Clinical Impact of a Protocolized Kidney Donor Follow-up System.

BACKGROUND: Adequate kidney donor management after donation is increasingly emphasized due to concerns of renal function impairment after nephrectomy with increasing life expectancy. In this study, the clinical impact of a protocolized kidney donor follow-up system by nephrologists was evaluated. METHODS: A total of 427 living kidney donors underwent nephrectomy from January 2010 to December 2014 and were followed for at least 2 years at the Samsung Medical Center. Donors were followed-up by nephrologists after the establishment of a donor clinic with systemized protocols in January 2013. The primary outcomes were incidence of post-donation low estimated glomerular filtration rate (eGFR) and renal function adaptability. Secondary outcomes were changes in compliance and incidence of hyperuricemia and microalbuminuria. RESULTS: The patients were divided into 2 groups according to the time of nephrectomy: the pre-donor clinic period (n = 182) and the donor clinic period (n = 172). Preoperative eGFR in patients in the pre-donor clinic period was higher than that in patients in the donor clinic period. After donation, poor renal adaptation was less frequent in the donor clinic period compared to the pre-donor clinic period. Low eGFR tended to be less common during the donor clinic period. Shorter mean outpatient clinic visit intervals with more visits within 6 months after donation and earlier detection of de novo hyperuricemia were found during the donor clinic period. CONCLUSION: A protocolized donor clinic run by nephrologists may improve post-nephrectomy renal outcomes and compliance and facilitate better management of potential risk factors of chronic kidney disease in donors.

Predictive Factors of Renal Adaptation After Nephrectomy in Kidney Donors.

BACKGROUND: Despite compensatory hyperfiltration in remaining nephrons following donor nephrectomy, some donors show impaired renal adaptation and low estimated glomerular filtration rate (eGFR). We investigated the factors predicting early renal adaptation after nephrectomy and identified kidney donors at risk of inadequate renal adaptation. METHODS: A total of 265 living kidney donors from 2010 to 2013 were retrospectively analyzed. Renal function was serially followed for 6 months after the operation. Regression analyses were performed to identify the independent predictors of low eGFR (eGFR <60 mL/min/1.73 m2) and impaired renal adaptation (%Modification of Diet in Renal Disease [MDRD] <66% of baseline eGFR). RESULTS: A total of 148 donors belonged to the low eGFR group, and changes in eGFR (ΔeGFR) at postoperative (PO) 1 day and 1 month were identified as independent predictors of low eGFR. Impaired renal adaptation was related to age, ΔeGFR PO 2-3 days, and ΔeGFR PO 1 month. Early renal adaptation was associated with age, male gender, and residual kidney computerized tomography angiography (CTA) volume. The best sensitivity and specificity were obtained with a cutoff value of ΔeGFR 31 at PO 1 day and 1 month for predicting low eGFR and with a value of ΔeGFR 27 at PO 2-3 days and 1 month for predicting impaired renal adaptation. CONCLUSIONS: Our study showed that the degree of early renal adaptation determines subsequent renal function in kidney donors. Closer monitoring and management may be required in old or male donors with small residual CTA kidney volume as well as donors with persistent ΔeGFR >27 within 1 month of nephrectomy.

Prevalence, demographic variation and psychological correlates of exposure to police victimisation in four US cities.

