Implementation of a Hepatocellular Carcinoma Surveillance Program in a Community-Based Integrated Health System in Patients With Hepatitis C Cirrhosis.

INTRODUCTION: Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes. METHODS: In this retrospective cohort study, we assessed preinclusion and postinclusion HCC surveillance patterns among 597 patients with hepatitis C virus cirrhosis enrolled in a program at an integrated health system between 2013 and 2020. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre-enrollment and postenrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging examination (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan-Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality. RESULTS: The surveillance program significantly improved surveillance completion (77.6% vs 5.0%, P < 0.001) and proportion time covered (80.9% vs 15.8%, P < 0.001). Compared with prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs 44.8%, P < 0.001), early-stage (85.2% vs 44.8%, P < 0.001), with smaller maximum diameter (median 2.3 vs 3.2 cm), and more likely to undergo curative therapy (92.5% vs 72.4% P = 0.010). Survival was improved compared with prevalent cases hazard ratio (HR) 0.23 (0.11-0.51) after adjusting for age and Model for End Stage Liver Disease score. DISCUSSION: Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with hepatitis C virus cirrhosis. These findings may inform similar interventions by other healthcare systems.

MCN portfolio: An efficient portfolio prediction and selection model using multiserial cascaded network with hybrid meta-heuristic optimization algorithm.

Generally, financial investments are necessary for portfolio management. However, the prediction of a portfolio becomes complicated in several processing techniques which may cause certain issues while predicting the portfolio. Moreover, the error analysis needs to be validated with efficient performance measures. To solve the problems of portfolio optimization, a new portfolio prediction framework is developed. Initially, a dataset is collected from the standard database which is accumulated with various companies' portfolios. For forecasting the benefits of companies, a Multi-serial Cascaded Network (MCNet) is employed which constitutes of Autoencoder, 1D Convolutional Neural Network (1DCNN), and Recurrent Neural Network (RNN) is utilized. The prediction output for the different companies is stored using the developed MCNet model for further use. After predicting the benefits, the best company with the highest profit is selected by Integration of Artificial Rabbit and Hummingbird Algorithm (IARHA). The major contribution of our work is to increase the accuracy of prediction and to choose the optimal portfolio. The implementation is conducted in Python platform. The result analysis shows that the developed model achieves 0.89% and 0.56% regarding RMSE and MAE measures. Throughout the analysis, the experimentation of the developed model shows enriched performance.

AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study.

In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.

Models to Predict Development or Recurence of Hepatocellular Carcinoma (HCC) in Patients with Advanced Hepatic Fibrosis.

PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the United States (U.S.).1 The purpose of this review is to highlight published models that predict development of HCC and estimate risk of HCC recurrence after treatments. RECENT FINDINGS: There have been several models created for both de novo HCC and HCC recurrence, with the more recent models using a combination of age, sex, decompensation, and laboratory values (platelet count, albumin, bilirubin), and liver disease etiology to predict both 5 and 10-year HCC incidence. For chronic hepatitis C, sustained virologic response has been a useful component of understanding HCC risk reduction. BMI and diabetes have been utilized in non-alcoholic fatty liver disease (NAFLD) models to predict HCC risk. For HCC recurrence after treatment (for both surgical resection and liver transplant), tumor size and number, vascular invasion, alpha-fetoprotein (AFP) and neutrophil to lymphocyte ratio (NLR) are all components of HCC recurrence risk models. Although numerous HCC risk prediction models have been established over the last several years, challenges remain including how to best incorporate these models into clinical practice, improve surveillance for NAFLD-HCC development, and determine timing and duration of post-resection recurrence surveillance.

Performance study of a sterilization box using a combination of heat and ultraviolet light irradiation for the prevention of COVID-19.

