Publications by authors named "Jerzy Jaroszewicz"

100 Publications

HCV resistance-associated substitutions following direct-acting antiviral therapy failure - Real-life data from Poland.

Infect Genet Evol 2021 Jun 1;93:104949. Epub 2021 Jun 1.

Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice, Poland.

Background: This study analysed the NS3 and NS5A mutation frequencies, persistence and drug susceptibility in a cohort of real-life patients, with failed hepatitis C virus (HCV) therapy following directly acting antiviral (DAA) treatment.

Methods: NS3/NS5A Sanger sequences from 105 patients infected with HCV genotype (G) 1a (6,5.7%), G1b (94,89.5%), G3a (4,3.8%), and G4 (1,1.0%) post DAA treatment failure were analysed. NS3 and NS5A resistance-associated substitutions (RASs) were identified using the geno2pheno algorithm and associated with clinical variables. Time trends were examined using logistic regression.

Results: NS5A RAS were found in 87.9% of sequences derived from patients exposed to this class of agents, whereas NS3 RAS was found in 59.1% of HCV protease-exposed subjects. The frequency of the NS3 RAS increased with fibrosis stage, from 40.0% among F0/F1 individuals to 81.8% among patients with liver cirrhosis (F4, p = 0.094). NS5A mutation frequencies were 7.6% for 28A/V/M, 10.6% for 30 K/Q/R, 42.4% for 31I/F/M/V, and 75.8% for 93H. For NS3, the most common RASs were 56F-23.7%, 168A/E/I/Y/T/V-14.0%, and 117H-5.4%. Susceptibility to glecaprevir/pibrentasvir, velpatasvir/voxlaprevir, and elbasvir/grazoprevir was retained in 92.9%, 43.4%, and, 25.3% of patients, respectively. The frequency of NS3 RAS decreased with time elapsed from failure to sampling (p = 0.034 for trend). NS5A RAS frequency remained stable over the 24-months.

Conclusions: Following DAA treatment failure, NS5A and NS3 RASs were common with increasing frequency among patients with advanced liver disease. In most cases, despite the presence of RASs, susceptibility to DAA combinations with higher genetic barrier was retained.
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http://dx.doi.org/10.1016/j.meegid.2021.104949DOI Listing
June 2021

Impact of Kidney Failure on the Severity of COVID-19.

J Clin Med 2021 May 10;10(9). Epub 2021 May 10.

Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-089 Białystok, Poland.

Background: Patients with kidney failure are at an increased risk of progression to a severe form of coronavirus disease 2019 (COVID-19) with high mortality. The current analysis was aimed to assess the impact of renal failure on the severity of COVID-19 and identify the risk factors of the fatal outcome in this population.

Methods: The analysis included patients from the SARSTer database, a national real-world study evaluating treatment for COVID-19 in 30 Polish centers. Data were completed retrospectively and submitted online.

Results: A total of 2322 patients were included in the analysis. Kidney failure was diagnosed in 455 individuals (19.65%), of whom 373 presented moderate stage and 82 patients, including 14 dialysis individuals, presented severe renal failure. Patients with kidney failure were significantly older and demonstrated a more severe course of COVID-19. The age, baseline SpO, the ordinal scale of 4 and 5, neutrophil and platelet count, estimated glomerular filtration rate, and C-reactive protein concentration as well as malignancy and arterial hypertension were the independent predictors of 28-day mortality in logistic regression analysis.

Conclusions: Underlying kidney disease in patients with COVID-19 is among the leading factors associated with a higher risk of severe clinical presentation and increased mortality rate.
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http://dx.doi.org/10.3390/jcm10092042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126240PMC
May 2021

Brain-derived neurotrophic factor as a potential diagnostic marker in minimal hepatic encephalopathy.

Clin Exp Hepatol 2021 Mar 2;7(1):117-124. Epub 2021 Feb 2.

Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.

Introduction: Minimal hepatic encephalopathy (MHE) is a common complication of liver cirrhosis not only leading to a decrease in the quality of life, but also predicting development of overt encephalopathy. The diagnosis of MHE usually relies on a combination of neuropsychological tests, while robust serum biomarkers are lacking. We aimed to assess serum concentrations of brain-derived neurotrophic factor (BDNF) in MHE patients.

