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.

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.

Observations of mineralised tissues of teeth in X-ray micro-computed tomography.

BACKGROUND: The one of the most recent imaging technology is X-ray microtomography which allows non-invasive three-dimensional visualisation of structures. It also offers the opportunity to conduct a comprehensive quantitative analysis of the tested objects such as measuring the shares of the various phases, determining the material density and distribution of the size of pores and particles. The aim of the paper was to present an overview on the applicability and relevance of X-ray microtomography in the study of mineralised tissues of the teeth. MATERIALS AND METHODS: The article is based on the most recent and significant literature and own observations. RESULTS: The use of X-ray microtomography in dentistry has recently increased and includes, inter alia, the assessment of the density of minerals in enamel and dentin, the detection of demineralisation in an artificially and a naturally induced caries, the automatic measurement of the depth of cavities in dentin, the measurement of the amount of removed dentin in preparation of carious lesions by various methods, the assessment of microleakage around fillings and fissure sealants, cortical bone density measurement, evaluation of root canal morphology, comparison of the accuracy of root canal working and filling by various methods. CONCLUSIONS: X-ray microtomography offers within the analysis of mineralised tissues - complex structures of bone, teeth and biomedical materials, turn out to be indispensable since it opens new opportunities for cognitive and implementation research.

Development and evaluation of a baseline-event-anticipation score for hepatitis delta.

Hepatitis delta is considered the most severe form of viral hepatitis, but variables associated with disease progression are poorly defined. This study aimed to identify risk factors associated with worse clinical outcome in patients with hepatitis delta and to develop a clinical score to determine their risk of experiencing liver-related morbidity or mortality. We followed 75 HBsAg-anti-HDV-positive patients with hepatitis delta for up to 16 years (median 5 years). The baseline-event-anticipation score (BEA score) was developed based on variables associated with the development of liver-related clinical complications. Age, region of origin, presence of cirrhosis, albumin, INR, hyperbilirubinemia and thrombocytopenia were all associated with the development of an event in the training cohort. The BEA score included age, sex, region of origin, bilirubin, platelets and INR. Points were allocated according to hazard ratios, and three risk groups were defined: BEA-A mild risk, BEA-B moderate risk and BEA-C high risk. Hazard ratios of BEA-B and BEA-C patients for liver-related clinical endpoints were 9.01 and 25.27 vs BEA-A with an area under curve of the receiving operating characteristic curve of 0.88. The accuracy of the BEA score was confirmed in two independent validation cohorts followed in Barcelona (n = 77) and Düsseldorf (n = 62). Delta hepatitis is associated with a very severe long-term outcome. The BEA score is easy to apply and predicts with a very high accuracy the development of liver-related complications in patients with hepatitis delta.

Clinical value and safety of liver biopsies in patients transplanted for hepatitis C virus-related end-stage liver disease.

BACKGROUND: Hepatitis C is the leading indication for liver transplantation. Differentiation between recurrent graft hepatitis C (RGH-C) and graft rejection (GR) is challenging. Liver biopsy is standard to diagnose both conditions; however, little information is available regarding this procedure in hepatitis C virus (HCV)-infected liver transplant recipients. METHODS: Liver biopsies (n = 211) from all consecutive patients (n = 138) transplanted for hepatitis C at Hannover Medical School between January 2000 and October 2011 were screened, and a final cohort of 96 patients with 196 biopsies was included. Indications, histopathological findings, and biopsy-related complications were documented. Modifications in the treatment based on the biopsy result and the biochemical outcome were analyzed. RESULTS: Most biopsies (196/211, 93%) were representative. Five patients (2.5%) developed non-fatal biopsy-related complications. Biopsy results were GR (35%), RGH-C (31%), and other diagnoses (34%). GR was independently associated with lower albumin (P = 0.025) and higher bilirubin levels (P = 0.011). Treatment was modified based on the biopsy result in 25% of cases. Alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and bilirubin levels improved in 41%, 25%, and 31% of cases 4 weeks post biopsy respectively. ALT improvements were more significant in patients with GR than in those with RGH-C. CONCLUSION: Liver biopsy in HCV-infected liver transplant recipients is safe and representative in >90% of cases. GR is independently associated with lower albumin and higher bilirubin levels.

Development of a protocol for the quantitative determination of HBeAg using the Elecsys® HBeAg immunoassay.

Loss of hepatitis 'e' antigen (HBeAg) in patients with HBeAg-positive chronic hepatitis B is associated with improved long-term clinical outcome and is defined as a goal of antiviral treatment by clinical practice guidelines. Recent studies suggest that baseline levels and on-treatment monitoring of HBeAg levels may identify patients most likely to respond to therapy. The aim of this study was the development of a protocol for the quantitative determination of HBeAg using the Elecsys® HBeAg immunoassay. The linear range of the Elecsys® HBeAg immunoassay was established using recombinant HBeAg and five different diluents. The assay was validated against the Paul Ehrlich Institute (PEI) international standard serum. Linearity was demonstrated up to a cut-off index (COI) of 1000, independent of the diluent used. Optimal linearity was obtained using the Elecsys® Universal Diluent. Using the PEI reference standard, conversion factors were established as 4.50 COI for 1 PEIU/mL corresponding to 0.222 PEIU/mL for a COI of 1. Based on the results from these analyses, a simple algorithm for the quantitative measurement of HBeAg using the Elecsys® HBeAg immunoassay was developed. Using a simple algorithm with an initial 1:40 dilution, the Elecsys® HBeAg assay provides robust quantification of serum HBeAg in an easy-to-use and rapid system. The use of a commercially available, standardized diluent improves comparability between laboratories.

