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.

Analysis of Deaths among HIV-Infected Patients Hospitalized in 2009-2018 in Main Centre of Infectious Disease in Region of Lower Silesia in Poland, Detailing Lesions in the Central Nervous System.

Background and Objectives: Patients living with HIV (PLWH), especially those diagnosed too late or not receiving treatment with antiretroviral drugs in the stage of advanced immunodeficiency AIDS for various reasons, develop additional opportunistic infections or AIDS-defining diseases that may contribute directly to the death of these patients. Material and Methods: In this work, we focused on disorders of the central nervous system (CNS) by retrospectively analyzing the symptoms, clinical and autopsy diagnoses of patients diagnosed with HIV infection who died in the provincial specialist hospital in the Lower Silesia region in Poland. Results: The autopsy was performed in 27.4% cases. The cause of death was determined to be HIV-related/AIDS-associated in 78% patients. The most common AIDS-defining CNS diseases in our cohort were toxoplasmosis and cryptococcosis. Conslusions: The presented results of the most common causes of changes in the central nervous system among deceased HIV-infected patients are comparable to the results of studies by other scientists cited in the publication.

The role of anthranilic acid in the increase of depressive symptoms and major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a and oral ribavirin.

Background: Tryptophan metabolism via the kynurenine pathway is considered the link between the immune and endocrine systems. Dysregulation of serotonergic transmission can stem from the direct influence of interferon-α on the activity of serotonergic receptors 5-HT1A and 5-HT2A, and from its indirect effect on tryptophan metabolism. Induction of the kynurenine pathway increases the concentration of neurotoxic kynurenine metabolites, and the activity of kynurenine derivatives is linked to the onset of depression. The aim of our study was to evaluate the relationships between depressive symptoms and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, indolamine 2,3-dioxygenase (IDO) activity and tryptophan availability to the brain. Methods: The study followed a prospective longitudinal cohort design. We evaluated 101 patients with chronic hepatitis C who were treated with pegylated interferon-α2a, and 40 controls who were awaiting treatment. We evaluated the relationships between total score on the Montgomery-Åsberg Depression Rating Scale and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, IDO activity and tryptophan availability to the brain. A logistic regression model was adapted for the diagnosis of major depressive disorder at each time point, taking into account changes in parameters of the kynurenine pathway between a given time point and the baseline measurement. Results: Of the treated patients, 44% fulfilled the criteria for major depressive disorder at least once during the 24 weeks of treatment. Anthranilic acid concentrations were significantly increased compared to baseline for all time points except week 2. Tryptophan availability showed a significant decrease (ß = -0.09, p = 0.01) only in week 12 of treatment. Over time, kynurenine, tryptophan and anthranilic acid concentrations, as well as IDO activity and tryptophan availability to the brain, were significantly associated with total score on the Montgomery-Åsberg Depression Rating Scale. A logistic regression model revealed that participants with decreased tryptophan availability to the brain at 12 weeks of treatment and participants with increased anthranilic acid concentrations at week 24 of treatment were at increased risk for diagnosis of major depressive disorder (odds ratios 2.92 and 3.59, respectively). Limitations: This study had an open-label design in a population receiving naturalistic treatment. Conclusion: The present study provides the first direct evidence of the role of anthranilic acid in the pathogenesis of inflammation-induced major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a.

DRESS syndrome as a complication of treatment of hepatitis C virus-associated post-inflammatory liver cirrhosis with peginterferon α2a and ribavirin.

Various skin and systemic symptoms may develop as a complication of treatment with different medications and medicinal substances. One of them is a relatively rare drug reaction with eosinophilia and systemic symptoms, referred to as DRESS syndrome. The morphology of skin lesions and the patient's general health can differ; the management involves withdrawal of drugs suspected of triggering DRESS syndrome, and administration of local and systemic glucocorticosteroids. In this paper we present a case of a patient with HCV associated chronic hepatitis, treated with peginterferon α2a (PEG-IFN-α2a) and ribavirin, who developed skin lesions and systemic symptoms typical of DRESS syndrome.

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.

Effectiveness and safety of direct-acting antivirals in the therapy of HCV-infected elderly people.