Material And Methods: Serum BDNF was assessed in 78 patients with liver cirrhosis (53 male, median age 55 years) and 40 healthy individuals. 43 subjects underwent extensive evaluation for MHE by psychometric hepatic encephalopathy score (PHES) and inhibitory control test (ICT) or critical flicker frequency (CFF).

Results: Serum BDNF was twofold lower in liver cirrhosis compared to healthy subjects [13.6 (7.8-22.6) vs. 33.0 (24.1-40.7) ng/ml, < 0.001] and its decrease reflected a degree of liver insufficiency assessed by model for end-stage liver disease (MELD). BDNF showed a negative correlation with bilirubin ( = -0.35, = 0.005) and international normalized ratio (INR) ( = -0.37, = 0.003), and positive with platelets (PLT) ( = 0.36, = 0.004), while no associations with age, sex, body mass index (BMI), waist-hip ratio (WHR), creatinine and ammonia were noted. Importantly, subjects with a diagnosis of MHE by at least two modalities showed the lowest levels of BDNF [10.9 (2.5-14.4) vs. 19.9 (9.3-29.4) ng/ml, < 0.01]. Patients with self-reported sleep disturbances had significantly lower serum BDNF [13.0 (2.5-23.4) vs. 20.0 (8.4-31.3) ng/ml, = 0.04].

Conclusions: The lowest serum BDNF concentration was noted in patients with MHE and sleep disturbances, which suggests a role in pathophysiology of hepatic encephalopathy but also as a potential biomarker.
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http://dx.doi.org/10.5114/ceh.2021.103242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122095PMC
March 2021

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

World J Gastroenterol 2021 May;27(18):2177-2192

Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-540, Poland.

Background: The introduction of direct-acting antiviral drugs into clinical practice has revolutionized the treatment of chronic hepatitis C, making it highly effective and safe for patients. However, few researchers have analyzed the factors causing therapy failure in some patients.

Aim: To analyze factors influencing the failure of direct antiviral drugs in the large, multicenter EpiTer-2 cohort in a real-world setting.

Methods: The study cohort consisted of patients with chronic hepatitis C treated at 22 Polish centers from 2016-2020. Data collected from the online EpiTer-2 database included the following: hepatitis C virus (HCV) genotype, stage of fibrosis, hematology and liver function parameters, Child-Turcotte-Pugh and Model for End-stage Liver Disease scores, prior antiviral therapy, concomitant diseases, and drugs used in relation to hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) coinfections. Adverse events observed during the treatment and follow-up period were reported. Both standard and machine learning methods were used for statistical analysis.

Results: During analysis, 12614 patients with chronic hepatitis C were registered, of which 11938 (mean age: 52 years) had available sustained virologic response (SVR) data [11629 (97%) achieved SVR and 309 (3%) did not]. Most patients (78.1%) were infected with HCV genotype 1b. Liver cirrhosis was diagnosed in 2974 patients, while advanced fibrosis (F3) was diagnosed in 1717 patients. We included patients with features of hepatic failure at baseline [ascites in 142 (1.2%) and encephalopathy in 68 (0.6%) patients]. The most important host factors negatively influencing treatment efficacy were liver cirrhosis, clinical and laboratory features of liver failure, history of hepatocellular carcinoma, and higher body mass index. Among viral factors, genotype 3 and viral load also exerted an influence on treatment efficacy. Classical statistical analysis revealed that treatment ineffectiveness seemed to be influenced by the male sex, which was not confirmed by the multivariate analysis using the machine learning algorithm (random forest). Coinfection with HBV (including patients with on-treatment reactivation of HBV infection) or HIV, extrahepatic manifestations, and renal failure did not significantly affect the treatment efficacy.

Conclusion: In patients with advanced liver disease, individualized therapy (testing for resistance-associated variants and response-guided treatment) should be considered to maximize the chance of achieving SVR.
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http://dx.doi.org/10.3748/wjg.v27.i18.2177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117732PMC
May 2021

Acute Coronary Tree Thrombosis After Vaccination for COVID-19.

