Rapid detection of pathogens using lyotropic liquid crystals.

Lyotropic liquid crystals play an important role in many biological environments, such as micelles, liposomes, and phospholipid bilayers of cell membranes. In this work, we explore the performance of lyotropic liquid crystals as biosensors for macromolecules, proteins and whole microorganisms in hydrophilic media, i.e., the natural media where these specimens exist. The aim is to detect specific targets employing simple, unpowered sensors that can be used in the field, with minimum additional equipment. A number of different structures have been explored. The novelty in this work is the inclusion of a new optical effect, flow enhanced amplification, that allows for the semiquantitative detection of microscopic targets in lyotropic liquid crystal cells using the naked eye only.

Monodomain Blue Phase Liquid Crystal Layers for Phase Modulation.

Liquid crystal "Blue Phases" (BP) have evolved, in the last years, from a scientific curiosity to emerging materials for new photonic and display applications. They possess attractive features over standard nematic liquid crystals, like submillisecond switching times and polarization- independent optical response. However, BPs still present a number of technical issues that prevent their use in practical applications: their phases are only found in limited temperature ranges, thus requiring stabilization of the layers; stabilized BP layers are inhomogeneous and not uniformly oriented, which worsen the optical performance of the devices. It would be essential for practical uses to obtain perfectly aligned and oriented monodomain BP layers, where the alignment and orientation of the cubic lattice are organized in a single 3D structure. In this work we have obtained virtually perfect monodomain BP layers and used them in devices for polarization independent phase modulation. We demonstrate that, under applied voltage, well aligned and oriented layers generate smoother and higher values of the phase shift than inhomogeneous layers, while preserving polarization independency. All BP devices were successfully stabilized in BPI phase, maintaining the layer monodomain homogeneity at room temperature, covering the entire area of the devices with a unique BP phase.

Predictors of Poor Prognosis in Recurrent Hepatitis C After Liver Transplantation.

BACKGROUND: Hepatitis C is a common indication for liver transplantation (LT). Hepatitis C virus (HCV) recurrence is universal in viremic patients. This recurrence is frequently very aggressive, with graft loss in less than 5 years. Our aim is to detect which factors are related to worse fibrosis at 1 year post-LT. PATIENTS AND METHODS: Records of all HCV-positive transplanted patients in Hospital Universitario Nuestra Señora de la Candelaria from 1996 to 2014 were collected. The variables analyzed were donor and recipient age and gender, hypertension, diabetes, viral genotype, viral load at LT, hepatocellular carcinoma in the explant, anticoagulation or antiplatelet treatment, year of transplantation, and mean levels of tacrolimus in the first month. Severe recurrence was defined as fibrosis F3 by biopsy, liver stiffness > 9.5 kPa by transient elastography, or hepatic venous pressure gradient > 5 mm Hg at 1 year post-LT. Univariate and multivariate analyses were performed. RESULTS: From a sample of 112 patients, 88 patients met inclusion criteria. Mean recipient age was 52.8 ± 8.0 years and 70.5% were men. Mean donor age was 46.4 ± 16.1 years and 59.1% were men. Severe recurrence occurred in 23.9%. Univariate analyses showed 3 variables were statistically significant: donor age (P = .03), recipient age (P = .008), and presence of hepatocellular carcinoma (P = .01). Only the 2 first variables remained significant in the multivariate model (P = .009 and P = .044 respectively). Hepatocellular carcinoma was probably related to older recipients becoming a confounding factor. CONCLUSIONS: In our study, donor and recipient age both conferred a worse prognosis in terms of fibrosis progression in patients with liver transplant due to HCV.

Risk factors of hepatocellular carcinoma recurrence after liver transplantation: accuracy of the alpha-fetoprotein model in a single-center experience.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) and cirrhosis after a liver transplantation (LT) is a major concern, and a strict Milan criteria selection of candidates does not accurately discriminate the relapse rate after LT. PURPOSE: This study sought to analyze the risk factors affecting tumor recurrence after LT for related cirrhosis HCC and the application of the French prognostic model (preLT alpha-fetoprotein [AFP], size, number) in a single center. METHODS: In a retrospective observational study of LT for HCC and cirrhosis, clinicopathological features were analyzed. Also, the preoperative and postoperative AFP model score was calculated with a cutoff of 2. RESULTS: Of 480, 109 patients underwent cadaveric LT for HCC. Eight of them had a relapse (7%). High AFP level, AFP model score >2, high pathological tumor-node-metastasis (pTNM) stage, poor differentiation, macrovascular-microvascular invasion, infiltration, and R1 margin were statistically significant (P < .05) for recurrence. Also, in the preoperative model, AFP score >2 was a predictor of worse survival (1-, 3-, 5-, 10-year survival of 81%, 51%, 30%, 30% vs 90%, 76%, 73%, 69% in ≤2, with P = .005). Regarding the postoperative model, similar results were found (1-, 3-, 5-, 10-year survival of 84%, 47%, 37%, 37% vs 90%, 78%, 73%, 52%, P = .028) between AFP model score >2 and ≤2, respectively. However, Milan and up-to-7 criteria were not accurate in recurrence nor in survival. CONCLUSIONS: The French AFP model has proven to be a more discerning prognostic tool than other established criteria in the prediction of recurrence and survival. Also, in postoperative prognosis, pathological risk factors for relapse such as pTNM, differentiation grade, macrovascular-microvascular invasion, infiltration, and R1 margin have been predictors of recurrence.

