Efficacy and Safety of Direct-Acting Antivirals in Elderly Patients with Chronic Hepatitis C: A Nationwide Real-Life, Observational, Multicenter Study from Turkey.

BACKGROUND: The number and proportion of elderly patients living with chronic hepatitis C are expected to increase in the coming years. We aimed to compare the real-world efficacy and safety of direct-acting antiviral treatment in elderly and younger Turkish adults infected with chronic hepatitis C. METHODS: In this multicenter prospective study, 2629 eligible chronic hepatitis C patients treated with direct-acting antivirals between April 2017 and December 2019 from 37 Turkish referral centers were divided into 2 age groups: elderly (≥65 years) and younger adults (<65 years) and their safety was compared between 2 groups in evaluable population. Then, by matching the 2 age groups for demographics and pretreatment risk factors for a non-sustained virological response, a total of 1516 patients (758 in each group) and 1244 patients (622 in each group) from the modified evaluable population and per-protocol population were included in the efficacy analysis and the efficacy was compared between age groups. RESULTS: The sustained virological response in the chronic hepatitis C patients was not affected by the age and the presence of cirrhosis both in the modified evaluable population and per-protocol population (P = .879, P = .508 for modified evaluable population and P = .058, P = .788 for per-protocol population, respectively). The results of the per-protocol analysis revealed that male gender, patients who had a prior history of hepatocellular carcinoma, patients infected with non-genotype 1 hepatitis C virus, and patients treated with sofosbuvir+ribavirin had a significantly lower sustained virological response 12 rates (P < .001, P = .047, P = .013, and P = .025, respectively). CONCLUSION: Direct-acting antivirals can be safely used to treat Turkish elderly chronic hepatitis C patients with similar favorable efficacy and safety as that in younger adults.

The diagnostic utility of the "Thwaites' system" and "lancet consensus scoring system" in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients.

BACKGROUND: Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The "Thwaites' system" and "Lancet consensus scoring system" are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. METHODS: A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The "Thwaites' system" and "Lancet consensus scoring system" scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The "Thwaites' system" and "Lancet consensus scoring system" suggest a high probability of TBM with scores ≤4, and with scores of ≥12, respectively. RESULTS: A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. CONCLUSION: Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.

Assessment of histopathological alterations in patients with chronic hepatitis B infection following long-term oral antiviral therapy.

OBJECTIVES: To evaluate the histopathological changes in the liver after oral antiviral therapy in patients with chronic hepatitis B. METHODS: A total of 79 HBeAg-negative and positive patients who had been on lamivudine, entecavir, or tenofovir disoproxil for at least 3 years prior to inclusion were enrolled between March 2015 and 2016, retrospectively. There were 23 patients on lamivudine, 21 patients on entecavir, and 35 on tenofovir. All patients underwent a follow-up liver biopsy. Biochemical, serological, virological and histopathological data were recorded in all patients and were compared after at least 3 years of treatment with oral antiviral agents. Results: Histological activity index scores were reduced in patients who received lamivudine (p=0.011), entecavir (p=0.002), and tenofovir (p=0.001). Also, in contrast with a significant improvement in fibrosis scores in lamivudine (p=0.033) and tenofovir (p=0.001) groups no improvements were found in patients who received entecavir (p=0.090). Conclusion: Long term treatment with oral antiviral agents was associated with biochemical, virological, serological, and histopathological improvements. Long-term use of anti-viral agents as well as continuous suppression of HBV DNA are prerequisites for histopathological improvement.

Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study.

OBJECTIVE: Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes. METHODS: Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain. RESULTS: A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1-28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002-1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000-0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.3-2.7, p = 0.0001) were associated with diffuse inflammation. CONCLUSIONS: In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses.

Are serum quantitative hepatitis b surface antigen levels, liver histopathology and viral loads related in chronic hepatitis b-infected patients?

