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.

Treatment of the most difficult-to-cure hepatitis C virus-infected population with sofosbuvir / velpatasvir.

INTRODUCTION: Pangenotypic therapies for infections with hepatitis C virus (HCV), although universal and highly effective, entail a risk of treatment failure. OBJECTIVES: Our study aimed to identify the population of HCV­infected patients most difficult to cure with the sofosbuvir / velpatasvir (SOF/VEL) regimen. PATIENTS AND METHODS: The effectiveness of the SOF/VEL regimen with a possible addition of ribavirin (RBV) was evaluated in populations known to be less responsive to treatment, and then in a population characterized by the combination of all factors impairing effectiveness, comprising patients treated with this regimen in the EpiTer­2 multicenter retrospective study. RESULTS: A total of 2267 patients were treated with SOF/VEL±RBV. Of those, 2078 (96.4%) achieved sustained virologic response. The cure rate was 93.5% among 646 patients infected with genotype (GT) 3, 92.3% among 635 patients with cirrhosis, 95.5% in a population of 1233 men, and 94.1% among 421 patients with body mass index (BMI) above 30. An analysis in a group of 43 men with cirrhosis and obesity infected with GT3 showed the effectiveness of pangenotypic therapy at only 79.1%, falling to 66.7% in individuals with previous treatment failure. CONCLUSIONS: In a large population of SOF/VEL­treated HCV­infected patients, we showed relatively low effectiveness of the regimen in treatment­experienced men with cirrhosis and obesity, infected with GT3. Triple therapy should be considered when initiating the treatment of HCV infections in this group, which, however, needs to be confirmed in further studies. Previous studies were conducted in less demanding populations, because they did not take into account sex and BMI, which significantly affect the treatment effectiveness.

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.

Gene-Editing and RNA Interference in Treating Hepatitis B: A Review.

The hepatitis B virus (HBV) continues to cause substantial health and economic burdens, and its target of elimination may not be reached in 2030 without further efforts in diagnostics, non-pharmaceutical prevention measures, vaccination, and treatment. Current therapeutic options in chronic HBV, based on interferons and/or nucleos(t)ide analogs, suppress the virus replication but do not eliminate the pathogen and suffer from several constraints. This paper reviews the progress on biotechnological approaches in functional and definitive HBV treatments, including gene-editing tools, i.e., zinc-finger proteins, transcription activator-like effector nucleases, and CRISPR/Cas9, as well as therapeutics based on RNA interference. The advantages and challenges of these approaches are also discussed. Although the safety and efficacy of gene-editing tools in HBV therapies are yet to be demonstrated, they show promise for the revitalization of a much-needed advance in the field and offer viral eradication. Particular hopes are related to CRISPR/Cas9; however, therapeutics employing this system are yet to enter the clinical testing phases. In contrast, a number of candidates based on RNA interference, intending to confer a functional cure, have already been introduced to human studies. However, larger and longer trials are required to assess their efficacy and safety. Considering that prevention is always superior to treatment, it is essential to pursue global efforts in HBV vaccination.

Does a detectable HCV RNA at the end of DAA therapy herald treatment failure?

BACKGROUND & AIMS: The study aimed to assess the phenomenon of achieving sustained virologic response (SVR) in patients with detectable ribonucleic acid (RNA) of hepatitis C virus (HCV) at the end of treatment (ET) with direct-acting antivirals (DAA), find how this is affected by the type of regimen, and how patients experiencing this differed from non-responders with detectable HCV RNA at the ET. METHODS: The study included all consecutive patients with detectable HCV RNA at the ET selected from the EpiTer-2 database, a retrospective national multicentre project evaluating antiviral treatment in HCV-infected patients in 2015-2023. RESULTS: Of the 16106 patients treated with IFN-free regimens with available HCV RNA assessment at the ET and at follow-up 12 weeks after treatment completion (FU), 1253 (7.8%) had detectable HCV RNA at the ET, and 1120 of them (89%) finally achieved SVR. This phenomenon was significantly more frequent in pangenotypic regimens, 10.3% vs. 4.7% in genotype-specific options (p < 0.001), and the highest proportion was documented for glecaprevir/pibrentasvir (13.7%), and velpatasvir/sofosbuvir ± ribavirin (6.9%). Patients ET + FU- treated with these two pangenotypic regimens (n = 668) had less advanced liver disease, were less frequently infected with genotype (GT) 3, and were significantly more likely to be treatment-naïve than 61 non-responders. CONCLUSIONS: We documented 7.8% rate of patients with detectable HCV RNA at the ET, of whom 89% subsequently achieved SVR, significantly more frequently in the population treated with pangenotypic regimens. Less severe liver disease, more often GT3 infection, and a higher percentage of treatment-naive patients distinguished this group from non-responders.