Aims Victimisation by the police is purported to be widespread in cities in the USA, but there is limited data on police-public encounters from community samples. This is partly due to an absence of measures for assessing police violence exposure from the standpoint of civilians. As such, the demographic distribution and mental health correlates of police victimisation are poorly understood. The aims of this study were to present community-based prevalence estimates of positive policing and police victimisation based on assessment with two novel measures, and to test the hypotheses that (1) exposure to police victimisation would vary across demographic groups and (2) would be associated with depression and psychological distress. METHODS: The Survey of Police-Public Encounters study surveyed adults residing in four US cities to examine the prevalence, demographic distribution and psychological correlates of police victimisation. Participants (N = 1615) completed measures of psychological distress (K-6 scale), depression (Patient Health Questionnaire 9) and two newly constructed measures of civilian-reported police-public encounters. Both measures were developed to assess police victimisation based on the WHO domains of violence, which include physical violence (with and without a weapon, assessed separately), sexual violence (inappropriate sexual contact, including public strip searches), psychological violence (e.g., threatening, intimidating, stopping without cause, or using discriminatory slurs) and neglect (police not responding when called or responding too late). The Police Practices Inventory assesses lifetime history of exposure to positive policing and police victimisation, and the Expectations of Police Practices Scale assesses the perceived likelihood of future incidents of police victimisation. Linear regression models were used to test for associations between police-public encounters and psychological distress and depression. RESULTS: Psychological violence (18.6%) and police neglect (18.8%) were commonly reported in this sample and a substantial minority of respondents also reported more severe forms of violence, specifically physical (6.1%), sexual (2.8%) and physical with a weapon (3.3%). Police victimisation was more frequently reported by racial/ethnic minorities, males, transgender respondents and younger adults. Nearly all forms of victimisation (but not positive policing) were associated with psychological distress and depression in adjusted linear regression models. CONCLUSIONS: Victimisation by police appears to be widespread, inequitably distributed across demographic groups and psychologically impactful. These findings suggest that public health efforts to both reduce the prevalence of police violence and to alleviate its psychological impact may be needed, particularly in disadvantaged urban communities.

The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea.

Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73-19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61-27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95-284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.

Efficiency of professional tooth brushing before ultrasonic scaling.

OBJECTIVES: This study aimed to examine the effect of dental plaque biofilm removal with a toothbrush, an interdental brush and dental floss by a dental hygienist prior to ultrasonic scaling on treatment times and client satisfaction. METHODS: This study was conducted among adults who received scaling after agreeing to participate in this study at a dental clinic in Seoul, Korea, from July to September 2012. Thirty-seven subjects received modified scaling (M-scaling) which is ultrasonic scaling after plaque control with a toothbrush and dental floss by a dental hygienist, and 37 subjects received routine ultrasonic scaling (R-scaling). Univariate and multivariate analyses and chi-squared and t-tests were conducted using SAS. This study was approved by the Kangwon Institutional Review Board. RESULTS: Significant differences were found between the outcomes of M- and R-scaling for both the ultrasonic scaling time (M-scaling, 7.41 ± 6.18 min; R-scaling, 23.22 ± 6.92 min) and the total tooth cleaning time (M-scaling, 15.92 ± 7.70 min; R-scaling, 23.22 ± 6.92 min) (P < 0.001). Subject satisfaction with the scaling process was not significantly different between M-scaling (4.54 ± 0.80) and R-scaling (4.84 ± 0.44). CONCLUSIONS: These findings indicated that removing the dental plaque biofilm with a toothbrush and dental floss by a hygienist before scaling with an ultrasonic device was more effective in reducing the working time of the dental hygienist.

Alcohol consumption and persistent infection of high-risk human papillomavirus.

Alcohol consumption is a possible co-factor of high-risk human papillomavirus (HR-HPV) persistence, a major step in cervical carcinogenesis, but the association between alcohol and continuous HPV infection remains unclear. This prospective study identified the association between alcohol consumption and HR-HPV persistence. Overall, 9230 women who underwent screening during 2002-2011 at the National Cancer Center, Korea were analysed in multivariate logistic regression. Current drinkers [odds ratio (OR) 2·49, 95% confidence interval (CI) 1·32-4·71] and drinkers for ⩾5 years (OR 2·33, 95% CI 1·17-4·63) had a higher risk of 2-year HR-HPV persistence (HPV positivity for 3 consecutive years) than non-drinkers and drinkers for <5 years, respectively (vs. HPV negativity for 3 consecutive years). A high drinking frequency (⩾twice/week) and a high beer intake (⩾3 glasses/occasion) had higher risks of 1-year (OR 1·80, 95% CI 1·01-3·36) HPV positivity for 2 consecutive years) and 2-year HR-HPV persistence (OR 3·62, 95% CI 1·35-9·75) than non-drinkers. Of the HPV-positive subjects enrolled, drinking habit (OR 2·68, 95% CI 1·10-6·51) and high consumption of beer or soju (⩾2 glasses/occasion; OR 2·90, 95% CI 1·06-7·98) increased the risk of 2-year consecutive or alternate HR-HPV positivity (vs. consecutive HPV negativity). These findings suggest that alcohol consumption might increase the risk of cervical HR-HPV persistence in Korean women.

