Real-World Data from Turkey: Is Sofosbuvir/Ledipasvir With or Without Ribavirin Treatment for Chronic Hepatitis C Really Effective?

BACKGROUND: In this study, we aimed to investigate the efficacy and safety of sofosbuvir-based therapies in the treatment of chronic hepatitis C in real-world clinical practice. METHODS: Data from patients with chronic hepatitis C treated with SOF/LDV ± RBV or SOF/RBV in 31 centers across Turkey between April 1, 2017, and August 31, 2018, were recorded in a nationwide database among infectious disease specialists. Demographics, clinical, and virological outcomes were analyzed. RESULTS: A total of 552 patients were included in the study. The mean age of the patients was 51.28 ± 14.2, and 293 (55.8%) were female. The majority had HCV genotype 1b infection (65%), 75.04% of the patients underwent treatment, and non-cirrhosis was present at baseline in 381 patients (72.6%). SOF/LDV ± RBV treatment was given to 477 patients and 48 patients received SOF/RBV according to HCV genotype. The total SVR12 rate was 99% in all patients. Five patients experienced disease relapse during the study and all of them were genotype 2. In patients infected with HCV GT2, SVR12 was 77.3%. SVR was 100% in all patients infected with other HCV genotypes. All treatments were well tolerated by patients without causing severe adverse events. Side effects and side effects-associated treatment discontinuation rates were 28.2% and 0.4%, respectively. Weakness (13.7%) was the common side effect. CONCLUSION: The present real-world data of 525 patients with HCV genotypes 1, 1a, 1b, 3, 4, and 5 who underwent SOF/LDV ± RBV treatment in Turkey demonstrated a high efficacy and safety profile. HCV GT2 patients should be treated with more efficacious treatment.

Real-world efficacy, safety, and clinical outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin combination therapy in patients with hepatitis C virus genotype 1 or 4 infection: The Turkey experience experience.

BACKGROUND/AIMS: mbitasvir/paritaprevir/ritonavir (OMV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) combination has demonstrated excellent rates of sustained virologic response (SVR) and a very good safety profile in patients with the chronic hepatitis C virus (HCV) genotype 1 or 4 infections. We aimed to investigate the effectiveness and safety of OMV/PTV/r ± DSV ± RBV combination regimen in a real-world clinical practice. MATERIALS AND METHODS: Data from HCV genotype 1 and 4 patients treated with OMV/PTV/r ± DSV ± RBV (n=862) in 34 centers across Turkey between April 1, 2017 and August 31, 2018 were recorded in a large national database. Demographic, clinical, and virologic data were analyzed. RESULTS: The mean age of the patients was 55.63, and 430 patients (49.9%) were male. The majority had HCV genotype 1b infection (77.3%), and 66.2% were treatment-naïve. Non-cirrhosis was present at baseline in 789 patients (91.5%). SVR12 rate was 99.1% in all patients. Seven patients had virologic failure. No significant differences were observed in SVR12 according to HCV genotypes. HCV RNA was undetectable at treatment week 4 in 90.9%, at treatment week 8 in 98.5%, and at the end of treatment (EOT) in 98.9%. SVR12 ratio was significantly higher in the non-cirrhotic patients compared to that in the compensated cirrhotic patients. Rates of adverse events (AEs) in the patients was 59.7%. CONCLUSION: The present real-life data of Turkey for the OBV/PTV/r ± DSV ± RBV treatment of patients with HCV genotype 1b, 1a, or 4 infection from 862 patients demonstrated high efficacy and a safety profile.