BACKGROUND: The introduction of direct-acting antivirals (DAAs) with their effectiveness and safety has revolutionized the approach to treating hepatitis C virus (HCV) infections. Nevertheless, elderly patients have often been excluded from clinical trials, so the results of real-world studies are particularly important in the context of the geriatric population. The study aimed to analyze the effectiveness and safety of antiviral DAA treatment in HCV-infected patients over the age of 65, with notable inclusion of those over the age of 85. METHODS: The analyzed patients were divided by age into three groups: group A (65-74 years), group B (75-84 years) and group C (85 years or older). Patients started DAA based therapy at 22 hepatology centers between July 2015 and December 2022. RESULTS: A total of 3505 elderly patients were included in the analysis, and this group consisted of 2501 patients in group A, 893 in group B, and 111 in group C. The study population, regardless of age, was dominated by women. Patients had a high prevalence of comorbidities (84.9%, 92.2%, and 93.7%, respectively) as well as a high rate of concomitant medications. The sustained virological response was 97.9% in groups A and B and 100% in group C. The therapy was well-tolerated, with a comparable safety profile observed in all analyzed groups. CONCLUSIONS: DAA-based therapies are highly effective and well tolerated by the elderly patients, including those over 85. Age should not be a barrier to treatment, but careful management is necessary.

The Real-World Efficacy and Safety of Direct-Acting Antivirals for Chronic Hepatitis C in Patients Active Malignancies.

BACKGROUND: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs). METHODS: A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015-2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy. RESULTS: Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients. CONCLUSIONS: As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients.

Real-world experience with direct-acting antiviral therapy in HCV-infected patients with cirrhosis and esophageal varices.

BACKGROUND: Hepatitis C virus (HCV) infection affects 50 million people worldwide with around 242,000 deaths annually, mainly due to complications such as cirrhosis and hepatocellular carcinoma (HCC). Portal hypertension (PH) caused by cirrhosis leads to severe consequences, including esophageal varices (EV). This study aimed to evaluate the effectiveness and safety of direct-acting antiviral (DAA) treatment in patients with and without EV. METHODS: This retrospective analysis involved consecutive HCV-infected adults undergoing DAA therapy at 22 Polish hepatology centers from July 1, 2015, to December 31, 2022. Patients with cirrhosis were categorized based on the presence of EV diagnosed by gastroscopy. Treatment effectiveness was measured by sustained virologic response (SVR), with safety outcomes monitored for 12 weeks post-treatment. RESULTS: A population of 3393 HCV-infected patients with cirrhosis was divided into groups with (A, n = 976) and without (B, n = 2417) EV. Group A showed a significantly higher prevalence of comorbidities and concomitant medications. Genotype (GT)1b infections predominated in both groups, and GT3 infections were more common in the EV group. Group A exhibited more severe liver disease, and higher rates of decompensation, HCC, and HBV co-infection. SVR was significantly higher in group B (91.5% vs. 96.3%, p < 0.0001). Male gender, GT3, EV presence, and Child-Pugh grade B were identified as independent negative SVR predictors. Group A had a worse safety profile, with notably higher adverse event incidence and mortality. CONCLUSIONS: DAA therapies are highly effective and well tolerated in patients with cirrhosis, but EV presence predicts poorer virologic responses.

Real-life effectiveness of antiviral therapy for HCV infection with pangenotypic regimens in HIV coinfected patients.

BACKGROUND: The aim of this study was to evaluate the real-life efficacy of pangenotypic antivirals in HIV-HCV-positive patients. RESEARCH DESIGN AND METHODS: The analysis included 5650 subjects who were treated with pangenotypic anti-HCV drugs: 5142 were HCV-positive and 508 were HIV-HCV-positive. RESULTS: Patients with HCV-monoinfection were older (p < 0.0001), however patients with HCV-monoinfection had a higher proportion of advanced fibrosis F4 (p < 0.0001). There were no differences between the study groups in the rate of SVR12 in ITT-analysis (87,6% versus 93,9% in coinfection and monoinfection group, respectively; p > 0.05). However, there was a difference between study groups in PP-analysis, HIV/HCV and HCV, respectively 95.9% vs 97.9%, p = 0.0323. Additionally, there were a higher rate of patients who did not apply for follow-up (SVR12) in coinfected patients (7,9% vs 3,6% respectively p = 0.0001). In multivariante analysis, factors associated with worse response to the pangenotypic anti-HCV therapy included male sex, HCV genotype 3, stage of fibrosis and decompensation of liver function and HIV coinfection. CONCLUSIONS: The real-life results of pangenotypic anti-HCV treatment are veryeffective in the group of HIV-HCV-coinfected patients. However, the finaleffectiveness is slightly lower than that obtained in HCV monoinfectedpatients.