SARS-CoV-2 virus and other pathogenic microbes are transmitted to the environment through contacting surfaces, which need to be sterilized for the prevention of COVID-19 and related diseases. In this study, a prototype of a cost-effective sterilization box is developed to disinfect small items. The box utilizes ultra violet (UV) radiation with heat. For performance assessment, two studies were performed. First, IgG (glycoprotein, a model protein similar to that of spike glycoprotein of SARS-COV-2) was incubated under UV and heat sterilization. An incubation with UV at 70 °C for 15 min was found to be effective in unfolding and aggregation of the protein. At optimized condition, the hydrodynamic size of the protein increased to ~171 nm from ~5 nm of the native protein. Similarly, the OD280 values also increased from 0.17 to 0.78 indicating the exposure of more aromatic moieties and unfolding of the protein. The unfolding and aggregation of the protein were further confirmed by the intrinsic fluorescence measurement and FTIR studies, showing a 70% increase in the ß-sheets and a 22% decrease in the α-helixes of the protein. The designed box was effective in damaging the protein's native structure indicating the effective inactivation of the SARS-COV-2. Furthermore, the incubation at 70 °C for 15 min inside the chamber resulted in 100% antibacterial efficacy for the clinically relevant E.coli bacteria as well as for bacteria collected from daily use items. It is the first detailed performance study on the efficacy of using UV irradiation and heat together for disinfection from virus and bacteria.

Prevalence of Spontaneous Clearance of Hepatitis C Virus Infection Doubled From 1998 to 2017.

Strategic planning for hepatitis C virus (HCV) screening and treatment requires up-to-date information on the prevalence of HCV spontaneous clearance. Published estimates of HCV spontaneous clearance range from 15% to 60%.1-3 We conducted an observational study over 20 years to evaluate trends in the prevalence of HCV spontaneous clearance. Our goals were to estimate the proportion of HCV-antibody-positive patients who were viremic, and to identify factors associated with viremia, thus facilitating prediction of the number of patients needing treatment.

No Difference in Effectiveness of 8 vs 12 Weeks of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C in Black Patients.

BACKGROUND & AIMS: Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen. METHODS: We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naïve, no cirrhosis, no HIV infection, level of HCV RNA <6 million IU/mL) and were treated for 8 or 12 weeks from October 2014 through December 2016. We used χ2 analyses to compare sustained virologic response 12 weeks after the end of treatment (SVR12) among patients treated for 8 vs 12 weeks, and adjusted Poisson models to identify factors associated with receipt of 12 weeks of therapy among patients eligible for 8 weeks. RESULTS: Of 2653 patients eligible for 8 weeks of treatment with ledipasvir and sofosbuvir, 1958 (73.8%) received 8 weeks of treatment and 695 (26.2%) received 12 weeks; the proportions of patients with SVR12 were 96.3% and 96.3%, respectively (P = .94). Among 435 black patients eligible for the 8-week treatment regimen, there was no difference in the proportions who achieved an SVR12 following 8 vs 12 weeks' treatment (95.6% vs 95.8%; P = .90). Male sex, higher transient elastography or FIB-4 scores, higher INR and level of bilirubin, lower level of albumin, obesity, diabetes, and ≥15 alcohol drinks consumed/week were independently associated with receiving 12 weeks of treatment among patients eligible for the 8-week treatment regimen, but were not associated with reduced SVR12 after 8 weeks of treatment. CONCLUSION: In an observational study of patients who received ledipasvir and sofosbuvir treatment for HCV genotype 1 infection, we found that contrary to guidelines, 8-week and 12-week treatment regimens do not result in statistically significant differences in SVR12 in black patients. Patient characteristics were associated with receipt of 12-week regimens among patients eligible for 8 weeks, but were not associated with reduced SVR12 after 8 weeks. Shorter treatment courses might therefore be more widely used without compromising treatment effectiveness.

Safety and efficacy of current direct-acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV-TARGET study.

Data outside of clinical trials with direct-acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct-acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. CONCLUSION: In a large prospective observational cohort study, direct-acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (Hepatology 2017;66:1090-1101).

Surface Functionalization of Ti6Al4V via Self-assembled Monolayers for Improved Protein Adsorption and Fibroblast Adhesion.

