Five-Years Outcome Analysis of 142 Consecutive Hepatocellular Carcinoma Patients Treated with Doxorubicin Eluting Microspheres 30-60 µm: Results from a Single-Centre Prospective Phase II Trial.

PURPOSE: To assess prospectively long-term results of doxorubicin-loaded HepaSphere 30-60 µm in consecutive patients with hepatocellular carcinoma (HCC) not amenable to curative treatments. PATIENTS AND METHODS: Single-center study from June 2011 to December 2015 in 151 patients treated with 75 mg of doxorubicin per HepaSphere vial. Baseline: Barcelona Clinic Liver Cancer BCLC A/B was 49.3%/50.7%, and median diameter 6.1 cm (mean 6.7 ± 2.0). Liver function, local response (mRECIST), liver time to progression (LTTP), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were recorded. RESULTS: Final analysis included 142 patients with median follow-up of 46.8 months (range 4-72) without grade 4/5 AEs, and 30-day mortality was 0%. Mean number of scheduled treatments was 2.6 (range 1-3) and on demand 3 (range 1-8). Complete response for single tumor ≤ 5 cm was 75.0% and 66.7% for Child A and Child B, while for > 5 cm was 28.6% and 11.8%, respectively. OS was 31.0 months (mean 33.3 ± 15.2; range 8-69), notably for BCLC A 41 months (mean 41.1 ± 15.3; range 13-69) and for BCLC B 26.0 (mean 26.0 ± 10.5; range 8-51). OS at 1, 3 and 5 years: 95.8%, 75.7% and 21.4% for BCLC A, and 94.4%, 36.1% and 2.7% for BCLC B. Median LTTP for BCLC A was 11 months (mean 11.9 ± 4.7; range 3-24) and 7.5 for BCLC B (mean 7.9 ± 2.9). Local response was significant for OS and LTTP (p < 0.0001), while size and lesion number affected LPFS and OS (p < 0.001). CONCLUSIONS: HepaSphere 30-60 µm loaded with doxorubicin provides a safe and effective treatment option for patients with HCC.

Seroepidemiological investigation of Toxocara canis in a female Greek pregnant population in the area of Athens.

UNLABELLED: The purpose of this study was to investigate the of areas where the soil is contaminated by Toxocara ova and also to assess seroepidemiological positivity in a Greek pregnant women population (ELISA IgG test). MATERIALS AND METHODS: The authors carried out an examination of soil samples collected from different areas of Athens and Piraeus (Kazakos method). Blood serum was only collected from pregnant women living and conducting activities in places close to the places where the soil sample's were collected for at least a decade (ELISA IgG assay). RESULTS: The authors suggest a correlation between the positive response in the ELISA assay IgG antibodies and the activities of people where soil was contaminated by Toxocara eggs. In conclusion, the prevalence of Toxocara canis infection in a population of Greek pregnant women was found to be a rate of 17.16% and the soil contamination rate of 17.08%.

Factors associated with delayed hospital arrival among patients with acute myocardial infarction: a cross-sectional study in Greece.

BACKGROUND: It is proven that early admission to hospital contributes significantly to the successful management of acute myocardial infarction (AMI). AIM: This study aimed to examine the factors associated with delayed hospital arrival among patients with AMI. METHODS: A cross-sectional study among 477 AMI patients was conducted during a 2-year period in two large tertiary hospitals in Greece. Structured face-to-face interviews were conducted and information regarding their socio-demographic characteristics, medical history and factors that might be correlated with delayed hospital arrival were collected. RESULTS: The main factors that were found to be correlated with delayed hospital arrival among AMI patients were the absence of companion/attendant/escort present during the AMI [odds ratio (OR) 2.1, 95% confidence interval (CI) 0.98-4.4, P = 0.049], previous medical history of diabetes mellitus (OR 3.4, CI 1.6-7.2, P = 0.002), absence of dyspepsia (OR 9.2, CI 3.6-23.3, P < 0.001) and nausea/vomiting symptoms (OR 16.9, CI 4.1-69.1, P < 0.001), and also being at a distance of more than 10 km from the hospital (OR 19.6, CI 5.4-70.6, P < 0.001). CONCLUSION: A number of factors that might delay hospital arrival among patients with AMI should be taken into account in healthcare service planning. Health policy actions that will improve the accessibility to healthcare services, the restructuring of the Greek primary healthcare system and the provision of effective patient education by nurses could reduce the pre-hospital delay. LIMITATIONS: The study was conducted in two hospitals which limits the generalization of the findings. Also, the onset of AMI symptoms relied on self-report by the patients.