JACC Cardiovasc Interv 2021 05;14(9):e103-e104

3rd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Silesian Centre for Heart Diseases, Medical University of Silesia, Katowice, Poland.

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http://dx.doi.org/10.1016/j.jcin.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092130PMC
May 2021

Real-world direct-acting antiviral treatment in kidney transplant and hemodialysis patients: the EpiTer-2 multicenter observational study.

Ann Gastroenterol 2021 5;34(3):438-446. Epub 2021 Feb 5.

Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok (Tadeusz W. Łapiński, Robert Flisiak).

Background: Patients who undergo hemodialysis (HD) or kidney transplantation (KTx) previously had limited possibilities for treatment of hepatitis C virus (HCV) infection. Direct-acting antivirals (DAA) give these patients a chance of virus eradication and safe transplantation. The aim of this study was to evaluate the effectiveness and safety of DAA in KTx and HD patients in real-world settings.

Methods: Sustained virologic response (SVR) and treatment safety were analyzed in KTx and HD patients from the EpiTer-2 database, which included HCV-infected subjects treated with DAA between 2015 and 2019. Additionally, for KTx patients, changes in creatinine concentration, estimated glomerular filtration rate (eGFR), proteinuria within a year after treatment, and changes in the need for calcineurin inhibitors were assessed.

Results: Among 10,152 patients from the EpiTer-2 database 148 were selected, 85 after KTx and 63 undergoing HD. The most common genotype, 1b HCV, was found in 73% and 86% of patients, respectively. Cirrhosis was noted in 10% and 19%, respectively. The most common DAA regimen after KTx was sofosbuvir/ledipasvir (54%), whereas in HD patients it was ombitasvir/paritaprevir/ritonavir +/- dasabuvir (56%). All patients with available follow-up results achieved SVR. No deaths, kidney loss or acute rejection episodes were noted. The most common adverse effects in both groups were anemia and weakness. One year after treatment, creatinine concentration, eGFR and proteinuria remained stable in the majority of patients.

Conclusion: DAA treatment of HCV infection demonstrated high effectiveness and safety in hemodialyzed patients and patients who had undergone KTx in this real-world study.
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http://dx.doi.org/10.20524/aog.2021.0595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079881PMC
February 2021

Tocilizumab Improves the Prognosis of COVID-19 in Patients with High IL-6.

J Clin Med 2021 Apr 9;10(8). Epub 2021 Apr 9.

Department of Infectious Diseases, Jan Kochanowski University, 25-369 Kielce, Poland.

Despite direct viral effect, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore, tocilizumab (TOC), a monoclonal antibody against IL-6 receptors, was considered as a possible therapeutic option. Patients were selected from the SARSTer database, containing 2332 individuals with COVID-19. Current study included 825 adult patients with moderate to severe course. Analysis was performed in 170 patients treated with TOC and 655 with an alternative medication. The end-points of treatment effectiveness were death rate, need for mechanical ventilation, and clinical improvement. Patients treated with TOC were balanced compared to non-TOC regarding gender, age, BMI, and prevalence of coexisting conditions. Significant effect of TOC on death was demonstrated in patients with baseline IL-6 > 100 pg/mL (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.08-0.57). The best effectiveness of TOC was achieved in patients with a combination of baseline IL-6 > 100 pg/mL and either SpO2 ≤ 90% (HR: 0.07) or requiring oxygen supplementation (HR: 0.18). Tocilizumab administration in COVID-19 reduces mortality and speeds up clinical improvement in patients with a baseline concentration of IL-6 > 100 pg/mL, particularly if they need oxygen supplementation owing to the lower value of SpO2 ≤ 90%.
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http://dx.doi.org/10.3390/jcm10081583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070099PMC
April 2021

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

Liver Int 2021 Mar 2. Epub 2021 Mar 2.

Regional Center for Diagnosis and Treatment of Viral Hepatitis and Hepatology, John Paul II Hospital, Kraków, Poland.

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.
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http://dx.doi.org/10.1111/liv.14858DOI Listing
March 2021

Neurologic manifestations of COVID-19. Authors' reply.