BACKGROUND/AIMS: Fluctuations in hepatitis B virus (HBV) DNA and alanine transaminase (ALT) levels complicate assessment of the phases of chronic hepatitis B (CHB) infection and correct identification of the inactive HBV carrier state. In this study, we aimed to examine the role of HBsAg quantification (qHBsAg) in the identification of the phases of HBV and to evaluate its association with liver histopathology. PATIENTS AND METHODS: Inactive HBV carriers (IC) (n = 104) and CHB patients (n = 100) were enrolled in the study. Demographic characteristics of patients were evaluated; biochemical parameters and serum qHBsAg levels were studied, and liver biopsy and histopathology were assessed. RESULTS: Serum qHBsAg levels were found to be significantly low in IC (5150.78 ± 8473.16 IU/mL) compared with the HBeAg-negative CHB (7503.21 ± 8101.41 IU/mL) (P = 0.001) patients. The diagnostic accuracy of qHBsAg to differentiate HBeAg-negative CHB from IC was found to be moderate (c-statistic: 0.695) and the cutoff level for qHBsAg in diagnosis was found as 1625 IU/mL (specificity: 80%; sensitivity: 49%). No correlation was noted between serum qHBsAg level and ALT, histologic activity index (HAI), and fibrosis in IC and CHB. A moderate and positive correlation was observed between the serum qHBsAg level and HBV-DNA in HBeAg-positive CHB patients. CONCLUSIONS: Serum qHBsAg levels may prove to be useful in the differentiation between IC and HBeAg-negative CHB when used in conjunction with HBV DNA. Furthermore, patients diagnosed solely on the basis of HBV DNA and ALT may present with higher grade and stage of liver histopathology than expected.

[Two cases of visceral leishmaniasis from Kahramanmaras, Turkey]. / Kahramanmaras'da saptanan iki viseral leysmanyazis olgusu.

Turkey is an endemic area for cutaneous leishmaniasis (CL) according to the data of World Health Organization. CL is more widely distributed in Sanliurfa region (located at south-eastern part of Anatolia) of Turkey, while visceral leishmaniasis (VL) is reported sporadically from all parts of Turkey, especially in pediatric cases. However VL has not been reported from our region yet. Here we report two cases of VL from Kahramanmaras region (located at eastern part of South Anatolia), one of which was a 57-year-old immuncompromised patient and the other was a 18-year-old immunocompetent patient. The common symptoms of the patients were high fever, hepatosplenomegaly and pancytopenia. The diagnosis of both patients was made by demonstration of the amastigotes of parasite in Giemsa-stained smears prepared from bone marrow aspiration samples, and isolation of promastigotes from cultures in NNN medium. The isolates were identified as Leishmania donovani with PCR and sequencing methods. Both of the patients were treated successfully with liposomal amphotericin B, resulting in complete cure. In conclusion, cases with fever of unknown origin, hepatosplenomegaly, pancytopenia and hypergammaglobulinemia should be considered in terms of VL especially in Kahramanmaras region.

Preliminary data of the Surveillance of Surgical Site infections at Gaziantep University Hospital.

Surgical site infection (SSI) is a major surgical complication that leads to mortality, morbidity and socioeconomic losses. The objective of this study is to determine the rate of SSIs, the pathogens involved in the infections and the associated antimicrobial sensitivity patterns in the surgical clinics of our hospital. This study was conducted in all surgical departments of our hospital except ophthalmology. Patients (n = 1397) who had surgery for any reason and who stayed in the hospital for at least 48 h were enrolled in this study. The criteria issued by the Centers for Disease Control and Prevention was utilized in defining and diagnosing SSI. During the study, SSIs developed in 131 (9.4%) of 1397 patients. The development of a SSI resulted in an additional 12.8 days of hospital stay. Gram-negative microorganisms constituted 74.6% of the pathogens responsible for the SSIs. The most commonly isolated microorganisms were Escherichia coli (32.8%), Pseudomonas spp. (13.4%) and Enterococcus spp. (11.9%). Methicillin resistance in Staphylococcus aureus and coagulase-negative staphylococci was 83.3% and 100%, respectively. No vancomycin resistance was detected in the enterococci. The rates of extended spectrum beta lactamase production in E. coli and Klebsiella strains were 86.3% and 42.8%, respectively. SSI surveillance studies should be performed to decrease the rate of SSIs.

Levels of malondialdehyde, myeloperoxidase and nitrotyrosine in patients with chronic viral hepatitis B and C.

OBJECTIVES: Oxidative stress is one of the potential biochemical mechanisms involved in the pathogenesis of chronic viral hepatitis. The aim of the present study was to determine levels of oxidative stress in a large group of chronic viral hepatitis (CVH) patients who had not received antiviral treatment, and to assess the relationship between these parameters and viral load, fibrosis score and necro-inflammation of the liver. MATERIAL AND METHODS: Two hundred CVH patients and 107 healthy subjects were included in this study. Malondialdehyde, myeloperoxidase and nitrotyrosine levels were determined. RESULTS: Malondialdehyde levels were significantly higher in the CVH patients than in the control group (p < 0.05), whereas myeloperoxidase activities were significantly lower (p < 0.001). There was no statistically significant difference between nitrotyrosine levels of the patients and the controls (p > 0.05). Additionally, no significant correlation was shown between these markers and viral load, necro-inflammation and fibrosis of the liver in chronic viral hepatitis patients. CONCLUSIONS: The data from this study demonstrate that there is a disturbance in oxidative balance in patients with chronic viral hepatitis, but this imbalance was not correlated with viral load, necro-inflammatory activity or fibrosis of the liver.