The Outcome of Antifungal Prophylaxis with Posaconazole in Patients with Acute Myeloid Leukemia: A Single-Center Study

Objective: Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality among neutropenic patients undergoing chemotherapy for acute myeloid leukemia (AML) and stem cell transplantation. The aim of this study was to evaluate the real-life impact of posaconazole prophylaxis. Materials and Methods: Eighty-four adult patients were included with AML under remission induction chemotherapy and posaconazole prophylaxis. The 34 patients in the control group did not receive primary antifungal prophylaxis. The period between June 2006 and January 2009, when antifungal prophylaxis was not administered (control group), was retrospectively compared to the period between December 2010 and May 2012 when primary oral posaconazole prophylaxis was administered in similar conditions (posaconazole group) according to the use of antifungal agents for treatment, breakthrough infections, galactomannan performance, and the necessity for performing bronchoalveolar lavage (BAL) procedures. Results: The two groups were compared according to the use of antifungal agents; progression to a different antifungal agent was found in 34/34 patients (100%) in the control group and in 9/84 patients (11%) in the posaconazole group (p<0.001). There were four breakthrough IFIs (4/84, 4.8%) in the posaconazole group and 34 IFIs in the control group (p<0.001). In addition, 15/34 patients (44%) in the control group required BAL compared to 11/84 patients (13%) in the posaconazole group (p<0.001). Posaconazole treatment was discontinued within 7-14 days in 7/84 patients (8.3%) due to poor oral compliance related to mucositis after chemotherapy. Conclusion: Posaconazole appears to be effective and well-tolerated protection against IFIs for AML patients.

Protease Inhibitors Drug Resistance Mutations in Turkish Patients with Chronic Hepatitis C.

BACKGROUND: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. MATERIALS AND METHODS: 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. RESULTS: In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. CONCLUSION: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment.

Brucellosis: a retrospective evaluation of 164 cases.

INTRODUCTION: Brucellosis is a public health problem that is prevalent in several developing countries. METHODS: The clinical and laboratory characteristics of 164 cases of brucellosis in Bursa, Turkey, were retrospectively evaluated. RESULTS: The ages of the 164 patients ranged from 15-85 years. All of the patients underwent the Rose Bengal test and 163 (99.4%) patients tested positive. 122 (74.4%) patients were diagnosed with acute brucellosis, 31 (18.9%) with subacute brucellosis and 11 (6.7%) with chronic brucellosis. Focal involvement was found in 101 (61.6%) patients. Although patients with focal involvement had a higher white blood cell count (p = 0.002), those without focal involvement had higher aspartate transaminase and alanine transaminase values, and lower platelet values (p = 0.005, 0.007 and 0.039, respectively). Spondylodiscitis was observed on imaging in 58 (66.7%) of the 87 patients who presented with back pain. Among the 118 patients who were examined within the first month of treatment, 79 (66.9%) responded to treatment. The relapse rate was 11.6% among all 164 patients. CONCLUSION: Brucellosis should be considered as a differential diagnosis among patients who present with fever, and joint or back pain. Focal involvement should be investigated in the presence of leucocytosis, and subacute or chronic forms of brucellosis. To identify cases of spondylodiscitis, radiography should be performed in patients who present with back pain.

[The Pneumocystis jirovecii colonization in bronchoalveolar lavage (BAL) and bronchial washing and the comparison of methods which are used in diagnosis]. / Bronkoalveoler lavaj (BAL) ve bronsiyal lavaj yapilan hastalardaki Pneumocystis jirovecii kolonizasyonu ve tanida kullanilan yöntemlerin karsilastirmasi

