The Prevalence of Depression and Its Potential Link to Liver Fibrosis in Patients Diagnosed With Chronic Hepatitis C Virus Infection Prior to the Initiation of Direct-Acting Antiviral Treatment.

Introduction Chronic hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, including depression. This study aimed to determine the prevalence of depression in treatment-naive HCV patients and explore its potential association with liver fibrosis severity. Methodology A consecutive cohort of 50 treatment-naive HCV patients without coinfections was enrolled over six months. Depression was assessed using the Hamilton Depression Rating Scale (HAM-D), and the liver fibrosis stage was evaluated using Fibroscan elastography. Results The cohort comprised 62% females (n=31) and 38% males (n=19), with ages ranging from 27 to 76 years. HAM-D scores indicated mild depression in 78% (n=39) and moderate depression in 16% (n=8) of patients. Notably, patients with mild depression displayed varying degrees of liver fibrosis (F0, F1, and F2), while all patients with moderate depression had advanced fibrosis (F3). Based on the multiple regression model, fibrosis was a statistically significant independent predictor with an unstandardized regression coefficient (B) of 3.115 (p=0.007). Conclusions Our findings point to a high prevalence of depression in treatment-naive HCV patients. Interestingly, there might be a link between depression severity and the stage of liver fibrosis, with advanced fibrosis potentially associated with more severe depression.

Results of Response-Guided Therapy with Pegylated Interferon Alpha 2a in Chronic Hepatitis B and D.

Pegylated interferon alpha 2a continues to be used for the treatment of chronic hepatitis D. The reported on-treatment virologic response varies between 17 and 47%, with relapses in more than 50% of these patients. No stopping rules have been defined, and the duration of the treatment is not clearly established, but it should be between 48 and 96 weeks. In total, 76 patients with compensated liver disease treated with peg-interferon according to the Romanian National protocol for the treatment of hepatitis D were retrospectively included. The duration of treatment was up to 96 weeks, with the following stopping rules: less than a 2 log HDV RNA decrease by week 24 and less than a 1 log decrease every 6 months afterwards. Six months after stopping the treatment, it can be restarted for unlimited cycles. The inclusion criteria were aged above 18, HBs Ag-positive, HDV RNA detectable, ALT above ULN and/or liver fibrosis at least F1 at liver biopsy, or Fibrotest and/or Fibroscan higher than 7 KPa and/or inflammation at least A1 at liver biopsy or Fibrotest. We monitored our patients for a total period of 4 years (including those that repeated the cycle). After the first 6 months of treatment, 27 patients (35.5%) had a greater than 2 log HDV RNA decrease, 19 of them achieving undetectable HDV RNA. Seventeen patients (22.3%) had undetectable HDV RNA 24 weeks after stopping 96 weeks of treatment, and none relapsed in the following 2 years. Of these 17 patients, 6 were cirrhotic, and 4 had F3. Undetectable HDV RNA at 24 weeks was the only parameter that predicted a long-term suppression of HDV RNA. In 49 patients, the treatment was stopped after 6 months according to protocol, but it was restarted 6 months later. Five of these patients finished a 48-week course of treatment; none achieved undetectable HDV RNA. During the first course of therapy, 45 patients had at least one moderate adverse reaction to treatment. In one patient, the treatment was stopped due to a serious adverse event (osteomyelitis). Treatment doses had to be reduced in 29 patients. The virologic response at week 24 can select the patients who will benefit from continuing the treatment from those who should be changed to another type of medication when available.

Comparative evaluation of aggressiveness traits in staphylococcal strains from severe infections versus nasopharyngeal carriage.