Pol Arch Intern Med 2021 02 26;131(2):208-209. Epub 2021 Feb 26.

Department of Infectious Diseases and Hepatology, Medical University of Silesia, Katowice, Poland

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http://dx.doi.org/10.20452/pamw.15840DOI Listing
February 2021

SARS-CoV-2/COVID-19 in multiple sclerosis patients receiving disease-modifying therapy.

Clin Neurol Neurosurg 2021 02 29;201:106451. Epub 2020 Dec 29.

Department of Otorhinolaryngology and Oncological Laryngology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Poland.

At the end of 2019, the COVID-19 pandemic began, which at the time of writing continues to be a serious problem for many areas of medicine, including neurology. Since patients with multiple sclerosis (MS) often exhibit motor disability and receive disease-modifying therapy (DMT), which has an immunosuppressive effect, it is plausible that this will affect the susceptibility of MS patients to COVID-19, as well as the course of this disease. However, current data indicate that the use of DMT does not cause negative prognosis in COVID-19 sufferers, but the motor disability progression associated with MS does. In this study, we present the case reports of 4 patients with relapsing-remitting MS, who developed COVID-19, and despite the use of DMT the course of the disease was mild. Two patients were treated with dimethyl fumarate, one with Interferon β1b and one with glatiramer acetate. One of the patients using dimethyl fumarate had lymphopenia. All patients had symptoms of COVID-19 from the nervous system, the most frequent being headache, which occurred in all patients. The aim of this article is to present a case series of four patients with MS and COVID-19, and to discuss the available literature on COVID-19 in patients with MS, with particular consideration of the impact of DMT.
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http://dx.doi.org/10.1016/j.clineuro.2020.106451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831713PMC
February 2021

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

J Gastroenterol Hepatol 2020 Nov 10. Epub 2020 Nov 10.

Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland.

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.
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http://dx.doi.org/10.1111/jgh.15337DOI Listing
November 2020

Neurological symptoms as a clinical manifestation of coronavirus disease 2019: implications for internists.

Pol Arch Intern Med 2021 01 21;131(1):54-62. Epub 2020 Aug 21.

Numerous experimental and clinical studies have proven that the new severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has a tropism for the nervous system. The infection of the nervous system by SARS‑CoV‑2 can occur via the nasal route through trans‑synaptic pathways. Coronaviruses can infect neurons and glial cells through angiotensin‑converting enzyme 2 receptors or by endocytosis. The infection of the central nervous system accompanied by coronavirus disease 2019-related systemic inflammation leads to the impairment of the blood-brain barrier and triggers a neuroinflammatory response with reactive astrogliosis and microglial activation. In addition, brain stem cells are being damaged, which results in respiratory distress. Apart from typical symptoms of COVID‑19 associated with the involvement of the respiratory system, neurological manifestations such as headache, dizziness, myalgia, anosmia, ageusia, encephalopathy, encephalitis, stroke, epileptic seizures, rhabdomyolysis, and Guillain-Barré syndrome are related to SARS‑CoV‑2 infection. In this review, we focused on the currently known neurological manifestations of COVID‑19, which could be considered mainly in asymptomatic patients with COVID‑19 and, if noted, may limit the transmission of coronavirus infection.
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http://dx.doi.org/10.20452/pamw.15575DOI Listing
January 2021

Searching for the optimal population for hepatitis C virus screening in Poland.

Clin Exp Hepatol 2020 Jun 30;6(2):74-76. Epub 2020 Apr 30.

Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland.

Aim Of The Study: The purpose of the study was to select the optimal target population for a possible national hepatitis C virus (HCV) screening program in Poland, based on the most recent available data.

Material And Methods: The analysis included 723,654 participants from different populations screened for anti-HCV. Testing was performed in the whole blood using rapid anti-HCV kits. Presence of HCV RNA was additionally demonstrated in some anti-HCV positive patients with the real-time polymerase chain reaction method.

