Hepatitis C: efficacy and safety in real life.

Interferon-free combinations were registered in 2014 and 2015 for the treatment of chronic HCV infection. As a result, real-world experience has been gathered in the last year and this paper presents data available in September 2016. Real-world studies on the efficacy of the ledipasvir/sofosbuvir (LDV/SOF)±ribavirin (RBV) regimen showed a sustained virologic response (SVR) rate of between 91% and 98%. The SVR rate in the 13858 patients included in this paper was 94%, and 92% in the 3506 patients with cirrhosis. In a number of recently published real-world studies evaluating ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±RBV, the SVR rate was between 92% and 100%. The SVR rate of the 4260 patients included in the studies in this paper was 97% and the rate was the same in the 1647 patients with cirrhosis. Recently, data evaluating SOF/simeprevir±RBV showed an SVR rate >90%, while in combination with daclatasvir this rate reached approximately 95%. The safety data available for LDV/SOF±RBV and OBV/PTV/r±DSV±RBV show that discontinuation due to adverse events was necessary in no more than 3% of patients and the frequency of serious adverse events was between 0 and 11%, in particular in real-world studies. Because of the similar efficacy and safety, real-world data support the use of either the LDV/SOF±RBV or OBV/PTV/r±DSV±RBV regimen in patients with genotypes 1 or 4. There is still not enough real-world data in patients with genotype 3 and other genotypes.

The importance of sCD40 and sCD40L concentration in patients with chronic HCV infection and HIV co-infection.

CD40 receptor is activated by ligand CD40L (CD154) which is synthesized in inflammation by NK cells, monocytes and lymphocytes B. TRAF proteins are activated in cells by CD40 stimulation and next they stimulate different enzymatic pathways. High concentrations of CD40L stimulate CD40, and consequently STAT enzyme system inhibits the expression ofnonstructural proteins ofHCV NS3 and NS5A and E2 core in infected human hepatocytes. PURPOSE. The aim of the study was to evaluate the concentration of soluble components of the complex: sCD40 and sCD40L in the serum of patients infected with HCV and HCV/HIV-1 co-infected. The effect ofHCV genotype, HIV and HCV viral load and rs12979860 polymorphism on serum sCD40 and sCD40L was established among the patients. The influence of the number of CD3+, CD4+ and CD8+ on the concentrations of sCD40 and sCD40L was evaluated in the HIV-1 infected group MATERIALS AND METHODS. Serum concentrations of sCD40 and sCD40L were determined using ELISA in 68 HCV infected patients including 39 HCV monoinfected and 29 HCV/HIV-1 co-infected. RESULTS. Serum concentration of sCD40 and sCD40L was significantly higher in HCV and HCV/HIV coinfected patients compared to healthy subjects (25.7 and 23.2 v. 8.5 pg/ml and 12.7 and 7.3 v. 0.79 ng/ml). The concentration of sCD40L in patients with genotype CC rs12979860 was significantly higher compared to patients with Non-CC genotypes (11.8 v. 7.6 ng/ml, p < 0.018). CONCLUSIONS. High levels of sCD40 and sCD40L were detected among patients with chronic HCV and HCV/ HIV-1 infection The high concentration of sCD40L correlates with CC rs12979860 genotype.

SNP RS12979860 related spontaneous clearance of hepatitis c virus infection in HCV/HIV-1 coinfected patients.