Despite their commensal status, staphylococci can become problematic pathogens expressing multiple and redundant virulence factors. This study aimed to evaluate aggressiveness markers comparatively in staphylococcal strains isolated from severe infections versus asymptomatic carriage in order to identify clinically relevant bacterial traits that could easily be detected in clinical practice and could be suggestive for particular host-pathogen interactions such as cyto-adhesion or biofilm formation, ultimately orienting the clinical decision-making process. We have used in vitro phenotypic methods to assess adhesion to and invasion of eukaryotic cells, biofilm development, and expression of soluble virulence factors in 92 Staphylococcus spp. strains. The adhesion index, invasion capacity, biofilm formation and expression of soluble factors did not differ significantly between clinical and commensal strains. The major bacterial traits we found to be significantly more prevalent in clinical staphylococci were the aggregative adhesion pattern (P = 0.012), cluster adhesion (P = 0.001) and tetrad morphology (P = 0.018). The aggregative adhesion pattern was correlated with higher cyto-adhesion (P < 0.001), higher invasion capacity (P = 0.003) and lower Carmeli scores (P = 0.002). Three major bacterial traits, namely tetrad morphology, aggregative adhesion pattern, and resistance to methicillin (acronym: TAM), can be used to compute an aggressiveness score (SAS) predictive of the staphylococcal strain's virulence and capacity to initiate and develop a biofilm-driven chronic infectious process versus a fulminant acute infection, in a susceptible host.

Primary Hepatic Marginal Zone Lymphoma in a Patient with Chronic Hepatitis C.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is a low-grade malignant lymphoma that appears frequently in the stomach, but other sites can also be involved: the intestinal tract, lungs, head, neck, skin, thyroid, breasts and liver. Recently, epidemiological evidences support the idea that there is an association between hepatitis C and B-cell non-Hodgkin lymphomas (that include MALT as a subtype). Primary non-Hodgkin lymphomas confi ned only to the liver are very rare (only 0.016% of all cases of all non-Hodgkin's lymphomas) and MALT is not the most frequent type. We present the case of a male patient, age 62, known with chronic hepatitis C, previously relapser a" er a 72 week treatment with peg-interferon alfa and ribavirin that was diagnosed at three years a" er the relapse with multiple focal liver lesions. One of the tumors was surgically removed and the histological exam performed demonstrated an extranodal marginal zone lymphoma with small B-cell with plasmacytoid diff erentiation confi ned only to the liver. Direct acting antiviral (DAA) therapy was started, but the virologic clearance was not obtained by week 10, leading to a change of DAA regimen at week 12. The antiviral therapy was continued until week 24. Imaging showed an increase in number and size of the focal lesions until week 12. At week 12 chemo- and immune-therapy was started with bendamustine and rituximab. A" erwards the evolution was favorable, the patient being now in complete remission and with undetectable viral load.

Clostridium Difficile Associated Disease: Burden of and Predictors for in Hospital Fatal Outcome. Results of a Hospital-Based Study, Bucharest, Romania.

INTRODUCTION: In the last 15 years Clostridium difficile infection became a typical new emergent threat worldwide. Our aim was to describe the risk factors associated with fatal outcome of Clostridium difficile associated disease (CDAD) cases treated in 2012 in "Dr Victor Babes" Infectious and Tropical Diseases Hospital, a 450 beds teaching clinic from Bucharest, Romania. MATERIAL AND METHODS: Retrospective cohort study - the case records of hospitalized patients in the year 2012, presenting with diarrhea and that tested positive for C difficile through toxin A and B assays were reviewed. Data collected through chart review of CDAD were demographic and clinical. A Charlson comorbidities index score was allocated to each case. An EpiInfo data base was fed with demo and clinical data - software's facilities were used for univariate analysis (Chi square) and also for logistic regression. RESULTS: In study were included all 326 hospitalization episodes with a discharge diagnosis of CDAD in 2012. Overall, 30 of the 326 CDAD patients (9.2%) versus 289 of the 18636 non-CDAD patients (1.55%) died during their hospital stay, resulting in a relative risk of pre-discharge death of 5.93 (4.14- 8.50) for CDAD patients, a CDAD attributable risk of death of 7.65 per 100 patients and a CDAD attributable fraction of 83.15 % (70.1-86%). Unconditional logistic regression retained as fatal outcome predictors the following: (a) a Charlson comorbidity index score >3: (OR: 3.03; CI 95%: 1.21-7.54), (b) ICU stay: (OR: 15.81; CI 95%: 4.47- 55.89) and (c) age >64 years: (OR: 2.95; CI 95%: 1.15-7.69). CONCLUSION: Our findings add to the understanding of Clostridium difficile fatal outcome and they have implications for prevention and therapy - the case fatality of 9.2% underlines the importance of the increased efforts in CDAD prevention.

