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.

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.

Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland.

Over the past two decades Clostridium difficile infection (CDI) has appeared as a major public health threat. We performed a retrospective study based on the records of patients hospitalized for CDI at the University Hospital in Krakow, Poland, between 2008 and 2014. In the study period, CDI occurred in 1009 individuals. There were 790 (78%) individuals who developed infection only once, whereas 219 (22%) developed infection more than once. The percentage of deaths within 14 days of CDI confirmation was 2·4%, with a mean age of 74·2 ± 15·9 years. Crude mortality was 12·9% in medical wards, 5·6% for surgical wards and 27·7% in the ICU setting. The time span between diagnosis and death was 5·1 days on average. Between 2008 and 2012 a 6·5-fold increase of CDI frequency with a posterior stabilization and even reduction in 2013 and 2014 was observed. According to the data analysed, 2/3 patients in our population developed CDI during their hospitalization even though they were admitted for different reasons. Medical wards pose a significantly higher risk of CDI than the surgical ones. Age is a risk factor for CDI recurrence. In the case of patients who died, death occurred shortly after diagnosis. The first CDI episode poses much higher risk of mortality than the consecutive ones.

Clostridium difficile the hospital plague.

Clostridium difficile infection (CDI) has become one of the major public health threats in the last two decades. An increase has been observed not only in the rate of CDI, but also in its severity and mortality. Symptoms caused by this pathogen are accompanied by intense local and systemic inflammation. We confirmed that Raman microspectroscopy can help us in understanding CDI pathogenesis. A single erythrocyte of patients with CDI shows a difference, approximately 10 times, in the intensity of the Raman spectra at the beginning of hospitalization and after one week of treatment. The intensity level is an indicator of the spread of the inflammation within the cell, confirmed by standard laboratory tests. Many of the observed bands with enormously enhanced intensity, e.g. 1587, 1344, 1253, 1118 and 664 cm(-1), come from the symmetric vibration of the pyrrole ring. Heme variation of recovered cells in the acute CDI state between the first and the seventh day of treatment seems to show increased levels of oxygenated hemoglobin. Intense inflammation alters the conformation of the protein which is reflected in the significant changes in the amide I, II and III bands. There is an observed shift and a significant intensity increase of 1253 and 970 cm(-1) amide III and skeletal protein backbone CC stretching vibration bands, respectively. Principal Component Analysis (PCA) was used to find the variance in the data collected on the first and seventh day. PC2 loading in the 1645-1500 cm(-1) range shows an increase of heme, Tyr, Trp, or Phe vibrations because of changes in the protein microenvironment due to their exposure. Positive maxima at 1621, 1563 and 1550 in the PC2 loading originated from the ring vibrations. These observations indicate that Clostridium difficile toxins induce cytopathogenicity by altering cellular proteins.

The role of local and systemic cytokines in patients infected with Clostridium difficile.

It is widely accepted that the pathogenesis of Clostridium difficile infection (CDI) is multifactorial, dependent on pathogen virulence factors produced by the organism as well as disorders of the gastrointestinal tract, the alteration in intestinal flora and the immune response of the host. In particular, the immune response in the course of CDI and the involvement of cytokines in the pathogenesis of CDI is not fully understood. The aim of our study was to evaluate the relationship between proinflammatory and anti-inflammatory cytokines and the course of CDI in vivo. We prospectively studied 80 patients. Our study group included 40 patients aged 30-87 years (mean age 66.9 years) with CDI hospitalized at Infectious Diseases Department and Gastroenterology and Hepatology Clinic, University Hospital in Cracow, and 40 healthy volunteers aged 24-62 years (mean age 51.1 years). The serum concentrations of cytokines IL-1ß, IL-6, IL-8, IL-10, tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and prostaglandin E2 (PGE2) were measured using ELISA assays. Additionally, the routine biochemical parameters were assessed including the following: white blood cells with differential leukocyte count, platelets counts, and blood plasma levels of creatinine, alanine transaminase, and C-reactive protein were determined. We noted a significant increase in the concentration of the following cytokines in the CDI group when compared to the control group: IL-1b (4.7 vs. 3.6 pg/ml), IL-6 (21.0 vs. 0.04 pg/ml), IL-10 (8.5 vs. 0.5 pg/ml), TNF-α (7.1 vs. 0.09 pg/ml). In addition the serum concentration of MPO (1056.0 vs. 498.0 pg/ml), and PGE2 (2036.7 vs. 1492.0 pg/ml) showed a significant increase in CDI patients as compared with control subjects. Most CDI patients did not show any increase in the concentration of IL-8. We did observe a direct relationship between TNF-α and creatinine. The course of CDI is characterized by an initial local inflammatory process followed by a systemic inflammatory response, which manifests clinically as fever, and includes leukocytosis, an increase in the level of neutrophils in the blood, and an increase in the serum concentrations of TNF-α, IL-1ß, IL-6, IL-10, MPO and PGE2. Despite the leading role of IL-8 in the local inflammatory process, we postulate TNF-α and IL-6 play a key role in the systemic inflammatory response in CDI, and the plasma TNF-α level seems to act as a major factor of poor prognosis in patients with CDI.

