Changes in Inflammatory Markers after Administration of Tocilizumab in COVID-19: A Single-Center Retrospective Study.

The COVID-19 pandemic requires the development of effective methods for the treatment of severe cases. We aimed to describe clinical outcomes and changes in inflammatory markers in Polish patients treated with tocilizumab. The medical charts of SARS-CoV-2-positive patients treated in the Department of Infectious Diseases between 4 March and 2 September 2020 were retrospectively analyzed. The patients who received tocilizumab according to the Polish Association of Epidemiologists and Infectiologists guidelines were selected for the study. We identified 29 individuals who received tocilizumab, out of whom 11 (37.9%) died. The individuals who died had significantly higher maximal interleukin-6 (IL-6) and lactate dehydrogenase (LDH) serum levels than survivors. After administration of tocilizumab, further increase in LDH and IL-6 was a prognostic factor for unfavorable outcomes. Among inflammatory markers, 7-day mean of IL-6 serum concentration was the best predictor of death (cut-off: ≥417 pg/mL; area under ROC curve = 0.81 [95% Confidence Interval: 0.63-0.98]). The serum concentrations of inflammatory markers before administration of tocilizumab did not predict the outcome, whereas IL-6 and LDH measurements after administration of tocilizumab seemed to be of predictive value.

Exposure to hepatitis E virus in hemodialysis patients from west-central Poland.

Hepatitis E virus (HEV) causes travel-related but also locally acquired infections in industrialized parts of the world, including European countries. Food and blood transfusions are possible sources of transmission. Infections caused by zoonotic variants of the virus (particularly HEV-3) may progress to chronic liver disease in a nonnegligible proportion of immunocompromised people. The aim of this study was to assess the prevalence of serological markers of HEV infection in 189 patients on renal replacement therapy (RRT, currently on hemodialysis, HD) living in west-central Poland and to determine the factors related to HEV exposure in this group. Testing was carried out using commonly used commercial assays (Wantai Biological Pharmacy Enterprise Co, Beijing, China). Anti-HEV IgG was detected in 94 patients (49.7%); none of the participants had anti-HEV IgM or HEV Ag. Patients on RRT (HD) for less than 6 months were significantly more likely to be anti-HEV IgG-positive than dependent of RRT (HD) for more than half a year (80% vs 47%; P = .014). Exposure to HEV in patients from west-central Poland is frequent, but no clear sources of this infection have been identified. There were no serological features of ongoing liver disease caused by HEV in the study subjects.

Circulating interferon-λ3 and post-vaccination antibodies against the surface antigen of hepatitis B virus in hemodialysis patients exposed to hepatitis E virus.

Responsiveness to the hepatitis B virus (HBV) vaccination in hemodialysis (HD) patients who had been exposed to the hepatitis E virus (HEV) and persistently generate antibodies against HEV remains unknown. Interferon (IFN)-λ3 positively correlates with the surface HBV antibodies (anti-HBs) in both healthy and HD subjects. We aimed to show whether HD patients differ in circulating IFN-λ3 and vaccine-induced anti-HBs titers concerning natural HEV immunization. HBV/HCV negative HD patients (31 HEV IgG positive, 45 HEV negative), HBV vaccinated and receiving booster doses as needed, had been tested for anti-HBs titers (CMIA) and IFN-λ3 concentrations (ELISA) in the blood collected before a dialysis session. There were no differences in circulating IFN-λ3 and anti-HBs titers between both groups. In responders to the HBV vaccine, there was a positive correlation between plasma IFN-λ3 levels and anti-HBs titers (r = 0.505, adjusted P = 0.01 in HEV exposed subjects; r = 0.523, adjusted P = 0.001 in controls). HEV past infection does not attenuate post-vaccination anti-HBs generation and does not influence a correlation between circulating IFN-λ3 levels and anti-HBs titers.

Comparative Seroprevalence of Hepatitis A And E Viruses in Blood Donors from Wielkopolska Region, West-Central Poland.

The objective of the present study was to investigate the seroprevalence of HAV and HEV in Polish blood donors (BDs). One hundred and ten randomly selected healthy BDs, living in Wielkopolska Region were tested for anti-HAV IgG and anti-HEV IgG with commercial assays. The seroprevalence of anti-HAV was 11.8%; anti-HEV were detected in 60.9% of BDs (p < 0.0001). Consumption of risky food was more common in anti-HEV-positive BDs (59.1% vs. 33.3%; p = 0.01). Twelve out of 20 BDs (60%) with no history of travel abroad were exposed to HEV. Wielkopolska Region, Poland should be regarded as a new HEV infection-hyperendemic area in Europe.

