Real life results of direct acting antiviral therapy for HCV infection in HIV-HCV-coinfected patients: Epi-Ter2 study.

The aim of this study was to evaluate the baseline demographics and real-life efficacy of direct acting antivirals (DAAs) in HIV-HCV-positive patients as compared to patients with HCV monoinfection. The analysis included 5690 subjects who were treated with DAAs: 5533 were HCV-positive and 157 were HIV-HCV-positive. Patients with HCV-monoinfection were older (p < .0001) and in HIV-HCV group there were more men (p < .0001). Prevalence of genotype 1a (p = .002), as well as of genotypes 3 and 4 (p < .0001) was higher in HIV-HCV-coinfected patients. Genotype 1b was more frequent (p < .0001) in the HCV-mono-infection group. Patients with HCV-monoinfection had a higher proportion of fibrosis F4 (p = .0004) and lower proportion of fibrosis F2 (p < .0001). HIV-HCV-coinfected individuals were more often treatment-naïve (p < .0001). Rates of sustained viral response after 12 weeks did not differ significantly between both groups (95.9% versus 97.3% in coinfection and monoinfection group, respectively; p > .05). They were, however, influenced by HCV genotype (p < .0001), stage of hepatic fibrosis (p < .0001), male sex (p < .0001), BMI (p = .0001) and treatment regimen modifications (p < .0001). Although factors associated with worse response to therapy (male sex, genotype 3) occurred more often in the HIV coinfection group, real-life results of DAAs did not differ significantly between both populations.

Durability of virologic response, risk of de novo hepatocellular carcinoma, liver function and stiffness 2 years after treatment with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin in the AMBER, real-world experience study.

We followed for 2 years patients treated with direct-acting agents (DAA) to assess long-term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator-initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2-year follow-up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child-Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post-treatment follow-up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2-year follow-up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2-year monitoring for possible disease progression.

Treatment of HCV infection in Poland at the beginning of the interferon-free era-the EpiTer-2 study.

The aim of the EpiTer-2 study was to analyse patient characteristics and their medication for HCV infection in Poland at the beginning of the interferon-free era. Analysis of data of HCV infected patients treated during the initial period of availability of interferon-free regimens in Poland, who started therapy after 1 July 2015 and had available an efficacy evaluation report before 30 June 2017 was undertaken. A total of 2879 patients with chronic hepatitis C were entered, including 46% with liver cirrhosis. The most common was genotype 1b (86.8%). The study population was gender balanced, the majority of patients were overweight or obese and 69% presented comorbidities, with the highest prevalence that for hypertension. More than half of patients were retreated due to failure of previous therapy with pegylated interferon and ribavirin. Almost two-third of patients received current therapy with ombitasvir/paritaprevir/ritonavir±dasabuvir (OPrD) ±ribavirin. Other patients received mostly sofosbuvir-based regimens including combination with ledipasvir and pegylated interferon and ribavirin for genotype 3-infected patients. Efficacy of treatment in the whole study population measured as intent-to-treat analysis was 95%. The most frequent regimen, administered for patients infected with genotype 1b, was 12 weeks of OPrD, resulting in an SVR rate of 98%. At least one adverse event was reported in 38% of patients, and the death rate was 0.8%. In conclusion, data from the EpiTer-2 study confirmed the excellent efficacy and safety profile of the real-world experience with recently introduced therapeutic options for genotype 1 HCV infection, but demonstrated weakness of the current therapeutic programme regarding genotype 3 infections.

Hepatitis C virus core antigen as a possible alternative for evaluation of treatment effectiveness after treatment with direct-acting antivirals.

