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 (HCV) genotype 1 NS5A resistance-associated variants are associated with advanced liver fibrosis independently of HCV-transmission clusters.

OBJECTIVES: The aim of the study was to characterize the differences in the frequencies of NS3 and NS5A resistance-associated variants (RAVs) among Polish therapy-naive genotype 1 (G1) hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients including clustering patterns and association of RAV frequency with liver fibrosis. METHODS: NS3/NS5A RAVs were identified by population sequencing in 387 directly acting antiviral treatment-naive G1-infected individuals (54 with genotype 1a (G1a) and 333 with genotype 1b (G1b)). Liver fibrosis was assessed based on histopathology or ultrasound elastography. Phylogenetic clusters were identified using maximum likelihood models. For statistics, chi-squared or two-sided Fisher's exact tests and multivariate logistic regression models were used, as appropriate. RESULTS: NS3 RAVs were found in 33.33% (18/54) for G1a and 2.62% (8/297) for G1b whereas NS5A variants were present in 5.55% (3/54) G1a and 9.31% (31/333) G1b sequences. Variations in NS5A 31 and 93 codon positions were found only in G1b (4.2% (14/333) for L31I/F/M and 5.39% (17/333) for Y93H). NS5A RAVs were more frequent among patients with advanced liver fibrosis (17.17% (17/99) for F3-F4 versus 6.94% (17/245) for F0-F2; p 0.004) or liver cirrhosis (20.34% (12/59) for F4 versus 7.72% (22/285) for F0-F3; p 0.003). Liver cirrhosis (F4) was associated with higher odds ratio of the NS5A RAVs among HCV-infected patients (odds ratio 2.34, 95% CI 1.004-5.291; p 0.049). NS5A RAVs were less frequent among sequences forming clusters and pairs (5.16% (8/155) versus 11.21% (26/232); p 0.039). CONCLUSIONS: Presence of NS5A RAVs correlated with progression of liver fibrosis and represents de novo selection of variants rather than transmission of drug resistance. Hence, the presence of NS5A RAVs may be a predictor for a long-lasting 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.

Invariant sway properties in children.

The ability to maintain upright body posture depends on the biomechanical properties of a body and on the execution of control programs. The aim of this study was to determine how the structural growth of the human body, between ages 7-18, affects spontaneous sway parameters and to determine how the visual feedback positional task changes body sway parameters. The selected parameters of postural sway were evaluated in 57 children aged 7-18, while they stood with their feet together for 30 s. The experiment consisted of two different tasks: free standing with no feedback (No feedback), and free standing with additional visual feedback (Feedback). No statistically significant correlation between sway parameters and developmental factors (body height, body mass, and age) in the No Feedback task was found. Statistically significant correlations were found between age and most of the sway parameters in the Feedback task. The execution of voluntary feedback resulted in an increase in the total sway (20%), while the total area decreased nearly two-times. The invariance of sway amplitude supports the view that the same activation patterns can be utilized by children aged 7-18, despite the changes in body dimensions.

Rapid correction of prothrombin time after low-dose recombinant factor VIIA in patients undergoing orthotopic liver transplantation.

Orthotopic liver transplantation (OLTx) is associated with a major risk of blood loss resulting from portal hypertension, collateral circulation, and clotting disturbances. Application of a recombinant factor VIIa (rFVIIa) has been reported to promptly correct clotting abnormalities reducing the risk of intraoperative bleeding. This study included 8 patients who underwent OLTx for end-stage liver cirrhosis, with protrombin times (PT) exceeding the upper limit of normal by more than 4 seconds before surgery. All subjects were administered a small single intravenous dose of rFVIIa [mean 68.37 microg/kg body mass (range, 32.88-71.64)] 10 minutes prior to the skin incision. The PT was then measured 15 minutes later, following graft reperfusion, and 12 hours since drug application. All patients showed rapid correction of PT within 15 minutes after injection (median PT before injection 20.25 seconds vs 11.5 seconds after injection, P <.0001). Following the reperfusion PT was found to be prolonged again. These values are not significantly differ from those before surgery and are comparable to PT values after reperfusion in patients who did not receive rFVIIa. None of the patients developed thromboembolic complications. In conclusion, lower than recommended dose of rFVIIa caused rapid improvement in the PT shortly after injection. After reperfusion PT became prolonged again, which may account for the lack of thromboembolic complications observed in this group of patients.