Comparison of cadaveric kidney transplantation from in-center and external center donors.

INTRODUCTION: Renal transplantation is the best treatment modality for end-stage renal disease. We investigated the effects of donor source on renal allograft and patient survival in deceased donor transplants. METHODS: We analyzed retrospectively 190 cadaver kidney transplants performed in our center from January 2000 to December 2009. Of these, 136 kidneys were harvested in our transplantation center and 54 were from external donors. Primary outcome of graft survival was assessed with the Kaplan-Meier method and the significance of possible variables was determined with the Cox proportional hazard model. RESULTS: There was no difference between groups in the age of donor and recipient, recipient body mass index, duration of dialysis, or panel reactive antibody >30%. Twenty recipients lost their grafts (14 from external donors and 6 from internal donors). Graft survival at 1, 3, and 5 years was 99.2%, 97.3%, and 95.5% for in-center donors and 98.1%, 88.9%, and 86.2% for external donor transplants (P = .01). There was no difference in patient survival rates between the groups. Acute rejection episodes (hazard ratio [HR], 13.2; P < .001) and external hospital donor (HR, 9.3; P = .008) were independent factors associated with failure. Higher age of recipient was associated with increased patient death rate (HR, 1.2; P = .02). CONCLUSION: Graft survival of cadaveric transplants from in-center donors was better than that of transplants from external center donors. Acute rejection episodes and location of harvest were significant factors for graft survival. Further study is needed to evaluate the effects of center-level factors on allograft outcomes.

Association between pre-donation serum uric acid concentration and change in renal function after living kidney donation in women.

BACKGROUND: Reduction in renal mass after unilateral nephrectomy causes functional and structural changes in the remaining kidney. AIM: We aimed to investigate the association between pre-donation serum uric acid (SUA) concentration and the change in renal function after living kidney donation. METHODS: This retrospective study included 413 living kidney donors from a single centre. We collected medical history and laboratory findings at baseline and 6 months after donation. Renal function was assessed by calculating the estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. Main outcomes were the percentage change in eGFR from before to 6 months after donation and the percentage of patients whose eGFR decreased by >25% after donation compared with the pre-donation baseline value. RESULTS: Mean age was 40 ± 11 years, and eGFR was 106 ± 14 mL/min/1.73 m(2). In women, the SUA concentration was linearly associated with the change in eGFR after donation independently of baseline eGFR (standardised coefficient - 0.16, P = 0.04). Multiple logistic analysis showed that a 59.5 µmol/L increase in baseline SUA concentration was associated with a 1.7-fold higher risk of a > 25% decrease in eGFR after donor nephrectomy (95% confidence interval, 1.2-2.5; P = 0.007) in women. In contrast, SUA concentration was not an independent risk factor of decrease in eGFR after donor nephrectomy in men. CONCLUSIONS: Pre-donation SUA concentration is associated independently with the change in renal function after donor nephrectomy in women but not in men.

Presence of vesicoureteral reflux in the graft kidney does not adversely affect long-term graft outcome in kidney transplant recipients.