INTRODUCTION: Pneumocystis pneumonia (PCP) which is caused by Pneumocystis jirovecii is usually seen in the patients whose immune system is supressed. It is seriously seen an opportunist infection. In our study; totally 100 bronchoalveolar lavage (BAL) and bronchial washing samples collected by pulmonary disease department. Which belong to the patients in the clinics, and out patient clinic of the bronchoscopy material were evaluated. MATERIALS AND METHODS: The BAL and bronchial washing were evaluated by the help of methenamine silver stain (Gomori/Grocott), toluidine blue O stain, Wright-Giemsa stain, immun fluorescent antibody (IFA) stain, nested polymerase chain reaction (PCR). RESULTS: In the BAL and bronchial washing samples the agent couldn't be shown by the help of methenamine silver (Gomori/Grocott), toluidine blue O, Wright-Giemsa staining. In 13 patients with IFA test the cysts of P. jirovecii were determined. In 16 patients with nested PCR; the DNA of P. jirovecii were determined. In 8 patients by using PCR and IFA test P. jirovecii was determined. When the samples which had P. jirovecii were analyzed; 13 of them were BAL and 8 of them were bronchial washing. When the phenomenon groups were evaluated according to age, gender, smoking, hypertension, diabetes mellitus, chronic obstructive pulmonary disease (COPD), cerebrovascular accident (CVA), congestive cardiac failure (CCF), staying in the hospital in the last three months, using antibiotics and radiological findings; there wasn't a statistical meaningful relation between P. jirovecii positivity and these situations. When the phenomenon groups were evaluated according to PCR and IFA positivity; in IFA and PCR positive patients for immunosupressive there was a meaningful differances (p= 0.003). The positive 28.6 % of cases were immunosuppressed and the 3.8% of PCR or IFA negative cases were immunosupressed. When PCR method was compared with IFA which is called gold standard for sensitivity and specificity; sensitivity was found 61.5% and specificity was found 90.8%. IFA and PCR diagnosis test results were compatible (With McNemar test p= 0.581). CONCLUSION: Diagnostic sensitivity of staining methods for P. jirovecii in immunocompromised HIV negative patients are found to be low and it was shown that IFA and nested PCR methods have not parallel results.

Fatal cryptococcal meningitis in a patient with chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) are susceptible to infections, especially opportunistic infections. We have described a patient with CLL who had cryptococcal meningitis. Despite lack of previous immunosuppressive treatment history, the patient experienced serious and fatal fungal infection. Physicians should be alert for a diagnosis of cryptococcal meningitis in patient with CLL who developed fever and headache.

[Travel related urinary schistosomiasis: case report]. / Seyahat iliskili üriner sistozomiyaz: olgu sunumu.

Schistosomiasis is the second most frequent parasitic infection worldwide after malaria and is a major public health problem in various countries of the world. In our country due to the increasingf travel to endemic regions, the number of cases is also rising. We report herein a case of schistosomiasis who resided in Africa five years earlier and was referred to hospital with hematuria. Direct microscopic examination of the urine specimen revealed Schistosoma haematobium eggs. Epidemiology and clinical significance of schistosomiasis are also discussed.

[Investigation of the presence of HBV-DNA in isolated anti-HBc positive cases and their importance in blood banking]. / Izole anti-HBc pozitif olgularda HBV-DNA varliginin arastirilmasi ve bu olgularin kan bankaciligi açisindan önemi.

Despite the decrease in transfusion-transmitted hepatitis B virus (HBV), it is still one of the main problems in transfusion medicine. Recent studies have shown that HBV is transmissible to recipients from HBsAg negative donations. This study was aimed to detect anti-HBc, anti-HBs and HBV-DNA positivity in HBsAg negative cases and to determine whether a reconsideration is required for HBV screening policies in blood banking. In this study, anti-HBs and anti-HBc total was investigated in 9282 HBsAg negative donor samples by commercial ELISA (Orto-Clinical Diagnostics, Vitros, Brazil) system and HBV-DNA by real-time PCR method (QIAGEN, Artus 3000, Germany). In 9282 HBsAg negative samples, anti-HBc positivity rate was 18% (1679/9282). Anti-HBs negativity was detected in 15% (n=225) of these anti-HBc positive sera. Among the isolated anti-HBc positive (HBsAg negative, anti-HBc positive, anti-HBs negative) 225 serum samples 218 were investigated for HBV-DNA presence and one sample was found to be positive (0.45%). When the samples not tested due to insufficient serum amount were excluded, the total rate of isolated anti-HBc positivity in the study region was 2.5% (225/9107) and HBV-DNA positivity in the HBsAg negative group was 0.011% (1/9100). The annual number of blood donations in our center was about 21.000, thus the rate of HBV transmission from HBsAg negative donors could be estimated as 2.3 patients/year. Although the rate of HBV transmission due to HBV-DNA positivity among HBsAg negative blood donors is low, this risk should always be kept in mind in transfusion medicine.