Unusual presentation of neurobrucellosis: a solitary intracranial mass lesion mimicking a cerebral tumor : a case of encephalitis caused by Brucella melitensis.

Among the diverse presentations of neurobrucellosis, solitary intracranial mass lesions are extremely rare. To the best of our knowledge, we describe here the second case of neurobrucellosis mimicking a cerebral tumor caused by Brucella melitensis. The mass lesion was clinically and radiologically indistinguishable from a brain tumor. The diagnosis was established by isolating Brucella melitensis in a blood culture and a positive Wright's agglutination test on the cerebrospinal fluid at 1:320 titers. Paraffin sections of the cerebral mass showed nongranulomatous encephalitis. We suggest that patients with an isolated intraparenchymal mass lesion with nongranulomatous encephalitis should also be studied for brucellosis in endemic areas.

Antioxidant defense in patients with chronic viral hepatitis B and C type.

BACKGROUND: The aim of the present study was to determine erythrocyte glutathione, superoxide dismutase, catalase, glutathione peroxidase, and serum total antioxidant response levels in a large chronic viral hepatitis group who had no antiviral treatment, and also the relationship of these parameters with viral load, fibrosis score, and necro-inflammation of the liver. METHODS: 200 patients who were diagnosed with chronic viral hepatitis and 107 healthy subjects were included in this study. Antioxidant parameters were measured spectrophotometrically. The viral load was assayed using a polymerase chain reaction technique. Histopathologic findings in the liver were scored as necro-inflammatory activity and fibrosis according to Ishak-Knodell score. RESULTS: Erythrocyte superoxide dismutase, catalase, glutathione peroxidase activities, glutathione, and serum total antioxidant response levels were significantly lower in patients than in controls (p < 0,001). Additionally, no significant correlation was found between these markers and viral load, necro-inflammation, and fibrosis of the liver in patients with chronic viral hepatitis. CONCLUSIONS: Our data suggest the insufficiency of an antioxidant barrier in patients with chronic viral hepatitis, but the decrease in antioxidant systems was not correlated with viral load, necro-inflammatory activity, and fibrosis score in the liver.

TNF-alpha, TGF-beta, IL-10, IL-6 and IFN-gamma gene polymorphisms as risk factors for brucellosis.

Polymorphisms in the regulatory regions of cytokine genes can affect the level of cytokine production, and may be associated with predisposition to infectious diseases as well as different clinical outcomes. The aim of this study was to investigate the association of the polymorphisms of IL-6 (-174), IL-10 (-1082, -819), IFN gamma (+874), TGF beta (codon 10, codon 25) and TNF alpha (-308) genes with brucellosis in terms of susceptibility and resistance to the disease or occurrence of focal complications. A case control study was carried out in 85 patients with brucellosis and 85 healthy controls. We studied the polymorphisms of IL-6, IL-10, IFN-gamma, TGF-beta 1 and TNF alpha genes, using the polymerase chain reaction with sequence-specific primers. The IL-10 CT, TGF-beta 1 codon 10 CC and TGF-beta 1 codon 25 GG genotypes were significantly more frequent in the patients compared to the controls. The IL-10 CC genotype was higher in the controls than in the patients. In addition, the IL-6 (-174) GG genotype was more frequent in the patients without focal forms, while the GC genotype was more frequent in the patients with focal forms. Our results showed that polymorphisms of IL-10 (-819) and TGF beta 1 codons 10 and 25 were associated with susceptibility or resistance to brucellosis. The IL-6 (-174) GC genotype may be a risk factor for the development of focal complications of brucellosis, whereas the GG genotype may be a protective factor against brucellosis.

Different manifestations of nervous system involvement by neurobrucellosis.

OBJECTIVES: To assess the clinical categories, laboratory, radiological findings, and treatment outcomes of patients with neurobrucellosis. METHODS: This retrospective study was designed at the Infectious Diseases and Clinical Microbiology Department, Faculty of Medicine of Gaziantep University, Gaziantep, Turkey between 2003 and 2006. In this period, 300 patients with brucellosis were diagnosed, and 13 patients with neurobrucellosis are described. Diagnosis of neurobrucellosis was based on the isolation of Brucella spp. from CSF and/or CSF standard tube agglutination (STA) ≥ 1/40, lymphocytic pleocytosis, increased protein in CSF and STA ≥ 1/320 in blood. The mean adenosine deaminase level was 12.15 u/L in CSF. The duration of antimicrobial treatment varied with the clinical response of the patient. RESULTS: We divided the 13 patients with neurobrucellosis into 4 different groups according to clinical presentation: meningoencephalitis in 8 patients, cerebral demyelination in one patient, myelitis in one patient, and neuropsychiatric disorder in 3 patients. The most common clinical form of neurobrucellosis was meningoencephalitis. There was no mortality in any of the cases. CONCLUSION: Applying these diagnostic criteria can help both early diagnosis of neurobrucellosis and differentiation from other CNS involvement in endemic regions.