Segmental movements of the spine during treadmill walking with normal speed.

OBJECTIVE: The aim of the present work is to investigate the segmental movement patterns of the spine during normal treadmill gait. DESIGN: The spine movement during treadmill gait of ten healthy subjects (five men and five women) has been investigated using an optoelectronic measuring system. METHODS: The spine was divided into seven segments, from C(7) to S(2). The subjects walked with their normal speed. All data were normalized to per cent of the gait cycle. The normal patterns of the spine segment movements were found in the sagittal and the frontal planes. RESULTS: The behaviour of the spine can be described as the motion of a stiff element with superimposed small, inter-segmental movements. These small inter-segmental movements were found both in the sagittal and the frontal planes. CONCLUSIONS: The small inter-segmental movements could play an important role in the reduction of the energy consumption during gait and in maintenance of the equilibrium. RELEVANCE: Any disability affecting the spine should result in changing spine movement pattern during gait, thus changing the overall gait pattern. Therefore, treatment and rehabilitation should not discard the influence of the spine malfunctioning, regardless of its nature.

Application of biomechanical growth models of the quantitative evaluation of the motor system in children.

To evaluate the effectiveness of rehabilitation methods, and to assess the progress of the rehabilitation process in an individual patient, quantitative methods are necessary. The large number of motor system parameters makes the problem of data collection time-consuming and expensive. A quantitative evaluation of the child's motor system is an assessment of a combination of the growth and rehabilitation processes. The aim of the study was to establish methods of differentiation between these two processes. The chosen anthropometric measures, biomechanical parameters of the lower leg segment, maximal voluntary extension and flexion torques of lower leg and chosen gait parameters, were measured in various groups of healthy children 6-18 years old. Mathematical functions were calculated describing these parameters against developmental parameters (body mass, body stature, age). Using the maximal correlation criterion the best growth parameters were established. Normalized databases for these parameters were developed. It is suggested that, using their approach, differentiation between the influences of growth and rehabilitation processes can be achieved, thus eliminating the need for tedious data collection.

[Viral hepatitis as a nosocomial infection in the western Pomeranian region in the years 1984-1990]. / Wirusowe zapalenie watroby jako zakazenie szpitalne na Pomorzu Zachodnim w latach 1984-1990.

Within last six years almost 25% hospitalized cases of viral hepatitis (1390 among 5748 patients) were diagnosed as nosocomial infections. Transfusion anamnesis was excluded in 80% patients with type B hepatitis and in 43% patients with NANB hepatitis. One case of nosocomial hepatitis for every 1000 hospitalized in this region was calculated.

[Anti-HCV antibodies among hemodialysed and kidney-transplanted patients]. / Markery hepatitis C (anty-HCV) u chorych dializowanych i po przeszczepie nerek.

We have studied from two hemodialysed centers to determine the prevalence of hepatitis C virus infection in hemodialysis 142 patients and 147 renal-transplant patients. Serum samples were tested for antibody by "Ortho HCV 2.0 ELISA test System" second generation assay. Antibody to hepatitis C virus was detected in 81 (57.04%) and 85 (57.82%) patients respectively. Age-related differences were not clear, but significantly were noted in hemodialysis patients. Patients with a history blood transfusion in both groups tended to have significantly high anti-HCV positivity rate. There was a tendency for a longer duration of hemodialysis to coincide with higher positivity anti-HCV.

[A case of Listeria meningoencephalitis with a fatal result]. / Przypadek listeriozowego zapalenia osrodkowego ukladu nerwowego zakonczony zejsciem smiertelnym.

A fatal case of severe meningoencephalitis caused by Listeria monocytogenes in a compromised alcoholic has been described. Unconsciousness, full meningeal symptoms with slight lateralisation of signs, seizures, respiratory failure within three days before death have been observed.

[A case of spontaneous elimination of HBsAg and seroconversion of HBe after infection with HCV virus]. / Przypadek spontanicznej eliminacji HBsAg oraz serokonwersji w ukladzie HBe po zakazeniu wirusem HCV.

A case of chronic type B hepatitis with HBsAg persisting for 15 years and its clearance as well as HBeAg-->HBeAb seroconversion and histological improvement after acute HCV superinfection is described. Possible mechanisms of suppressive effects of acute HCV superinfection on the established HBV infection is discussed.