Real-World Efficacy and Safety of an 8-Week Glecaprevir/Pibrentasvir Regimen in Children and Adolescents with Chronic Hepatitis C-Results of a Multicenter EpiTer-2 Study.

The aim of the study was to analyze the effectiveness and safety of anti-HCV treatment based on a pangenotypic direct-acting antiviral (DAA) regimen with glecaprevir/pibrentasvir (GLE/PIB) in children. The multi-center study was conducted in HCV-infected children who were treated in the period from November 2022 to January 2023. The analysis included 23 pediatric patients with a mean (SD) age of 9.61 (3.68) years. The cohort included 13 girls and 10 boys. The most common HCV genotypes were GT1b (n = 9, 39.1%), GT1a (n = 6, 26.1%) and GT3 (n = 5, 21.7%). The SVR was assessed at 12 weeks after the end of treatment and was 100% for both girls and boys. The conducted study showed a very good tolerance of the treatment in the entire analyzed group and confirmed a very high efficacy and safety for 8-week treatment with GLE/PIB in children over three years of age. It seems that our study is the first on the real-world use of an 8-week GLE/PIB pangenotypic therapy in a group of children aged 3-12 years and the first in Europe for adolescents aged 12-17.

Pangenotypic triple versus double therapy in HCV-infected patients after prior failure of direct-acting antivirals.

Aim of the study: Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population. Material and methods: The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023. Results: The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively. Conclusions: A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender.

Change in the Clinical Picture of Hospitalized Patients with COVID-19 between the Early and Late Period of Dominance of the Omicron SARS-CoV-2 Variant.

This study aimed to compare the clinical picture of COVID-19 in the initial and later period of Omicron dominance and to identify populations still at risk. A retrospective comparison of the clinical data of 965 patients hospitalized during the early period of Omicron's dominance (EO, January-June 2022) with 897 patients from a later period (LO, July 2022-April 2023) from the SARSTer database was performed. Patients hospitalized during LO, compared to EO, were older, had a better clinical condition on admission, had a lower need for oxygen and mechanical ventilation, had less frequent lung involvement in imaging, and showed much faster clinical improvement. Moreover, the overall mortality during EO was 14%, higher than that in LO-9%. Despite the milder course of the disease, mortality exceeding 15% was similar in both groups among patients with lung involvement. The accumulation of risk factors such as an age of 60+, comorbidities, lung involvement, and oxygen saturation <90% resulted in a constant need for oxygen in 98% of patients, an 8% risk of mechanical ventilation, and a 30% mortality rate in the LO period. Multiple logistic regression revealed lower odds of death during the LO phase. Despite the milder course of infections caused by the currently dominant subvariants, COVID-19 prophylaxis is necessary in people over 60 years of age, especially those with comorbidities, and in the case of pneumonia and respiratory failure.

Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders.