Results: Altogether 3,548 anti-HCV positive individuals were identified, so the prevalence rate in the whole studied population was 0.5%. The highest percentage (1.2%) was shown by diagnostic laboratories, which offered rapid testing for patients visiting their offices during the HCV awareness campaign. Relatively high anti-HCV prevalence of 0.6-0.7% was noted in hospitals and in private medical centers, as well as during music concerts. Surprisingly, the lowest prevalence (0.2%) was observed in general practitioners' offices. Among 502 anti-HCV positive individuals tested additionally for HCV RNA, viremic presence was demonstrated in 40%.

Conclusions: Anti-HCV testing in Poland should be carried out using rapid anti-HCV kits at the patients' admission to the hospitals and should also be offered to patients during their visits for any purpose in diagnostic laboratories or private medical centers.
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http://dx.doi.org/10.5114/ceh.2020.94969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380468PMC
June 2020

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

Expert Rev Anti Infect Ther 2020 10 27;18(10):1045-1054. Epub 2020 Jun 27.

Department of Infectious Diseases and Hepatology, Medical University of Białystok , Białystok, Poland.

Objectives: The aim of the study was to analyze the prevalence and clinical characteristics of HCV/HBV coinfection and to evaluate the rate of HBV-reactivation during anti-HCV therapy in a large real-world study.

Methods: Analyzed population consisted of 10,152 chronic hepatitis C patients treated with DAA between 2015 and 2019 in a nationwide study. Prior to the DAA all subjects had HBsAg and 60% anti-HBc testing.

Results: 111 of 10,152 patients (1.1%) had detectable HBsAg and 1239 of 6139 (20.2%) anti-HBcAb. The prevalence of occult hepatitis B was 0.48%. HCV/HBV patients were younger with a higher proportion of males, HIV-coinfected, and advanced fibrosis. They were less often diagnosed with diabetes but more often with chronic kidney disease. In HBsAg(+) subjects with baseline HBV-DNA available 6/102 (5.9%) HBV-reactivations during or after DAA therapy were observed, and in two (1.9%) significant hepatic flares were noted. In HBsAg(-)/anti-HBc(+) group 2 (0.16%) reactivations were observed only in patients undergoing immunosuppressive therapy.

Discussion: Data from a large European cohort suggest a relatively low risk of HBV-reactivation during DAA-therapy for HCV infection in HBsAg(+) patients. In HBsAg(-)/anti-HBc(+) HBV-reactivation seems to be limited to subjects with immunodeficiency. Importantly, previous exposure to HBV and occult hepatitis B is present in a significant proportion of HCV-infected.
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http://dx.doi.org/10.1080/14787210.2020.1782189DOI Listing
October 2020

Clinical significance of asymptomatic [i]Clostridium difficile[/i] colonisation in patients undergoing antibiotic treatment.

Przegl Epidemiol 2020 ;74(1):3-10

Medical University of Silesia in Katowice, Department of Infectious Diseases and Hepatology in Bytom.

Background: [i]Clostridium difficile[/i] infections become a serious problem in terms of nosocomial infections, as well as a consequence of common use of antibiotics.

Aim: The aim of the study was to evaluate [i]Clostridium difficile[/i] carriage in patients admitted to the Clinical Department of Infectious Diseases and Hepatology without acute or chronic diarrhea and to assess the impact of antibiotic treatment on the development of enteritis in hospital. Other factors that may affect the risk of infection were also analyzed.

Results: Fourteen patients (14%) were carriers of [i]Clostridium difficile[/i] at admission. Second assessment taken after fourteen days of antibiotic treatment showed decrease in GDH antigen prevalence to eight subjects (12.1%). Three patients (3%) had diarrhea during hospitalization, and the toxins A and/or B were found in them.

Conclusions: The frequency of [i]Clostridium difficile[/i] carriage among adults in Poland may be underestimated. Screening for Clostridium difficile GDH antigen may be useful although do not provide definite prognosis of symptomatic disease during ceftriaxone treatment. The risk of Clostridium difficile infection may be reduced mainly by rationalizing antibiotic therapy and following appropriate procedures.
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http://dx.doi.org/10.32394/pe.74.01DOI Listing
March 2021

Clinical Usefulness of the Inhibitory Control Test (ICT) in the Diagnosis of Minimal Hepatic Encephalopathy.

