SARS-CoV-2 dominance period, the median rate of HAV infections was 0.053 per 105, with a four-fold increase being observed from February 2022 (when the migration of war refugees from Ukraine began) to August 2022. The presented results can serve as a reference point for further observations in Central Europe. The HAV epidemiological situation is unlikely to escalate in Poland but requires further monitoring.

Revolutionizing hepatitis C treatment: next-gen direct-acting antivirals.

INTRODUCTION: With the introduction of highly effective and safe therapies with next-generation direct-acting antivirals (DAAs), that act without interferon, hepatitis C virus (HCV) infection remains the only treatable chronic infectious disease. AREAS COVERED: The review aims to provide an overview of the therapy revolution with a description of specific DAAs, their mechanisms of action, a summary of the safety and efficacy of specific regimens, and a discussion of populations requiring special therapeutic approaches. EXPERT OPINION: DAAs are highly effective, safe, and easy to use. However, challenges such as access to health services and loss of patients from the cascade of care, especially in groups disproportionately affected by HCV infection, such as substance abusers, make it difficult to achieve the WHO's goal of HCV elimination. The proposed strategy to combat these difficulties involves a one-step approach to diagnosing and treating the infection, the availability of long-lasting forms of medication, and the development of an effective vaccine. The aforementioned opportunities are all the more important as the world is facing an opioid epidemic that is translating into an increase in HCV prevalence. This phenomenon is of greatest concern in women of childbearing age and in those already pregnant due to treatment limitations.

Hepatitis C virus (HCV) is an insidious pathogen. Most people infected with HCV will develop chronic infections that may not give any symptoms for years or decades but eventually lead to liver disease and liver cancer. It is essential to diagnose infected individuals as soon as possible and start the treatment to increase the elimination of the virus from the organism and prevent harmful long-term effects.Fortunately, these goals are possible nowadays, and this is due to a remarkable example of translational research at work. The discovery of the virus in 1989 (for which Harvey J. Alter, Michael Houghton, and Charles M. Rice received the Nobel Prize in 2020) was followed by the rapid development of diagnostic tests and later by the introduction of the first interferon therapies, which had numerous shortcomings. The revolution started in 2011 when the first oral drugs that act directly on HCV (direct-acting antivirals, DAAs) were registered. Another giant leap for HCV treatment was made in 2018 when the combinations of DAAs that act on different HCV genotypes were introduced.In this paper, we review in detail the DAAs used to treat HCV infection and explain different combinations in which they can be used while showing their favorable safety profile, short-term and convenient treatment regimen, and impressive effectiveness in clearing HCV infection. Although we believe eliminating HCV is eventually reachable, we also argue that there is room for improvement. HCV testing and DAAs availability must improve in selected groups, including people without health insurance, prisoners, and drug addicts. There are still people living with chronic HCV infection without knowing it. Their identification and start of effective treatment is equal to savings in future medical care related to liver disease and cancer, not to mention benefits from the individual health perspective. In addition, and in line with a popular phrase that prevention is better than cure, it is reasonable to pursue the development of the HCV vaccine, which is currently unavailable. The last word on managing the health burden caused by this pathogen is yet to be said.