[Retrospective evaluation of patients who were diagnosed as infectious mononucleosis between 1984-2005]. / 1984-2005 Yillari arasinda enfeksiyöz mononikleoz tanisi alan hastalarin retrospektif olarak degerlendirilmesi.

In this study, the clinical and laboratory features of 26 infectious mononucleosis (IMN) cases who have been diagnosed between the years of 1984-2005 were evaluated retrospectively. The mean age of the patients was 26+/-11 years, the rate of being hospitalized was 65%, and mean hospitalization period was 9.2+/-6 days. Fever (81%), weakness (50%), sore throat (50%), headache (50%) and swollen neck (35%) were the most common symptoms, while in the physical examination cervical lymphadenopathy (81%), splenomegaly (69%), hyperemic pharynx (65%), hepatomegaly (54%) and tonsillitis (50%) were observed. Laboratory results yielded leukocytosis in 21%, leucopenia in 12%, anemia in 44%, thrombocytopenia in 5% and elevated transaminase levels in 84% of the patients. Of the patients 15 (57.7%) had the history of using antibiotics before the diagnosis. Serological diagnosis was performed by Paul-Bunnel test and/or IgM positivity against Epstein-Barr virus (EBV) viral capsid antigen (VCA). Tonsillo-pharyngitis secondary to edema and respiratory distress due to lymphadenopathy pressure were detected in four patients, whereas pancytopenia was established only in one patient, as complications. This study emphasized that, although IMN is a self-limited infection, the diagnostic difficulties may arise when the clinical course is atypical, and rarely seen life-threatening complications may also develop during IMN course.

Antiviral therapy in neonatal cholestatic cytomegalovirus hepatitis.

BACKGROUND: Neonatal hepatitis refers to a heterogeneous group of disorders, caused by many factors including cytomegalovirus infection, revealing similar morphologic changes in the liver of an infant less than 3 months of age. Approximately 40% of cholestasis in infants is due to neonatal hepatitis. It may cause latent or acute cholestatic or chronic hepatitis, including cirrhosis in immunocompetant infant. METHODS: Twelve infants diagnosed with neonatal cytomegalovirus hepatitis in the last one year were included in the study. Group 1 consisted of seven babies treated with ganciclovir for 21 days. Group 2 included five cases who did not receive antiviral treatment. Physical examination, biochemical, serologic and virologic tests were done for both groups at the time of diagnosis and in the third month. RESULTS: Initial levels of total bilirubin, aminotransferases, gamma glutamyl transpeptidase, and alkaline phosphatase revealed a significant decrease after the treatment in Group 1 (p < 0.05) when compared with Group 2. This study revealed that ganciclovir treatment is a safe and effective in cases with cholestatic hepatitis. Similarly, all the patients in the treatment group had evidence of improvement serologically and virologically, while the comparison group did not reveal any significant change(p < 0.01). CONCLUSION: The clinical spectrum of perinatal infection varies from an asymptomatic infection or a mild disease to a severe systemic involvement, including central nervous system. The treatment in the early period of infection improved serologic markers and cholestatic parameters significantly. Further studies will lead us to clarify the efficacy of ganciclovir treatment in the early period of cytomegalovirus hepatitis, and the preventive role of anti-viral therapy on progressive liver disease due to cholestasis and hepatitis in neonatal cytomegalovirus infection.

