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.

Hepatitis A and hepatitis A virus/HIV coinfection in men who have sex with men, Warsaw, Poland, September 2008 to September 2009.

We describe the epidemiology and characteristics of hepatitis A among men who have sex with men (MSM)who had been hospitalised due to the infection in Warsaw, Poland, from September 2008 to September 2009. A total of 50 men were analysed; their median age was 28 years (range: 17­43). None had travelled to hepatitis A-endemic regions during the six months before hospitalisation nor had they been vaccinated against hepatitis A. Of the 50 men, 40 had been tested before hospitalisation or on admission for the presence of anti-HIV antibodies: six were coinfected with HIV.The six HIV-positive MSM were significantly older than those who were HIV negative ­ median age: 37 years(range: 26­43) versus 28 years (range: 17­43); p=0.02.No difference in disease severity or the duration of hospitalisation was observed, however, between the two groups. Our study underlines the need to screen MSM for hepatitis A and to vaccinate them against hepatitis A. Given the ages of the MSM in our study,we recommend that this be carried out in Poland when the MSM are aged 20­35 years. This should apply not only to MSM with multiple casual partners but also to those in monogamous relationships.

High prevalence of genotype 4 among hepatitis C virus-infected intravenous drug users in north-eastern Poland.

The aim of this study was to describe the distribution of hepatitis C genotypes among intravenous drug users in north-eastern Poland. The study group included intravenous drug users recruited at a drug treatment center and a clinic for HIV-infected patients. HCV infection was confirmed by qualitative nested RT-PCR to test for the presence of HCV RNA. Genotypes were determined by 5'UTR sequencing and comparing the results with known genotype sequences. Among 111 HCV-infected and HCV-RNA-positive intravenous drug users, the most prevalent genotypes were 1 (38.7%), 3 (37.8%), and 4 (23.4%). Most infections with genotype 4 (88.5%) were found among HCV-HIV-coinfected drug users. The study demonstrated a high prevalence of genotype 4 (23.4%) among HCV-infected Polish drug users.

Concentrations of ssDNA in liver tissue and its correlation with sFas and sFasL in serum of patients infected with HBV, HCV, HCV and HIV.

PURPOSE: The concentration of nucleic acids that undergo apoptosis (ssDNA) determines the actual activity of programmed cell death. ssDNA concentrations in liver tissue of patients with chronic HBV, HCV and HCV and HIV infections were assessed. The concentration of this nucleic acid was analyzed in relation to the concentrations of serous apoptosis indicators, sFas and sFasL receptor proteins, the activity of inflammatory processes and fibrosis in liver tissue as well as HBV, HCV and HIV viraemia. PATIENTS: The study included 153 patients: 48 chronic HBV infected, 86 chronic HCV infected and 19 HCV and HIV infected. PATIENTS AND METHODS: The concentrations of HBV-DNA, HCV-RNA and HIV-RNA were determined by use of RT-PCR method. CD3+, CD4+ and CD8+ lymphocytes count were detected in HIV infected patients' blood by use of a flow cytometer. The concentration of ssDNA was determined by use of monoclonal antibodies and ELISA tests. The concentrations of sFas and sFasL in serum were determined by use of an immunoenzymatic method (ELISA). RESULTS: The concentration of ssDNA in liver tissue of both HCV and HBV infected patients was higher in comparison to those co-infected with HCV and HIV (1332 x 10(-6) g/mg, +/-664 x 10(-6); vs 1508 x 10(-6) microg/mg, +/-810 x 10(-6); vs 886 x 10(-6) microg/mg, +/- 388 x 10(-6); p < 0.004). No correlation between ssDNA concentration and HBV and HCV viraemia was observed. In patients infected with HCV genotype 3, the concentration of ssDNA was 1343 x 10(-6) microg/mg, +/-700 x 10(-6), comparable from patients infected with genotype 1, 296 x 10(-6) microg/mg, +/- 615 x 10(-6). The highest concentration of ssDNA in liver tissue was detected in HBV infected patients with low inflammatory activity (1645 x 10(-6) microg/mg, +/-987) and low fibrosis (1606 x 10(-6) microg/mg, +/- 876 x 10(-6). Mild inflammatory changes and low fibrosis were observed in all HCV and HIV infected patients. No correlation between ssDNA concentration in liver tissue and HIV viraemia (r = 0.03; p = 0.90), HCV, CD8+ and CD4+ count (r = -11; p = 0.66) was observed. The concentration of ssDNA among HCV and HIV infected patients correlated with the concentration of sFas in serum (r = 0.52; p < 0.02). CONCLUSIONS: HCV, HBV and HIV viraemias do not correlate with ssDNA concentration in liver tissue. In patients with HCV and HIV infections, CD4+ and CD3+ counts do not correlate with the concentration of ssDNA in liver tissue. HIV infection seems to inhibit apoptosis processes in liver tissue of HCV and HIV co-infected patients. In the case of HCV and HIV infections, the concentration of sFas in serum correlates with the concentration of ssDNA in liver tissue.

