Treatment initiation rates of patients with positive anti-hepatitis C virus results in tertiary hospitals in Turkey.

INTRODUCTION: The aim of this national, multicenter, cross-sectional, retrospective chart review study was to determine the proportion of patients in Turkey who received hepatitis C virus (HCV) treatment after receiving positive anti-HCV results during HCV screening. METHODOLOGY: Data related to patients' demographics, laboratory results, time interval from obtaining a positive anti-HCV result to treatment initiation, specialty of the physician requesting anti-HCV screening, and type of hospital were analyzed. RESULTS: Among 1,000 patients who received a positive anti-HCV result, 50.3% were male and 78.5% were screened for HCV-RNA. Among HCV-RNA screened patients, 54.8% (n = 430) had a positive result. Among patients who tested positive for HCV-RNA, 72.8% received HCV treatment in line with their positive anti-HCV results. The median time from obtaining a positive anti-HCV result to initiation of HCV treatment was 91.0 days (interquartile range 42.0 to 178.5). Non-surgical branches requested HCV-RNA testing more frequently than surgical branches (p < 0.001). The rate of access to HCV treatment was higher among patients screened in university hospitals than among patients screened in training and research hospitals (p < 0.001). CONCLUSIONS: Our results indicate a higher rate of treatment initiation among patients with HCV infection than is described in the published literature. Furthermore, the time from screening to treatment initiation was considerably shorter compared with other international studies. However, since HCV-RNA testing was not requested in a significant portion of patients with a positive anti-HCV test result, there might be a large patient population with HCV who do not receive treatment.

Five-year follow-up of 96 weeks peginterferon plus tenofovir disoproxil fumarate in hepatitis D.

BACKGROUND & AIMS: Until recently, pegylated interferon-alfa-2a (PEG-IFNa) therapy was the only treatment option for patients infected with hepatitis D virus (HDV). Treatment with PEG-IFNa with or without tenofovir disoproxil fumarate (TDF) for 96 weeks resulted in HDV RNA suppression in 44% of patients at the end of therapy but did not prevent short-term relapses within 24 weeks. The virological and clinical long-term effects after prolonged PEG-IFNa-based treatment of hepatitis D are unknown. METHODS: In the HIDIT-II study patients (including 40% with liver cirrhosis) received 180 µg PEG-IFNa weekly plus 300 mg TDF once daily (n = 59) or 180 µg PEG-IFNa weekly plus placebo (n = 61) for 96 weeks. Patients were followed until week 356 (5 years after end of therapy). RESULTS: Until the end of follow-up, 16 (13%) patients developed liver-related complications (PEG-IFNa + TDF, n = 5 vs PEG-IFNa + placebo, n = 11; p = .179). Achieving HDV suppression at week 96 was associated with decreased long-term risk for the development of hepatocellular carcinoma (p = .04) and hepatic decompensation (p = .009). Including complications irrespective of PEG-IFNa retreatment status, the number of patients developing serious complications was similar with (3/18) and without retreatment with PEG-IFNa (16/102, p > .999) but was associated with a higher chance of HDV-RNA suppression (p = .024, odds ratio 3.9 [1.3-12]). CONCLUSIONS: Liver-related clinical events were infrequent and occurred less frequently in patients with virological responses to PEG-IFNa treatment. PEG-IFNa treatment should be recommended to HDV-infected patients until alternative therapies become available. Retreatment with PEG-IFNa should be considered for patients with inadequate response to the first course of treatment. CLINICAL TRIAL REGISTRATION: NCT00932971.

Long-term Treatment With Tenofovir Alafenamide for Chronic Hepatitis B Results in High Rates of Viral Suppression and Favorable Renal and Bone Safety.

OBJECTIVES: Results from two Phase 3 studies, through 2 years, in chronic hepatitis B infection (CHB) showed tenofovir alafenamide (TAF) had similar efficacy to tenofovir disoproxil fumarate (TDF) with superior renal and bone safety. Here, we report updated results through 5 years. METHODS: Patients with HBeAg-negative or -positive CHB with or without compensated cirrhosis were randomized (2:1) to TAF 25 mg or TDF 300 mg once daily in double-blind (DB) fashion for up to 3 years, followed by open-label (OL) TAF up to 8 years. Efficacy (antiviral, biochemical, serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters, were evaluated by pooled analyses. RESULTS: Of 1298 randomized and treated patients, 866 receiving TAF (DB and OL) and 432 receiving TDF with rollover to OL TAF at year 2 (n = 180; TDF→TAF3y) or year 3 (n = 202; TDF→TAF2y) were included. Fifty (4%) TDF patients who discontinued during DB were excluded. At year 5, 85%, 83%, and 90% achieved HBV DNA < 29 IU/mL (missing = failure) in the TAF, TDF→TAF3y, and TDF→TAF2y groups, respectively; no patient developed TAF or TDF resistance. Median eGFR (by Cockcroft-Gault) declined < 2.5 mL/min, and mean declines of < 1% in hip and spine bone mineral density were seen at year 5 in the TAF group; patients in the TDF→TAF groups had improvements in these parameters at year 5 after switching to OL TAF. CONCLUSIONS: Long-term TAF treatment resulted in high rates of viral suppression, no resistance, and favorable renal and bone safety.