Hepatitis C virus sensitivity to combined antiviral therapy in liver transplant versus immunocompetent patients.

Recurrent hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) frequently causes allograft failure, because viral aggressiveness has been shown to be increased among immunosuppressed patients. Several studies have reported lower efficacy of antiviral therapy after OLT associated with worse tolerability. The aim of this study was to compare the logarithmic falls in viral loads at 4 and 12 weeks of treatment with pegylated interferon alpha and ribavirin among OLT versus immunocompetent patients. OLT patients (group 1) were recruited from 3 Spanish centers. Two age- and sex-matched controls (group 2) were randomly assigned to each case. We excluded coinfection with human immunodeficiency virus or hepatitis B or cholestatic hepatitis. Among group 1 (n = 66) were 72.7% men with an overall mean age of 52.7 +/- 10.1 years; 90.9% were genotype 1. The mean baseline viral load was 6.0 +/- 0.6 log10 IU/mL, and 19% of patients had cirrhosis. Among group 2 (n = 132) were 72.7% men with an overall mean age of 50.1 +/- 10.1 years; 92.4% were genotype 1. The mean baseline viral load was 5.9 +/- 0.5 log10 IU/mL, and 17% of patients had cirrhosis. There were no significant differences in patient characteristics between the 2 groups. The logarithmic falls in viral loads at 4 weeks of treatment were similar in groups 1 and 2: 2.3 +/- 2.1 vs 2.4 +/- 1.9 log10 IU/mL (P = .49); they were also similar at 12 weeks of treatment: 3.9 +/- 1.9 vs 3.7 +/- 2.4 log10 IU/mL (P = .66). In conclusion, in our study HCV sensitivity to combined antiviral therapy was the same among transplant versus immunocompetent patients.

Hepatitis C virus recurrence after liver transplantation: influence of immunosuppressive regimens on viral load and liver histology.

Cyclosporine has recently been reported to produce in vitro suppression of hepatitis C virus replication driven by blockade of cyclophilins, an effect not shown for tacrolimus. However, the clinical consequence of this in vitro finding have not been well studied in vivo. We compared viral load and fibrosis in transplanted patients receiving monotherapy with tacrolimus or cyclosporine. Patients with recurrent hepatitis C after transplantation were selected from two tertiary centers with the following inclusion criteria: monotherapy with tacrolimus or cyclosporine for more than 12 months before viral load measurement, no antiviral treatment, corticosteroids stopped within 12 months after transplantation. HIV, hepatitis B, and active infection by cytomegalovirus were excluded. Patient characteristics, viral load, and fibrosis were compared by univariate analysis between the cyclosporine and tacrolimus groups. Significant variables, viral load, and fibrosis were included in a multivariate model. Sixty-six patients were included, 46 on tacrolimus and 20 on cyclosporine. Fifty-six were male, and the mean age was 55.3 +/- 10.1 years. Fibrosis (Ishak score) was 3.9 +/- 1.9 in the cyclosporine group and 2.7 +/- 1.9 in the tacrolimus group (P = .019). Viral load (log(10)IU/mL) was 5.8 +/- 0.5 and 5.9 +/- 0.5, respectively (P = .7) and time since liver transplantation was 95.3 +/- 47.7 and 41.1 +/- 16.8 months (P = .0001). In the multivariate model, viral load (P = .65) and fibrosis (P = .24) were not significantly different and only time since transplantation remained significant (P = .0001). In conclusion, viral load was not different in patients with tacrolimus as compared with cyclosporine, and the lower fibrosis observed in the cyclosporine group lacked significance when considered together with time since liver transplantation.

Scarce influence of corticosteroid boluses on long-term viral load and liver histology in transplanted patients with recurrent hepatitis C.