Opportunistic infections and other AIDS-defining illnesses in Poland in 2000-2002.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) led to a decreased incidence of the most severe opportunistic infections (OIs) in HIV-infected patients. In Poland, HAART became widely used in 1998. MATERIALS AND METHODS: This study was based on data from medical records data collected in the years 2000-2002 from medical centers for HIV-infected patients in Poland. The aim of the study was to determine the incidence of opportunistic infections (OIs) and other AIDS defining illnesses (ADIs). The chi(2) test was used to determine any significant trends. RESULTS: The incidence of ADIs was 6.8, 6.5 and 4.8/100 persons/year in 2000-2002, respectively. The most common diagnosed OIs were: fungal infections, tuberculosis, recurrent pneumonia, PCP and toxoplasmosis. In patients receiving HAART (HAART+) the incidence of ADIs was significantly lower than in non-ARV-treated as well as in all HIV+ (p < 0.02, p < 0.001, p < 0.001, respectively). A significant decrease in the incidence of ADIs in HAART+ patients between 2000 and 2002 (p < 0.0001) was observed. From 25% to 30% of ADIs among HAART+ patients were diagnosed within the first 3 months of antiretroviral therapy. In HAART+ patients the most common ADIs were fungal infections and tuberculosis. The diagnosis of ADIs resulted in the recognition of HIV status in 8.7-8.9% of patients. CONCLUSIONS: Five years after the introduction of HAART the incidence of ADIs had declined. Fungal infections and tuberculosis were the most common OIs in HIV+ patients in Poland.

Transforming growth factor beta1 and prostaglandin E2 concentrations are associated with bone formation markers in ulcerative colitis patients.

Osteoporosis is a significant complication of a multifactoral etiology associated with inflammatory bowel disease. The aim of study was to evaluate the relationships between bone mineral density as well as bone turnover markers and inflammatory activity modulators (i.e., PGE2 and TGFbeta1) in ulcerative colitis (UC). Twenty-one active ulcerative colitis subjects and 14 healthy individuals were included into the study. We observed no significant differences in serum concentrations of osteoprotegerin and osteocalcin, as well as bone mineral density between UC patients and healthy individuals. Plasma concentrations of PGE2, TGFbeta1 and TNF-alpha were significantly higher in UC patients than in controls. Serum osteocalcin demonstrated a positive correlation with both serum PGE2 and plasma TGFbeta1. Moreover there was significant correlation between osteoprotegerin and TGFbeta1 as well as serum TNF-alpha concentrations. In conclusion a positive association between PGE2 and TGFbeta1 and bone formation markers-osteoprotegerin and osteocalcin, as well as a comparable BMD in UC patients and healthy individuals was shown. Our results may indicate that increase of PGE2 as well as TGFbeta1 concentrations may play a protective role against bone loss in ulcerative colitis patients.