SCREENING OF PROTEASE INHIBITORS RESISTANCE MUTATIONS IN HEPATITIS C VIRUS ISOLATES INFECTING ROMANIAN PATIENTS UNEXPOSED TO TRIPLE THERAPY.

Although the European recommendations include the use of new antiviral drugs for the treatment of hepatitis C, in Romania the current treatment remains interferon plus ribavirin. First generation viral protease inhibitors (i.e. boceprevir, telaprevir), which have raised the chances of obtaining viral clearance in up to 70% of infection cases produced by genotype 1 isolates, have not been introduced yet as standard treatment in our country. The success of these new antivirals is limited by the occurrence and selection of resistance mutations during therapy. We set-up a molecular study aiming to detect any resistance mutations to boceprevir and telaprevir harbored by hepatitis C isolates infecting Romanian patients naïve to viral protease inhibitors. Since these new antivirals are efficient and approved for genotype 1 infection, viral samples were genotyped following a protocol previously developed by our research group. We analyzed by both population sequencing and molecular cloning and sequencing the NS3 protease region of hepatitis C virus isolates infecting patients which were not previously exposed to boceprevir and telaprevir. All the analyzed samples were subtype 1b and resembled the samples collected in recent years from Romanian patients. Molecular cloning followed by sequencing showed great intra-host diversity, which is known to represent the source of isolates with different resistance phenotypes. Both population sequencing and molecular cloning followed by clone sequencing revealed two boceprevir resistance mutations (T54S and V55A), respectively, a telaprevir resistance mutation (T54S) in the sequences obtained from a patient with chronic hepatitis C. To our knowledge, this is the first study indicating the existence of pre-treatment resistance mutations to boceprevir and telaprevir in hepatitis C virus isolates infecting Romanian patients.

Alarming increase in tuberculosis and hepatitis C virus (HCV) among HIV infected intravenous drug users.

INTRODUCTION: In the last years, we observed an alarming increase in the number of newly diagnosed HIV infected intravenous drug users (IDUs) co-infected with hepatitis viruses or with severe bacterial infections. The aim of our study was to assess the incidence, the demographic and clinical characteristics of IDUs diagnosed with HIV, HCV and tuberculosis (TB). MATERIALS AND METHODS: Prospective study on HIV infected IDUs with HCV and TB admitted in a single centre between January 2009 and April 2014. Data were compared to a group of HIV infected IDUs without TB. Statistical analysis was performed using Graphpad Prism 4.01. RESULTS: Out of 450 HIV infected IDUs, 134 (29.7%) were diagnosed with HIV, HCV and TB. TB incidence among IDUs increases from 0% in 2009 to 30.2% in 2013. The TB coinfected patients had a mean age at diagnosis of 30 [15-56] years; were in majority males, 106 (84.4%); from urban areas, 120 (89.5%); and had significantly lower education level (85% vs 68.3%, p<0.0001) and higher rates of unemployment (80% vs 55%, p<0.0001) than those without TB. The median CD4 cell count was lower in the TB versus non TB IDUs (143 vs 472/mm(3), p<0.0001). TB infected IDUs tend to be more frequently late presenters (59.7 vs 24.6, p<0.0001) and to have advanced HIV disease (47.7 vs 7.59%, p<0.0001) than those without TB. TB cultures were positive in 64 (47.7%) patients, 3 (2.2%) had multidrug resistant TB and 2 (1.5%) had extended drug resistance. Disseminated and/or extrapulmonary TB was diagnosed in 51 patients (38%). The overall mortality rate was higher in TB compared to non TB IDUs (19.4% vs 8.2%, p=0.0007), disseminated TB being associated with the most severe immunosuppression (median CD4 cell count 42/mm(3)) and the highest mortality rate (27.4%). CONCLUSIONS: The incidence of TB in HIV/HCV coinfected IDUs was high and rose over the time. TB infection was more frequent in patients with severe immunosuppression and the mortality rate was higher in IDUs with disseminated and/or extrapulmonary disease. IDUs are important candidates for acquiring and transmitting HIV infection, viral hepatitis and TB, being difficult to control due to their high-risk behaviours. Strengthening of HIV transmission prevention strategies, particularly in identified risk groups, is mandatory.