Recurrent meningitis--a review of current literature.

The paper discusses epidemiology, aetiology and the most important predisposing factors associated with recurrent meningitis, as well as the possibilities to prevent this particularly challenging clinical problem. The frequency of recurrent meningitis is estimated to be 2-9%. However, the case fatality is lower compared to a single episode of meningitis. The main causes of recurrent meningitis are considered to be: head injury, congenital or acquired (post-traumatic or post-surgical) cranial or spinal defects, chronic intracranial inflammation, complement system dysfunction, as well as congenital and acquired humoral or cellular immunodeficiency.

Effectiveness of pangenotypic retreatment of chronic hepatitis C after prior failure of pangenotypic therapies.

INTRODUCTION: Despite the overall excellent efficacy of pangenotypic direct­acting antiviral (DAA) options, there is still a small percentage of patients with hepatitis C virus (HCV) infection who do not respond to the therapy. OBJECTIVES: This analysis was designed to evaluate the effectiveness of pangenotypic retreatment in the cases of pangenotypic therapy failure. PATIENTS AND METHODS: The study included patients treated with the pangenotypic regimen, selected from the EpiTer­2 database, a real­world project evaluating DAA­based treatment in Poland. RESULTS: Of a total 15 123 patients, 4345 received 1 course of the pangenotypic treatment (PAN group) and 48 patients were retreated with pangenotypic regimens after a failure of the pangenotypic therapy (PAP group). The patients from the PAP group were more often men (79% vs 53%; P <0.001), had higher median (interquartile range [IQR]) body mass index (27.5 [25.7-30.1] vs 25.7 [22.9-28.7] kg/m2; P <0.001), were more often infected with genotype 3 (58% vs 27%; P <0.001), and more frequently had liver cirrhosis (46% vs 21%; P <0.001) than the patients in the PAN group. Importantly, no significant difference in the treatment effectiveness was found between the PAP and PAN groups with sustained virologic response (SVR) rate of 89.6% vs 93.7% (P = 0.39) in intention­to­treat, and 91.5% vs 97.6% (P = 0.17) in the per-protocol analysis. The selection of a specific retherapy regimen did not affect SVR. CONCLUSIONS: Our study demonstrated the excellent effectiveness of pangenotypic regimens and confirmed that most DAA nonresponders could be successfully retreated with another pangenotypic regimen. The best retreatment strategy is a triple pangenotypic regimen, especially in patients with unfavorable response factors, such as genotype 3 infection, cirrhosis, and male sex.

HTR1A, TPH2, and 5-HTTLPR Polymorphisms and Their Impact on the Severity of Depressive Symptoms and on the Concentration of Tryptophan Catabolites during Hepatitis C Treatment with Pegylated Interferon-α2a and Oral Ribavirin (PEG-IFN-α2a/RBV).

BACKGROUND: Seeing that there are no data about associations between serotonin gene polymorphism and tryptophan catabolite concentration during PEG-IFN-α2a treatment, the aim of the current study is to examine (a) the associations between polymorphisms within the HTR1A, TPH2, and 5-HTT genes and the severity of depression symptoms and (b) the relationships among rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms and indoleamine 2,3-dioxygenase (IDO) activity, as well as kynurenine (KYN), tryptophan (TRP), kynurenic acid (KA), and anthranilic acid (AA) concentrations. MATERIALS AND METHODS: The study followed a prospective, longitudinal, single-center cohort design. The severity of the depressive symptoms of 101 adult patients with chronic HCV infections was measured during PEG-IFN-α2a/RBV treatment. We used the Montgomery-Åsberg Depression Rating Scale (MADRS) to assess the severity of depressive symptoms. The subjects were evaluated six times-at baseline and at weeks 2, 4, 8, 12, and 24. At all the time points, MADRS score, as well as KYN, TRP, KA, and AA concentrations, and IDO activity were measured. At baseline, rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms were assessed. RESULTS: Subjects with C/C genotypes of 5-HT1A and lower-expressing alleles (S/S, LG/LG, and S/LG) of 5-HTTLPR scored the highest total MADRS scores and recorded the highest increase in MADRS scores during treatment. We found associations between TRP concentrations and the TPH-2 and 5-HTTLPR rs25531 genotypes. CONCLUSIONS: Our findings provide new data that we believe can help better understand infection-induced depression as a distinct type of depression.