The diagnostic value of cytokine and nitric oxide concentrations in cerebrospinal fluid for the differential diagnosis of meningitis.

PURPOSE: In several cases of meningitis routinely used diagnostic procedures are unable to identify the cause of this disease. The objective of the present study was to determine whether proinflammatory cytokine (tumour necrosis factor (TNF-α), interleukin-1ß (IL-1ß), interleukin-8 (IL-8)) and nitric oxide (NO) concentrations in the CSF are useful markers for the differential diagnosis of meningitis. MATERIAL AND METHODS: Sixty-seven patients (42 patients with bacterial meningitis and 25 patients with viral meningitis) were included in the present study. In the investigated group, the TNF-α, IL-1ß and IL-8 concentrations in the CSF samples collected on the day of admission were assessed. Furthermore, the NO concentrations were assessed in 23 patients. RESULTS: The results revealed that the measurement of proinflammatory cytokines in CSF can aid in a differential diagnosis. In particular, a high concentration of TNF-α may be a sensitive and specific marker of a bacterial aetiology of the neuroinfection. In the present study, TNF-α concentrations greater than 75.8 pg/ml differentiated between bacterial and viral meningitis with 100% sensitivity and specificity. The NO concentration in the CSF was also significantly greater in patients with bacterial meningitis than in those with viral meningitis. CONCLUSIONS: The assessment of TNF-α, IL-1ß and IL-8 concentrations in the CSF is useful in the differential diagnosis of neuroinfection. Because many factors may influence NO production in the central nervous system (CNS), it is not clear whether NO values can be used for the differential diagnosis of meningitis, and further studies are required.

[The role of cytokines in bacterial meningitis]. / Rola cytokin w bakteryjnym zapaleniu opon mózgowo-rdzeniowych.

Bacterial meningitis is the serious infection of the central nervous system (CNS), and stimulated by bacteria inflammatory host response has crucial role in its pathogenesis. The most important elements of this response are cytokines, especially tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10), which have antiinflammatory activity. Production of cytokines in the CNS triggers a cascade of inflammatory mediators. Better understanding of mechanisms which take place during the course of the bacterial meningitis can be useful in differential diagnosis, prognosis and treatment of this disease. Investigations on the role of cytokines in the bacterial meningitis, have great therapeutic implications, and can result in introduction to the treatment antiinflammatory drugs, which can help to reduce mortality rate and number of complications.

[Meningitis with acute respiratory distress syndrome in adults and jaundice--case report]. / Zapalenie opon mózgowo-rdzeniowych przebiegajace z zespolem ostrej niewydolnosci oddechowej u doroslych i zóltaczka--opis przypadku.

The case of leptospirosis with adult respiratory distress syndrome (ARDS) and severe jaundice in young abattoir worker has been presented. Institution of invasive therapeutic methods: continuous mandatory ventilation (CMV) with positive end-expiratory pressure (PEEP) and plasmapheresis, together with antibioticotherapy resulted in complete recovery. We discuss some characteristic features of the leptospirosis, which with the data from epidemiological history can lead to early diagnosis of this forgotten disease.

[Post-traumatic bacterial meningitis]. / Pourazowe ropne zapalenia opon mózgowordzeniowych.

10 patients with posttraumatic bacterial meningitis were treated in the Department of Infectious Diseases of the Jagielloniam University--Collegium Medicum during the period of 63 months. Traffic accidents were responsible for 80% of all cases of trauma. The most common place of injury was the base of anterior cranial fossa. Infecting agent was established in 8 cases. Gram-positive aerobic cocci (Streptococcus pneumoniae, Enterococcus faecalis, and Enterococcus spp.) were found in 4 patients, Gram-negative aerobic cocci (Neisseria meningitidis) in 2 patients, and Gram-negative aerobic rods (Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella spp, Escherichia coli) in 3 patients. Streptococcus pneumoniae was still highly sensitive to penicillin, ampicillin and cefotaxime. Enterococcus faecalis and Enterococcus spp. were sensitive to vancomycin and teicoplanin. Neisseria meningitidis was sensitive to penicillin, cefotaxime, amoxicillin/clavulonate. Gram negative aerobic rods were sensitive to third-generation cephalosporins, carbapenems and aminoglycosides. Among 10 patients treated for posttraumatic bacterial meningitis 1 patient died and in 1 preserved vegetative state was diagnosed. In 4 patients severe or moderate disabilities developed, however 4 recovered completely. 6 patients after regression of the CNS infection were qualified to neurosurgical intervention. In 3 patients reconstructive operation of the basis of anterior cranial fossa with tissue glue Beriplast P. was done, the recovery was complete. 3 patients didn't agree to surgical operation, and we don't know what has happened with them. They have not come to the control visit.

Evaluation of the effectiveness of vaccination against diphtheria among medical staff of the chair and the Jagiellonian University Hospital of Infectious Diseases in Cracow, Poland. Some epidemiological observations.