[The course of acute HCV infection in patients with chronic non-A, non-B hepatitis]. / Przebieg ostrego zakazenia HCV u chorych na przewlekle zapalenie watroby NANB.

Among 52 patients with chronic non-A, non-B hepatitis, observed for many years in the Department of Infectious Diseases of Pomeranian Medical Academy, retrospectively diagnosed towards HCV infection, 45 proved to be anti-HCV positive. Sera stored in the bank of sera were examined using 2nd generation tests: ABBOTT HCV EIA (Abbott), ORTHO RIBA (Ortho Diagnostics) and UBI HCV EIA (Organon), showing 85% of positivity. Mostly HCV infection was connected with the blood transfusion. The course of acute phase of HCV infection was mild, short lasting, with no or sporadic extrahepatic symptoms; the activity of aminotransferases and the bilirubin level were of average value. The only characteristic feature of the acute HCV infection was fluctuating aminotransferase activity, which can be the good sign of progression.

[A patient with abdominal actinomycosis--diagnostic problems]. / Chora z promienica brzuszna--problemy diagnostyczne.

The difficulties in diagnosis of abdominal actinomycosis are presented. Clinical manifestations and colonoscopy suggested malignancy. Final diagnosis was made on the basis of pathological assessment of resected sigmoid. Authors underline that in case of "negative" pathomorphological results of material obtained during endoscopy from lesions suspected, benign disease should be consider including anctinomycosis and intraoperative pathomorphological examination should be performed.

[Effectiveness of antiviral treatment of patients with chronic hepatitis C (a Polish multicenter study)]. / Efektywnosc leczenia przeciwwirusowego przewleklego zapalenia watroby typu C (wieloosrodkowe badania pòlskie).

Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient.

[Magnesium status in children and adolescents with celiac disease]. / Stan odzywienia magnezem u dzieci i mlodziezy z celiakia.

UNLABELLED: Magnesium deficiency has been reported in patients with classical coeliac disease. Classical coeliac disease has been recently very rare, but the frequency of the silent or latent form has increased. The aim of the study was to evaluate the magnesium status in patients with coeliac disease diagnosed according to ESPGAN criteria. 41 GFD(+) patients aged 6-18 years, who were on a gluten-free diet (GFD) for 2.8 to 17.3 years (mean 11 years); with normal villous structure and IgAEmA(-), and 32 GFD(-) patients aged 5-17 years, with villous atrophy and IgAEmA(+): 8--after 7/12-13/12 of gluten challenge, 4--with late onset of coeliac disease, 20--with silent coeliac disease. All of the children did not have any other disorders. Magnesium status was examined by using: an i.v. Mg-loading test (30 mmol/1.73 m2); Mg urinary excretion and Mg concentration in serum, erythrocytes, and in hair. Abnormal values in GFD(+) and GFD(-) patients were found in: Mg i.v. loading test (retention > 40%) in 20 vs 34%, serum Mg (< 0.7 mmol/l) in 7 vs 3%, erythrocytes Mg (< 1.8 mmol/l) in 20 vs 25%. The reversed statistically significant correlation was found between Mg retention and Mg urinary excretion (R = -0.293, p = 0.009). No other statistically significant correlations were found. CONCLUSION: The magnesium deficiency was present in all patients with classical coeliac disease, but only in 1/5 of patients with coeliac disease on a gluten-free diet and in 1/5 of patients with silent coeliac disease.

[Reasons for magnesium deficiency in children with coeliac disease]. / Przyczyny niedoboru magnezu u dzieci i mlodziezy z celiakia.