UNLABELLED: CC genotype of SNP rs 12979860 promotes spontaneous HCV clearance in monoinfected patients. The aim of this analysis was evaluation of impact of rs12979860 polymorphism on HIV or HCV viral load, CD3, CD4 and CD8 count as well as HCV clearance among HCV/HIV coinfected patients. MATERIALS AND METHODS: The study included 41 consecutive HCV/HIV coinfected patients. HIV RNA, HCV RNA, HCV genotype and rs12979860 polymorphism sequence as well as CD3, CD4 and CD8 cells count were analyzed in all patients. RESULTS: CC genotype rs12979860 was identified in 16 from 41 patients. During at least 4 years follow-up, five genotype CC patients (31%) became HCV RNA undetectable, that was not a case in CT and TT patients. No statistical differences in HIV viral load and the number of CD3, CD4 and CD8 related to rs12979860 polymorphism were observed. The baseline level of HCV RNA in patients with CC genotype was significantly lower compared to patients with non-CC genotypes (88546 +/- 74181 vs. 726021 +/- 30709 IU/mL). CONCLUSION: CC genotype related to SNP rs 12979860 can affect the lower level of HCV viral load compared to patients with CT and TT genotypes and promotes spontaneous clearance of HCV RNA in HCV/HIV coinfected patients.

[The occurrence of HCV genotypes and single polynucleotide polymorphisms of rs12979860 among HCV infected patients in northeastern Poland]. / Wystepowanie genotypów HCV i polimorfizmu SNP rs12979860 wsród zakazonych HCV pólnocno-wschodniej Polski.

UNLABELLED: HCV is responsible for the development of chronic hepatitis C, cirrhosis and hepatocellular carcinoma. The Polish population is mainly dominated by genotype 1 infections, genotypes 3 and 4 are less common. Studies have shown that changes in SNPrs12979860 of human chromosome 19 affect their ability to eliminate infection both spontaneously and during the antiviral therapy. THE AIM OF THIS STUDY was to evaluate the frequency of different HCV genotype infections in the Podlasie region during the period from 2002 to 2011 and to determine the frequency of particular genes associated with rs12979860 polymorphism amongst patients both eligible for treatment and currently undergoing the treatment. METHODS. Research and evaluation of the genotypes was performed in 923 cases of HCV and in 126 cases genes rs 12.97986 were identified (97 patients infected with genotype 1, 17--genotype 3 and 12--genotype 4). HCV infection was confirmed by the detection of HCV-RNA and it's genotype in serum with RT-nested--PCR (Syngen Biotech, USA). Rs12979860 polymorphism was detected by sequencing, using PCR. The final scores were determined using 3500 Genetic Analyzer (Applied Biosystems, Foster City, USA). RESULTS: HCV infection was more frequent among men (60%). Genotype 1 was found in 66% of patients, genotype 3 in 27% and genotype 4 in 7% of patients. During period of 10 years slow increase of genotype 4 HCV infection prevalence was observed. Among patients infected with genotype 1 HCV waiting for the treatment and those who already completed antiviral therapy the presence of genotype C/C was found in 21%, C/T in 59% and T/T in 20%. CONCLUSIONS: The most common in Northeastern Poland is genotype 1 of HCV. There has been a slow increase of infections with genotype 4. In 79% of patients infected with genotype 1 ofHCV genotypes C/T or T/T have been found which is an adverse prognostic factor of the treatment.

[Respiratory functional impairment in patients with liver cirrhosis]. / Zaburzenia wydolnosci oddechowej u chorych na marskosc watroby.

UNLABELLED: End stage of liver disease can cause the respiratory tract dysfunction. Early diagnosis of hepatopulmonary syndrome can affect the therapy and determine the timing and risks of orthotopic liver transplantation. The aim of the study was to determine the respiratory distress in relation to liver damage assessed with scoring scales of Child-Pugh, MELD, GAHS, as well as fibrinogen and albumin levels. MATERIAL AND METHODS: Respiratory disorders were diagnosed by spirometry and plethysmography. The study included 71 patients with alcoholic liver cirrhosis. The results obtained were analyzed using the nonparametric Spearman correlation test and U-Mann-Whitney test. RESULTS: Analysis showed that the severity of liver damage leads to significant deterioration in DLCO/VA, (Child-Pugh: r = -0.22; p < 0.04; the concentration of albumin: r = -0.24; p < 0.03). Depending on the scale GAHS correlation between the severity of liver failure and the deterioration rate Tiffeneau (FEV1/VC; r = -0.30; p < 0.004), reduction in TGV (r = -0.39; p < 0.0004), TLC (r = -0.27; p < 0.01) and RV (r = -0.31; p < 0.004) has been observed. CONCLUSIONS: Among patients with liver cirrhosis there are mainly restrictive pulmonary disorders and the difficulty of gas diffusion in the alveoli. These disorders correlate with the severity of liver damage assessed with Child-Pugh or GAHS classifications and albumin concentration.