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.

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.

Changes in characteristics of patients with hepatitis C virus-related cirrhosis from the beginning of the interferon-free era.

BACKGROUND: Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease. One of them is liver cirrhosis, which occurs in about 20% of patients chronically infected with the hepatitis C virus (HCV). Direct-acting antivirals (DAAs), which replaced interferon (IFN)-based regimens, significantly improved the prognosis of this group of patients, increasing HCV eradication rates and tolerability of therapy. Our study is the first to assess changes in patient profile, effectiveness, and safety in the HCV-infected cirrhotic population in the IFN-free era. AIM: To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the years. METHODS: The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology centers. The retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter database. The measure of treatment effectiveness was the percentage of sustained virologic response (SVR) calculated after excluding patients lost to follow-up. Safety data collected during therapy and the 12-wk post-treatment period included information on adverse events, including serious ones, deaths, and treatment course. RESULTS: The studied population (n = 3577) was balanced in terms of gender in 2015-2017, while the following years showed the dominance of men. The decline in the median age from 60 in 2015-2016 to 57 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and comedications. Treatment-experienced patients dominated in 2015-2016, while treatment-naive individuals gained an advantage in 2017 and reached 93.2% in 2021. Genotype (GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent years. The effectiveness of the therapy was comparable regardless of the period analyzed, and patients achieved an overall response rate of 95%, with an SVR range of 72.9%-100% for the different therapeutic regimens. Male gender, GT3 infection, and prior treatment failure were identified as independent negative predictors of therapeutic success. CONCLUSION: We have documented changes in the profile of HCV-infected cirrhotic patients over the years of accessibility to changing DAA regimens, confirming the high effectiveness of IFN-free therapy in all analyzed periods.

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.

Real-world effectiveness of genotype-specific and pangenotypic direct-acting antivirals in HCV-infected patients with renal failure.

Aim of the study: The aim is to summarize the effectiveness and safety of genotype-specific and pangenotypic hepatitis C virus (HCV) treatments in patients with renal failure. Material and methods: In the EpiTer-2 database, which includes data from 22 hepatology centers in Poland, 593 patients with HCV infection and kidney failure were identified. According to KDIGO 2022, they fulfilled the criteria of chronic kidney disease. Patients were divided into two groups: treated with genotype-specific regimens (n = 428) and pangenotypic options (n = 165), in relation to the stage of kidney disease determined using the glomerular filtration rate (GFR) (Cockcroft and Gault equation). Two separate groups were created for hemodialyzed patients (n = 134) and patients after kidney transplantation (n = 89). Results: In a total of 593 patients, 78.7% were treatment-naïve and 23.9% had liver cirrhosis, in 27.5% of cases decompensated. In both groups, the dominant genotype was GT1b. Among patients treated with genotype-specific regimens, LDV/SOF ± RBV, OBV/PTV/r + DSV ± RBV, and GZR/EBR ± RBV treatments were given to 31.5%, 31.5%, and 34.8% of patients respectively. In pangenotypic regimens, GLE/PIB was chosen in 50.3%. Ninety-six percent and 98.8% of patients in the genotype-specific regimen and 88.5% and 94.8% in the pangenotypic regimen achieved a sustained virologic response at 12 weeks (SVR12) in the intention-to-treat and per protocol population respectively. Liver cirrhosis was identified as a risk factor for virological failure. During the study, 14 patients died, 7 in each of the two groups, none related to the antiviral treatment. Conclusions: Both types of treatment regimens are equally effective and safe in patients with renal failure. The stage of renal failure or transplant does not influence the antiviral response.