Clinical outcome of lamivudine-resistant chronic hepatitis B patients with compensated cirrhosis under adefovir salvage treatment. Importance of HCC surveillance.

BACKGROUND: Data concerning the outcome of lamivudine-resistant (LAM-R) chronic hepatitis B (CHB) patients with compensated cirrhosis under adefovir (ADV) treatment are limited. The aim of our study was to evaluate the medium term outcome of these, high-risk for fatal events, patients. METHODS: 31 LAM-R patients with compensated cirrhosis who had been treated with ADV monotherapy (n=8) or ADV plus LAM (n=23) for a mean of 27.6 months, were evaluated. Virological response (VR) was defined as HBV-DNA levels <10(4) copies/ml within the first year of treatment. RESULTS: Twenty-three patients (74.19%) achieved VR. Six patients (19.35%) developed ADV-related mutations (annual incidence 11%). Liver-related death, liver decompensation and hepatocellular carcinoma (HCC) were observed in 12.9%, 16.12% and 16.12% of patients, respectively. HCC (annual incidence 9.1%) was the main cause of liver decompensation (4/5, 80%) and of liver-related deaths (3/4, 75%). HCC development was not related to patients' age (p=0.440), HBeAg status (p=0.245), HBV genotype (p=0.598), baseline ALT levels (p=0.981), baseline viral load (p= 0.464), VR (p=0.504) as well as emergence of ADV resistance (p=0.871). CONCLUSIONS: ADV suppresses viral replication in more than 70% of LAM-R cirrhotic patients during the first year of treatment. Despite that, HCC is frequently observed in these high-risk patients, irrespective of virological response or emergence of ADV resistance.

Predictive value of complete and partial early virological response on sustained virological response rates of genotype-4 chronic hepatitis C patients treated with PEG-interferon plus ribavirin.

OBJECTIVES: To investigate early viral kinetics, sustained virological response (SVR) rates and their predictors, in treatment-naïve, genotype-4-infected, chronic hepatitis C (CHC) patients treated with PEG-IFNalpha2b plus ribavirin. PATIENTS AND METHODS: In total, 58 patients were retrospectively analyzed. Early virological response (EVR) was defined as undetectable HCV-RNA (<50 IU/ml) at week 12 (complete, cEVR) or at least a 2 log decrease in HCV-RNA levels (partial, pEVR). RESULTS: Thirty-one patients exhibited SVR (53.4%), 17 (29.3%) were non-responders and 10 (17.2%) relapsed. Thirty-seven patients (63.8%) exhibited EVR. The positive predictive values of EVR, cEVR and pEVR for the SVR achievement were 83.87, 54.83, and 29.03%, whereas their negative predictive values were 59.25, 77.77, and 81.48%, respectively. Both cEVR (OR 0.040, p = 0.042) and EVR (OR 0.016, p = 0.006) independently predicted SVR. Baseline viral load (p < 0.001), age (p = 0.035) and stage of liver disease (p = 0.04) were significantly related to the EVR achievement, whereas only baseline viral load (p = 0.003) and ethnicity (p = 0.025) predicted cEVR. CONCLUSIONS: Partial or complete EVR represent independent predictors of SVR in genotype-4-infected CHC patients, regardless of their baseline parameters. The absence of pEVR, rather than the absence of cEVR, should be used as an early indication for discontinuation of treatment in these patients.