Interferon­λ4 gene polymorphisms, circulating interferon λ3, and clinical variables in hemodialysis patients exposed to hepatitis E virus.

Introduction Factors associated with hepatitis E virus (HEV) infection are rarely recognized in patients on renal replacement therapy (RRT), and the results of studies are inconsistent. Objectives We aimed to search for determinants of HEV seroprevalence among polymorphisms of the interferon­λ4 gene (IFNL4) associated with seroclearance of hepatotropic viruses (IFNL4 rs12979860, rs8099917 near IFNL4), circulating interferon λ3 (IFN­λ3), and clinical variables of patients treated with hemodialysis (HD) in a HEV­endemic region. Patients and methods The study was carried out in 90 HD patients. HEV open reading frame 2 antigen (HEV Ag), immunoglobulin M and G antibodies to HEV (anti­HEV IgM and anti­HEV IgG, respectively) and IFN­λ3 were tested, and IFNL4 polymorphic variants (rs8099917, rs12979860) were genotyped. Survival analysis was conducted concerning anti­HEV IgG positivity. Results In the study group, there were 37.8% anti­HEV IgG­positive subjects. None was HEV Ag or anti­HEV IgM positive. HD modalities utilizing high­flux dialyzers (adjusted odds ratio [OR], 3.586; 95% confidence interval [CI], 1.142-11.263; P = 0.03) as well as major homozygosity in rs8099917 (adjusted OR, 4.933; 95% CI, 1.516-16.054; P = 0.008) and rs12979860 (adjusted OR, 3.537; 95% CI, 1.136-11.014, P = 0.03), but not circulating IFN­λ3 levels, were positive determinants of anti­HEV IgG positivity. Liver enzyme activities and C­reactive protein levels tested as response variables to HEV exposure, as well as survival probability, were not different between patients stratified by anti­HEV IgG positivity. Conclusions Among HD patients, IFNL4 polymorphisms and treatment with high­flux HD are explanatory variables for isolated anti­HEV IgG positivity indicating spontaneous HEV resolution.

Exposure to hepatitis E virus, hepatitis A virus and Borrelia spp. infections in forest rangers from a single forest district in western Poland.

BACKGROUND: Hepatitis E virus (HEV) infection is an emerging problem in developed countries. At least 2 zoonotic genotypes of the virus (HEV-3 and HEV-4) infect human beings. There are some data suggesting that forest rangers (FRs) can be at a higher risk of contact with HEV. OBJECTIVES: The aim of this study was to assess the prevalence of HEV exposure markers in FRs from a single forest district in Greater Poland in relation to anti-HAV (hepatitis A virus) IgG, and anti-Borrelia spp. IgM and IgG antibodies. MATERIAL AND METHODS: In total, 138 participants (48 FRs and 90 blood donors - BDs) were tested for anti-HEV IgM and IgG (EUROIMMUN Medizinische Labordiagnostika AG, Luebeck, Germany) and 96 individuals (48 FRs and 48 BDs) were tested for anti-HAV IgG (ARCHITECT immunoassays, Abbott Laboratories, Wiesbaden, Germany); anti-Borrelia IgM and IgG (EUROIMMUN kits) were assessed in FRs only. RESULTS: Anti-HEV markers were detected in 3 participants (2.2%; IgM in 1 FR, IgG in 2 BDs), less frequently than anti-HAV (16 out of 96 individuals, about 17%; FRs 19% vs BDs 15%) or anti-Borrelia antibodies (18 out of 48 individuals, 37.5%) (p < 0.0001 for both). Older study participants (≥45 years of age) were more frequently HAV-seropositive (29% vs 4% of the younger individuals; p = 0.0012). CONCLUSIONS: We failed to unequivocally prove HEV exposure in FRs. The HAV seroprevalence in this study paralleled the situation in the general population. Exposure to Borrelia spp. in FRs was common.

Underestimation of hepatitis E virus seroprevalence in soldiers from the Polish Special Forces.

No abstract.

Hepatitis E virus antibodies in HIV-infected patients and blood donors from western Poland: A preliminary report.