Oxidative stress biomarkers in the serum and plasma of patients with non-alcoholic fatty liver disease (NAFLD). Can plasma AGE be a marker of NAFLD? Oxidative stress biomarkers in NAFLD patients.

Still little is known about the redox abnormalities in patients with non-alcoholic fatty liver disease (NAFLD). The purpose of the study was to find the relationship between enzymatic and non-enzymatic antioxidants, redox homeostasis and oxidative damage in 67-patients with NAFLD. The study population was divided into patients with non-alcoholic fatty liver (early NAFLD, n = 29) and patients with non-alcoholic steatohepatitis (advanced NAFLD, n = 38). Redox biomarkers: enzymatic antioxidants (Cu - Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR)); non-enzymatic antioxidants and redox status (reduced glutathione (GSH), total antioxidant capacity (TAC)); and oxidative damage products (total oxidant status (TOS), advanced glycation end products (AGE), malondialdehyde (MDA), and DNA/RNA oxidative damage) were determined in the serum/plasma samples. The activity of SOD, GPx, GR and levels of GSH, TOS, AGE, MDA, and DNA/RNA oxidative damage were significantly elevated in early NAFLD and advanced NAFLD group compared to controls (p < .001). There was a positive correlation between AGE, TAC and ALT activity (R = 0.34, p = .04; R = 0.36, p = .03, respectively) in advanced NAFLD group. Interestingly, ROC analysis for AGE showed good discriminatory ratio for patients with minimal steatosis (BARD score 0-1) vs. moderate steatosis (BARD score 2-4), AUC = 0.76. Plasma AGE can be a potential non-invasive biomarker differentiating NAFLD patients.

Intestinal fatty acid binding protein (I-FABP) as a possible biomarker of ileitis in patients with ulcerative colitis.

BACKGROUND: One of nine types of FABP, intestinal fatty acid binding protein (I-FABP) is primarily limited to the mature enterocytes of the small intestine, with only trace amounts identified in the stomach and large intestine. The aim of this study was to investigate the use of I-FABP as a possible plasma marker of intestinal injury in patients with ulcerative colitis (UC). MATERIAL AND METHODS: The study group consisted of 42 patients (11 females and 31 males) with active ulcerative colitis (UC), aged from 24 to 74 years (mean age: 41.8+/-3.5 years). Plasma I-FABP concentrations and hsCRP were compared using endoscopic pictures scored according to the system developed by Meyers et al., and analysed in the context of inflammatory process extension: pancolitis, or distal or left side colitis. RESULTS: The mean serum I-FABP concentration /mL), whereas individuals with left-side colitis had a mean I-FABP concentration of 61.8+/-8.5 pg/mL. Significant serum I-FABP elevation was observed in UC patients with a severe form of the disease, in contrast to the serum I-FABP concentration in patients with the mild form (260.5+/-60.6 vs. 61.5+/-7.9 pg/mL). CONCLUSION: The elevated serum I-FABP concentration in patients with UC may indicate ileitis. I-FABP may be a useful marker of the extended inflammatory process.

The Effect of Smoking on Posttraumatic Pseudoarthrosis Healing after Internal Stabilization, Treated with Platelet Rich Plasma (PRP).

