Summary
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.
Summary
We followed for 2 years patients treated with direct‐acting agents (DAA) to assess long‐term durability of virologic response, improvement of liver function, reduction in liver stiffness (LS) ...and risk of hepatocellular carcinoma (HCC). The study included patients from 16 hepatologic centres involved in the AMBER, investigator‐initiated study on treatment of chronic hepatitis C patients within a programme preceding EU registration of ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. A total of 204 patients among 209 from the primary study were enrolled, 200 with available testing at 2‐year follow‐up (2yFU) with undetectable HCV RNA (198 responders and 2 nonresponders retreated). During 2yFU, 4 patients died, 17 had hepatic decompensation and 3 needed liver transplantation. De novo hepatocellular carcinoma was diagnosed in 4 and its recurrence in 3 patients. Significant decreases in bilirubin, MELD, Child‐Pugh scores and liver stiffness, and increases in albumin level were observed during 2yFU. Strengths of the study were a fixed period of post‐treatment follow‐up, prospective character of the study and high proportion of available patients from the primary study. The major weaknesses were lack of a comparative arm and relatively insufficient number of patients for subsets analysis. In conclusion, 2‐year follow‐up confirmed durability of virologic response after treatment of HCV infection with ombitasvir/paritaprevir/ritonavir±dasabuvir±ribavirin. It was accompanied by significant improvement of major measures of hepatic function and reduction of hepatic stiffness. Successful therapy did not prevent hepatic decompensation, HCC or death in cirrhotics that support the need for longer than 2‐year monitoring for possible disease progression.
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.
Summary
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.
Over the past two decades Clostridium difficile infection (CDI) has appeared as a major public health threat. We performed a retrospective study based on the records of patients hospitalized for CDI ...at the University Hospital in Krakow, Poland, between 2008 and 2014. In the study period, CDI occurred in 1009 individuals. There were 790 (78%) individuals who developed infection only once, whereas 219 (22%) developed infection more than once. The percentage of deaths within 14 days of CDI confirmation was 2·4%, with a mean age of 74·2 ± 15·9 years. Crude mortality was 12·9% in medical wards, 5·6% for surgical wards and 27·7% in the ICU setting. The time span between diagnosis and death was 5·1 days on average. Between 2008 and 2012 a 6·5-fold increase of CDI frequency with a posterior stabilization and even reduction in 2013 and 2014 was observed. According to the data analysed, 2/3 patients in our population developed CDI during their hospitalization even though they were admitted for different reasons. Medical wards pose a significantly higher risk of CDI than the surgical ones. Age is a risk factor for CDI recurrence. In the case of patients who died, death occurred shortly after diagnosis. The first CDI episode poses much higher risk of mortality than the consecutive ones.
It is widely accepted that the pathogenesis of Clostridium difficile infection (CDI) is multifactorial, dependent on pathogen virulence factors produced by the organism as well as disorders of the ...gastrointestinal tract, the alteration in intestinal flora and the immune response of the host. In particular, the immune response in the course of CDI and the involvement of cytokines in the pathogenesis of CDI is not fully understood. The aim of our study was to evaluate the relationship between proinflammatory and anti-inflammatory cytokines and the course of CDI in vivo. We prospectively studied 80 patients. Our study group included 40 patients aged 30-87 years (mean age 66.9 years) with CDI hospitalized at Infectious Diseases Department and Gastroenterology and Hepatology Clinic, University Hospital in Cracow, and 40 healthy volunteers aged 24-62 years (mean age 51.1 years). The serum concentrations of cytokines IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and prostaglandin E2 (PGE2) were measured using ELISA assays. Additionally, the routine biochemical parameters were assessed including the following: white blood cells with differential leukocyte count, platelets counts, and blood plasma levels of creatinine, alanine transaminase, and C-reactive protein were determined. We noted a significant increase in the concentration of the following cytokines in the CDI group when compared to the control group: IL-1b (4.7 vs. 3.6 pg/ml), IL-6 (21.0 vs. 0.04 pg/ml), IL-10 (8.5 vs. 0.5 pg/ml), TNF-α (7.1 vs. 0.09 pg/ml). In addition the serum concentration of MPO (1056.0 vs. 498.0 pg/ml), and PGE2 (2036.7 vs. 1492.0 pg/ml) showed a significant increase in CDI patients as compared with control subjects. Most CDI patients did not show any increase in the concentration of IL-8. We did observe a direct relationship between TNF-α and creatinine. The course of CDI is characterized by an initial local inflammatory process followed by a systemic inflammatory response, which manifests clinically as fever, and includes leukocytosis, an increase in the level of neutrophils in the blood, and an increase in the serum concentrations of TNF-α, IL-1β, IL-6, IL-10, MPO and PGE2. Despite the leading role of IL-8 in the local inflammatory process, we postulate TNF-α and IL-6 play a key role in the systemic inflammatory response in CDI, and the plasma TNF-α level seems to act as a major factor of poor prognosis in patients with CDI.