UNLABELLED: Magnesium (Mg) deficiency is often noted in patients with coeliac disease (CD). The aim of the study was the analysis of the reasons of this deficiency in children with CD, diagnosed according to ESPGAN criteria. MATERIAL: The study was performed on 41 patients aged 6-18 years adhering to strict gluten-free diet GFD(+) for mean 11 years, with normal small intestine mucosa, and IgAEmA(-), and on 32 patients aged 5-17 years on gluten containing diet, with classical CD, silent CD or after gluten challenge--GFD(-). In this group the villous atrophy of the small intestine and IgAEmA(+) were observed. In 18 of these patients Mg deficiency was found using Mg-loading test (30 mmol/1.73 m2). METHODS: The following parameters were analysed: type of the disease, observance of gluten-free diet, sex, and living place. Mg, Ca, Na, protein, fat, and dietary fiber intake was assessed using food frequency questionnaire method, and steatorrhea using faecal fat excretion (g/24 h). RESULTS: The frequency of Mg deficiency was similar in both sexes, occasionally in children from small towns (4.5%), and more often in children from big cities (31.5%), and village (34.4%). Dietary Mg intake below RDA was observed in 23% of children from GFD(+) group, in 19% from GFD(-) one, and in 17.6% in children with Mg deficiency. Insufficient Mg intake was found in 18.2% of children from small towns, in 17.6% from big cities, and in 12.5% from villages; Ca in 36.6%, 58.8%, and 59.3%, and protein in 18.2%, 35.3%, and in 34.4% respectively. In all groups of children high intake of fat and Na was observed. Dietary fiber intake was within the recommended values. All children with classical CD had increased fat excretion (mean 25.9 g/24 h), in other patients it was within normal values [GFD(+) mean 1.95 g/24 h, in GFD(-) without diarrhoea 1.7 g/24 h. CONCLUSIONS: Magnesium deficiency in children with CD depends on the form of the disease, adhering to GFD, diarrhoea with steatorrhea, and/or low Mg intake with the diet.

Gait in laboratory analysis.

This article presents the basic concepts in the laboratory diagnostics of gait. The value of the kinetic and kinematic methods is indicated for the evaluation of mobility in children with cerebral palsy. Gait disorders in children with spastic hemiplegia and bilateral hemiplegia are presented in the form of models of the most common disturbances of locomotion.

The impact of a ketogenic diet and liver dysfunction on serum very long-chain fatty acids levels.

Peroxisomes play an essential role in mammalian cellular metabolism, particularly in oxidation fatty acid pathways. Serum very long-chain fatty acids (VLCFA), the main biochemical diagnostic parameters for peroxisomal disorders, were examined in 25 neurological patients with epilepsy on a ketogenic diet and 27 patients with liver dysfunction. The data show that patients on a ketogenic diet have increased levels of C22:0 and C24:0, but not C26:0, and normal C24:0/C22:0 and C26:0/C22:0. Patients with liver insufficiency showed a slightly elevated level of C26:0, a normal level of C24:0 and a decreased level of C22:0; thus in 21/27 the ratio of C24:0/C22:0 was increased and 15/27 the ratio of C26:0/C22:0 was increased.

Risk score based PEG Interferon alpha 2b and Ribavirin treatment response estimation model for genotype 1 chronic hepatitis C patients.

PURPOSE: Attempt to create simple practical algorithm for prospective assessment of PEG interferon/ribavirin related treatment response in individuals with chronic hepatitis C (CHC) basing on the risk factors defined prior to the treatment initiation. MATERIAL/METHODS: Retrospective assessment of 45 female and 39 male previously untreated CHC patients aged 20 to 73 years, with genotype 1, undergoing standard treatment with PEG-IFNa2b+RBV was performed. For the final analysis 78 patients were included (38 effectively treated and 40 treatment failures). Thirty-six sustained virological response (SVR) related factors, which were routinely measured before treatment initiation were compared (including physical, biochemical, serologic and histopathologic). From this group the risk factors of the highest predictive value for treatment failure were selected. Cut-off values for statistical significance were defined for each parameter, with risk score (RS) calculated and compared in the group with and without SVR. RESULTS: Seven factors related to treatment failure were identified: HCV>600000 IU/L, blood platelet count <150000/ul, GGTP>45 IU/ml, total serum protein<7.8 g/dl, glycaemia>105 mg/dl, detectable HBc IgG antibodies and cirrhosis. In the group with RS 1 the likelihood of SVR was 70% (p<0.028), while in patients with RS 3 the response was reduced to 23.8% (p<0.016), with no SVR achieved among patients with RS >3. CONCLUSIONS: Low risk score (0-2) is associated with high probability of treatment success with scores >3 predictive for treatment failure. The presented model is a simple tool for prediction of treatment success for clinical use before PegIFN/RBV treatment initiation among genotype 1 CHC patients.