In Poland, twenty-five cases of diphtheria, mostly among adults (including five foreigners) in the region adjacent to the eastern border were registered in the years 1992-1996. In 1993-1994, because of the threat of diphtheria infection, 41 healthy members of the medical staff of the University Hospital of Infectious Diseases in Kraków, mainly women aged 25-57 years were immunized with Td and d vaccines with a 6-month interval between courses. Prior to vaccination, 17(41%) individuals showed a lack of diphtheria antibodies as determined with a passive haemagglutination test. 14 of them were aged 30-49 years. Six months after the 2nd dose of vaccine, all seronegative persons had developed a protective level of antibodies. Moreover, all vaccinated subjects showed a statistically significant increase of the antibody titre between the first and last serological examinations.

[Modifications in treatment of tetanus and prognosis--observations from the Cracow Department of Infectious Diseases]. / Zmiany w leczeniu tezca, a rokowanie--obserwacje krakowskiej Kliniki chorób Zakaznych.

The assessment of modifications in the tetanus treatment, which included using metronidazol and midazolam instead penicillin and diazepam, was presented. According to our own observations and previous investigations, mentioned above changes in the tetanus therapy improve survival rate, reduce psychiatric disturbances and shorten hospitalisation time.

[Remarks on injuries which were the source of tetanus and were based on observations from the Clinic of Infectious Diseases in Cracow]. / Uwagi o urazach bedacych przyczyna tezca na podstawie obserwacji Kliniki Chorób Zakaznych w Krakowie.

From 1992 to 1996, 95 patients with tetanus were treated in the Chair and Department of Infectious Diseases in Cracow. Most of them came from rural area, and at old age (median 68 years). Small, trivial skin injuries were the most often identified portal of entry. Only few patients applied to doctor after injury for prophylaxis against tetanus. The authors emphasise that small skin injuries, which may be portal of entry for tetanus, should not be left abandoned.

[Encephalitis as a severe complication of rubella--case report]. / Zapalenie mózgu ciezkim powiklaniem rózyczki--opis przypadku.

The case of severe encephalitis in the course of rubeola in young woman was presented. The self-limited increased level of aminotransferases and hyperglycaemia were reported during the course of disease. Any late complications of the encephalitis were observed and the patient was discharge from the hospital in good condition.

[Diagnostic difficulties in encephalitis: two case reports]. / Trudnosci diagnostyczne w zapaleniach mózgu--opis dwóch przypadków.

The differential diagnosis of psychiatric symptoms in encephalitis, especially in the early phase of the disease may be very difficult. It is particularly hard to distinguish it from the classic psychosis. The diagnostic problems have been presented on the basis of analysis of two case reports of the acute encephalitis in young persons. The presence of fever and pathological changes in the CSF were the most important indicators that helped to establish the diagnosis of encephalitis during the phase of acute psychopathological disorders.

[Tuberculosis of the lymph nodes with esophageal-cutaneous fistula in a patient with AIDS]. / Gruzlica wezlów chlonnych z przetoka przelykowo-skórna u chorego na AIDS.

A case of patient with the tuberculosis of lymph nodes and esophago-cutaneous fistula in the course of AIDS has been presented. A valve has been formed within fistula enabling to visualize a free passage only after an oral contrast administration. It is worth noting that tuberculosis frequently accompany severe course of AIDS.

[Conservative treatment of hepatic amebic abscesses]. / Leczenie zachowawcze ropni amebowych watroby.

A case is presented of hepatic amebic abscesses in a young man after return from India. After establishing of the aetiology of the disease conservative treatment was started which was completed with success. The authors point to the possibility of transmission of amoeba dysentery to Poland due to journeys to tropical or subtropical countries.

Measurement of radial bone mineral density in patients after heart transplantation.

Limited physical activity, steroidotherapy and immunosuppression are known risk factors for the development of osteoporosis. The purpose of our current work was to investigate whether patients after heart transplantation (Htx) have an increased incidence of osteoporosis. We compared bone mineral density (BMD) in 32 post-transplant patients with a reference group of 1548 healthy age-matched males. Measurement of BMD was carried out with a Dtx 100 Osteometer on the distal and ultradistal segment of the non-dominant radius. Our results revealed a decreased BMD in HTx patients ranging from 6.9 to 10% in the ultradistal (p = 0.0446) and from 0.4 to 3.5% in the distal segment (p = 0.0593).

[The effect of diabetes and cholelithiasis on the course and consequences of acute viral hepatitis type B]. / Wplyw cukrzycy i kamicy zólciowej na przebieg i nastepstwa ostrego wirusowego zapalenia watroby typu B.

Course and consequences of acute hepatitis B on the group of 40 patients with diabetes mellitus and 21 patients with cholelithiasis were estimated with respect to the group has consisted of 82 person with acute hepatitis B without coexisting disorders. Hospitalization time has been longer on the group with diabetes mellitus or cholelithiasis and activity of serum alanine aminotransferase (AlAT) has brought back to normal longer than on the control group. Maximal activity of serum AlAT has been higher on the control group and maximal bilirubin concentration in serum the patients with diabetes mellitus or cholelithiasis has not differed from the control group. Acute hepatitis B passed into chronic hepatitis or cirrhosis of the liver on the group with diabetes mellitus or cholelithiasis frequently, has been observed.