Treatment of chronic hepatitis B.

Approximately 350-420 million people worldwide are chronically infected with hepatitis B virus (HBV). Chronic hepatitis B can result in liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Reactivation of hepatitis B is possible in patients with inactive or resolved hepatitis B often leading to liver failure. Those sequelae may be prevented by effective antiviral therapy. Interferon alfa, pegylated interferon alfa and five direct antiviral nucleoside and nucleotide analogues are approved for the treatment of chronic hepatitis B. Still, whom to treat, which therapy regimen to use, and when to begin treatment remain the challenges in the management HBV-infected patients. This review focuses on the current treatment concepts for chronic hepatitis B.

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.

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.

Serum adiponectin and leptin levels in psoriatic patients according to topical treatment.

OBJECTIVES: Psoriasis has been considered as a systemic disease associated with obesity, cardiovascular diseases and metabolic syndrome. Adipokines have influence on many metabolic processes. Aim of this study was to evaluate the effect of conventional topical treatment on serum adiponectin and leptin levels in patients with psoriasis. METHODS: Forty-nine patients with relapse of plaque-type psoriasis and 16 healthy controls were examined. Blood samples were collected before therapy and after 14 days of application. Serum adiponectin and leptin concentrations were examined by enzyme-linked immunosorbent assay for correlations with effectiveness of topical treatment. RESULTS: Adiponectin and leptin serum levels were significantly decreased in psoriatic patients in comparison to the controls. As a result of the topical treatment, serum adiponectin level did not significantly change. Serum leptin level increased significantly, still remaining lower than in the controls. CONCLUSIONS: Leptin might be a useful marker in assessing the efficacy of the treatment for psoriasis.

Dominance of hepatitis C virus (HCV) is associated with lower quantitative hepatitis B surface antigen and higher serum interferon-γ-induced protein 10 levels in HBV/HCV-coinfected patients.

Different viral dominance patterns have been documented in coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) based on HBV DNA and HCV RNA quantification. In most cases, HCV is dominant and suppresses HBV replication. In vitro studies revealed that there is most probably no direct interference between HBV and HCV replication. We hypothesized that indirect mechanisms mediated by host immune responses might be responsible for the different dominance patterns. In this study we analysed quantitative hepatitis B surface antigen (HBsAg) as a marker for immune control of HBV and interferon γ-induced protein 10 (IP-10) as host marker for the endogenous interferon in 85 patients with HBV/HCV coinfection. Levels of HBsAg were closely associated with viral dominance patterns in 85 HBV/HCV-coinfected patients. HBsAg levels were lowest in patients with HCV dominance, even lower compared with HBV-monoinfected patients undergoing treatment with nucleos(t)ide analogues (NA) but comparable to low replicative HBsAg carriers. An increase in HCV RNA during follow up was associated with HBsAg decline. Patients with HCV dominance had significantly higher serum IP-10 levels compared with HBV-dominant patients or HBV-monoinfected patients treated with NA. Lower HBsAg and higher IP-10 levels in HCV-dominant HBV/HCV-coinfected patients suggest that HCV suppresses HBV DNA replication and also HBsAg production by immune mechanisms.

Hepatitis B core-related antigen (HBcrAg) levels in the natural history of hepatitis B virus infection in a large European cohort predominantly infected with genotypes A and D.

Hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. HBcrAg combines the antigenic reactivity resulting from denatured hepatitis B e antigen (HBeAg), HBV core antigen and an artificial core-related protein (p22cr). In Asian patients, high levels of HBcrAg have been suggested to be an independent risk factor for hepatocellular carcinoma, while low levels could guide safe cessation of treatment with nucleos(t)ide analogues. We here studied HBcrAg levels in different phases of HBV infection in a large European cohort predominantly infected with genotypes A and D: HBeAg-positive immune tolerance (n = 30), HBeAg-positive immune clearance (IC) (n = 60), HBeAg-negative hepatitis (ENH) (n = 50), HBeAg-negative inactive/quiescent carrier phase (c) (n = 109) and acute hepatitis B (n = 8). Median HBcrAg levels were high in the immune tolerance and immune clearance phases (8.41 and 8.11 log U/mL, respectively), lower in ENH subjects (4.82 log U/mL) but only 2.00 log U/mL in ENQ subjects. Correlation between HBcrAg and HBV DNA varied among the different phases of HBV infection, while HBcrAg moderately correlated with hepatitis B surface antigen in all phases. ENQ patients had HBcrAg levels <3 log U/mL in 79%, in contrast to only 12% in the ENH group. HBcrAg levels vary significantly during the different phases of HBV infection. HBcrAg may serve as valuable marker for virus replication and reflect the transcriptional activity of intrahepatic cccDNA. In HBeAg-negative patients, HBcrAg may help to distinguish between inactive carriers (ENQ) and those with active disease (ENH).