Metabolic disturbances in liver 1H MR spectroscopy in HIV and HCV co-infected patients as a potential marker of hepatocyte activation.

PURPOSE: To evaluate proton magnetic resonance spectroscopy (1H MRS) features in order to assess hepatocellular activation in chronic hepatitis C and human immunodeficiency virus/hepatitis C (HIV/HCV) co-infected patients. MATERIAL AND METHODS: Liver in vivo 1H MR spectra were obtained in 14 patients with hepatitis C virus infection (HCV), 20 HIV/HCV co-infected individuals, and 24 healthy volunteers. Resonances of lipids, glutamine/glutamate (Glx), phosphomonoesters (PME), glycogen/glucose (Glc) were assessed and metabolite ratios to total lipids (TL) were calculated. RESULTS: A significant increase in Glx/TL and PME/TL was observed in the HCV group as compared to healthy individuals. Patients with HIV and HCV co-infection had a further increase of all metabolite ratios. Changes in metabolite ratios were due to both the increase in particular metabolite contents and to the decrease in lipid levels. HIV/HCV-infected patients treated with highly active anti-retroviral therapy (HAART) showed elevated PME and Glx levels and significantly decreased TL compared to patients not undergoing anti-retroviral treatment. CONCLUSIONS: Our findings suggest clinical usefulness of liver 1H MR spectroscopy in detecting even slight disturbances in liver metabolism.

Cerebral MR spectroscopy in neurologically asymptomatic HIV-infected patients.

PURPOSE: To detect early metabolic changes in the brain of neurologically asymptomatic HIV-infected patients with normal MR imaging and to find the correlation between 1H MR results and immune status. MATERIAL AND METHODS: Twenty neurologically asymptomatic HIV seropositive patients underwent MR imaging and single-voxel 1H MR spectroscopy (MRS) using a PRESS sequence. For all patients, the signals from N-acetyl-aspartate (NAA), choline-containing compounds (Cho), creatine-phosphocreatine (Cr) and myoinositol (mI) were compared with 32 healthy volunteers as metabolite ratios and metabolite areas to non-suppressed water area ratios. RESULTS: In HIV patients, the NAA/Cho ratio was significantly lower ( p < 0.01), but there were no changes in NAA/Cr ratio. A statistically significant reduction in NAA/H2O and Cr/H2O (both p < 0.05) was observed. For the immune status there was a statistically significant correlation (r=0.47, p<0.05) between CD4 counts and NAA/H2O ratio. A significant increase in Cho/Cr ( p<0.001) and mI/Cr ( p<0.01) ratios in HIV patients was found, but Cho/H2O and mI/H2O concentrations were non-significantly increased. CONCLUSION: These results indicate that neuronal loss and gliosis in HIV-infected patients may be associated with impairment of energy metabolism. The spectral changes found suggest that 1H MRS can be used for early detection of brain damage induced by HIV.

The evaluation of dentition status in HIV-infected patients.

PURPOSE: The aim of the study was the evaluation of dentition status in patients infected with HIV. MATERIAL AND METHODS: We examined 30 HIV + patients, aged 20-46 and 30 non-infected subjects as the control group. Oral hygiene and dentition status were estimated. Oral hygiene status using simplified OHI-plague index according to Green and Vermilion. Dentition status was analysed using decay intensity index (DMF) as well as teeth loss index according to Rogowiec. The results were analysed in dependence on HIV infection with regard to infection time. RESULTS: The results point to a high intensity of decay in HIV+ patients (23.66). There was a positive correlation between infection time and decay intensity and teeth loss evaluated using Rogowiec index. Unsatisfactory oral hygiene status (OHI > or = 1) was observed in 53.33% of infected patients. There is a relation between infection time and oral hygiene status. OHI-plague index increased in patients with infection time longer than 5 years up to 2.99 (patients with shorter than 5 years infection time--1.17 and the control group--0.57). CONCLUSIONS: 1. There is a positive correlation between HIV infection and dentition status and oral hygiene. 2. Infection time influences index values: decay intensity, teeth missing, and oral hygiene. 3. HIV+ subjects are patients of high necessity of therapy and because of their basic disease they should come within broadened health education and prophylactic activities.