Int J Environ Res Public Health 2020 05 22;17(10). Epub 2020 May 22.

Department of Infectious Diseases and Hepatology, Medical University of Bialystok, 15-540 Bialystok, Poland.

: Minimal hepatic encephalopathy (MHE) refers to a number of neuropsychiatric and neurophysiological disorders in patients with cirrhosis who do not show abnormalities on physical examination or in clinical tests. The aim of this study was to determine the prevalence, risk factors, and predictive value of minimal hepatic encephalopathy and the usefulness of the inhibitory control test (ICT) in the diagnosis. : Seventy patients (mean age 53 years, range 24-77) with liver cirrhosis were enrolled in the study. MHE was diagnosed based on PHES (psychometric hepatic encephalopathy score) and ICT. PHES and ICT were validated in a group of 56 control subjects. : Minimal hepatic encephalopathy was diagnosed using PHES in 21 patients (30%). ICT diagnosed MHE in 30 patients (42%), and the test had a sensitivity of 65% and a specificity of 57% compared to PHES. The ICT score (lures/target accuracy rate) correlated with the age of subjects (R = 0.35, = 0.002) and only slightly with education (education in years R = -0.22, = 0.06). MHE diagnosed with PHES or ICT was associated with a significantly higher model of end-stage liver disease (MELD) score in the follow-up. MHE diagnosed with ICT was correlated with a significantly higher incidence of symptoms of decompensated cirrhosis ( = 0.02) in the follow-up. : ICT had moderate sensitivity and specificity in diagnosing MHE compared to PHES. Importantly, MHE detected with PHES or ICT was associated with poorer survival and a more severe progression of the disease.
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http://dx.doi.org/10.3390/ijerph17103645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277853PMC
May 2020

Lymphocyte-To-Monocyte Ratio as the Best Simple Predictor of Bacterial Infection in Patients with Liver Cirrhosis.

Int J Environ Res Public Health 2020 03 6;17(5). Epub 2020 Mar 6.

Department of Infectious Diseases, Andrzej Frycz Modrzewski Krakow University, 30-705 Krakow, Poland.

: The aim of this study was to assess the diagnostic performance of new morphology-related indices and Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores during hospitalization in predicting the onset of bacterial infection in patients with liver cirrhosis. : A total of 171 patients (56.9% males; median age 59 years; total number of hospitalizations 209) with liver cirrhosis were included in this observational study. The diagnosis of cirrhosis was made on the basis of clinical, biochemical, ultrasonic, histological, and endoscopic findings. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), modified aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), Fibrosis-4 index (FIB-4), platelet-to-lymphocyte ratio (PLR), neutrophil-to-monocyte ratio (NMR), and CTP and MELD scores were calculated for the cases of patients with cirrhosis. Bacterial infection was diagnosed in 60 of the 209 (28.7%) hospitalizations of patients with cirrhosis. The most common infections were urinary tract infection (UTI), followed by pneumonia and sepsis. The more severe the liver failure, the greater the bacterial infection prevalence and mortality. Patients with decompensated liver cirrhosis were infected more often than subjects with compensated cirrhosis (50.0% vs. 12.9%, = 0.003). The calculated MELD score, CTP, NLR, LMR, AAR, monocyte count, and C-reactive protein (CRP) concentration were also related to the bacterial infection prevalence, and mortality areas under the curve (AUC) were 0.629, 0.687, 0.606, 0.715, 0.610, 0.648, and 0.685, respectively. The combined model with two variables (LMR and CTP) had the best AUC of 0.757. The most common bacteria isolated from patients with UTI were , , and . Gram-negative bacteria were also responsible for spontaneous bacterial peritonitis (SBP), and together with gram-positive and , these microorganisms were isolated from blood cultures of patients with sepsis. Significant differences were found between CTP classification, MELD score, NLR, LMR, AAR, CRP, and PLR in patients with cirrhosis with, or without, bacterial infection. Bacterial infection prevalence is relatively high in patients with liver cirrhosis. Although all analyzed scores, including the LMR, NLR, aspartate aminotransferase (AST)/alanine aminotransferase (ALT), CRP, CTP, and MELD, allowed the prediction of bacterial occurrence, the LMR had the highest clinical utility, according to the area under the curve (AUC) and odds ratio (OR).
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http://dx.doi.org/10.3390/ijerph17051727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084714PMC
March 2020

Actinomycosis - a forgotten chronic infectious disease - case report series.