Disturbed or delayed healing remains one of the most serious fracture-related complications, despite bone capacity for internal regeneration and reabsorption. Considerable progress in the understanding and treatment of fractures has been noted. The aim of our study was to evaluate treatment outcome in patients (smokers and non-smokers) with post-traumatic pseudoarthrosis. HYPOTHESIS: Determinate when administration of growth factors is most beneficial, and whether it accelerates bone union. MATERIAL AND METHODS: The study included patients treated for post-traumatic pseudoarthrosis resulting from multiple bone fractures. The study group and controls were further subdivided into: non-smokers, non-smokers >2 years after quitting, and smokers. Independent tests were performed for men and women. The study group, apart from other methods of treatment, received concentrated PRP (platelet-rich plasma) to aid the process of bone healing, or in cases of delayed healing confirmed by radiological assessment on follow-up visits. RESULTS: Mean time of fracture healing was 8 weeks for non-smokers and non-smokers >2 years after quitting, whereas in smokers the healing process was significantly prolonged (18 weeks in both, men and women). CONCLUSIONS: The risk for infection is smaller in non-smokers as compared to smokers, with the latter being at an elevated risk for bone inflammation and delayed union.

[Long-term effects of HBV treatment Peg-IFN alfa-2a alone or combined with lamivudine]. / Przewlekle zapalenie watroby typu B leczone Peg-IFN alfa-2a w monoterapii lub skojarzeniu z lamiwudyna--wyniki obserwacji dlugoterminowej.

The long-term outcomes showed a special place of IFN alfa-2a in therapy of chronic hepatitis B. Multivariate analysis revealed that patients who received 48 weeks treatment PegIFN-alfa-2a with reduction of serum ALT level and suppression of HBV-DNA replication will have a chance to keep this effect in the future. The results of long term follow-up showed that IFN alfa-2a improves prognosis in terms of reduction of progression to cirrhosis and hepatocellular carcinoma.

[Growth factors in chronic hepatitis C]. / Czynniki wzrostowe w przewleklym wirusowym zapaleniu watroby typu C.

UNLABELLED: GROWTH FACTORS: HGF, PDGF, TNF-alpha, IL-6 have important role in liver regeneration. The aim of our study was the evaluation of serum growth factors concentration in chronic hepatitis C. Studied growth factors and cytokines levels were analyzed in relation to inflammatory and fibrotic changes in liver. MATERIAL AND METHODS: Seventy-five chronic hepatitis C patients were enrolled in this study. All patients had liver biopsy performed and the microscopic examination of liver tissues were analized according to Scheuer's classification. Serum concentrations of growth factors in patients' serum were assessed by use of ELISA method. The control group consisted of 20 healthy individuals. RESULTS AND CONCLUSIONS: Serum HGF, PDGF, TNF-alpha level showed significant elevation in the chronic hepatitis C compared to healthy controls. There was a statistically significant correlation between serum HGF and inflammatory activity and fibrosis stage. HGF seems to play an important function during chronic HCV infection.

[Tuberculosis and HIV infection--main diagnostic and therapeutic problems]. / Gruzlica a zakaienie HIV--glówne problemy diagnostyczne i terapeutyczne.

Tuberculosis pertains to every third HIV-positive person in a world. Therefore HIV infection is considered the most evident risk factor for the primary tuberculosis or relapse of latent tubercular infection. Pulmonary tuberculosis is the most frequent clinical presentation in HIV-positive individuals, although the frequency of extrapulmonary tuberculosis is increasing with the CD4+ count reduction. Tuberculin skin testing and bacteriological tests are regarded as a "gold standard" of diagnosis. Molecular diagnostics and evaluation of a whole-blood interferon-gamma release assay for the detection of Mycobacterium tuberculosis are not cost-effective therefore their application is limited. DOTS programs are recommended for the antimycobacterial treatment in HIV-infected patients. The increasing drug resistance of Mycobacterium tuberculosis (multi-drug resistant tuberculosis--MDRTB) is emerging problem in the field of tuberculosis management.

Toxic hepatitis caused by the excretions of the Phyllomedusa bicolor frog - a case report.

