Psychosexual development in men with congenital hypogonadotropic hypogonadism on long-term treatment: a mixed methods study.

INTRODUCTION: Congenital hypogonadotropic hypogonadism (CHH) is a rare, genetic, reproductive endocrine disorder characterized by absent puberty and infertility. Limited information is available on the psychosocial impact of CHH and psychosexual development in these patients. AIM: The aim of this study was to determine the impact of CHH on psychosexual development in men on long-term treatment. METHODS: A sequential mixed methods explanatory design was used. First, an online survey (quantitative) was used to quantify the frequency of psychosexual problems among CHH men. Second, patient focus groups (qualitative) were conducted to explore survey findings in detail and develop a working model to guide potential nursing and interdisciplinary interventions. MAIN OUTCOME MEASURES: Patient characteristics, frequency of body shame, difficulty with intimate relationships, and never having been sexually active were assessed. Additionally, we collected subjective patient-reported outcomes regarding the impact of CHH on psychological/emotional well-being, intimate relationships, and sexual activity. RESULTS: A total of 101 CHH men on long-term treatment (>1 year) were included for the analysis of the online survey (mean age 37 ± 11 years, range 19-66, median 36). Half (52/101, 51%) of the men had been seen at a specialized academic center and 37/101 (37%) reported having had fertility-inducing treatment. A high percentage of CHH men experience psychosexual problems including difficulty with intimate relationships (70%) and body image concerns/body shame (94/101, 93%), and the percentage of men never having been sexually active is five times the rate in a reference group (26% vs. 5.4%, P < 0.001). Focus groups revealed persisting body shame and low self-esteem despite long-term treatment that has lasting impact on psychosexual functioning. CONCLUSIONS: CHH men frequently experience psychosexual problems that pose barriers to intimate relationships and initiating sexual activity. These lingering effects cause significant distress and are not ameliorated by long-term treatment. Psychosexual assessment in CHH men with appropriate psychological support and treatment should be warranted in these patients. Dwyer AA, Quinton R, Pitteloud N, and Morin D. Psychosexual development in men with congenital hypogonadotropic hypogonadism on long-term treatment: A mixed methods study. Sex Med 2015;3:32-41.

Blood pressure change and outcome in acute ischemic stroke: the impact of baseline values, previous hypertensive disease and previous antihypertensive treatment.

BACKGROUND: Management of blood pressure (BP) in acute ischemic stroke is controversial. The present study aims to explore the association between baseline BP levels and BP change and outcome in the overall stroke population and in specific subgroups with regard to the presence of arterial hypertensive disease and prior antihypertensive treatment. METHODS: All patients registered in the Acute STroke Registry and Analysis of Lausanne (ASTRAL) between 2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin score more than 2. A local polynomial surface algorithm was used to assess the effect of BP values on outcome in the overall population and in predefined subgroups. RESULTS: Up to a certain point, as initial BP was increasing, optimal outcome was seen with a progressively more substantial BP decrease over the next 24-48 h. Patients without hypertensive disease and an initially low BP seemed to benefit from an increase of BP. In patients with hypertensive disease, initial BP and its subsequent changes seemed to have less influence on clinical outcome. Patients who were previously treated with antihypertensives did not tolerate initially low BPs well. CONCLUSION: Optimal outcome in acute ischemic stroke may be determined not only by initial BP levels but also by the direction and magnitude of associated BP change over the first 24-48 h.

Recurrent idiopathic neuroretinitis: natural history and effect of treatment.