[Bacterial strains isolated from systemic infections and reported for evaluation and antibiotic resistance surveillance by the "Dr. Victor Babes" Clinical Hospital for Infectious and Tropical Diseases, Bucharest]. / Tulpini bacteriene izolate din infectii sistemice si raportate pentru evaluarea si supravegherea rezistentei la antibiotice în SCBIT "Dr. Victor Babes", Bucuresti.

AIM: Testing antibiotic resistance of bacterial strains (compulsor, reported for EARSS surveillance) isolated from patients hospitalised for systemic infection in the "Dr. V. Babe" Hospital for Infectious and Tropical Diseases during 01.01.2005-11.11.2009, for a dynamic evaluation and for the surveillance of resistance emergence for certain classes of antibiotics. MATERIAL AND METHODS: Bacterial isolation: BacT/ALERT system; strain identification in classic and automated system (ATB Expression. VITEK 2C): antibioresistance: disk-difussion method (NCCLS 2005--CLSI 2009), MIC (E-Test, ATB/ Expression, VITEK 2C). Screening of ESBL-producing strains performed with double disk-difussion method (DDD). Reference strains used: S. aureus ATCC 25923, S. pneumoniae ATCC 49619, E. coli A TCC 25922, Enterococcus fiecalis ATCC 29212. RESULTS: During the studied period, 245 bacterial strains have been isolated, identified and tested (Staphylococcus aureus / 70, Streptococcus pneumoniae / 61, Enterococcus faecalis / 18, Enterococcus faecium / 5, Neisseria meningitidis / 18, E. coli / 73). out of 166 hemocultures and 79 cerebrospinal fluids / CSF. The average incidence of MRSA strains in systemic infections was 34.28%. 44.28% of the S. aureus strains were resistant to erythromycin, 17.14% to cyprofloxacyne, 15.71% to rifampicine, 14.49% to gentamycine. No strain resistant to vancomycine and linezolide. Streptococcus pneumoniae presented an average high resistance to penicillin G of 11.47%. and a 1.63% resistance to third generation cephalosporines. 0% resistance to vancomycine and rifampicine. 7/ 18 Enterococcus faecalis strains and 4/5 Enterococcus faecium strains presented high level resistance to gentamycine (CN 120 microg/disk) and no strain was resistant to vancomycine, teicoplanin or linezolid. The 18 Neisseria meningitidis strains were all sensitive to beta-lactams, macrolides, fluoroquinolones and cloramphenicol. For the 73 Escherichia coli strains, the average incidence of ESBL-producing isolates was 10.95%, the average resistance to ampicillin was 58.90%, to gentamycine--13.88% and to cyprofloxacin--20.83%. No strain resistant to carbapenemes and amikacine. CONCLUSIONS: For the systematic surveillance of antibiotic resistance there is a need for a harmonised protocol of data gathering and strain selection and the rigurous implementation of correct evaluating methods for antibiotic resistance in the microbiology laboratory. Carbapenemes. glycopeptides and oxazolidinones still present a major effectiveness in the first intention treatment of systemic infections.

Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia.

BACKGROUND: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acquired pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in hospitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP. METHODS: In this prospective, double-blind, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (Day 10-21 post-therapy). RESULTS: Of the 428 patients who received at least one dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxacin. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxacin. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature discontinuation of study drug or study withdrawal because of any adverse event were similar for both study drugs. CONCLUSION: These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP. TRIAL REGISTRATION: NCT00081575.

[Use of systemic antibacterial agents at a university emergency clinic in Bucharest, in the year 2008]. / Observatii privind utilizarea agentilor antibacterieni sistemici într-o clinica universitara de urgenta din municipiul Bucuresti în anul 2008.