INTRODUCTION: We studied the incidence of vesicoureteral reflux (VUR) in the graft kidney and its effect on the occurrence of urinary tract infection (UTI) and long-term graft function. METHODS: We performed a retrospective analysis of 64 adult kidney transplant recipients based upon voiding cystourethrography at 12 months post-transplantation. Patients underwent analysis of survival, incidence of UTIs beyond 1 year, and graft function. RESULTS: Thirty-seven male and 27 female patients in the study populations showed a mean age 42 years. VUR in the transplanted kidney at 12 months post-transplant occurred among 78.1% (50/64) of subjects: grade I (n = 6), grade II (n = 30), or grade III (n = 14) reflux. Patients followed for a median 61 months (range 44-74s) showed 11 cases of UTIs in 9 subjects. There were no significant differences in clinical characteristics or incidence of, UTIs according to the presence or severity of VUR (P = .81) or the Serum creatinine and estimated glomerular filtration rate values at 12, 36, 48, or 60 months post-transplantation. CONCLUSIONS: VUR present in 78.1% of patients after kidney transplantation affected neither graft functions or graft survival. The incidence of UTI did not differ according to the presence of VUR.

Assessment of extent of breast cancer: comparison between digital breast tomosynthesis and full-field digital mammography.

AIM: To compare the accuracy of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) in preoperative assessment of local extent of breast cancer. MATERIALS AND METHODS: Lesion sizes of breast cancers on DBT and FFDM images were independently evaluated by breast radiologists. Each lesion was flagged as either mis-sized or not depending on whether the assessment of size at imaging was within 1 cm of the lesion size at surgery. Additional analyses were made by mammographic parenchymal density and by lesion size, using 2 cm as the boundary to separate the two subgroups. Statistical comparisons were performed using a repeated measures linear model on the percent mis-sized. P-values < 0.05 were considered statistically significant. RESULTS: The dataset included 173 malignant breast lesions (mean size 23.8 mm, 43% of lesions were ≤2 cm in size) in 169 patients, two-thirds of which had heterogeneously or extremely dense breasts. Overall, the percentage of lesions mis-sized at DBT was significantly lower than at FFDM (19% versus 29%, p = 0.003). There was significantly less mis-sizing at DBT in both heterogeneously dense breasts (11.1% difference between DBT and FFDM, p = 0.016) and extremely dense breasts (15.8% difference, p = 0.024). DBT also had significantly less mis-sizing than FFDM in the subgroup of lesions that were ≤2 cm in size (14.7% difference, p = 0.005). CONCLUSION: DBT was significantly superior to FFDM for the evaluation of lesion size overall, and specifically for small lesions and for lesions in dense breasts. The superiority of DBT versus FFDM increased with parenchymal density.

Hormonal differences between female kidney transplant recipients and healthy women with the same gynecologic conditions.

BACKGROUND: End-stage renal disease is associated with severe abnormalities in reproductive function. However, the abnormalities are reversed by successful kidney transplantation. The aim of the present study was to compare hormonal levels between recipients with successful kidney transplantations and healthy women with the same gynecologic conditions. METHODS: The study group consisted of 31 women of reproductive age with end-stage renal disease who underwent successful kidney transplantation. The ratio of the control group, composed of healthy woman, to the study group was 3:1 matched for age and symptoms. RESULTS: Abnormal bleeding (n = 14) and infertility were the most common gynecologic conditions in kidney transplant recipients. The levels of estrogen (E2) and follicle-stimulating hormone (FSH) in the study group were higher than in the control group, but the levels of progesterone (P4) and luteinizing hormone (LH) were lower in the study group than in the control group. There were no significant differences in prolactin and thyroid-stimulating hormone between the two groups. The incidence of infertility in patients who receive steroid was higher than those with no steroid use (P = .007). CONCLUSIONS: Compared with healthy age- and symptom-matched women, female kidney transplant recipients have increased levels of E2 and FSH and decreased levels of P4 and LH. These differences in hormone profiles may predispose kidney transplant recipients to increased risk of gynecologic pathologies.

Rabbit antithymocyte globulin compared with basiliximab in kidney transplantation: a single-center study.