Przegl Epidemiol 2020 ;74(4):644-651

Actinomycosis is one of the greatest 'chameleons' among infectious diseases. It may imitate inflammation, abscess or a neoplasmatic tumor. Moreover, correct diagnosis is even more challenging due to the fact that the disease takes on various forms like: cervicocephalic, abdominal, or affects the reproductive organs. In order to highlight the diagnostic difficulties of actinomycosis, we have decided to describe six cases of female patients (aged 31-73 years, mean age: 52 years) hospitalized due to actinomycosis in the Department of Infectious Diseases and Hepatology between 2014-2019. Additionally, a case of one patient was described in detail as the course of her disease was exceptionally non-specific. Only in 2 of 6 patients the primary diagnosis was correct. The four other patients were initially suspected with cancer or inflammation. Three of the patients were diagnosed with the abdominal form of actinomycosis, one - neck and head, and one presented both locations. Only histopathological examinations during invasive procedures allowed to state the final diagnosis. An adequate diagnosis was associated with a number of additional tests and delayed appropriate treatment. WBC and CRP were within normal range in all patients. Four patients completed treatment successfully after 60-192 days, one is still on therapy and one is lost to follow-up. In conclusion, common features of actinomycosis presented in this case series include predominance of female gender, abdominal localization and lack of typical symptoms. What is more, therapy with antibiotics, mainly doxycycline and beta-lactams resulted in complete regression of lesions in the majority of cases. Given the examples of our patients we believe that actinomycosis should be considered in the differential diagnosis of all abdominal tumors, especially in women. Abbreviations: WBC - white blood cells, CRP - C-reactive protein, CT - computed tomography, IUD - Intra-Uterine Device, i.v. - intravenous.
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http://dx.doi.org/10.32394/pe.74.55DOI Listing
January 2020

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

Adv Med Sci 2020 Mar 13;65(1):12-17. Epub 2019 Dec 13.

Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Białystok, Poland.

Purpose: Since 2017 treatment-naïve patients infected with genotype 1b of hepatitis C virus and minimal or moderate fibrosis can be treated with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir (OPrD) for 8 weeks according to updated Summary of Product Characteristics. The aim of our study was to assess the comparative efficacy of 8 and 12-weeks therapy with OPrD in large cohort of patients eligible for 8 weeks regimen treated in real-world setting.

Materials And Methods: We analysed data of 3067 HCV genotype 1b infected patients treated with OPrD between 2015 and 2017. Final analysis included patients with none, minimal or moderate fibrosis (F0-F2).

Results: A total of 771 patients were enrolled in the study, including 197 (26%) treated for 8-weeks and 574 patients fulfilling criteria for 8-weeks but assigned to 12-weeks regimen. Majority of patients had no or minimal fibrosis (F0-F1). Longer treatment duration was more often administered in patients with moderate fibrosis, comorbidities, concomitant medications. SVR was achieved in 186 (94%) patients treated for 8 weeks and 558 (97%) for 12 weeks (p = 0.07). After exclusion of lost to follow-up patients, sustained virological response (SVR) rate reached 95% and 99%, respectively (p = 0.01). We were not able to identify factors associated with non-response.

Conclusions: This real-word experience study confirmed similar, high effectiveness of 8 and 12-weeks regimens of OPrD in genotype 1b HCV infected patients with non-advanced fibrosis. Despite of reduced SVR rate after 8-weeks regimen, there is no need to extend therapy to 12-weeks in vast majority of such patients and no need to add ribavirin.
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http://dx.doi.org/10.1016/j.advms.2019.09.002DOI Listing
March 2020

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

J Gastroenterol Hepatol 2020 Jul 16;35(7):1238-1246. Epub 2020 Jan 16.

Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok, Poland.