Clostridium difficile infection (CDI) has become one of the major public health threats in the last two decades. An increase has been observed not only in the rate of CDI, but also in its severity ...and mortality. Symptoms caused by this pathogen are accompanied by intense local and systemic inflammation. We confirmed that Raman microspectroscopy can help us in understanding CDI pathogenesis. A single erythrocyte of patients with CDI shows a difference, approximately 10 times, in the intensity of the Raman spectra at the beginning of hospitalization and after one week of treatment. The intensity level is an indicator of the spread of the inflammation within the cell, confirmed by standard laboratory tests. Many of the observed bands with enormously enhanced intensity, e.g. 1587, 1344, 1253, 1118 and 664 cm(-1), come from the symmetric vibration of the pyrrole ring. Heme variation of recovered cells in the acute CDI state between the first and the seventh day of treatment seems to show increased levels of oxygenated hemoglobin. Intense inflammation alters the conformation of the protein which is reflected in the significant changes in the amide I, II and III bands. There is an observed shift and a significant intensity increase of 1253 and 970 cm(-1) amide III and skeletal protein backbone CC stretching vibration bands, respectively. Principal Component Analysis (PCA) was used to find the variance in the data collected on the first and seventh day. PC2 loading in the 1645-1500 cm(-1) range shows an increase of heme, Tyr, Trp, or Phe vibrations because of changes in the protein microenvironment due to their exposure. Positive maxima at 1621, 1563 and 1550 in the PC2 loading originated from the ring vibrations. These observations indicate that Clostridium difficile toxins induce cytopathogenicity by altering cellular proteins.
In several cases of meningitis routinely used diagnostic procedures are unable to identify the cause of this disease. The objective of the present study was to determine whether proinflammatory ...cytokine (tumour necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8)) and nitric oxide (NO) concentrations in the CSF are useful markers for the differential diagnosis of meningitis.
Sixty-seven patients (42 patients with bacterial meningitis and 25 patients with viral meningitis) were included in the present study. In the investigated group, the TNF-α, IL-1β and IL-8 concentrations in the CSF samples collected on the day of admission were assessed. Furthermore, the NO concentrations were assessed in 23 patients.
The results revealed that the measurement of proinflammatory cytokines in CSF can aid in a differential diagnosis. In particular, a high concentration of TNF-α may be a sensitive and specific marker of a bacterial aetiology of the neuroinfection. In the present study, TNF-α concentrations greater than 75.8 pg/ml differentiated between bacterial and viral meningitis with 100% sensitivity and specificity. The NO concentration in the CSF was also significantly greater in patients with bacterial meningitis than in those with viral meningitis.
The assessment of TNF-α, IL-1β and IL-8 concentrations in the CSF is useful in the differential diagnosis of neuroinfection. Because many factors may influence NO production in the central nervous system (CNS), it is not clear whether NO values can be used for the differential diagnosis of meningitis, and further studies are required