BACKGROUND: It is estimated that 58 million people worldwide are infected with the hepatitis C virus (HCV). Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect profile. This has changed with the introduction of direct-acting antivirals (DAA), although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be demonstrated. AIM: To evaluate the effectiveness and safety of DAA in patients with various mental illnesses. METHODS: This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers, including 942 individuals diagnosed with a mental disorder (anxiety disorder, bipolar affective disorder, depression, anxiety-depressive disorder, personality disorder, schizophrenia, sleep disorder, substance abuse disorder, and mental illness without a specific diagnosis). The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness (n = 13330). Antiviral therapy was considered successful if serum ribonucleic acid (RNA) of HCV was undetectable 12 wk after its completion [sustained virologic response (SVR)]. Safety data, including the incidence of adverse events (AEs), serious AEs (SAEs), and deaths, and the frequency of treatment modification and discontinuation, were collected during therapy and up to 12 wk after treatment completion. The entire study population was included in the intent-to-treat (ITT) analysis. Per-protocol (PP) analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing treatment. RESULTS: Among patients with mental illness, there was a significantly higher percentage of men, treatment-naive patients, obese, human immunodeficiency virus and hepatitis B virus-coinfected, patients with cirrhosis, and those infected with genotype 3 (GT3) while infection with GT1b was more frequent in the population without psychiatric disorders. The cure rate calculated PP was not significantly different in the two groups analyzed, with a SVR of 96.9% and 97.7%, respectively. Although patients with bipolar disorder achieved a significantly lower SVR, the multivariate analysis excluded it as an independent predictor of treatment non-response. Male sex, GT3 infection, cirrhosis, and failure of previous therapy were identified as independent negative predictors. The percentage of patients who completed the planned therapy did not differ between groups with and without mental disorders. In six patients, symptoms of mental illness (depression, schizophrenia) worsened, of which two discontinued treatments for this reason. New episodes of sleep disorders occurred significantly more often in patients with mental disorders. Patients with mental illness were more frequently lost to follow-up (4.2% vs 2.5%). CONCLUSION: DAA treatment is safe and effective in HCV-infected patients with mental disorders. No specific psychiatric diagnosis lowered the chance of successful antiviral treatment.

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.

Retrospective Analysis of the Effectiveness of Remdesivir in COVID-19 Treatment during Periods Dominated by Delta and Omicron SARS-CoV-2 Variants in Clinical Settings.

Continuous evaluation of real-world treatment effectiveness of COVID-19 medicines is required due to the ongoing evolution of SARS-CoV-2 and the possible emergence of resistance. Therefore, this study aimed to analyze, in a retrospective manner, the outcomes in patients hospitalized with COVID-19 during the pandemic waves dominated by Delta and Omicron variants and treated with remdesivir (RDV) (n = 762) in comparison to a demographically and clinically matched group not treated with any antivirals (n = 1060). A logistic regression analysis revealed that RDV treatment was associated with a significantly lower risk of death during both Delta wave (OR = 0.42, 95%CI: 0.29-0.60; p < 0.0001) and Omicron-dominated period (OR = 0.56, 95%CI: 0.35-0.92; p = 0.02). Moreover, RDV-treated groups were characterized by a lower percentage of patients requiring mechanical ventilation, but the difference was not statistically significant. This study is the first real-world evidence that RDV remains effective during the dominance of more pathogenic SARS-CoV-2 variants and those that cause a milder course of the disease, and continues to be an essential element of COVID-19 therapy.

Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C.

Chronic infection with the hepatitis C virus (HCV) remains a major health problem affecting approximately 58 million people worldwide. In the era of interferon (IFN)-based regimens, patients particularly infected with genotypes 1 and 4 achieved a low response rate. The implementation of direct-acting antivirals changed the landscape of HCV treatment. The increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by 2030. In the following years, there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the revolution. The optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over time. Patients treated with antiviral therapies were younger in successive periods, less burdened with comorbidities and comedications, more frequently treatment-naïve and had less advanced liver disease. Before the IFN-free era, specific subpopulations such as patients with HCV/HIV coinfection, those with a history of previous treatment, patients with renal impairment or with cirrhosis had lower chances for a virologic response. Currently, these populations should no longer be considered difficult to treat. Despite the high effectiveness of HCV therapy, there is a small percentage of patients with treatment failure. However, they can be effectively retreated with pangenotypic rescue regimens.

Genotype 4 hepatitis C virus-a review of a diverse genotype.

PURPOSE: Hepatitis C virus (HCV) infection remains a major health problem and one of the leading causes of chronic liver disease worldwide. The purpose of this paper was to summarize knowledge about the epidemiology of HCV genotype (GT) 4 infection, similarities and differences with other genotypes, specific problems associated with this genotype, and treatment regimens used to treat GT4-infected patients. METHODS: We performed an accurate search for literature using the PubMed database to select high-quality reviews and original articles concerning this topic. RESULTS: GT4 with a global prevalence of 8% takes third place, closing the global HCV podium in terms of frequency. However, there are regions where GT4 infections are dominant, such as sub-Saharan and North Africa, and the Middle East. The disease course and complications are generally similar to those of chronic hepatitis C caused by other genotypes, although the faster progression of fibrosis was demonstrated in patients with coexisting schistosomiasis. In the era of interferon-based therapy, GT4-infected patients were described as difficult to treat due to suboptimal response. A breakthrough in the treatment of HCV-infected patients, including those with GT4 infection, was the introduction of direct-acting antiviral drugs. CONCLUSIONS: The availability of safe and effective therapy has created a real opportunity for HCV eradication in line with the goal set by the World Health Organization. An example of a country where this is happening is Egypt, where GT4 accounts for more than 90% of HCV infections. There, broad access to therapy has been effectively supported by population-based screening.