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.
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http://dx.doi.org/10.1111/jgh.14936DOI Listing
July 2020

Effect of comedication on ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin therapy in chronic hepatitis C - a real-world study.

Clin Exp Hepatol 2019 Sep 5;5(3):215-223. Epub 2019 Sep 5.

Department of Infectious Diseases and Hepatology, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland.

Aim Of The Study: This multicentre study aimed to examine the actual risk for drug-drug interactions in a cohort of Polish patients, and their impact on antiviral therapy.

Material And Methods: Concomitant medications were analyzed in hepatitis C virus (HCV)-infected patients treated with still valuable therapy with OBV/PTV/r ± DSV ± RBV. An established online tool (http://www.hep-druginteractions.org/) was used to assess potential drug interactions. To assess the impact of comedications on virologic outcomes, HCV RNA levels were measured at given time points during and after the treatment. The results were compared between subgroups depending on the number of drugs used.

Results: Among the 209 patients included in this multicentre study, concomitant medications were taken by 140 (67.0%) patients. Modification of treatment due to expected interactions was required in 33 (15.8%) patients, of whom nine (4.3%) had at least one comedication replaced or discontinued. Sustained virologic response rates ranged from 95.1% to 100.0%, and were lowest in patients taking one to five comedications who were null-responders to pegylated interferon or cirrhotic.

Conclusions: Although most HCV-infected patients received concomitant medications, only some required treatment modification. OBV/PTV/r ± DSV ± RBV was effective in all subgroups, irrespective of the number of comedications taken. Multimorbidity and polypharmacy in patients with chronic hepatitis C should not discourage the decision to initiate antiviral therapy, although caution should be exercised for potential drug-drug interactions.
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http://dx.doi.org/10.5114/ceh.2019.87634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781817PMC
September 2019

Prophylaxis of hepatitis B virus (HBV) infection reactivation - recommendations of the Working Group for prevention of HBV reactivation.

Clin Exp Hepatol 2019 Sep 5;5(3):195-202. Epub 2019 Sep 5.

Department of Paediatrics, Haematology and Oncology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland.

Hepatitis B virus (HBV) is one of the main causes of chronic liver diseases and hepatocellular carcinoma. After infection the majority of HBV-infected patients achieve immune control leading to HBV-DNA stabilization at a low level. The risk of HBV reactivation rises significantly when HBV-infected patients receive immunosuppressive treatments. Presented recommendations provide guidelines for management of patients scheduled or undergoing therapies, which through their immunomodulatory activity contribute to the impairment of antiviral immunity, including chemotherapy, immunosuppressive treatment or biological therapy.
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http://dx.doi.org/10.5114/ceh.2019.87631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781818PMC
September 2019

Soluble immune markers in the different phases of chronic hepatitis B virus infection.

Sci Rep 2019 10 1;9(1):14118. Epub 2019 Oct 1.

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.

Chronic hepatitis B virus (HBV) infection may follow four different consecutive phases, which are defined by virology as well as biochemical markers and differ in terms of prognosis and need for antiviral treatment. Currently, host responses reflected by immune markers are not considered in this definition. We aimed to study soluble immune markers and their distribution in different phases of chronic HBV infection. In this cross-sectional retrospective study, we investigated a panel of 14 soluble immune markers (SIM) including CXCL10 in 333 patients with chronic HBV infection. In a small cohort of HBeAg positive patients we analyzed SIM before and after HBeAg seroconversion and compared seroconverters to patients with unknown outcome. Significant differences were documented in the levels of several SIM between the four phases of chronic HBV infection. The most pronounced difference among all investigated SIM was observed for CXCL10 concentrations with highest levels in patients with hepatitis. TGF-β and IL-17 revealed different levels between HBeAg negative patients. HBeAg positive patients with HBeAg seroconversion presented higher amounts of IL-12 before seroconversion compared to HBeAg positive patients with unknown follow up. SIM such as CXCL10 but also IL-12, TGF-β and IL-17 may be useful markers to further characterize the phase of chronic HBV infection.
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http://dx.doi.org/10.1038/s41598-019-50729-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773856PMC
October 2019