BACKGROUND: Previous reports have emphasized the self-limited nature of idiopathic neuroretinitis. There is less information about a subgroup of patients who suffer recurrent episodes with worse visual outcome. We sought to better characterize the clinical features of recurrent idiopathic neuroretinitis including the effects of immunosuppressive treatment. METHODS: Retrospective chart review of neuroretinitis patients from a single institution from 1983 to 2008. Inclusion criteria included two or more episodes of acute visual loss with disc oedema and macular exudates in a star pattern. Cases due to a specific infectious or inflammatory aetiology were excluded. RESULTS: Forty-one patients were included with an average follow up of 67 months. Median age at the time of the first episode was 28 years (range 10-54 years). Attacks were bilateral sequential in 34 patients (83%). We documented a total of 147 episodes in 75 eyes with an average of 3.6 attacks per patient. The average interval between attacks was 3 years. Visual field loss had a nerve fibre bundle pattern in most cases. Only 36% of eyes retained 6/12 or better visual acuity and greater than two-thirds of their visual field. Long-term immunosuppressive treatment in 13 patients decreased the attack rate by 72%. CONCLUSIONS: Recurrent idiopathic neuroretinitis typically affects young adults, with no gender preference. Recovery is limited and visual loss is cumulative with repeated attacks, often resulting in severe permanent visual loss. Immunosuppressive treatment appears to lessen the attack frequency.

Intravenous lacosamide for treatment of status epilepticus.

Objectives -  Treatment of established status epilepticus (SE) requires immediate intravenous anticonvulsant therapy. Currently used first-line drugs may cause potentially hazardous side effects. We aimed to assess the efficacy and safety of intravenous lacosamide (LCM) in SE after failure of standard treatment. Methods -  We retrospectively analyzed 39 patients (21 women, 18 men, median age 62 years) from the hospital databases of five neurological departments in Germany, Austria and Switzerland between September 2008 and January 2010 who were admitted in SE and received at least one dose of intravenous LCM. Results -  Types of SE were generalized convulsive (n = 6), complex partial (n = 17) and simple partial (n = 16). LCM was administered after failure of benzodiazepins or other standard drugs in all but one case. Median bolus dose of LCM was 400 mg (range 200-400 mg), which was administered at 40-80 mg/min in those patients where infusion rate was documented. SE stopped after LCM in 17 patients, while 22 patients needed further anticonvulsant treatment. The success rate in patients receiving LCM as first or second drug was 3/5, as third drug 11/19, and as fourth or later drug 3/15. In five subjects, SE could not be terminated at all. No serious adverse events attributed to LCM were documented. Conclusions -  Intravenous LCM may be an alternative treatment for established SE after failure of standard therapy, or when standard agents are considered unsuitable.

Presentation and treatment outcome of diverticulitis in younger adults: a different disease than in older patients?

PURPOSE: The severity and most appropriate treatment of diverticulitis in young patients are still controversial. The aim of this study is to compare young patients (<or=50 years) with older patients (>50 years) regarding clinical and radiologic parameters of acute left colonic diverticulitis and to determine whether differences exist in presentation and treatment. METHODS: We reviewed medical records of 271 consecutive patients with left colonic acute diverticulitis admitted to our institution from 2001 through 2004: 71 patients were aged 50 years or younger and 200 patients were older than 50. Clinical and radiologic parameters were analyzed. Conservative treatment was standardized, and included antibiotic therapy and bowel rest. Criteria for emergency surgical treatment were diffuse peritonitis, pneumoperitoneum, and septic shock. RESULTS: Conservative treatment alone was successful in 64 patients (90.1%) in the younger group and in 152 patients (76%) in the older group (P = .017). The percentage of patients requiring surgery at admission or during the hospital stay was significantly lower in younger than in older patients (5.6% vs 20.5%, P = .007), and the percentage of patients requiring emergency end colostomy was higher (although not significantly) in the older group (1.4% vs 9.0%, P = .059). No differences in rate of successful conservative treatment were observed between patients with a first episode and those with recurrence in either age group (P = .941 in the younger group; P = .227 in the older group). CONCLUSION: Young age is not a predictive factor of poor outcome in the management of first or recurrent episodes of acute diverticulitis. Patients older than 50 years more frequently need emergency surgical treatment.

Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial.