Although metallic biomaterials find numerous biomedical applications, their inherent low bioactivity and poor osteointegration had been a great challenge for decades. Surface modification via silanization can serve as an attractive method for improving the aforementioned properties of such substrates. However, its effect on protein adsorption/conformation and subsequent cell adhesion and spreading has rarely been investigated. This work reports the in-depth study of the effect of Ti6Al4V surface functionalization on protein adsorption and cell behavior. We prepared self-assembled monolayers (SAMs) of five different surfaces (amine, octyl, mixed [1:1 ratio of amine:octyl], hybrid, and COOH). Synthesized surfaces were characterized by Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy, contact angle goniometry, profilometry, and field emission scanning electron microscopy (FESEM). Quantification of adsorbed mass of bovine serum albumin (BSA) and fibronectin (FN) was determined on different surfaces along with secondary structure analysis. The adsorbed amount of BSA was found to increase with an increase in surface hydrophobicity with the maximum adsorption on the octyl surface while the reverse trend was detected for FN adsorption, having the maximum adsorbed mass on the COOH surface. The α-helix content of adsorbed BSA increased on amine and COOH surfaces while it decreased for other surfaces. Whereas increasing ß-turn content of the adsorbed FN with the increase in the surface hydrophobicity was observed. In FN, RGD loops are located in the ß-turn and consequently the increase in Δ adhered cells (%) was predominantly increased with the increasing Δ ß-turn content (%). We found hybrid surfaces to be the most promising surface modifier due to maximum cell adhesion (%) and proliferation, larger nuclei area, and the least cell circularity. Bacterial density increased with the increasing hydrophobicity and was found maximum for the amine surface (θ = 63 ± 1°) which further decreased with the increasing hydrophobicity. Overall, modified surfaces (in particular hybrid surface) showed better protein adsorption and cell adhesion properties as compared to unmodified Ti6Al4V and can be potentially used for tissue engineering applications.

Safety and Efficacy of Simeprevir/Sofosbuvir in Hepatitis C-Infected Patients With Compensated and Decompensated Cirrhosis.

UNLABELLED: Risks and benefits of simeprevir plus sofosbuvir (SIM+SOF) in patients with advanced cirrhosis are unknown. We assessed the safety and sustained virological responses (SVR) of SIM+SOF with and without ribavirin (RBV) in patients with Child-Pugh (CP)-B/C versus CP-A cirrhosis and compared to matched untreated controls. This study was of a multicenter cohort of adults with hepatitis C virus genotype 1 and cirrhosis treated with SIM+SOF with/without RBV for 12 weeks. Controls were matched on treatment center, age, CP class, and Model for End-Stage Liver Disease (MELD) score. Of 160 patients treated with SIM+SOF with/without RBV, 35% had CP-B/C and 64% had CP-A, with median baseline MELD 9 (interquartile range, 8-11). Sustained virological response at week 12 (SVR12) was achieved by 73% of CP-B/C versus 91% of CP-A (P < 0.01). CP-B/C versus CP-A had more early treatment discontinuations (11% vs. 1%), adverse events (AEs) requiring hospitalization (22% vs. 2%), infections requiring antibiotics (20% vs. 1%), and hepatic decompensating events (20% vs. 3%; all P < 0.01). There were 2 deaths: 1 CP-B/C (liver related) and 1 CP-A (not liver related). In multivariate analysis, CP-B/C independently predicted lack of SVR12 (odds ratio, 0.27; 95% confidence interval: 0.08-0.92). In comparing SIM+SOF-treated patients versus matched untreated controls, AEs requiring hospitalization (9% vs. 13%; P = 0.55), infections (8% vs. 6%; P = 0.47), and events of decompensation (9% vs. 10%; P = 0.78) occurred at similar frequency. CONCLUSIONS: SIM+SOF with/without RBV has lower efficacy and higher rates of AEs in patients with CP-B/C cirrhosis, compared to CP-A. Frequency of adverse safety outcomes were similar to matched untreated controls, suggesting that safety events reflect the natural history of cirrhosis and are not related to treatment.

Safety and efficacy of sofosbuvir-containing regimens in hepatitis C-infected patients with impaired renal function.

BACKGROUND & AIMS: Renal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR). METHODS: HCV-TARGET database is a multicentre, longitudinal 'real-world' treatment cohort. RESULTS: A total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m(2) . Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400-1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes. CONCLUSIONS: Sustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m(2) ) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.

Facility- and Patient-Level Factors Associated with Esophageal Variceal Screening in the USA.