Mycobacterial cervical lymphadenitis.

Cervical lymphadenitis is the most common head and neck manifestation of mycobacterial infections. The incidence of mycobacterial cervical lymphadenitis has increased. It may be the manifestation of a systemic tuberculous disease or a unique clinical entity localized to neck. It remains a diagnostic and therapeutic challenge because it mimics other pathologic processes and yields inconsistent physical and laboratory findings. A high index of suspicion is needed for the diagnosis of mycobacterial cervical lymphadenitis. A unilateral single or multiple painless lump, mostly located in posterior cervical or supraclavicular region can occur. A thorough history and physical examination, tuberculin test, staining for acid-fast bacilli, radiologic examination, fine-needle aspiration and PCR will be instrumental in arriving at an early diagnosis early institution of treatment before a final diagnosis can be made by biopsy and culture. It is important to differentiate tuberculous from nontuberculous mycobacterial cervical lymphadenitis because their treatment protocols are different. Tuberculous adenitis is best treated as a systemic disease with antituberculosis medication. Atypical infections can be addressed as local infections and are amenable to surgical therapy.

Increased pleural fluid adenosine deaminase in brucellosis is difficult to differentiate from tuberculosis.

Pleural involvement in brucellosis is very rare. Current knowledge on brucella pleuritis is limited to a few case studies, and pleural adenosine deaminase (ADA) in brucellosis has not been studied previously. We report the pleural fluid characteristics, including ADA, of two cases with brucella pleurisy. Analysis of the pleural fluids revealed exudative effusions with increased ADA level, decreased glucose concentration, and lymphocyte predominance. The similarity with tuberculous pleurisy was remarkable. We suggest that brucellosis should be considered in the differential diagnosis of tuberculosis, especially in regions endemic for both diseases.

Hearing status in brucellosis.

BACKGROUND: Although brucellosis can lead to multisystem complications, involvement of the ear in brucellosis is rarely reported in the literature. The purpose of this study was to assess the hearing status of patients with brucellosis. STUDY DESIGN: Thirty-two patients with brucellosis were included in the study. Pure tone and speech audiometry and tympanometry were performed in the patients. RESULTS: The mean pure tone averages of the patients were within normal limits and were similar in both ears (P > 0.05). The pure tone averages of the patients with or without anti-Brucella treatment were not significantly different (P > 0.05) and were within the normal limits. When the hearing levels of these patients were compared at the frequencies of 250, 500, 1000, 2000, 4000, and 8000 Hz, there was no significant difference as well (P > 0.05). CONCLUSIONS: Peripheral brucellosis does not appear to be associated with hearing loss.

Serum cytokine levels in Bell's palsy.

OBJECTIVE: To assess the significance of the serum levels of the cytokines (interleukine (IL-6, IL-8, IL-1b, IL-2r, and tumor necrosis factor alpha (TNF - alpha)) in the patients with Bell's palsy. STUDY DESIGN: A clinical and laboratory study in which serum cytokine levels were compared between the patients who had Bell's palsy and healthy controls. METHODS: Twenty-three patients with Bell's palsy and 30 healthy volunteers were included in the study. The blood samples of the patients and controls were obtained, and serum IL-1b, IL-2r, IL-6, IL-8, and TNF- alpha levels determined with chemiluminescence enzyme immunometric assay on an Immulite Immunoassay. The serum of the patients was taken between 2 days and 1 month after the disease. The assay was not in vitro lymphocyte stimulation. RESULTS: The IL-6, IL-8 and TNF- alpha levels were significantly higher in Bell's palsy than in controls (p < 0.05). The IL-1b and IL-2r levels were similar in both groups (p > 0.05). The levels of cytokine IL-6, IL-8, TNF- alpha, IL-1b, IL-2r did not correlate with the degree of recovery (p > 0.05). CONCLUSION: An alteration in the concentration of the cytokines is expected not only in many inflammatory and infectious diseases but also in Bell's palsy. Cytokines are not stored or preformed within cells. Therefore, high cytokine levels (IL-6 and IL-8, and TNF- alpha) should represent their production in response to underlying pathology in Bell's palsy, or these cytokines may be pathogenetic factors in Bell's palsy. However, serum levels of these cytokines do not help determine the prognosis in Bell's palsy as far as the results of this study are concerned.