BACKGROUND: In alcohol withdrawal, fixed doses of benzodiazepine are generally recommended as a first-line pharmacologic approach. This study determines the benefits of an individualized treatment regimen on the quantity of benzodiazepine administered and the duration of its use during alcohol withdrawal treatment. METHODS: We conducted a prospective, randomized, double-blind, controlled trial including 117 consecutive patients with alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, entering an alcohol treatment program at both the Lausanne and Geneva university hospitals, Switzerland. Patients were randomized into 2 groups: (1) 56 were treated with oxazepam in response to the development of signs of alcohol withdrawal (symptom-triggered); and (2) 61 were treated with oxazepam every 6 hours with additional doses as needed (fixed-schedule). The administration of oxazepam in group 1 and additional oxazepam in group 2 was determined using a standardized measure of alcohol withdrawal. The main outcome measures were the total amount and duration of treatment with oxazepam, the incidence of complications, and the comfort level. RESULTS: A total of 22 patients (39%) in the symptom-triggered group were treated with oxazepam vs 100% in the fixed-schedule group (P<.001). The mean oxazepam dose administered in the symptom-triggered group was 37.5 mg compared with 231.4 mg in the fixed-schedule group (P<.001). The mean duration of oxazepam treatment was 20.0 hours in the symptom-triggered group vs 62.7 hours in the fixed-schedule group (P<.001). Withdrawal complications were limited to a single episode of seizures in the symptom-triggered group. There were no differences in the measures of comfort between the 2 groups. CONCLUSIONS: Symptom-triggered benzodiazepine treatment for alcohol withdrawal is safe, comfortable, and associated with a decrease in the quantity of medication and duration of treatment.

Drinking Patterns and Their Predictive Factors in CONTROL: a 12-Month Prospective Study in a Sample of Alcohol-Dependent Patients Initiating Treatment.

Aims: To describe the drinking patterns and their baseline predictive factors during a 12-month period after an initial evaluation for alcohol treatment. Methods CONTROL is a single-center, prospective, observational study evaluating consecutive alcohol-dependent patients. Using a curve clustering methodology based on a polynomial regression mixture model, we identified three clusters of patients with dominant alcohol use patterns described as mostly abstainers, mostly moderate drinkers and mostly heavy drinkers. Multinomial logistic regression analysis was used to identify baseline factors (socio-demographic, alcohol dependence consequences and related factors) predictive of belonging to each drinking cluster. ResultsThe sample included 143 alcohol-dependent adults (63.6% males), mean age 44.6 ± 11.8 years. The clustering method identified 47 (32.9%) mostly abstainers, 56 (39.2%) mostly moderate drinkers and 40 (28.0%) mostly heavy drinkers. Multivariate analyses indicated that mild or severe depression at baseline predicted belonging to the mostly moderate drinkers cluster during follow-up (relative risk ratio (RRR) 2.42, CI [1.02-5.73, P = 0.045] P = 0.045), while living alone (RRR 2.78, CI [1.03-7.50], P = 0.044) and reporting more alcohol-related consequences (RRR 1.03, CI [1.01-1.05], P = 0.004) predicted belonging to the mostly heavy drinkers cluster during follow-up. Conclusion In this sample, the drinking patterns of alcohol-dependent patients were predicted by baseline factors, i.e. depression, living alone or alcohol-related consequences and findings that may inform clinicians about the likely drinking patterns of their alcohol-dependent patient over the year following the initial evaluation for alcohol treatment.

The data treatment dependent variability of U-Pb zircon ages obtained using mono-collector, sector field, laser ablation ICP-MS

U-Pb dating of zircons by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) is a widely used analytical technique in Earth Sciences. For U-Pb ages below 1 billion years (1 Ga), Pb-206/U-238 dates are usually used, showing the least bias by external parameters such as the presence of initial lead and its isotopic composition in the analysed mineral. Precision and accuracy of the Pb/U ratio are thus of highest importance in LA-ICPMS geochronology. We consider the evaluation of the statistical distribution of the sweep intensities based on goodness-of-fit tests in order to find a model probability distribution fitting the data to apply an appropriate formulation for the standard deviation. We then discuss three main methods to calculate the Pb/U intensity ratio and its uncertainty in the LA-ICPMS: (1) ratio-of-the-mean intensities method, (2) mean-of-the-intensity-ratios method and (3) intercept method. These methods apply different functions to the same raw intensity vs. time data to calculate the mean Pb/U intensity ratio. Thus, the calculated intensity ratio and its uncertainty depend on the method applied. We demonstrate that the accuracy and, conditionally, the precision of the ratio-of-the-mean intensities method are invariant to the intensity fluctuations and averaging related to the dwell time selection and off-line data transformation (averaging of several sweeps); we present a statistical approach how to calculate the uncertainty of this method for transient signals. We also show that the accuracy of methods (2) and (3) is influenced by the intensity fluctuations and averaging, and the extent of this influence can amount to tens of percentage points; we show that the uncertainty of these methods also depends on how the signal is averaged. Each of the above methods imposes requirements to the instrumentation. The ratio-of-the-mean intensities method is sufficiently accurate provided the laser induced fractionation between the beginning and the end of the signal is kept low and linear. We show, based on a comprehensive series of analyses with different ablation pit sizes, energy densities and repetition rates for a 193 nm ns-ablation system that such a fractionation behaviour requires using a low ablation speed (low energy density and low repetition rate). Overall, we conclude that the ratio-of-the-mean intensities method combined with low sampling rates is the most mathematically accurate among the existing data treatment methods for U-Pb zircon dating by sensitive sector field ICPMS.

ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment.

BACKGROUND AND OBJECTIVE: The in vivo implication of various cytochrome P450 (CYP) isoforms and of P-glycoprotein on methadone kinetics is unclear. We aimed to thoroughly examine the genetic factors influencing methadone kinetics and response to treatment. METHODS: Genotyping for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, ABCB1, and UGT2B7 polymorphisms was performed in 245 patients undergoing methadone maintenance treatment. To assess CYP3A activity, the patients were phenotyped with midazolam. RESULTS: The patients with lower CYP3A activity presented higher steady-state trough (R,S)-methadone plasma levels (4.3, 3.0, and 2.3 ng/mL x mg for low, medium, and high activity, respectively; P = .0002). As previously reported, CYP2B6*6/*6 carriers had significantly higher trough (S)-methadone plasma levels (P = .0001) and a trend toward higher (R)-methadone plasma levels (P = .07). CYP2D6 ultrarapid metabolizers presented lower trough (R,S)-methadone plasma levels compared with the extensive or intermediate metabolizers (2.4 and 3.3 ng/mL x mg, respectively; P = .04), whereas CYP2D6 poor metabolizer status showed no influence. ABCB1 3435TT carriers presented lower trough (R,S)-methadone plasma levels (2.7 and 3.4 ng/mL . mg for 3435TT and 3435CC carriers, respectively; P = .01). The CYP1A2, CYP2C9, CYP2C19, CYP3A5, and UGT2B7 genotypes did not influence methadone plasma levels. Only CYP2B6 displayed a stereoselectivity in its activity. CONCLUSION: In vivo, CYP3A4 and CYP2B6 are the major CYP isoforms involved in methadone metabolism, with CYP2D6 contributing to a minor extent. ABCB1 genetic polymorphisms also contribute slightly to the interindividual variability of methadone kinetics. The genetic polymorphisms of these 4 proteins had no influence on the response to treatment and only a small influence on the dose requirement of methadone.

A novel cyclosporin a aqueous formulation for dry eye treatment: in vitro and in vivo evaluation.

PURPOSE: The aim of the present study was the in vitro and in vivo evaluation of a novel aqueous formulation based on polymeric micelles for the topical delivery of cyclosporine A for dry eye treatment. METHODS: In vitro experiments were carried out on primary rabbit corneal cells, which were characterized by immunocytochemistry using fluorescein-labeled lectin I/isolectin B4 for the endothelial cells and mouse monoclonal antibody to cytokeratin 3+12 for the epithelial ones. Living cells were incubated for 1 hour or 24 hours with a fluorescently labeled micelle formulation and analyzed by fluorescence microscopy. In vivo evaluations were done by Schirmer test, osmolarity measurement, CyA kinetics in tears, and CyA ocular distribution after topical instillation. A 0.05% CyA micelle formulation was compared to a marketed emulsion (Restasis). RESULTS: The in vitro experiments showed the internalization of micelles in the living cells. The Schirmer test and osmolarity measurements demonstrated that micelles did not alter the ocular surface properties. The evaluation of the tear fluid gave similar CyA kinetics values: AUC = 2339 ± 1032 min*μg/mL and 2321 ± 881.63; Cmax = 478 ± 111 μg/mL and 451 ± 74; half-life = 36 ± 9 min and 28 ± 9 for the micelle formulation and Restasis, respectively. The ocular distribution investigation revealed that the novel formulation delivered 1540 ± 400 ng CyA/g tissue to the cornea. CONCLUSIONS: The micelle formulation delivered active CyA into the cornea without evident negative influence on the ocular surface properties. This formulation could be applied for immune-related ocular surface diseases.

Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment.

BACKGROUND AND OBJECTIVE: Recent in vitro studies have suggested an important role of cytochrome P450 (CYP) 2B6 and CYP2C19 in methadone metabolism. We aimed to determine the influence of CYP2B6, CYP2C9, and CYP2C19 genetic polymorphism on methadone pharmacokinetics and on the response to treatment. METHODS: We included 209 patients in methadone maintenance treatment on the basis of their response to treatment and their daily methadone dose. Patients were genotyped for CYP2B6, CYP2C9, and CYP2C19. Steady-state trough and peak (R)-, (S)-, and (R,S)-plasma levels and peak-to-trough plasma level ratios were measured. RESULTS: CYP2B6 genotype influences (S)-methadone and, to a lesser extent, (R)-methadone plasma levels, with the median trough (S)-methadone plasma levels being 105, 122, and 209 ng . kg/mL . mg for the noncarriers of allele *6, heterozygous carriers, and homozygous carriers (*6/*6), respectively (P = .0004). CYP2C9 and CYP2C19 genotypes do not influence methadone plasma levels. Lower peak and trough plasma levels of methadone and higher peak-to-trough ratios were measured in patients considered as nonresponders [median (R,S)-methadone trough plasma levels of 183 and 249 ng . kg/mL . mg (P = .0004) and median peak-to-trough ratios of 1.82 and 1.58 for high-dose nonresponders and high-dose responders, respectively (P = .0003)]. CONCLUSION: Although CYP2B6 influences (S)-methadone plasma levels, given that only (R)-methadone contributes to the opioid effect of this drug, a major influence of CYP2B6 genotype on response to treatment is unlikely and has not been shown in this study. Lower plasma levels of methadone in nonresponders, suggesting a higher clearance, and higher peak-to-trough ratios, suggesting a shorter elimination half-life, are in agreement with the usual clinical measures taken for such patients, which are to increase methadone dosages and to split the daily dose into several intakes.

Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study.

Objective This study assessed the efficacy and safety of canakinumab, a fully human anti-interleukin 1 beta monoclonal antibody, for prophylaxis against acute gouty arthritis flares in patients initiating urate-lowering treatment.Methods In this double-blind, double-dummy, dose-ranging study, 432 patients with gouty arthritis initiating allopurinol treatment were randomised 1:1:1:1:1:1:2 to receive: a single dose of canakinumab, 25, 50, 100, 200, or 300 mg subcutaneously; 4 x 4-weekly doses of canakinumab (50 + 50 + 25 + 25 mg subcutaneously); or daily colchicine 0.5 mg orally for 16 weeks. Patients recorded details of flares in diaries. The study aimed to determine the canakinumab dose having equivalent efficacy to colchicine 0.5 mg at 16 weeks.Results A dose-response for canakinumab was not apparent with any of the four predefined dose-response models. The estimated canakinumab dose with equivalent efficacy to colchicine was below the range of doses tested. At 16 weeks, there was a 62% to 72% reduction in the mean number of flares per patient for canakinumab doses >= 50 mg versus colchicine based on a negative binomial model (rate ratio: 0.28-0.38, p <= 0.0083), and the percentage of patients experiencing >= 1 flare was significantly lower for all canakinumab doses (15% to 27%) versus colchicine (44%, p<0.05). There was a 64% to 72% reduction in the risk of experiencing >= 1 flare for canakinumab doses >= 50 mg versus colchicine at 16 weeks (hazard ratio (HR): 0.28-0.36, p <= 0.05). The incidence of adverse events was similar across treatment groups.Conclusions Single canakinumab doses >= 50 mg or four 4-weekly doses provided superior prophylaxis against flares compared with daily colchicine 0.5 mg.