BACKGROUND: Hepatitis E virus (HEV) infection is an emerging problem in industrialized countries, including Europe. Little data exists on HEV seroprevalence in Poland. OBJECTIVES: The aim of this study was to assess the prevalence of anti-HEV IgG antibodies in Polish patients infected with the human immunodeficiency virus (HIV) and blood donors. MATERIAL AND METHODS: Two hundred and ten individuals (n = 105 of HIV-infected patients and n = 105 of ageand sex-matched blood donors from the same area; 178 men and 32 women), aged 18-50 (median age: 38 years), were tested for the presence of anti-HEV IgG antibodies with the EUROIMMUN Anti-Hepatitis E Virus (HEV) ELISA (IgG) tests (Lübeck, Germany). Additionally, some simple clinical and laboratory data was collected. RESULTS: The overall anti-HEV IgG prevalence was 2.4% (5/210). One HIV-positive patient (0.95%) and 4 blood donors (3.8%) were seropositive (p = 0.1745). All the HEV-exposed individuals were men with a history of travel abroad and no icteric disease in the past. CONCLUSIONS: Exposure to HEV infection among Polish HIV patients and blood donors seems to be uncommon. Data on this issue is scarce and conflicting for HIV-infected individuals. Further investigations applying different serological tests and concomitant HEV RNA testing are needed to reliably assess the risk and practical impact of HEV infection in Poland.

Hepatitis E virus IgG seroprevalence in HIV patients and blood donors, west-central Poland.

OBJECTIVE: To assess hepatitis E virus (HEV) seroprevalence in HIV patients and blood donors from one region in Poland. METHODS: A group of 490 persons (244 HIV patients and 246 blood donors) aged 18-55 years were examined using the anti-HEV IgG assay (Wantai Biological Pharmacy Enterprise, Beijing, China). An analysis of the association between certain factors and the presence of this HEV exposure marker was conducted in both groups. RESULTS: An HEV seropositivity rate of 50.2% was found. There was no difference in HEV seroprevalence between blood donors (49.6%, 122/246) and HIV patients (50.8%, 124/244) (p=0.569). The anti-HEV IgG positivity rate increased with age as follows: 36.2% (59/163) in persons aged 18-30 years, 52.0% (92/177) in individuals aged 31-40 years and 63.3% (95/150) in those aged 41-55 years. HEV infection occurred in 56.4% (31/55) of people who had never travelled abroad. CONCLUSIONS: Wielkopolska Region in west-central Poland is an area hyperendemic for HEV infection. In this part of Poland, the exposure of HIV-positive persons to this virus is not greater than that of healthy blood donors.

Genetic (KIR, HLA-C) and Some Clinical Parameters Influencing the Level of Liver Enzymes and Early Virologic Response in Patients with Chronic Hepatitis C.

Natural killer cells play an important role as effectors of innate immunity and regulators of adaptive immunity. They are important elements of the innate response to viral infections, which they detect using human leukocyte antigen (HLA) class I-binding receptors. Most polymorphic of these are killer cell immunoglobulin-like receptors (KIRs) which exist as two basic isotypes, activating or inhibitory receptors and are encoded by genes distributed differently in unrelated individuals. We searched for links between selected clinical data (including HCV viremia, liver enzymes level and liver histology parameters) and the presence of genes encoding these receptors and their ligands in hepatitis C virus-infected individuals subjected to pegylated interferon-α and ribavirin therapy. Genomic DNA samples from two hundred and ninety-two chronically infected patients were typed by polymerase chain reaction for the presence or absence of genes for KIRs and their ligands, class I HLA molecules, and clinical data of the patients were collected. Our results suggest an importance of clinical parameters and the contribution of KIR and HLA genes to the course of hepatitis C virus infection and the response to therapy. The study revealed that levels of liver enzymes before therapy were about 30% higher in patients who possessed a variant KIR2DS4 gene with 22-base pair deletion. Decrease of ALT activity after treatment was higher in HLA-C C2-positive than negative individuals. Beside it, patients demonstrated early virologic response to the therapy if the time lag before treatment was short, particularly in women.

Seroprevalence of anti-HEV IgG in 182 Polish patients.