Differences between the course of SARS-CoV-2 infections in the periods of the Delta and Omicron variant dominance in Poland.

INTRODUCTION: Up to now, COVID­19 caused more than 6 million deaths worldwide. So far, 5 variants of concerns have been identified, with Delta and Omicron being the subject of our analysis. OBJECTIVES: We aimed to compare baseline characteristics and outcomes of patients hospitalized during the Delta and Omicron predominance in Poland. PATIENTS AND METHODS: The study population consisted of 2225 patients divided into 2 groups depending on the variant with which they were infected during the corresponding period of the pandemic. RESULTS: During the Delta wave, the median age of patients was significantly lower (65 vs 73 years; P <0.001), and the cohort was significantly less burdened with comorbidities than during the Omicron surge. The Omicron­infected patients presented significantly less often in an unstable symptomatic state with SpO2 equal to or below 90% on admission (49.9% for Delta vs 29.9% for Omicron; P <0.001). Regardless of the pandemic period, the 2 most common early symptoms of COVID­19 were fever and cough. In­hospital treatment consisted of antiviral drugs, more frequently used in the Omicron wave, and immunomodulatory drugs, more frequently used during the Delta wave. The risk of mechanical ventilation was significantly lower in the patients infected with the Omicron variant (7.2% for Delta vs 3.1% for Omicron; P <0.001). For the age group above 80 years old, the risk of death was significantly higher during the Delta wave than during the Omicron wave. The risk of death was significantly lower in the patients treated with antiviral drugs regardless of the pandemic wave. CONCLUSIONS: The Delta variant is associated with a more severe clinical course of the disease and a higher risk of death than the Omicron variant.

Variability in the Clinical Course of COVID-19 in a Retrospective Analysis of a Large Real-World Database.

The COVID-19 pandemic proceeds in waves, with variable characteristics of the clinical picture resulting from the evolution of the SARS-CoV-2 virus. This study aimed to compare the epidemiological characteristics, symptomatology, and outcomes of the disease in patients hospitalized for COVID-19 during periods of different variants dominance. Comparing the periods of dominance of variants preceding the Delta variant, the Delta period was characterized by a higher share of hospitalized females, less frequent comorbidities among patients, and a different age distribution. The lowest need for oxygen therapy and mechanical ventilation was observed under Omicron dominance. The triad of classic COVID-19 symptoms, cough, fever, dyspnoea, and fatigue, were most prevalent during the Delta period, and significantly less common under the Omicron dominance. During the Omicron period, nearly twice as many patients as in the previous periods could be discharged from the hospital within 7 days; the overall 28-day mortality was significantly lower compared to that of the Delta period. It also did not differ between periods that were dominated by the BA.1 and BA.2 subvariants. The study indicates that the Omicron SARS-CoV-2 variant that dominated between January and June 2022 caused a disease which resembled the common cold, and was caused by seasonal alpha and beta-coronaviruses with a low pathogenicity for humans. However, one should note that this effect may not only have been related to biological features of the Omicron lineage, but may additionally have been driven by the increased levels of immunization through natural infections and vaccinations, for which we could not account for due to a lack of sufficient data.

Clinical characteristics and antiviral therapy in patients infected with hepatitis C virus in the interferon­free era.