Effect of ulcerative colitis activity on plasma concentration of transforming growth factor beta1.

Enhanced expression of transforming growth factor-beta1 (TGF-beta1) demonstrated in human colonic mucosa of patients with ulcerative colitis (UC), indicates its possible significance in the pathogenesis of this disease. The aim of this study was to evaluate plasma TGF-beta1 concentration in patients with different degrees of colonic mucosal injury, as a possible indicator of ulcerative colitis activity. TGF-beta1 concentration was measured with an enzyme immunoassay (EIA) in plasma of 45 patients with endoscopically confirmed UC. Values observed in UC patients (40.5+/-15.9 ng/ml) were significantly higher than in healthy people (18.3+/-11.6 ng/ml) and higher than in patients with irritable colon syndrome (ICS), (20.5+/-13.6 ng/ml). The highest plasma TGF-beta1 (58.6+/-112.1 ng/ml) was in patients with the severe UC course. TGF-beta1 level analysed in all UC patients revealed significant positive correlation with scored degree of mucosal injury (r=0.396;P<0.01). Among other possible laboratory markers of the disease activity, only C-reactive protein concentration demonstrated significant correlation. Enhanced production of TGF-beta1 can be related to inflammation activity. Measurement of plasma TGF-beta1 may be considered as a biomarker of the disease activity.

[The role of transforming growth factors beta in pathogenesis of ulcerative colitis]. / Rola transformujacych czynników wzrostu beta w patogenezie wrzodziejacego zapalenia jelita grubego.

Transforming growth factor beta is the protein playing a principal role in the intercellular signalling. The most important functions are: control of cellular growth, differentiation and migration. Moreover it stimulates synthesis of extracellular matrix proteins, modulates immune response and is responsible for angiogenesis, wound formation and tissue reconstruction. All these activities are involved in the development or healing of inflammatory bowel diseases. The role of transforming growth factors beta in the pathogenesis of ulcerative colitis are discussed in this paper.

[Magnetic resonance imaging and spectroscopic metabolites assessment in brain cryptococcosis]. / Rezonans magnetyczny i spektroskopowa ocena metabolitów tkanki mózgowej w przebiegu kryptokokozy oun.

Cryptococcus neoformans is the causative agent of cryptococcosis and cryptococcal meningitis, which are serious pathological conditions affecting up to 10% of patients with AIDS. In this paper we present results magnetic resonance imaging and spectroscopic metabolites (1H MR) in brain cryptococcosis. In 1 HMR spectroscopy we find decreased metabolic ratios to nonsaturated water (H2O) signal N-acetylaspartate (NA/H2O, creatine (Cr/H20), choline (Cho/H2O). We show increased mioinositol to H2O ratio. Spectroscopy results suggest about massive neuronal injury and accompanying gliosis in brain cryptococcosis.

Plasma and mucosal prostaglandin E2 as a surrogate marker of ulcerative colitis activity.

BACKGROUND: Enhanced production of prostaglandin E2 was observed in the course of inflammatory bowel diseases. The study was undertaken to determine whether mucosal and plasma concentrations of PGE2 can be considered as a surrogate marker of bowel inflammation activity in patients with ulcerative colitis. METHODS: Prostaglandin E2 concentration was measured with an EIA in biopsies of rectal mucosa and plasma of 79 patients with ulcerative colitis and 12 controls. Endoscopic picture was scored and compared with plasma and mucosal PGE2, as well as with possible laboratory markers of the disease activity, including C-reactive protein, albumin, gamma-globulin, haemoglobin concentrations, and sedimentation rate, white blood count and platelets count. RESULTS: Plasma and mucosal PGE2 demonstrated in ulcerative colitis exceeded control level over five and three fold respectively. They increased depending on the scored degree of mucosal injury, demonstrated through significant positive correlation (r = 0.437 and r = 0.525). Among other possible laboratory markers of the disease activity, only sedimentation rate revealed significant correlation (r = 0.288). CRP demonstrated weak association with the disease activity and there was almost lack of any association in respect to white blood count, and albumin or gamma-globulin concentrations. CONCLUSION: These data confirm possible usefulness of plasma or mucosal PGE2 measurement in patients with ulcerative colitis as a possible marker of inflammation. Moreover, as a prognostic factor it can reduce the number of endoscopic procedures.