Clinical significance of hepatitis B surface antigen in cord blood of hepatitis B e-antigen-negative chronic hepatitis B virus-infected mothers.

Vertical transmission of hepatitis B virus (HBV) infection during the perinatal period is the major cause of HBV transmission. The aim of our study was to evaluate the serological and virological profiles of HBV infection in cord blood samples obtained from HBeAg-negative chronic HBV-infected women, at delivery, and to investigate their relationship with the clinical outcome (possible transmission of HBV) in neonates receiving the currently approved passive-active immunoprophylaxis schedule. Sixteen women (32%) exhibited HBsAg positivity in the cord blood but HBV-DNA has not been detected in any of the 50 cord blood samples evaluated. We conclude that HBsAg can be transferred through the placental barrier, as with other proteins, in about one third of HBeAg-negative chronic HBV-infected pregnant women, irrespective of the maternal viral load, the mode of delivery or the placenta HBV pathology. The clinical impact of this phenomenon on the intrauterine-transplacental or perinatal transmission of HBV infection and/or passive-active immunoprophylaxis failure does not seem to be important.

Differential viral kinetics in treated genotype 4 chronic hepatitis C patients according to ethnicity.

Data concerning the efficacy of PEG-IFN alpha 2a plus ribavirin treatment in treatment-naive, genotype 4-infected chronic hepatitis C (CHC) patients from Europe are limited. Hence the aim of this study was to investigate the viral kinetics as well as the sustained virological response (SVR) rates and their predictors, in these patients. One hundred and twenty-three patients were retrospectively analysed. Early (EVR) and late virological response (LVR) was confirmed by undetectable (<50 IU/mL) serum HCV-RNA at week 12 and week 24 of treatment, respectively. SVR was confirmed by undetectable serum HCV-RNA at the end of treatment as well as 6 months later. Overall, 43.5% of patients exhibited SVR, 42.6% were nonresponders and 13.9% were relapsers. EVR was observed in 40.74% and LVR in 59.25% of them. The positive predictive values of EVR and LVR were 72.97% and 86.27% whereas their negative predictive values were 64.29% and 92.85%, respectively. EVR independently predicted SVR in Caucasian patients (P < 0.001) but not in Egyptian patients (P = 0.613), in whom the only independent predictor of SVR was the absence of cirrhosis (P = 0.004). LVR seems to be a better predictor of SVR than EVR in the vast majority of genotype 4-infected CHC patients, irrespective of ethnicity and all the other baseline parameters.

Surveillance for hepatitis B virus infection in pregnant women in Greece shows high rates of chronic infection among immigrants and low vaccination-induced protection rates: preliminary results of a single center study.

Epidemiological data on the prevalence of serological markers of hepatitis B virus (HBV) infection in pregnant women in Greece are limited. We evaluated the prevalence of HBV serological markers in a multinational population of pregnant women in Athens, Greece. The overall prevalence of hepatitis B surface antigen (HbsAg) was 4.1% with the highest rates among Albanian immigrants (12%). Relatively low vaccination-induced protection rates (32.5%) were observed, a finding suggesting that surveillance and immunisation programmes targeted at pregnant women are necessary.

Hepatitis B virus polymerase variants associated with entecavir drug resistance in treatment-naive patients.