OBJECTIVE: use of ATC/DDD (Anatomic Therapeutic Classification/Daily Defined Dose) methodology promoted by World Health Organization for calculating and analysis of systemic antimicrobial agents' annual rates of usage among the adult patients hospitalized in Bucharest municipality. METHODS: descriptive retrospective study conducted in the main university clinic for medical emergencies from Bucharest municipality. Consumption of systemic antimicrobial agents, taken from the clinic pharmacy's records, regarding the 2008 year, has been transformed in defined daily doses and aggregated by ATC subgroups. The number of patient days from 2008 was obtained from clinic administrative service. Antimicrobial agents' usage was expressed as consumption density rate by dividing the defined daily doses counts to the correspondent number of patient days. Analysis of consumption rates has been performed both by whole clinic and also stratified by departments of medical specialties: surgery, internal medicine and intensive care. RESULTS: In the year 2008, the patients carried in the clinic totalized 255,600 days of hospitalization; during the respective time in clinic there were used 36 of individual antibacterial agents that made up 184,857 defined daily doses. At the level of entire clinic the consumption rate of all systemic antimicrobial agents was 72.6 defined daily doses per 100 de patient days (DDD/PD); by medical specialties the indicator's values were 61.2 DDD/100 PD in the department of internal medicine specialties, 62.8 DDD/100 PD in the departament of surgical specialties and 126 DDD/100 PD in the medical/surgical intensive care unit, respectively. Almost 70% of the defined daily doses' total included five antimicrobial agents: co-amoxiclav, cefuroxim, cefoperazone + sulbactam, ciprofloxacine si metronidazol. By ATC subgroups, the top three consumption rates included penicillin plus beta-lactamase inhibitors, 2nd generation cefalosporines and fluorochinolons, respectively. Comparing the own rate with the distributions of NNIS (National Nosocomial Infection Surveillance) system form USA, demonstrated that the usage was into the expected limits for the majority of antimicrobial agents groups considered, excess usage being detected only in the case of 2nd generation cefalosporins (in non-intensive care sector) and in the case of carbapenems in the intensive care units, respectively. CONCLUSIONS: At the whole clinic level, the study detected a rate of systemic antimicrobial agents' usage similar with the correspondent values recently reported even from the South European states or form USA. Excessive usage (against the NNIS standard) might be mitigated through augmentation of the compliance with guidelines for prudent utilization of antimicrobial agents.

Comparative methods for genotyping hepatitis C virus isolates from Romania.

Accurate genotyping of hepatitis C virus (HCV) has clinical implications for treatment orientation and epidemiological impact in tracing the contamination sources. The aim of the study was to compare a genotyping assay by restriction fragment length polymorphism (RFLP) in the HCV 5'untranslated region (5'UTR) with sequencing in the 5'untranslated and NS5B regions. One hundred and three samples, collected between 2004 and 2006 from chronically infected patients with HCV, were tested with the 5'UTR and NS5B protocols. Of the total number of the samples tested by the 5'UTR-RFLP assay (n=103) the HCV subtype could be inferred by this method for 92 samples, by 5'UTR sequencing for 16 samples out of 23 tested (n=23) and by using the NS5B sequencing for all the samples tested (n=34). Our results showed that the HCV genotype distribution in Romania is: 1b--86.4%, 1a--10.7% and 4a--2.9%. In conclusion, RFLP screening in the 5'UTR is a convenient method for HCV genotyping and discrimination between 1b and non-1b genotypes but has a poor resolving power for subtyping and evaluation of the transmission routes. Sequencing in NS5B region is more adapted than RFLP and sequencing in 5'UTR for subtyping and epidemiological investigation.

Allele frequencies of 13 short tandem repeat (STR) loci in the Romanian population.

A population study on 13 tetra- and pentameric STR loci (D3S1358, VWA, D8S1179, D21S11, D18S51, D16S539, D2S1338, D19S433, THO1, FGA, ACTBP2 (SE33), Penta D and Penta E) was performed with Romanians from the Bucharest area.