INTRODUCTION: The highly effective and safe interferon (IFN)-free options were a breakthrough in the treatment of patients infected with hepatitis C virus (HCV). OBJECTIVE: The current analysis was designed to evaluate changes in the patient profile and antiviral treatment characteristics over time. PATIENTS AND METHODS: The study population consisted of 963 consecutive HCV­infected patients who started IFN­free regimens between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce, Poland. The analysis was carried out for 5 time intervals. RESULTS: The studied group was sex­balanced, with the median (interquartile range) age changing from 58 (44.8-63) in 2015-2016 to 43 (35-61) in 2020. The proportion of patients with comorbidities decreased over the years. The rate of treatment­naïve individuals increased from 40.9% in 2015-2016 to 91% in 2020, while the percentage of patients with liver cirrhosis decreased from 51.1% in 2015-2016 to 13.3% in 2020. Genotype­specific regimens dominated in the years 2015-2017, while pangenotypic options gained an advantage in 2019 and reached 91% in 2020. Overall effectiveness achieved 98.4% in the per­protocol analysis and was comparable over the years with lower efficacy among patients with liver cirrhosis and those infected with genotype 3. The therapy was well­tolerated, and the safety profile improved over time. CONCLUSIONS: The median age of HCV­infected patients decreased over the years. They were less burdened with comorbidities and comedications, more likely to be treatment­naïve, and had less advanced liver disease. The genotype­specific regimens, predominantly used at the beginning of the IFN­free era, were superseded by the pangenotypic regimens.

Real-world experience with molnupiravir during the period of SARS-CoV-2 Omicron variant dominance.

BACKGROUND: The real-world effectiveness of molnupiravir (MOL) during the dominance of Omicron SARS-CoV-2 lineage is urgently needed since the available data relate to the period of circulation of other viral variants. Therefore, this study assessed the efficacy of MOL in patients hospitalized for COVID-19 in a real-world clinical practice during the wave of Omicron infections. METHODS: Among 11,822 patients hospitalized after 1 March 2020 and included in the SARSTer national database, 590 were treated between 1 January and 30 April 2022, a period of dominance of the Omicron SARS-CoV-2 variant. MOL was administered to 203 patients, whereas 387 did not receive any antiviral regimen. Both groups were similar in terms of sex, BMI and age allowing for direct comparisons. RESULTS: Patients who did not receive antiviral therapy significantly more often required the use of Dexamethasone and Baricitinib. Treatment with MOL resulted in a statistically significant reduction in mortality during the 28-day follow-up (9.9 vs. 16.3%), which was particularly evident in the population of patients over 80 years of age treated in the first 5 days of the disease (14.6 vs. 35.2%). MOL therapy did not affect the frequency of the need for mechanical ventilation, but patients treated with MOL required oxygen supplementation less frequently than those without antivirals (31.7 vs. 49.2%). The time of hospitalization did not differ between groups. CONCLUSIONS: The use of molnupiravir in patients hospitalized for COVID-19 during the dominance of Omicron variant reduced mortality. This effect is particularly evident in patients over 80 years of age.

Pangenotypic and Genotype-Specific Antivirals in the Treatment of HCV Genotype 4 Infected Patients with HCV Monoinfection and HIV/HCV Coinfection.

The introduction of the direct-acting antivirals (DAA) has substantially improved the effectiveness of the therapy in patients with chronic hepatitis C. We aimed to compare the efficacy of pangenotypic and genotype-specific DAA in the cohort of genotype (GT) four patients with HCV monoinfection and HIV coinfection. A total of 662 GT4-infected patients treated in 2015-2020-of whom 168 (25.3%) were coinfected with HIV, selected from the retrospective EpiTer-2 database-were enrolled in the analysis. Among HIV-coinfected patients, 54% (90) were treated with genotype-specific regimens and 46% (78) with pangenotypic options, while among HCV-monoinfected patients, the rates were 72% and 28%, respectively. Significantly higher rate of males (67.9% vs. 57.7%, p = 0.01), a lower rate of liver cirrhosis (10.2% vs. 18.1%, p = 0.02), and higher of treatment-naïve patients (87.5% vs. 76.7%, p = 0.003) were documented in the HIV coinfected population. The overall sustained virologic response after exclusion of non-virologic failures was achieved in 98% with no significant difference between HIV-positive and HIV-negative patients, 96.2% vs. 98.5%, respectively. While the genotype-specific regimens resulted in a similar cure rate regardless of the HIV status, the pangenotypic options were more efficacious in patients with HCV monoinfection (99.3% vs. 94.4%, p = 0.05). Hereby, we demonstrated the high effectiveness and good safety profile of the DAA therapy in the population of HCV GT4 infected patients with HIV coinfection supporting the current recommendations to treat HCV/HIV coinfected patients with the same options as those with HCV monoinfection.

Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals?

Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.