Background: Chronic hepatitis C is a major public health problem around the world. In monitoring treatment efficacy, although costly and labour-intensive methods of molecular biology are often used, much cheaper and technically easier serological methods evaluating the concentration of HCV core antigen in serum are available. We evaluated HCVcAg quantification as a possible assessment of the treatment efficacy instead of HCV RNA quantification.Methods: We collected 514 serum samples from treated HCV infected patients. Quantitative evaluation of HCV RNA and HCVcAg was carried out before treatment, at the end of treatment, and at least 12 weeks following treatment termination. HCV RNA was determined by automated assay (Roche COBAS) and HCVcAg quantitation with ARCHITECT ci8200 analyser.Results: There was a significant correlation between HCVcAg and HCV RNA concentrations at baseline and follow-up visits, but not at the end of treatment. Among samples collected before the treatment, at the end of treatment and follow-up visit, concordance of HCV RNA and HCVcAg reached level of 98.1%, 98.9% and 98.7%, respectively. Diagnostic sensitivity, specificity, positive and negative predictive values of HCVcAg detection were >97%.Conclusions: HCVcAg measurement could be an alternative for determining HCV treatment efficacy after chemotherapy and could be an option in the diagnosis of HCV infection.

Real-world effectiveness and safety of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C: AMBER study.

BACKGROUND: Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies. AIM: To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions. METHODS: Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT. RESULTS: A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients. CONCLUSIONS: The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.

Epizootic situation and risk of rabies exposure in Polish population in 2000, with special attention to Lublin province.

In Poland in 2000 a total of 2,221 cases of animal rabies were reported, including 1,874 (84.4%) of wild animals. The evaluation of epizootic situation in 2000 has shown a few cases of animal rabies in western provinces of Poland, so in regions where a programme aimed at oral vaccination of foxes was introduced. Most cases of animal rabies were identified in the northeastern region, as well as in eastern and central Poland. In October 2000 in Warminsko-Mazurskie province (northeastern region of Poland) rabies was responsible for the death of 59-year-old woman, bitten by a rabid cat, and refused post-exposure specific antirabies prophylaxis. Among domestic animals, the highest incidence of rabies occurred in cattle--167 cases (7.5%), cats--113 (5.1%) and dogs--61 (2.7%). In the group of wild animals, red foxes accounted for 1,587 (71.5%) cases, raccoon dogs for 210 (9.5%) and martens for 36 (1.6%). People have been vaccinated against rabies in all provinces of Poland. The number of people vaccinated against rabies in regions adjoining the western border was much smaller compared to other provinces of Poland. The highest rates of using post-exposure prophylaxis occurred in northeastern regions of Poland (Warminsko-Mazurskie province) and eastern and central parts of Poland. On the basis of analysis of cases consulted in the dispensary of rabies prophylaxis in the Department of Infectious Diseases in Lublin, it can be concluded that the number of people with exposure to rabid animals is rather small. Most vaccinations are carried out when animals suspected of being rabid bite patients. These are primarily domestic animals--dogs and cats.

[Anti-Hbs level after the basic course of vaccination against hepatitis B in health care workers]. / Poziom przeciwcial anty-HBs u pracowników sluzby zdrowia po szczepieniu przeciwko wirusowemu zapaleniu watroby typu B.

Health care workers are the group at high hepatitis B virus (HBV) infection risk. Groups of physicians and nurses working in hospitals of Lublin have been vaccinated since 1989. The aim of this work was to assess the level of anti-HBs in different years after the basic course of vaccination. We have examined 166 persons, aged from 18 to 65 years, vaccinated with a yeast recombinant hepatitis B vaccine Engerix B (Smith Kline Biologicals). They completed the full cycle of vaccination according to the pattern of 0, 1, 6 months. Within the group of people who had got the third dose one year ago we found 100% of women and 88% of men with a protective level of anti-HBs (> or = 10 IU/l). Four years after the final inoculation differences between female and male population were even more significant: 93% of man had a protective level of anti-HBs. We have also found that humoral response was higher in the group of younger vaccinees (18-40 years). We propose that timing of booster vaccination should be scheduled on the basis of anti-HBs level. It seems to be necessary to control the level of anti-HBs at least 3 years after the last dose of vaccination.