[Antibodies against M2-antigen in differential diagnosis of primary biliary cirrhosis]. / Przeciwciala przeciw antygenowi M2 w diagnostyce róznicowej pierwotnej marskosci zólciowej watroby.

Measurement of antimitochondrial antibodies is established as a sensitive indicator for primary biliary cirrhosis, which has unfortunately limited diagnostic specificity. M2-antigen complex, consisted of four proteins of the inner mitochondrial membrane, has been found to be strongly associated with PBC. Clinical value of anti-M2 antibodies quantitative measurement with ELISA was analysed in 107 patients with carefully diagnosed liver diseases: acute viral hepatitis A, B, C (VHA, VHB, VHC; n = 41), chronic viral hepatitis B, C (CHB, CHC; n = 23), autoimmune hepatitis (AH; n = 6), liver cirrhosis (LC; n = 20), extrahepatic cholestasis (EC; n = 2) and primary biliary cirrhosis (PBC; n = 15). The highest values were found in PBC patients and varied from 92 to 167 U/l and dramatically exceeded normal range recommended by manufacturer (5 U/l). Mean value in this group (119.5 +/- 8.4 U/l) was significantly (p < 5 x 10(-8)) higher than in others, that varied from 1.3 +/- 0.2 up to 2.8 +/- 1.7 U/l in VHA and CHC groups respectively. Only two among 92 non-PBC patients have values over 10 U/l, but they reached only 15.8 (CHB) and 16.5 (CHC). Anti-M2 level in PBC patients demonstrated a significant positive correlation (r = 0.857) with the degree of liver insufficiency measured trough Child-Pugh score. From these data we can conclude, that quantitative measurement of anti-M2 antibodies with ELISA can serve as a very good screening for PBC, with 100% diagnostic sensitivity and specificity, if concentration of 20 U/l will be established as a pathognomic level.

[Vaccination against influenza and Guillain-Barre syndrome: are there any relations?]. / Szczepienia przeciwko grypie a zespól Guillain-Barré--wzajemne zaleznosci?

Influenza, a disease known for centuries, continues to be a major medical problem throughout the world with substantial economical and health impact. The risk of death related to influenza is higher among individuals over 65 years of age and those with chronic diseases. Vaccination against influenza was successfully applied in massive prophylaxis of the disease in different countries for many years. Although there are some well known and monitored adverse reactions to influenza vaccines, the evidence whether influenza vaccination might be causally associated with higher risk of Guillain-Barré syndrome is not clear. In this paper the available literature data concerning this problem were reviewed. Own experiences on influenza vaccination and plasmapheresis treatment of Guillain-Barré syndrome were presented.

[Transforming growth factor beta in pathogenesis of liver diseases]. / Transformujacy czynnik wzrostu beta w patogenezie chorób watroby.

Transforming growth factor (TGF-beta) is the protein playing a principal role in the intracellular signalling. The most important function is ability to stimulate synthesis of extracellular matrix proteins, what is responsible for wound formation and tissue reconstruction. The damage of hepatocytes is a signal for macrophages and platelets activation, resulting in release of TGF-beta and over-expression of genes responsible for morphologic and functional changes in Ito cells. They undergo transformation into myofibroblasts and become the source of extracellular matrix proteins, such as: collagens, fibronectin, laminin, entactin, tenascin, undulin. The consequence of their accumulation in the space of Disse and inside hepatic lobuli is fibrosis, which is the form of tissue healing in the place of necrosis. However continuous action of damaging agent leads to massive fibrosis and reconstruction of liver, what is clinically manifested as cirrhosis. The role of transforming growth factor beta in the pathogenesis of liver diseases and its possible use as an indicator of disease progression were discussed in this paper.