INTRODUCTION: Hepatitis E virus (HEV) infection is an emergent disease in developed countries. HEV seroprevalence in such areas significantly exceeds values expected when one considers infection with this virus only as a problem restricted to classical endemic regions. To date, no related data are available in Poland. In this study we aimed to obtain HEV seroprevalence data and compare them with similar data for hepatitis A virus (HAV) in Polish patients. MATERIAL/METHODS: From February 1st, 2013, to October 15th, 2013, we performed anti-HEV IgG (anti-HEV) tests (EIAgen HEV IgG Kit; Adaltis, Milano, Italy) in 182 patients (101 men and 81 women; 61 patients were HIV-positive) of one center in Poland, aged 19-85 (47.2 ± 14.2 years). RESULTS: We found a 15.9% seropositivity rate for anti-HEV (16.3% of the study population with an unequivocal test result) and 38.5% for anti-HAV. In 6 cases (3.4%), anti-HEV-positive persons had never travelled abroad. In contrast to HAV seroprevalence data, there was no significant difference in HEV seroprevalence between young adults (18-40 years) and older patients (p<0.0001 and p=0.0967, respectively). Anti-HEV were found in 21.3% of HIV-infected individuals. CONCLUSIONS: HEV infection may occur in Poland. Anti-HAV seropositivity among Polish patients is significantly higher than anti-HEV. In contrast to HAV, HEV seroprevalence is similar in younger and older patients. The clinical course of HEV infection in Polish citizens seems to be largely asymptomatic. Polish HIV patients may be more commonly exposed to HEV than similar individuals from other countries.

Contribution of genes for killer cell immunoglobulin-like receptors (KIR) to the susceptibility to chronic hepatitis C virus infection and to viremia.

BACKGROUND: Natural killer (NK) cells are an important element of innate immunity against viruses, although their numbers decrease in the liver during chronic HCV infection. NK cells express a large panel of inhibitory and activating receptors. The most polymorphic of these are killer cell immunoglobulin-like receptors (KIRs) which are encoded by multiple genes that may be present or absent in given individuals depending on their genotype. This variability results in differential susceptibility to viral infections and diseases, including HCV infection and its consequences. AIMS AND METHODS: The aim of this study was to test whether chronical infection with HCV and the viremia levels are associated with any KIR gene in the Polish population. We typed 301 chronically HCV-infected patients and 425 non-infected healthy individuals for the presence or absence of KIR genes and their ligands, HLA-C C1 and C2 groups as well as HLA-B and HLA-A Bw4-positive alleles. RESULTS: We found that males, but not females, possessing KIR2DS2 and KIR2DL2 genes had a 1.7 higher probability to become chronically HCV-infected than males negative for these genes (p=0.0213). In accord with this, centromeric B region, containing KIR2DS2 and KIR2DL2 genes, was also associated with chronic HCV infection in males. In addition, patients of both genders possessing KIR2DS3 but not KIR2DS5 gene exhibited, on average, 2.6 lower level of viremia than HCV-infected individuals with other genotypes (p=0.00282). This was evident in those infected at a young age. KIR2DS3-positive patients also had lower mean levels of bilirubin than KIR2DS3-negative ones (p=0.02862). CONCLUSION: Our results suggest a contribution of the KIR2DS2 and KIR2DL2 genes (cenB haplotype) to the susceptibility to chronic HCV infection, and an association of the KIR2DS3 gene in the absence of KIR2DS5 with low viremia levels.

Viral Hepatitis A in 108 Adult Patients During an Eight-Year Observation at a Single Center in Poland.

BACKGROUND: Hepatitis A is related to significant morbidity and occasional mortality. Based on data from the Polish National Institute of Hygiene, from 2000 to 2013 a mean of 213 hepatitis A cases were reported yearly. OBJECTIVES: The aim of the study was to assess selected data in adults hospitalized for symptomatic hepatitis A during an eight-year period in a single center in the Wielkopolska Region of Poland. MATERIAL AND METHODS: All the hepatitis A patients hospitalized in the center from 2005 to 2013 were analyzed retrospectively. Data were extracted from the medical records of these individuals. The disease was confirmed by anti-HAV IgM testing. RESULTS: In total, 108 patients (71 men and 37 women), aged 18-65 years, were identified. All but 1 patient recovered (99.1%) and in 6 cases (5.6%) a relapse occurred. Risk factors for hepatitis A were identified in 56 patients (52%), with travel abroad being the most common one (32 patients); 19 cases were secondary and 5 patients were men who have sex with men. One hepatitis A outbreak was noted in the region during the study period. Acalculous cholecystitis was found in 33.3% of the patients who underwent abdominal ultrasound. This tended to be more common among older individuals (47.8% in patients over 40 vs. 22.6% in patients aged 18-40, p=0.0521). Patients with this finding had significantly higher mean peak ALT in comparison to those with no gallbladder abnormalities. CONCLUSIONS: Although hepatitis A in adults is typically a benign, self-limited disease, it can occasionally have a fatal course. In a significant proportion of patients with an evident risk factor for hepatitis A, the possibility of active prophylaxis was not used. Hepatitis A should be regarded as a sexually transmitted infection. Acalculous cholecystitis is a frequent finding among adults with symptomatic hepatitis A.