The Kambô ritual consists of various types of skin scarification and subsequent application of Phyllomedusa bicolor secretion to the fresh wounds. In Europe, the ritual of Kambô is becoming more popular, but its use can lead to serious multiple organ damage, sometimes life-threatening. Our manuscript shows a patient with toxic liver damage probably associated with the Kambô ritual.

Helicobacter pylori infection among patients with liver cirrhosis.

BACKGROUND AND AIM: Inflammatory changes in the stomach caused by Helicobacter pylori indirectly and directly affect liver function. Moreover, the bacteria may worsen the course of the liver cirrhosis. The study aimed at evaluating the incidence of H. pylori infection among patients with liver cirrhosis, depending on the etiology and injury stage, scored according to Child-Pugh classification. Stage of esophageal varices and endoscopic inflammatory lesions in the stomach were evaluated, depending on the presence of H. pylori infection. PATIENTS AND METHODS: The study included 147 patients with liver cirrhosis: 42 were infected with hepatitis C virus, 31 were infected with hepatitis B virus, 56 had alcoholic liver cirrhosis, and 18 had primary biliary cirrhosis. Diagnosis of H. pylori infection was performed based on the presence of immunoglobulin G antibodies in serum. RESULTS: H. pylori infection was found in 46.9% of patients. The incidence of H. pylori infection among patients with postinflammatory liver cirrhosis was significantly higher (P=0.001), as compared with patients with alcoholic liver cirrhosis. Ammonia concentration was significantly higher in patients infected with H. pylori, compared with noninfected individuals (129 vs. 112 µmol/l; P=0.002). Incidence of H. pylori infection in patients without esophageal varices was significantly lower compared with patients with esophageal varices (14 vs. 60%; P<0.001). CONCLUSION: H. pylori infection is significantly more frequent among patients with postinflammatory liver cirrhosis (infected with hepatitis C virus or hepatitis B virus) than in patients with alcoholic liver cirrhosis or primary biliary cirrhosis. H. pylori infection correlates with elevated concentration of blood ammonia and the incidence of esophageal varices.

[The understanding of the term "iatrogeny"]. / Rozumienie terminu jatrogenia.

Iatrogeny is popularly considered to be the result of treatment. This reasoning is neither false nor is it exhaustive. This article is an attempt to specify the term "iatrogeny", analyses its causes as well as its links with the medical error and medical experiment. It was stated that iatrogeny is a result of an adverse effect which might be associated with either health - care workers or the health - care system generally. Unfavourable impact on patients' health can concern both psychological and physical condition. Therefore, the terms "iatropsychogeny" and "iatrosomatopathy" were distinguished. Iatrogenic effects accompanying medical experiments were considered specific and ethically justified ones, as far as they were carried out in precisely given conditions. They are regarded to be the price of progress in medicine. The health education of the society, versatile training of the medical staff and efficient health - care system are considered to be crucial to minimize iatrogenic influence on patients' health. Unfortunately, according to the reports from UK and USA, it is difficult and practically impossible to eliminate iatrogeny.

[Malaria and HIV co-infection]. / Zimnica wspólistniejaca z zakazeniem HIV.

The coexistence of malaria and HIV infection beyond inhabitants of sub-Saharan Africa, South America and South-East Asia arises a question whether there is an interaction between these two infections. This problem is extremely important in relation to pregnant women because of possibility of mother to child transmission. The available options are reviewed in the paper.

Real-world experience with ombitasvir/paritaprevir boosted with ritonavir and possibly combined with dasabuvir and ribavirin in HCV infection.