Beta 2-microglobulin and neopterin in patients with giardiasis.

The aim of the study was to evaluate serum beta 2-microglobulin (beta-2m) and neopterin (NPT) in in patients with giardiasis. Twenty-two patients with giardiasis were examined and compared with twelve healthy subjects as a control group. Serum beta-2m and NPT concentration were determined twice: at the moment of diagnosis of giardiasis and six months after antiparasitic treatment with metronidazole. It was shown that serum beta-2m concentration in patients with giardiasis was remarkably elevated. It decreased significantly, but six months after treatment it was still higher as compared to the control group. However, serum NPT before anti-parasitic treatment was slightly lower than in the control group, but after elimination of Giardia an increase of NPT concentration above control values was observed. It is concluded that Giardia infection leads to long-lasting disturbances in the immunological status of the host and may influence macrophage function and downregulate their parasiticidal effects.

Effects of ulcerative colitis activity on plasma and mucosal prostaglandin E2 concentration.

The aim of this study was to determine effects of changes in ulcerative colitis activity on mucosal and plasma PGE2 concentrations measured with an EIA in 49 patients who underwent sigmoidoscopy. The disease was diagnosed in 37 patients. Twelve patients with normal colonic mucosa served as controls. Patients were divided into three groups depending on the changes of endoscopic picture during a three-month follow-up. Some laboratory markers of the disease activity, such as C-reactive protein, albumin, gamma-globulin and hemoglobin concentrations, sedimentation rate, and white blood and platelets counts, were also evaluated. Initial examination revealed a significant, positive correlation of mucosal and plasma PGE2 concentration with endoscopic score. Follow-up of patients without significant progression of mucosal changes revealed constant and close to normal concentration of mucosal PGE2. Plasma PGE2 was higher at the second examination, yet without significant difference. Improvement of endoscopic picture resulted in significant decrease of plasma and mucosal PGE2 concentrations. Worsening of mucosal changes reflected endoscopically was associated with significant increase of PGE2. There were no remarkable changes in the values of analyzed laboratory markers of the disease activity. These results indicate the usefulness of mucosal or plasma PGE2 measurement as a possible prognostic marker in patients with ulcerative colitis.

Mucosal and plasma prostaglandin E2 in ulcerative colitis.

BACKGROUND/AIMS: Despite extensive studies, the role of prostaglandins in the course of inflammatory bowel diseases and their possible usefulness as predictive indicators of inflammation, remain largely speculative. The aim of this study was to determine whether mucosal and plasma concentrations of prostaglandin E2 (PGE2) are affected by the clinical course and degree of colonic injury in patients with ulcerative colitis. METHODOLOGY: PGE2 concentration was measured with an enzyme immunoassay (EIA) in biopsies of rectal mucosa and in the plasma of 38 patients with ulcerative colitis and 12 controls. Patients were divided into groups according to mild or severe clinical course of the disease, and with respect to scored endoscopical picture. RESULTS: Ulcerative colitis resulted in an increase of mucosal and plasma concentrations of PGE2, that was significantly elevated in patients with a severe clinical course of the disease. These concentrations increased depending on degree of mucosal injury. A significant, positive correlation with endoscopical score regarding plasma and mucosal PGE2 concentration, as well as between them, was found. CONCLUSIONS: Plasma and mucosal PGE2 rise simultaneously with degree of colonic injury. Because of a good correlation with mucosal injury and PGE2 content, measurement of plasma PGE2 could be considered as a possible surrogate marker of bowel inflammation.