[Clinical outcomes of superinfections with primary hepatotropic viruses in patients with chronic hepatitis B or C]. / Nastepstwa kliniczne nadkazen wirusami pierwotnie hepatotropowymi u chorych na przewlekle zapalenia watroby typu B lub C.

Chronic hepatitis B and C are among most important problems in contemporary hepatology. Natural history of the disease can be changed as a result of superinfection with other primary hepatotropic viruses. Clinical consequences of such events are uncommon subjects of clinical reports. Acute viral hepatitis occurring in HBV- or HCV-infected patients can result in severe exacerbation of liver disease, including acute liver failure; sometimes progression of liver disease toward liver cirrhosis is observed; HBV and/or HCV clearance is also possible. Because of potentially severe outcomes of superinfections, prevention of such events based on vaccinations and education about the risk related with additional infections should be implemented in the management of patients with chronic viral hepatitis B and C.

Results of antiviral treatment of patients with chronic hepatitis C: experience of Poznan centre.

INTRODUCTION: Hepatitis C virus (HCV) infection in Poland affects approximately 750 thousand persons. The prevention of cirrhosis and hepatocellular carcinoma, of which approximately 20% of patients with chronic hepatitis C virus are at risk, aims at eradication of the virus by applying antiviral treatment with pegylated interferon alpha with ribavirin. MATERIAL/METHODS: In this paper the results of the standard treatment of chronic hepatitis C in a population of 169 adult patients in whom it was started in the period of 01.01.2007-30.06.2008 are analyzed. Moreover, the influence of various clinical, biochemical and viral factors on achieving therapeutic success in the form of the sustained virological response (SVR) was studied. RESULTS: In the group of 128 patients who received the full course of antiviral treatment, the SVR was achieved by 67.2% of patients (86 persons), whereas regarding all 169 patients who started the therapy, the sustained disappearance of viremia was found in 53.2% of patients (90 persons). Regarding 155 persons in whom the treatment was not interrupted for reasons others than virology, this value was 55.5%. For the sustained disappearance of viremia the following was favorable: genotype 3 virus, age under 40 years, body mass up to 75 kg, correct value of body mass index (BMI), low gamma-glutamyl transpeptidase (GGTP) activity before the treatment, minimum advancement of liver fibrosis in a liver biopsy (S1), complete early biochemical response (cEBR), and moreover, the achievement of negation of viremia after 12 weeks of the treatment in a group of patients infected with genotype 1 (complete early virological response, cEVR). These factors were strongly correlated with each other and that is why an analysis by the method of logistic multiple regression was impossible. Adverse reactions to the treatment and other health problems were the reasons for earlier discontinuation of the standard therapeutic scheme in 14 patients, whereby the lack of an SVR occurred in 10 of them (71.5% which is 5.9% of the studied population).

Seroprevalence of hepatitis A virus antibodies (anti-HAV) in adult inhabitants of Wielkopolska region, Poland--the role of simple demographic factors.

INTRODUCTION AND OBJECTIVE: Based on the available epidemiologic data, Poland currently has the features typical for areas of very low endemicity for hepatitis A. The incidence of hepatitis A in the Wielkopolska region in years 2006-2008 was 0.68/100,000 inhabitants or significantly lower. The aim of this cross-sectional analysis was to evaluate the seroprevalence of anti-HAV antibodies in inhabitants of the Wielkopolska region of western Poland regarding some demographic factors. MATERIAL AND METHODS: In addition to testing anti-HAV antibodies, the medical history and demographic data, such as age, gender, place of residence, and level of education of 680 patients and 105 healthy blood donors were analyzed. RESULTS: Anti-HAV antibodies were observed in 235 cases (29.9%). In univariate regression analysis, the covariates correlated with positive anti-HAV testing were age, female gender and lower level of education. Only 6.2% of young adults were seropositive. Among study participants above the age of 50, anti-HAV antibodies were present in 64-100% of cases. An icteric disease consistent with hepatitis A diagnosis was identified in the histories of 10.2% of seropositive patients. CONCLUSIONS: The risk for contracting disease after exposure to HAV in young (<40 years old) inhabitants of the Wielkopolska region is high. Apart from older individuals, also women and people with a lower level of education are more frequently seropositive. A low level of immunity to HAV should be an indication for vaccination against HAV , especially in selected groups.