BACKGROUND: Induction therapy is used to reduce the incidence of acute rejection and to prevent or treat delayed graft function. We compared basiliximab with rabbit antithymocyte globulin (ATG) as induction therapies for kidney transplant recipients. METHODS: We retrospectively analyzed the clinical data from 514 patients who received ATG or basiliximab. The patients in the ATG group (n = 152) received ATG (1.5 mg/kg/d) for 5-7 days and those in the basiliximab group (n = 362) were given 2 doses of basiliximab (20 mg) on posttransplantation days 0 and 4. All patients received standard triple immunosuppressive therapy with calcineurin inhibitors, mycophenolate mofetil, and steroids. RESULTS: There were statistically significant differences in the incidences of delayed graft function, 1-year acute rejection rate, death-censored graft survival, and patient survival between the 2 groups, even though the ATG group had more kidney transplants from deceased donors, higher levels of panel reactive antibodies, and more retransplantations. The incidences of cytomegalovirus (CMV) infection and parvovirus infection in the ATG group were higher than those in the basiliximab group. However, there was no statistically significant difference in the incidence of CMV disease between the 2 groups. CONCLUSIONS: ATG is safe and efficacious for use in kidney transplant recipients. Our results suggest that ATG should be considered for induction therapy in high-risk patients, such as those who have a kidney allograft from a deceased donor, high levels of panel reactive antibodies, and are undergoing retransplantation.

Comparison between thymoglobulin and ATGAM as an induction agent in adult kidney transplantation: a single-center experience.

OBJECTIVE: The best antithymocyte globulin (ATG) preparation for induction suppression in kidney transplant recipients is still not clear. The aim of this study was to identify short- and long-term outcomes in kidney transplant recipients who received thymoglobulin or ATGAM as an induction agent. METHODS: We retrospectively reviewed patients who underwent kidney transplantation from 1996 to 2010. Recipients were classified according to the ATG preparation. RESULTS: One hundred fifty-two patients (64.4%) received thymoglobulin and 84 (35.6%) received ATGAM. The occurrence of delayed graft function in patients receiving thymoglobulin was higher than in patients receiving ATGAM (P = .005), but serum creatinine levels and acute rejection after kidney transplantation were not different between the two groups. The death-censored graft survival curve in thymoglobulin recipients was higher than in ATGAM recipients (P = .027). Bacterial infection was a predisposing factor for graft survival (P = .008). CONCLUSION: The efficacy of thymoglobulin induction is generally better than that of ATGAM induction, and prevention of bacterial infections was just as important as the use of ATG because bacterial infection was an important risk factor for graft failure.

Urinary angiotensinogen levels reflect the severity of renal histopathology in patients with chronic kidney disease.

BACKGROUND/AIMS: Recent studies have suggested that urinary angiotensinogen (AGT) reflects the activity of the intrarenal renin angiotensin system (RAS), which is involved in tissue injury in patients with chronic kidney disease. In this study, we investigated whether urinary AGT directly reflected the severity of histopathology in such patients. METHODS: AGT was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) on urine and plasma samples obtained from 58 patients on the day of renal biopsy. We measured the urinary transforming growth factor (TGF)-beta1, a representative cytokine of fibrogenic property, and analyzed the correlation among urinary TGF-beta1, urinary AGT, and the severity of renal injury. Mesangial proliferation, glomerulosclerosis, tubular atrophy and interstitial fibrosis were scored for the biopsied tissues. RESULTS: Urinary AGT levels correlated positively with proteinuria, urinary TGF-beta1 levels and diastolic blood pressure, but negatively with the estimated glomerular filtration rate (GFR). Urinary AGT concentrations were increased in patients with severe glomerulosclerosis, tubular atrophy and interstitial fibrosis. CONCLUSION: Urinary AGT levels correlated with the deterioration of renal function in patients with chronic kidney disease and reflected the histological severity of renal injury.

Combination treatment with corticosteroid, cyclosporine A, and mycophenolate in refractory nephrotic syndrome.