BACKGROUND AND AIM: The American Association for the Study of Liver Disease (AASLD) recommends screening for esophageal varices (EV) by esophagoduodenoscopy (EGD) in patients with cirrhosis to guide decisions regarding primary prophylaxis for EV hemorrhage. We aimed to identify patient and facility factors associated with EV screening in veterans with hepatitis C (HCV)-associated cirrhosis. METHODS: This was a population-based cohort study. Veterans with HCV and newly diagnosed cirrhosis between 1/1/2004 and 12/31/2005 and followed until 12/31/2011 were included. The primary outcome was receipt of EGD within 1 year of cirrhosis diagnosis. Patient- and facility-level factors associated with EV screening were determined. RESULTS: A total of 4230 patients with HCV cirrhosis were identified. During median follow-up of 6.1 years (IQR: 4.0-8.0), 21.5 % developed a decompensating event, and 38.3 % died. Fifty-four percent received an EGD, and 33.8 % had an EGD within guidelines. Median time from cirrhosis diagnosis to EGD was 72 days (IQR: 12-176). Factors independently associated with receipt of EV screening were a decompensation event (OR 1.16, CI 1.01-1.32) and gastroenterology/hepatology clinic access (OR 2.1, CI 1.73-2.46), whereas cardiovascular (OR 0.81, CI 0.69-0.95), mental health (OR 0.79, CI 0.68-0.91), and respiratory (OR 0.85, CI 0.72-0.99) comorbidities were associated with reduced likelihood of EV screening. CONCLUSION: EV screening per AASLD guidelines occurs in only one-third of patients. This missed opportunity was strongly associated with access to gastroenterology/hepatology specialty care. Additionally, providers may be relying on clinical cues (i.e., decompensation) to prompt referral for endoscopy suggesting education to improve compliance with guidelines is needed.

A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy.

BACKGROUND & AIMS: NS3/4A protease inhibitors, boceprevir or telaprevir, combined with peginterferon and ribavirin was the standard treatment for HCV genotype 1 and remains the only available direct antiviral drug based therapy in some countries. Efficacy and safety data in liver transplant recipients are limited. METHODS: This was a retrospective cohort study of 81 patients with genotype 1 HCV treated with boceprevir (10%) or telaprevir (90%) plus peginterferon and ribavirin at 6 US transplant centers (53% stage 3-4/4 fibrosis, 57% treatment experienced). The primary end point was undetectable HCV RNA 12 weeks after treatment completion (SVR12). RESULTS: The intent-to-treat SVR12 rate was 63% (51/81). Patients with an extended rapid virologic response, (undetectable HCV RNA at 4 and 12 weeks after starting boceprevir or telaprevir), had a higher rate of SVR12 than all other patients (85% vs. 15%, p<0.001). Adverse effects were common; 21% of patients experienced hemoglobin <8g/dl and 57% required blood transfusions during the first 16 weeks. Twenty seven percent were hospitalized and 9% died; all were liver-related. CONCLUSIONS: The addition of boceprevir or telaprevir to peginterferon and ribavirin yields SVR12 of 63% in liver transplant recipients with genotype 1 recurrent HCV, despite a high prevalence of advanced fibrosis and prior non-response to peginterferon and ribavirin. Rapid virologic response predicted a high likelihood of SVR. Despite a doubling of SVR rates, poor tolerability and high rates of adverse events were frequent and pose barriers to its widespread application.

Primary Care Utilization, Preventative Screening, and Control of Metabolic Syndrome in Metabolic Dysfunction-Associated Steatohepatitis Liver Transplant Recipients.

OBJECTIVES: Patients with pre-transplant metabolic dysfunction-associated steatohepatitis (MASH) are at high risk of metabolic syndrome (MetS) after liver transplant. While many patients are co-managed by a transplant team, most preventative screening and MetS management may occur in the primary care setting. We aimed to evaluate primary care utilization by MASH liver transplant recipients as well as MetS screening and control. METHODS: We conducted a retrospective chart review that included adults who underwent liver transplant for MASH or cryptogenic cirrhosis at a single institution from January 2010 to December 2016, had available primary care data, and at least 36-months of follow-up post-transplant. Measures included primary care utilization, adherence to screening guidelines, and control of MetS. We used Fischer's exact test to explore the association of primary care utilization with screening and control. RESULTS: A total of 37 patients met inclusion criteria with 366 visits reviewed. The median time to first visit was 68 days post-transplant and patients had a median of 9 total visits. Few patients met screening guidelines for diabetes (8.1%) or hyperlipidemia (10.8%). The percentage of patients with control of obesity, hypertension, diabetes, and hyperlipidemia decreased over the 36-month follow-up period. Primary care utilization was not associated with adherence to screening recommendations for diabetes (P = .141) or hyperlipidemia (P = .103). Higher primary care utilization was not associated with control of hypertension (P = .107), diabetes (P = .871), or hyperlipidemia (P = .999). CONCLUSION: More research is needed to investigate barriers to screening and management of MetS conditions in this high-risk patient population in the primary care setting as well as to optimize post-transplant care coordination.