Endovascular coiling compared with surgical clipping for the treatment of unruptured middle cerebral artery aneurysms: an update.

OBJECT: In 1999 we reported that 94% of unruptured middle cerebral artery (MCA) aneurysms managed prospectively between 1993 and 1997, according to a protocol favoring endovascular coiling, were best treated by surgical clipping. The goal of the current study was to delineate the most appropriate treatment option for unruptured MCA aneurysms today, considering the technical advances in imaging and in endovascular treatment. METHODS: 35 consecutive patients harboring 40 unruptured MCA aneurysms were treated between 1997 and December 2000. Patients with unruptured cerebral aneurysms are managed prospectively according to the same protocol as reported previously [1]: the primary treatment recommendation is endovascular packing with Guglielmi detachable coils (GDCs). Surgical clipping is recommended after failed attempt at coil placement or in the presence of angioanatomical features that contraindicate that type of endovascular therapy. RESULTS: One unruptured MCA aneurysm was treated by endovascular embolization, 37 unruptured MCA aneurysms were clipped, whereas 2 unruptured MCA aneurysms were trapped with simultaneous extracranial-intracranial revascularization. Postoperative angiography revealed complete exclusion of all aneurysms. Preservation of vascular permeability was demonstrated in all clip-reconstructed aneurysms, despite arterial branches frequently originating from the aneurysmal base. Cerebral revascularization of the distal MCA was successful in the 2 patients with giant aneurysms. None of the patients presented permanent disabling complications from the treatment of the unruptured MCA aneurysm. CONCLUSION: Despite major technical advances in imaging and in endovascular treatment of cerebral aneurysms, surgical clipping still is the most efficient treatment for unruptured MCA aneurysms at the beginning of the new millennium.

CONVERSION TO AFLIBERCEPT THERAPY VERSUS CONTINUING WITH RANIBIZUMAB THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEPENDENT ON MONTHLY RANIBIZUMAB TREATMENT.

PURPOSE: To compare the effects of converting to aflibercept therapy with continuing ranibizumab therapy in eyes with neovascular age-related macular degeneration requiring monthly ranibizumab treatment. METHODS: Patients were selected from the 104 patients (115 eyes) already enrolled in an "Observe and Plan" prospective case series that included treating neovascular age-related macular degeneration with ranibizumab for 24 months. Patients who still needed monthly retreatment at the end of a 2-year study were randomized to either continue ranibizumab therapy or to convert to aflibercept therapy. Outcome measures included average interval between treatments, resolution of exudative signs, number of retreatments, and change in visual acuity over 12 months (the third treatment year). RESULTS: Nineteen patients (21 eyes) met the inclusion criteria. Ten eyes were randomized to receive aflibercept, and 11 eyes remained on ranibizumab. Groups were balanced for baseline characteristics. Outcomes were similar in the 2 groups over a 12-month study duration, with no statistical difference. CONCLUSION: This comparative pilot study suggests that neovascular age-related macular degeneration requiring monthly retreatment with ranibizumab may respond in similar ways to both ranibizumab and aflibercept treatment. Larger sample sizes would be needed to confirm this observation.

Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy

BACKGROUND: Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in patients with chronic hepatitis C. We therefore performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms within the vitamin D cascade on chronic hepatitis C and its treatment. METHODS: Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and the 1α- hydroxylase were determined in a cohort of 468 HCV genotype 1, 2 and 3 infected patients who were treated with interferon-alfa based regimens. RESULTS: Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D3<10 ng/mL in 25% versus 12%, p<0.00001), which was in part reversible after HCV eradication. 25(OH)D3 deficiency correlated with SVR in HCV genotype 2 and 3 patients (63% and 83% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.001). In addition, the CYPB27-1260 promoter polymorphism rs10877012 had substantial impact on 1-25- dihydroxyvitamin D serum levels and SVR rates in HCV genotype 1, 2 and 3 infected patients. CONCLUSIONS: Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25- hydroxyvitamin D levels and CYPB27-1260 promoter polymorphism are associated with failure to achieve SVR in HCV genotype 1, 2, 3 infected patients.