[Primary biliary cirrhosis]. / Pierwotna marskosc zólciowa watroby.

Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterised by the destruction of small intrahepatic bile ducts. Although known for many years its etiology and pathogenesis still remains uncertain. Alterations of humoral and cellular immune functions suggests an autoimmune pathogenesis. Primary biliary cirrhosis typically affects middle-aged women who reports fatigue and itching. Diagnosis is usually based on abnormal biochemical tests of liver function, presence of antimitochodrial antibodies (especially anti-M2) and histologic evaluation of liver biopsy specimens. Relatively small number of diagnosed cases in Poland may be due to insufficient knowledge on this disease in our country.

Solid state speciation and potential bioavailability of depleted uranium particles from Kosovo and Kuwait.

A combination of synchrotron radiation based X-ray microscopic techniques (mu-XRF, mu-XANES, mu-XRD) applied on single depleted uranium (DU) particles and semi-bulk leaching experiments has been employed to link the potential bioavailability of DU particles to site-specific particle characteristics. The oxidation states and crystallographic forms of U in DU particles have been determined for individual particles isolated from selected samples collected at different sites in Kosovo and Kuwait that were contaminated by DU ammunition during the 1999 Balkan conflict and the 1991 Gulf war. Furthermore, small soil or sand samples heavily contaminated with DU particles were subjected to simulated gastrointestinal fluid (0.16 M HCl) extractions. Characteristics of DU particles in Kosovo soils collected in 2000 and in Kuwait soils collected in 2002 varied significantly depending on the release scenario and to some extent on weathering conditions. Oxidized U (+6) was determined in large, fragile and bright yellow DU particles released during fire at a DU ammunition storage facility and crystalline phases such as schoepite (UO(3).2.25H(2)O), dehydrated schoepite (UO(3).0.75H(2)O) and metaschoepite (UO(3).2.0H(2)O) were identified. As expected, these DU particles were rapidly dissolved in 0.16 M HCl (84 +/- 3% extracted after 2 h) indicating a high degree of potential mobility and bioavailability. In contrast, the 2 h extraction of samples contaminated with DU particles originating either from corrosion of unspent DU penetrators or from impacted DU ammunition appeared to be much slower (20-30%) as uranium was less oxidized (+4 to +6). Crystalline phases such as UO(2), UC and metallic U or U-Ti alloy were determined in impacted DU particles from Kosovo and Kuwait, while the UO(2,34) phase, only determined in particles from Kosovo, could reflect a more corrosive environment. Although the results are based on a limited number of DU particles, they indicate that the structure and extractability of DU particles released from similar sources (metallic U penetrators) will depend on the release scenarios (fire, impact) and to some extent environmental conditions. However, most of the DU particles (73-96%) in all investigated samples were dissolved in 0.16 M HCl after one week indicating that a majority of the DU material is bioaccessible.

HBV-DNA and sFas, sFasL concentrations in serum of healthy HBsAg carriers.

PURPOSE: Increased HBV-DNA concentration is a prognostic factor of disease progression in chronic hepatitis B patients. Moreover, active hepatic inflammation during HBV replication influences apoptosis intensification. The aim of this study was to estimate occurrence of HBV replication among carriers of HBsAg. Furthermore, we analysed the correlation between HBV replication and HBeAg or anti-HBe presence as well as known apoptosis indicators--sFas and sFasL concentration. MATERIAL AND METHODS: The study included 34 HBV infected patients, aged 20-43 yrs defined as HBsAg healthy carriers. HBV-DNA was extracted from patients' serum using two different DNA isolation kits: the QIAamp DNA Mini Kit (QIAGEN Ltd, USA) and the Gene Elute Mammalian Genomic DNA Miniprep Kit (Sigma, USA). HBV-DNA concentration in serum was measured by RT-PCR based on TaqMan Universal Master Mix (Applied Biosystems). The detection limit of this system was as few as 10 HBV-DNA copies/mL of serum. HBV-DNA concentration was calculated from a linear standard curve obtained between 10 and 10(8) DNA copies/reaction. HBeAg and anti-HBe in serum were detected by MEIA method (ABBOTT, Germany). The concentration of sFas and sFasL in serum was-estimated by ELISA method (Bender MedSystems, Austria). RESULTS: HBV active replication was detected in 79% HBsAg carriers. The HBV-DNA levels exceeding 10(5) copies/mL were observed in 64% patients. Among HBsAg carriers presenting HBeAg, HBV replication occurred more often and was more intensify than in HBsAg carriers presenting anti-HBe antibodies. The sFasL occurrence in serum of 56% HBsAg carriers shows an active apoptosis, independent from ALT and AST activity within normal ranges.

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.