[Polyclonal activation due to Epstein-Barr virus superinfection in a case with chronic hepatitis B]. / Kronik B hepatitli bir olguda Epstein-Barr virus süperenfeksiyonuna bagli poliklonal aktivasyon.

Primary infection with Epstein-Barr virus (EBV) often occurs subclinically during childhood, resulting in a latent infection of B lymphocytes. In this report, a chronic hepatitis B case who presented with a serologic profile mimicking acute hepatitis B virus (HBV) infection and exhibiting transient autoantibody positivities because of the polyclonal activation of B cells due to EBV reactivation has been presented. The test results of 56 years old male patient who suffered from fatigue and pain on the right upper quadrant, revealed high levels of liver enzymes (AST: 187 U/L, ALT: 569 U/L), positivity of HBsAg, anti-HBc IgG and anti-HBe, and negativity of anti-HBc IgM, HBeAg and anti-HBs. Since HBV-DNA level was found 405,974 copies/mL by quantitative real time polymerase chain reaction (PCR), the patient was taken into follow-up. At the 6th month AST and ALT levels further elevated (352 U/L and 609 U/L, respectively), and anti-HBc IgM and anti-HBs became positive in addition to the previous positive markers of HBV. With the suspicion of superinfection, further laboratory investigations yielded negative results in CMV-IgM and Paul Bunnel test, while positive results in EBV anti-VCA IgM and IgG, anti-EBNA IgM and IgG, anti-p22 IgM and IgG and anti-EA IgM. In the follow-up period high levels of autoantibody positivities [rheumatoid factor (42.200 U/ml), anti-nuclear antibody (1/100) and anti-Ro-52] together with increased levels of total IgG, IgM and IgA were detected. In the following months, the levels of transaminases, total immunoglobulins and HBV-DNA have distinctively decreased, and in the 20th month the previous HBV profile regained (HBsAg, anti-HBc IgG and anti-HBe positive, anti-HBc IgM and anti-HBs negative, HBV-DNA: 6984 copies/ml) and the other pathological test results returned to normal. As a result, ALT increases seen during the course of chronic hepatitis B should not always be considered as HBV manifestations and the unusual serologic patterns should be evaluated as a consequence of superinfection with various viral agents.

[Short communication: retrospective analysis of 21 HIV/AIDS cases]. / KISA bildiri: HIV/AIDS'li 21 olgunun retrospektif analizi.

In this study, 21 HIV/AIDS cases (18 male, 3 female; age range 17-64 years), followed up in the Department of Infectious Diseases of Uludag University Medical Faculty between 1997-2003 have been analyzed retrospectively, by means of epidemiological, clinical and laboratory aspects. Nineteen (90%) of them were heterosexual, and in 9 cases the diagnosis was coincidental during the blood donations or routine testing. The non-compliance rate of patients to antiretroviral treatment was found as 76%, and the most important factor for non-compliance was the difficulty in providing antiretroviral drugs. The most frequently encountered opportunistic infections were oropharyngeal candidiasis (n:5), herpes zoster (n:4) and community acquired pneumonia (n:4).

[The epidemiology of malaria in Bursa.]. / Bursa'da sitma epidemiyolojisi.

Malaria is still one of the important public health problems in Anatolia. Since Bursa is a well-developed industrial and agricultural province in the Marmara region, migration rate to this region from eastern and southeastern regions of Turkey is quite high. In this retrospective study, malaria cases detected by the Malaria Control Unit Division of the Bursa Health Directorship from 1986-2002 have been evaluated. The total number of slide-positive cases was 700. Out of the 700 cases of malaria, 695 (99.3%) were found to have been caused by Plasmodium vivax and 5 (0.7%), by P. falciparum. Of these cases, 68.8% were male and of the males, 18.4% were soldiers. The majority of the cases (70.5%) had come from the southeastern region of Anatolia. Positivity rates were found to be highest in 1995 (21%) and 1996 (18.5%). In this study, we have reviewed the malaria cases according to age, gender and occupation as well as transmission characteristics, locality and source of infection.