Ombitasvir/paritaprevir boosted with ritonavir and possibly combined with dasabuvir and ribavirin (OBV/PTV/r ± DSV ± RBV) is a new direct-acting antiviral (DAA) regimen which has improved efficacy of chronic hepatitis C virus (HCV) treatment significantly. OBV/PTV/r ± DSV ± RBV in clinical trials demonstrated sustained viral response (SVR) rates close to 100%. In this article we collected currently available data of 5726 patients for evaluation of OBV/PTV/r ± DSV ± RBV efficacy and safety in real-world experience. The sustained viral response rate in this large population was 97%, and it was exactly the same even in patients with liver cirrhotics. According to this meta-analysis, less than 3% of patients discontinued treatment due to adverse events.

Efficacy of HCV treatment in Poland at the turn of the interferon era - the EpiTer study.

THE AIM OF THE STUDY: Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016. MATERIAL AND METHODS: Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016. RESULTS: The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients (n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively. The sustained virologic response among 5646 G1 infected patients was the lowest with natural interferon α (7%, n = 70) or PegIFN (50%, n = 3779) with RBV, and improved in those receiving triple regimens of Peg-IFN + RBV combined with boceprevir (47%, n = 485), telaprevir (64%, n = 805), simeprevir (73%, n = 132) or sofosbuvir (70%, n = 23). The sustained virologic response with interferon-free regimens of sofosbuvir and RBV (n = 7), sofosbuvir and simeprevir (n = 53), and ledipasvir and sofosbuvir (n = 64) achieved 86%, 89% and 94% respectively. The highest SVR of 98% was observed with ombitasvir/paritaprevir combined with dasabuvir (n = 227). Patients infected with G3 (n = 896) and G4 (n = 220) received mostly Peg-IFN + RBV with SVR of 67% and 56% respectively. Interferon-free regimens were administered in 18 G3/G4 patients and all achieved an SVR. Sofosbuvir combined with Peg-IFN and RBV was administered to 33 patients with an SVR rate of 94%, and a similar rate was achieved among 13 G2 patients treated with interferon and RBV. CONCLUSIONS: We observed significant differences in efficacy of HCV regimens available in Poland at the turn of the interferon era. The data will be useful as a comparison for therapeutic options expected in the next few years.

Prevalence of HCV genotypes in Poland - the EpiTer study.

THE AIM OF THE STUDY: Was to assess current prevalence of hepatitis C virus (HCV) genotypes in Poland, including their geographic distribution and changes in a given period of time. MATERIAL AND METHODS: Data were collected with questionnaires from 29 Polish centers and included data of patients diagnosed with HCV infection between 1 January 2013 and 31 March 2016. RESULTS: In total, data of 9800 patients were reported. The highest prevalence was estimated for genotype 1b (81.7%), followed by 3 (11.3%), 4 (3.5%), 1a (3.2%) and 2 (0.2%). Genotype 5 or 6 was reported in 6 patients only (0.1%). The highest prevalence of genotype 1 was observed in central (lódzkie, mazowieckie, swietokrzyskie), eastern (lubelskie) and southern (malopolskie, slaskie) Poland. The highest rate for genotype 3 was observed in south-western (dolnoslaskie, lubuskie) and eastern (podlaskie, warminsko-mazurskie and podkarpackie) Poland. Compared to historical data, we observed an increasing tendency of G1 prevalence from 72.0% in 2003 to 87.5% in 2016, which was accompanied by a decrease of G3 (17.9% vs. 9.1%) and G4 (9.0% vs. 3.1%). CONCLUSIONS: Almost 85% of patients with HCV in Poland are infected with genotype 1 (almost exclusively subgenotype 1b), and its prevalence shows an increasing tendency, accompanied by a decrease of genotypes 3 and 4.

[Diagnostics of human granulocytic anaplasmosis]. / Diagnostyka ludzkiej anaplazmozy granulocytarnej.

Diagnostics of human granulocytic anaplasmosis. Human granulocytic anaplasmosis is one of recently emerging tick-borne diseases. The paper summarizes current opinions on diagnostics of this zoonosis, including the recent recommendations of ESCAR (European Society of Clinical Microbiology and Infectious Diseases Study Group on Coxiella, Anaplasma, Rickettsia and Bartonella).