[Beta 2-microglobulin in serum of patients with infectious mononucleosis]. / Beta 2-mikroglobulina w surowicy chorych na mononukleoze zakazna.

Serum beta 2-microglobulin concentrations were assayed in twenty patients with infectious mononucleosis. Pairs of sera taken from each patient in the first week of hospitalisation and two weeks later were tested. There was a significant increase of beta 2-microglobulin levels in these patients compared to the control group. A raised serum beta 2-microglobulin concentration persists during the convalescent period.

[Level of beta 2-microglobulin in serum of patients with acute viral hepatitis types A, B and C]. / Poziom beta 2-mikroglobuliny w surowicy krwi chorych na ostre wirusowe zapalenia watroby typów A, B i C.

Serum beta 2-microglobulin concentrations were assayed in 14 patients with acute hepatitis A, 16 with acute hepatitis B and 10 with hepatitis C. Serum samples were taken from each patient in the first and the second week of hospitalization and in the period of aminotransferase normalization. There was a significant increase of beta 2-microglobulin level in every type of hepatitis compared to the control group. A raised serum beta 2-microglobulin concentration persisted during convalescent period. It decreased gradually in type A and B of hepatitis. Serum beta 2-microglobulin level during convalescence in hepatitis C was similar to that of first weeks of hospitalization.

[Levels of soluble intracellular adhesion molecules 1 (sICAM-1) , soluble receptors for interleukin 2 (sIL-2R) and anti-Epstein-Barr viral capsid antigen (anti-VCA IgM) in blood serum during the course of infectious mononucleosis]. / Stezenie rozpuszczalnej czastki adhezji miedzykomórkowej 1 (sICAM-1) i rozpuszczalnego receptora dla interleukiny 2 (sIL-2R) oraz poziom przeciwcial przeciwko antygenowi kapsydowemu ebv (anty-VCA IgM) w surowicy krwi w przebiegu mononukleozy zakaznej.

The clinical picture of infectious mononucleosis and the consequences of EBV infection are due to immune response mechanisms. The level of soluble form of IL-2 receptor (sIL-2R) is thought to be a marker of T-cell activity, especially CD8+. Intercellular adhesion molecule (ICAM-1, CD 54) plays an important role in the process of antigen presentation. The aim of this study was to assess the serum concentration of sIL-2R, ICAM-1 and anti-VCA IgM in patients with infectious mononucleosis. The study group comprised 42 persons: 20 healthy subjects as a control group and 22 individuals with infectious mononucleosis. The highest anti-VCA IgM serum level in all patients was during the 1st day of hospitalization, and decreased in the 8th day of hospitalization. The lowest antibody concentration was observed when the symptoms and sings ceased. The level of sIL-2R was significantly increased and during farther hospitalization we observed lower, but still elevated concentrations. Our study has demonstrated statistically significant elevation of sICAM-1 level during the entire period of hospitalization. This data indicates the importance of antigen presentation process. Although the serum concentration of immune response mediators does not reflect their contents in organism, but is a useful method for in vivo examination.

Facial Cutaneous Anthrax in a Pregnant Woman: a Case Report.

Anthrax remains an uncommon, but worldwide problem, particularly in countries in which domestic animals and processing of animal by-products are an important part of the economy. The disease has received attention recently because of its potential for use in biologic warfare. In Poland during the last 10 years, several human cases of cutaneous anthrax occurred. We report here a case of a pregnant woman with this disease. The lesion was atypical and in a potentially dangerous location since it was on the upper part of the face; a site which could be associated wth either respiratory or central nervous system complications. The patient recovered without complication after antibiotic treatment and local surgery. The fetus and the subsequent labor and delivery were not affected. The case is presented as a reminder of the continued presence of this disease, of the need for attention to its special clinical signs and symptoms, of the need to supervise the agriculture and textile industries, such as by use of vaccines when appropriate, and of the increased concern about this disease in regard to biologic warfare.