It has been suggested that lamivudine therapy can preselect for hepatitis B virus (HBV) variants associated with resistance to entecavir (ETV) treatment. The aim of this study was to determine the prevalence of HBV variants associated with ETV resistance (rtI169T, rtT184G, rtS202I, rtM250V) in naive patients before and during lamivudine therapy. This retrospective study includes 111 untreated patients with chronic HBV infection, who were later treated with lamivudine therapy for at least 18 months. Serum samples were obtained before and during treatment. Variants related with ETV drug resistance were analysed by sequencing the HBV reverse transcriptase. Prior to lamivudine treatment, three cases (2.7%) had substitutions in the HBV polymerase gene corresponding to variants associated with ETV resistance (rtS202S/I). None of these patients had lamivudine-resistant variants. During lamivudine treatment, substitutions associated with ETV resistance were detected in 10 (9%) nonresponding patients who had not presented these changes before treatment. In 2/10 cases, these changes were observed before detection of lamivudine-resistant substitutions. In 10 of 12 nonresponders, one of them with ETV-related variants prior to treatment, these variants persisted to the end of therapy. Detection of variants related to ETV drug resistance in untreated patients with chronic HBV infection indicates that these variants are present in a significant proportion of the HBV quasispecies. This fact, as well as the emergence of ETV-resistant variants during lamivudine treatment, should be kept in mind when selecting candidates for ETV therapy.

Viral genotype and baseline load predict the response to adefovir treatment in lamivudine-resistant chronic hepatitis B patients.

BACKGROUND/AIMS: To determine the factors associated with virological response (VR), HBeAg loss or the emergence of adefovir (ADV)-related mutations in ADV-treated chronic hepatitis B (CHB) patients with lamivudine (LAM) resistance. METHODS: Fifty-four LAM-resistant CHB patients (46% HBeAg-positive) were treated with ADV monotherapy (n=28) or ADV plus LAM (n=26) for a mean of 30.4 months. RESULTS: Thirty-eight patients (70.4%) achieved VR defined as HBV-DNA levels <10(4)copies/ml within the first 12 months of treatment. Six (24%) of 25 HBeAg-positive patients exhibited HBeAg loss and 20% seroconverted to anti-HBe. Eight patients (14.8%) developed ADV-related mutations. In the multivariate analysis, female gender (HR=0.20, 95% CI: 0.05-0.76, p=0.018), HBeAg-negative (HR=0.37, 95% CI: 0.14-0.96, p=0.040) and low baseline HBV-DNA levels (HR=0.65, 95% CI: 0.45-0.95, p=0.027) were independent predictors of VR, whereas low HBV-DNA levels (HR=0.36, 95% CI: 0.11-1.20, p=0.095) and HBV-genotype D (HR=0.06, 95% CI: 0.004-0.84, p=0.037) independently predicted HBeAg loss. CONCLUSIONS: ADV therapy suppresses viral replication in more than 70% of LAM-R patients. Factors associated with virologic response are female gender, HBeAg-negative status and low baseline serum HBV-DNA levels. Genotype D HBV infection and low baseline HBV-DNA levels independently predict HBeAg loss.

Prophylactic and therapeutic use of recombinant activated factor VII in patients with cirrhosis and coagulation impairment.

Patients with cirrhosis and impaired coagulation often pose major therapeutic problems during bleeding episodes or invasive procedures. Recombinant activated factor VII (rFVIIa), which has been licensed for the treatment of haemophilia patients with factor VIII or IX inhibitors, has been occasionally used in cirrhotic patients. We present five patients with cirrhosis and coagulopathy who received 1-4 recombinant activated factor VII infusions either prophylactically in order to safely undergo an invasive procedure or therapeutically in order to control a severe bleeding episode which did not respond to standard supportive care. In particular, recombinant activated factor VII infusions were given in two patients before a percutaneous liver biopsy, in one patient before teeth extraction and in two patients with haemoperitoneum after an invasive procedure. Infusions of recombinant activated factor VII achieved rapid correction of prothrombin time in all cases allowing the safe performance of invasive procedures or resulting in efficient control of the bleeding episode. In conclusion, recombinant activated factor VII seems to be a rather promising agent for the prevention or treatment of complications of haemostasis impairment in cirrhotic patients. However, its exact role in this setting needs to be evaluated within well-designed, controlled clinical trials.