Corticosteroid boluses, which are the treatment for acute rejection episodes, have been shown to produce transient increases in viremia. However, their effect on long-term viral load, histological activity index (HAI), and fibrosis has not been well established. The aim of our study was to compare late viral load, HAI, and fibrosis in patients with versus without steroid boluses in the immediate posttransplant period. We analyzed patients transplanted due to hepatitis C virus. Inclusion criteria were: no change in immunosuppression (cyclosporine or tacrolimus with/without mycophenolate); no steroids in the previous 4 months; no antiviral treatment; liver biopsy and viral load determination >12 months after transplantation. Exclusion criteria were HIV, hepatitis B, and active cytomegalovirus infection. Nonparametric tests were used to compare viral load, HAI, and fibrosis (Ishak-score) among patients who received steroid boluses for an acute rejection episode (group 1) versus those who did not (group 2). Among the 48 selected patients were 38 men with the overall mean age of the entire group of 55.6 +/- 10.9 years. The mean period from liver transplantation was 53.25 +/- 33.4 months. Thirty-four (70.1%) were treated with tacrolimus and the rest, cyclosporine. Eleven (22.9%) had and 37 (77.1%) had not received corticosteroid boluses. The viral load was similar in groups 1 and 2 (5.74 +/- 0.54 vs 5.98 +/- 0.53 Log(10) IU per mL, P = .32). Fibrosis was also similar (2.5 +/- 1.6 vs 2.2 +/- 1.7, P = .56). However, HAI was higher in group 1 (7.5 +/- 1.7 vs 6.0 +/- 1.7, P = .026). In conclusion, although long-term viral load was similar in patients who had versus had not received one cycle of steroid boluses, the HAI was significantly higher in the former cohort, but had not resulted in greater fibrosis during the study follow-up.

Hepatitis C recurrence after liver transplantation: Viral and histologic response to full-dose PEG-interferon and ribavirin.

Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48-weeks of full-dose peg-interferon-alpha-2a (n = 4) or alpha-2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients > or =12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 +/- 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end-of-treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV-RNA (p = 0.005) and a length from LT to therapy between 2-4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease > or =1-log10 at week 4 and/or 2-log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg-interferon withdrawal in 16 (29%) subjects. In 15 patients with post-treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.

Accuracy of magnetic resonance cholangiography in the evaluation of late biliary complications after orthotopic liver transplantation.

INTRODUCTION: The aim of our study was to evaluate the role of magnetic resonance cholangiography (MRC) in the diagnosis of late biliary complications after orthotopic liver transplantation (OLT) and to assess the diagnostic accuracy of this imaging technique. MATERIALS AND METHODS: Seventy-one MRC were performed in 46 OLT patients with suspected biliary complication after T-tube removal. We used a fat-suppressed three-dimensional turbo spin-echo sequence (TR/TE 1800/700, ETL 100) with a 1.5-T magnet. The images and maximum intensity projections were evaluated by two radiologists. Diagnostic confirmation was obtained with percutaneous transhepatic cholangiography (PTC) (n = 10), endoscopic retrograde cholangiography (ERC) (n = 24), surgery (n = 5), and clinical and ultrasound follow-up (n = 30). RESULTS: The MRC studies were considered diagnostic by the two radiologists in 69 cases (97.2%). MRC had a sensitivity of 93%, a specificity of 97.6%, a positive predictive value of 96.3%, a negative predictive value of 95.2%, and a global diagnostic accuracy of 95.6% to detect late biliary complications in OLT patients. The interobserver agreement was excellent (kappa = .92). CONCLUSION: MRC is a reliable technique to detect and exclude late biliary complications after OLT.

Pegylated interferon and ribavirin for the recurrence of chronic hepatitis C genotype 1 in transplant patients.

The efficacy of pegylated interferon (p-IFN) and ribavirin (RB) in transplant patients is not well known. Chronic hepatitis C evolves in a more aggressive form after transplantation, causing a worse survival. Twenty-one naïve patients with recurrent chronic hepatitis C demonstrated by biopsy were treated for 48 weeks with p-IFN alpha2b (1.5 microg/kg/wk) and RB (>10.6 mg/kg/d). Quantification of RNA was performed (Amplicor Cobas 2.0 Roche) at baseline, 4, 12, 24, 48, and 72 weeks. A qualitative technique was used when quantitative levels were undetectable. At more than 1 year since liver transplantation we did not detect coinfection with human immunodeficiency virus or use steroid treatment. Among the cohort there were 16 men (76.2%). The mean overall age was 52 +/- 12 years. Time from liver transplant to treatment was 1637 +/- 1030 days. They were all infected with genotype 1. Eight patients received cyclosporine and the others tacrolimus. One patient was coinfected with hepatitis B virus and was receiving lamivudine. The mean initial histological activity index was 6.9 +/- 1.5 and fibrosis, 2.52 +/- 1.8 (Ishak). Two patients needed spleen embolization before the treatment. Two patients had to stop the treatment: one due to clinical intolerance, and the other one due to a cholangitis. In 14%, p-IFN doses were adjusted. In 32% RB was adjusted. Five (23.8%) did not respond at 24 weeks. Fourteen (66.7%) showed end-treatment responses but four relapsed at 72 weeks. A sustained viral response was achieved in 9 (42.8%). One patient died due to arterial thrombosis just after completing the treatment.