BACKGROUND/AIMS: Refractory nephrotic syndrome (NS) is problematic because the optimal therapy for this disease is unclear and because persistent NS progresses eventually to end-stage renal disease. We report our experience using a combination of corticosteroid, cyclosporine A (CsA), and mycophenolate mofetil (MMF) to treat 10 refractory NS patients. METHODS: Ten refractory NS patients, who showed resistance to corticosteroid and CsA, were treated with triple immunosuppressive therapy. Cyclophosphamide and MMF had been used previously in 6 patients, but had failed to induce remission. RESULTS: Triple immunosuppressive therapy was discontinued after 4 months in 1 patient because of progressive azotemia. Partial remission was achieved in 9 of the 10 patients after 10 months, and remission was maintained during the treatment (urine protein to creatinine ratio, mg/mg, baseline vs. 12th month; 5.7 ± 1.8 vs. 1.4 ± 0.7). Renal function was preserved in these 9 patients (estimated GFR, ml/min/1.73 m2, baseline vs. 12th month; 71.4 ± 29.1 vs. 68.9 ± 31.5). Of the 7 patients who discontinued triple immunosuppressive therapy, remission and renal function were maintained in 4 patients. CONCLUSION: Triple immunosuppressive therapy significantly reduced proteinuria and preserved renal function in refractory NS patients, indicating a promising role of this therapy for refractory NS.

The incidence and clinical outcome of YMDD mutants in hepatitis B surface antigen-positive renal allograft recipients after prolonged lamivudine therapy.

Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV), prolonged therapy may induce the development of LAM-resistant strains, YMDD mutants. Although YMDD mutants have impaired replication that leads to a benign clinical course compared with wild-type virus, some immunosuppressive agents may enhance replication of YMDD mutants, causing a severe hepatitis flare. We retrospectively investigated the incidence and clinical outcomes of YMDD mutants in renal allograft recipients on immunosuppressive treatment. Clinical records of 25 renal allograft recipients, who underwent renal transplantation between December 1997 and February 2006 were hepatitis B surface antigen positive at the time of transplantation, were reviewed. All patients received LAM treatment after renal transplantation. Over 9 to 98 months of follow-up, 16 patients (64.0%) maintained undetectable HBV DNA levels; however, 9 patients (36.0%) showed persistent or increased levels of HBV DNA. Seven were identified as having developed YMDD mutants. Although genotypic analysis was not performed, YMDD mutants were strongly suspected in another two patients, who developed severe hepatic dysfunction combined with high levels of HBV viremia at close to 2 years of LAM therapy. One patient recovered after hepatic transplantation and another patient died of hepatic failure. In conclusion, the incidence of YMDD mutants was similar to that of nonimmunosuppressed individuals; however, the presence of these mutants made it more likely for severe liver disease to develop in renal transplant recipients. Therefore, close monitoring for the development of YMDD mutants should be performed during LAM treatment, especially in this group of patients.

A case of scapulothoracic dissociation with brachial plexus injury: magnetic resonance imaging findings.

Scapulothoracic dissociation is defined as violent lateral or rotational displacement of the shoulder girdle from its thoracic attachments with severe neurovascular injury. We describe the radiographic and associated magnetic resonance (MR) imaging findings of a case of scapulothoracic dissociation with brachial plexus injury in a 17-year-old man, and include a review of the relevant literature.

Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP.

Dexamethasone (DEX) pretreatment protected hepatocytes from TNF-alpha plus actinomycin D (ActD)-induced apoptosis by suppressing caspase-8 activation and the mitochondria-dependent apoptosis pathway. DEX treatment upregulated cellular FLICE inhibitory protein (cFLIP) expression, but did not alter the protein levels of Bcl-2, Bcl-xL, Mcl-1, and cIAP as well as Akt activation. The increased cFLIP mRNA level by DEX was inhibited by ActD, indicating that DEX upregulates cFLIP expression at the transcriptional step. DEX also inhibited Jo2-mediated hepatocyte apoptosis by blocking the formation of the death-inducing signaling complex and caspase-8 activation. Specific downregulation of cFLIP expression using siRNA reversed the antiapoptotic effect of DEX by increasing caspase-8 activation. Moreover, DEX administration into mice increased cFLIP expression in the liver and prevented Jo2-induced hepatic injury by inhibiting caspase-8 and -3 activities. Our results indicate that DEX exerts a protective role in death receptor-induced in vitro and in vivo hepatocyte apoptosis by upregulating cFLIP expression.