Brucellar spondylitis: review of 25 cases.

OBJECTIVE: : Brucellar spondylitis is one of the most serious complications of brucellosis. It should be considered in patients who have back pain and neurologic disorders as well as systemic symptoms and findings in or from endemic areas such as Turkey. This report describes important features of the disease. METHODS: : Twenty-five patients with brucellar spondylitis were retrospectively evaluated in terms of their clinical, laboratory, and radiologic features and their response to different treatment regimens. RESULTS: : The most common symptoms of brucellar spondylitis were back pain, fever, and sweating. Rose Bengal tests were positive in all of these patients. Brucella species was isolated from blood cultures of 8 (32%) patients. Magnetic resonance imaging (MRI) showed that the lumbar segment was the most frequently involved region. Different combination regimens including 2 or 3 antibiotics were used. Combination of tetracycline (especially doxycycline) and streptomycin was the most widely used therapy regimen. Trimethoprim-sulfamethoxazole, ciprofloxacin, ofloxacin, and rifampin were also included in some combination therapies. In this series, the mean duration of antimicrobial therapy was 130 +/- 45.6 days (range, 77-281 days), and 92% of patients received therapy for >/= 90 days. There were no mortalities in this study. CONCLUSIONS: : Brucellar spondylitis should be considered in patients with back pain and neurologic disorders as well as systemic symptoms and findings in endemic areas. MR imaging is recommended in suspected cases. The patients can be treated effectively treated with appropriate antibiotic combinations. Follow up is important because relapses can occur.

Prevalence of transfusion transmitted virus infection and its effect on renal graft survival in renal transplant recipients.

OBJECTIVE: Little is known about the prevalence of transfusion transmitted virus (TTV) infection in renal transplant recipients (RTxs) and its effects on allograft survival. We investigated the prevalence of TTV and its effects on liver injury and graft survival in RTxs. MATERIAL AND METHODS: The study was performed in 33 consecutive RTxs (8 females, 25 males) and 100 blood donors (35 females, 65 males). A nested polymerase chain reaction was used to detect TTV DNA in serum. Serum creatinine and alanine aminotransferase (ALT) levels and 24-h protein excretion were determined in both TTV-positive and-negative patients. The total number of blood transfusions, the duration of hemodialysis and the total duration after transplantation were recorded in RTxs. In addition, hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) and hepatitis G virus DNA antibodies were determined in all patients. RESULTS: TTV DNA was detected in 51.5% of RTxs and in 7% of the control group and this difference was statistically significant (p < 0.01). In the RTx group, 64.7% of TTV-positive and 56.2% of TTV-negative patients had undergone a previous blood transfusion. However, the blood transfusion replacement rate, total duration of dialysis therapy and posttransplant period did not differ between these two groups. Five (15.1%) patients in the RTx group had abnormal liver function tests (ALT >40 IU/l). Of these patients, 2 were anti-HCV-positive, 1 was HBsAg-positive and anti-HCV- plus TTV DNA-positive and the serologic tests of the remaining 2 patients were all negative. Among the TTV-positive patients, 2 (11.7%) were anti-HCV-positive, 1 (5.8%) was HBsAg-positive and 3 (17.6%) were HGV DNA-positive. The baseline serum creatinine levels did not differ significantly between the TTV-positive and-negative patients, being 1.5 +/- 0.6 and 1.4 +/- 0.6 mg/dl, respectively ( p > 0.05). Two of the TTV-positive patients and 1 of the TTV-negative patients had proteinuria. A 1-year follow-up of TTV-positive and-negative patients demonstrated neither acute nor chronic graft rejection. CONCLUSION: In RTxs, TTV infection was more prevalent than in the normal population. In our patients the virus did not have an important effect on renal graft rejection and did not cause liver injury. However, the question of whether TTV infection may affect graft survival requires further long-term investigation in larger groups.