Quality-of-life scores improve after 96 weeks of PEG-IFNa-2a treatment of hepatitis D: An analysis of the HIDIT-II trial.

BACKGROUND & AIMS: Infection with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis with a high risk to develop clinical complications of liver disease. In addition, hepatitis delta has been shown to be associated with worse patient-reported outcomes. Until recently, only pegylated interferon alfa could be used to treat hepatitis delta. METHODS: Here, we investigated quality of life (QOL) as assessed by the Short Form 36 Health Survey (SF-36) in patients undergoing antiviral therapy with pegylated interferon alfa (PEG-IFNa-2a)-based treatment in the HIDIT-II trial. HIDIT-II was a randomized prospective trial exploring PEG-IFNa-2a with tenofovir disoproxil (TDF) or placebo for 96 weeks in patients with compensated hepatitis delta. Surveys completed by 83 study participants before, during, and after treatments were available. RESULTS: Overall, we observed a reduced QOL of HDV patients compared with a reference population, both in physical as well as mental scores. Interestingly, PEG-IFNa-2a treatment showed only minor impairment of the QOL during therapy. Moreover, HDV-RNA clearance was not associated with relevant changes in physical or social SF-36 scores, whereas an improvement of fibrosis during treatment was associated with increased QOL. Overall, slight improvements of the QOL scores were observed 24 weeks after the end of treatment as compared with baseline. TDF co-treatment had no influence on QOL. CONCLUSIONS: Overall, our findings suggest that PEG-IFNa-2a was reasonably tolerated even over a period of 96 weeks by hepatitis D patients reporting SF-36 questionnaires. Of note, several patients may benefit from PEG-IFNa-2a-based therapies with off-treatment improvements in quality of life.

Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial.

BACKGROUND: Hepatitis D is the most severe form of chronic viral hepatitis. Treatment guidelines recommend 1 year of peginterferon alfa, which is effective in 25-30% of patients only. Whether prolonged therapy with peginterferon alfa-2a for 96 weeks and combination therapy with tenofovir disoproxil fumarate (TDF) would increase hepatitis D virus (HDV) RNA suppression is unknown. We aimed to explore whether prolonged treatment of HDV with 96 weeks of peginterferon would increase HDV RNA response rates and reduces post-treatment relapses. METHODS: We did two parallel, investigator-initiated, multicentre, double-blind randomised, controlled trials at 14 study sites in Germany, Greece, Romania, and Turkey. Patients with chronic HDV infection and compensated liver disease who were aged 18 years or older were eligible for inclusion. All patients were HBsAg positive for at least 7 months, anti-HDV positive for at least 3 months, and HDV-RNA positive at the local laboratory at the screening visit. Patients were ineligible if alanine aminotransferase levels were higher than ten times above the upper limit of normal and if platelet counts were lower than 90 000 per µL, or if they had received interferon therapy or treatment with a nucleoside and nucleotide analogue within the preceding 6 months. Patients were randomly assigned by blinded stratified block randomisation (1:1) to receive 180 µg of peginterferon alfa-2a weekly plus either TDF (300 mg once daily) or placebo for 96 weeks. The primary endpoint was the percentage of patients with undetectable HDV RNA at the end of treatment assessed by intention to treat. The trials are registered as NCT00932971 and NCT01088659. FINDINGS: Between June 24, 2009, and Feb 28, 2011, we randomly assigned 59 HDV RNA-positive patients to receive peginterferon alfa-2a plus TDF and 61 to receive peginterferon alfa-2a plus placebo, including 48 (40%) patients with cirrhosis to the two treatment groups (23 in the peginterferon alfa-2a plus TDF group and 25 in the peginterferon alfa-2a plus placebo group). The primary endpoint was achieved in 28 (48%) of 59 patients in the peginterferon alfa-2a plus TDF group and in 20 (33%) of 61 patients in the peginterferon alfa-2a plus placebo group (odds ratio 1·84, 95% CI 0·86-3·91, p=0·12). We recorded 944 adverse events (459 in the peginterferon alfa-2a plus TDF group and 485 in the peginterferon alfa-2a plus placebo group). The most common adverse events were haematological, behavioural (eg, fatigue), musculoskeletal, influenza-like syndromes, and psychiatric complaints. INTERPRETATION: Addition of TDF resulted in no significant improvement in HDV RNA response rates at the end of treatment. These findings highlight that alternative treatment options are needed for hepatitis D. FUNDING: The HepNet Study-House (a project of the German Liver Foundation founded by the German Liver Foundation, the German Ministry for Education and Research, and the German Center for Infectious Disease Research), Hoffmann-La Roche, and Gilead Sciences.

HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey.

HIV-1 replication is rapid and highly error-prone. Transmission of a drug-resistant HIV-1 strain is possible and occurs within the HIV-1-infected population. In this study, we aimed to determine the prevalence of transmitted drug resistance mutations (TDRMs) in 1,306 newly diagnosed untreated HIV-1-infected patients from 21 cities across six regions of Turkey between 2010 and 2015. TDRMs were identified according to the criteria provided by the World Health Organization's 2009 list of surveillance drug resistance mutations. The HIV-1 TDRM prevalence was 10.1% (133/1,306) in Turkey. Primary drug resistance mutations (K65R, M184V) and thymidine analogue-associated mutations (TAMs) were evaluated together as nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations. NRTI TDRMs were found in 8.1% (107/1,306) of patients. However, TAMs were divided into three categories and M41L, L210W, and T215Y mutations were found for TAM1 in 97 (7.4%) patients, D67N, K70R, K219E/Q/N/R, T215F, and T215C/D/S mutations were detected for TAM2 in 52 (3.9%) patients, and M41L + K219N and M41L + T215C/D/S mutations were detected for the TAM1 + TAM2 profile in 22 (1.7%) patients, respectively. Nonnucleoside reverse transcriptase inhibitor-associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P, K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E, L76V, V82A/C/L/T, N83D, I84V, and L90M). In conclusion, long-term and large-scale monitoring of regional levels of HIV-1 TDRMs informs treatment guidelines and provides feedback on the success of HIV-1 prevention and treatment efforts.

The evaluation of microbiology and Fournier's gangrene severity index in 27 patients.

OBJECTIVES: The objectives of this study were to identify the causative microorganisms and factors associated with survival in patients with Fournier's gangrene and to determine the accuracy of the Fournier's gangrene severity index. MATERIALS AND METHODS: We retrospectively evaluated 27 patients with Fournier's gangrene who were treated and followed up at our hospital between January 2005 and December 2006. Biochemical, hematologic, and bacteriologic study results at admission and at the final evaluation, etiologic and predisposing factors at admission, physical examination findings, the timing and extent of surgical debridement, and antibiotic therapy used were all recorded. RESULTS: The admission laboratory parameters that were significantly correlated with outcome included urea, creatinine, sodium, and potassium; at the final evaluation, in addition to these parameters, hematocrit, albumin, and bicarbonate levels were also significantly associated with outcome. The mean Fournier's gangrene severity index score (FGSIS) at admission for survivors was 5.04+/-2.49 compared with 13.6+/-4.61 for non-survivors. There was a strong correlation between the FGSIS and mortality (p<0.0001). Escherichia coli and Pseudomonas aeruginosa were the most commonly isolated microorganisms. CONCLUSIONS: Patient metabolic status and predisposing factors are important in the prognosis of Fournier's gangrene. Hence, we believe that the FGSIS should be used clinically to evaluate therapeutic options and assess results.

The efficacy of dexamethasone treatment in adult patients with acute bacterial meningitis.

OBJECTIVE: To evaluate the efficacy of dexamethasone added to the treatment of adult patients with bacterial meningitis in our region. METHODS: One hundred and forty-four patients were randomized prospectively and evaluated to determine the efficacy of dexamethasone treatment in adult patients with acute bacterial meningitis at Dicle University Hospital, Diyarbakir, Turkey between January 2000 and December 2004. While the first group received ceftriaxone 4 gr/day plus dexamethasone, the second group received ceftriaxone 4 gr/day only. Dexamethasone was given 10-15 minutes before the first 8 mg dose of antibiotic treatment. It was continued at 16 mg/day for 3 days. RESULTS: The study included 144 patients with the diagnosis of acute bacterial meningitis. Cerebrospinal fluid (CSF) was analyzed at the time of admission, after 24-48 hours (Table 1), and at the end of treatment. Accordingly, CSF leukocyte level was found to be 1710+/-2140/mm3 in group 1 receiving dexamethasone treatment compared to 1950+/-2244/mm3 in group 2 (p=0.001). The consciousness in the group receiving dexamethasone improved significantly more rapidly than the control group (p=0.001). While mortality was 9.7% in the patient group receiving dexamethasone it was 16.7% in the control group, however, it was not significant (p=0.093). CONCLUSION: The use of dexamethasone in adult patients is still under debate, and the administration of dexamethasone 10-15 minutes before antibiotherapy to unconscious patients in a poor state of health, is effective in the clinical improvement of the patient.

A 6-year prospective surveillance study for healthcare associated infections in a neurology unit.

OBJECTIVE: To assess the epidemiology of healthcare-associated infections (HAIs) in a neurology unit in a university hospital. METHODS: The study was carried out prospectively at Dicle University Hospital, Diyarbakir, Turkey (1050-bed) between 1st January 1999 and 31st December 2004. Active surveillance for HAIs was performed by the infection control team, using the criteria proposed by the Centers for Diseases Control and Prevention (CDC) and National Nosocomial Infections Surveillance System (NNIS) methodology. RESULTS: During the 6-year follow up period, 219 HAIs episodes were detected in 203 patients out of 3323 in patients. The mean length of stay of patients with HAI was 28+/-5 days, while that of patients without infections was 11+/-1 days. Eighty-two patients died with HAIs, while 1330 died in the patients without infections. The overall incidence rates (HAI/100) and incidence densities (HAI/1000 days of stay) of HAIs were 6.6% and 4.4/1,000 patients-days. The most common HAIs by primary site were urinary tract infection (44.2%) and decubitus infection (30.4%). The most prevalent microorganisms were Escherichia coli (27%), Klebsiella species (14%), Pseudomonas aeruginosa (13%), Enterobacter species (12%), coagulase-negative Staphylococci (10%) and Staphylococcus aureus (7%). CONCLUSION: The results may contribute to observe the magnitude and characteristics of HAIs and to plan and evaluate policies and guidelines of infection control in neurology units.

Anti-hepatitis delta virus seroprevalence and risk factors in patients with hepatitis B in Southeast Turkey.

OBJECTIVE: To obtain regional epidemiological data on hepatitis delta virus (HDV, a defective virus) infections, the incidence of anti-HDV positivity and the associated risk factors in asymptomatic hepatitis B virus surface antigen (HBsAg) carriers and in patients with chronic active hepatitis B. METHODS: The study took place at Dicle University Hospital (Diyarbakir, Southeast of Turkey) between January 2002 and July 2004. Anti-HDV screening was performed in asymptomatic hepatitis B carriers (N=889) and in patients with chronic active hepatitis B infection (N=120). We explored the association between anti-HDV positivity and asymptomatic hepatitis B carrier status, presence of active hepatitis B, age, gender, the durations of HBsAg positivity and hepatitis B e antigen (HBeAg) positivity. RESULTS: In 6% of asymptomatic hepatitis B carriers (53/889) and in 27.5% of patients with chronic active hepatitis B (33/120) anti-HDV was positive. The incidence of anti-HDV positivity was significantly higher in patients with chronic active hepatitis B compared with asymptomatic carriers (p<0.001). A significant association between the duration of HBsAg carrier status (3.2 +/- 1.4 years) and anti-HDV positivity was also found (p<0.001). Age, gender, and HBeAg positivity were not significantly associated with anti-HDV positivity (p>0.05). CONCLUSION: Anti-HDV positivity was significantly more common in patients with chronic hepatitis B compared with asymptomatic hepatitis B virus (HBV) carriers in a region with a high prevalence of HBV infection. We found a significant relationship between the duration of HBsAg carrier status and anti-HDV positively, however, age, gender, and presence of HBeAg were not significantly associated with the development of anti-HDV positivity.

Multiresistant bacterial colonization due to increased nurse workload in a neurology intensive care unit.

OBJECTIVE: To determine the relationship between nurse workload and multiresistant bacteria colonization or infection (MRB+) in a neurology intensive care unit (ICU). METHODS: We studied the relationship between nurse workload and MRB+ development in patients who were hospitalized in Dicle University Neurology Department ICU, Turkey during a 6-month period from November 15, 2003 to April 15, 2004. The intensity of workload and procedures applied to the patients were scored with the Project de Recherche en Nursing (PRN) and the Omega scores. RESULTS: Of 138 patients followed, 71 (51.4%) were female and 67 (48.6%) were male. The mean age of females was 65.6+/-6.7 years, and of males was 62.2+/-15.8 years. The mean time of hospitalization in the ICU was 13+/-7.6 days. In 26 (18.8%) cultures taken from patients, multiresistant bacteria (MRB) were demonstrated. The development of MRB+ infection was correlated with length of stay (LOS), Omega 2, Omega 3, Total Omega, daily PRN, and total PRN (p<0.05). There was no correlation between development of MRB+ infection with gender, age, APACHE-II and Omega 1 scores (p>0.05). In the PRN system, when the workload of nurses was compared, it was seen that in the MRB colonized patient group, the workload of nurses was meaningfully higher than the MRB patient (-) group (p<0.001). CONCLUSION: As a result, the risk of MRB+ development in the ICU is directly proportional to understaffing, increased nurse workload, LOS, and procedures applied to patients. In management of nosocomial infection, it is crucial to increase the number of nurses in the ICU, and thus, decrease the workload.