Acute hepatitis C in an HIV-infected patient: a case report and review of literature.

With the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)-infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease.

Application of Shape Memory and Self-Healable Polymers/Composites in the Biomedical Field: A Review.

Shape memory-assisted self-healing polymers have drawn attention over the past few years owing to their interdisciplinary and wide range of applications. Self-healing and shape memory are two approaches used to improve the applicability of polymers in the biomedical field. Combining both these approaches in a polymer composite opens new possibilities for its use in biomedical applications, such as the "close then heal" concept, which uses the shape memory capabilities of polymers to bring injured sections together to promote autonomous healing. This review focuses on using shape memory-assisted self-healing approaches along with their respective affecting factors for biomedical applications such as tissue engineering, drug delivery, biomaterial-inks, and 4D printed scaffolds, soft actuators, wearable electronics, etc. In addition, quantification of self-healing and shape memory efficiency is also discussed. The challenges and prospects of these polymers for biomedical applications have been summarized.

Recipient-donor race mismatch for African American liver transplant patients with chronic hepatitis C.

African American (AA) recipient-donor race mismatch has been associated with graft loss and mortality, but studies of an association between race mismatch and hepatitis C virus (HCV) disease severity are lacking. HCV-infected adults from 4 US centers who underwent liver transplantation for the first time (n = 1093) were followed for a median of 3.05 years to determine the rates of advanced HCV disease (bridging fibrosis or cirrhosis) and graft failure; 11% of the patients were AA. The unadjusted cumulative rate of advanced fibrosis was higher in AAs than non-AAs (56% and 40% at 4 years, respectively, (P < 0.01), and 59% and 56% for AA recipient-donor-matched patients and AA recipient-donor-mismatched patients, respectively (P = 0.89). In adjusted models, both AA recipient race [hazard ratio (HR) = 1.47, 95% CI = 1.06-2.03, P = 0.02] and AA recipient-donor mismatch (versus match; HR = 1.48, 95% CI = 1.03-2.12, P = 0.03) were significant predictors of advanced fibrosis; other independent predictors were donor age (HR = 1.21, P < 0.01) and cytomegalovirus infection (HR = 1.55, P < 0.01). The 4-year unadjusted cumulative rates for HCV-associated graft loss were 10% and 17% for non-AAs and AAs, respectively (P < 0.01), and 0% and 21% for AA recipient-donor-matched patients and AA recipient-donor-mismatched patients, respectively (P < 0.01). In adjusted models, AA recipient-donor-mismatched patients had a 62% higher rate of graft loss than non-AA recipients (HR = 1.62, 95% CI = 1.14-2.29, P < 0.01), and AA recipient-donor-matched patients had a 76% lower rate of graft loss/mortality (HR = 0.24, 95% CI = 0.06-0.97, P = 0.05). In conclusion, AA recipient-donor-mismatched patients who are infected with HCV are at high risk for advanced HCV disease and HCV-related graft loss and constitute a patient group that will benefit from new therapeutic strategies for preventing graft loss.

Hepatitis C virus treatment and liver transplantation in the era of new antiviral therapies.

PURPOSE OF REVIEW: The new standard-of-care treatment for genotype 1 hepatitis C virus infection is a combination of PEG-interferon (PEG-IFN), ribavirin (RBV) and a protease inhibitor - telaprevir or boceprevir. As triple therapy is not yet approved for use in decompensated cirrhotics and liver transplant recipients, we examine the efficacy and safety of PEG-IFN, RBV and protease inhibitors in nontransplant populations to inform the current and future treatment paradigms for transplant candidates and recipients. RECENT FINDINGS: Protease inhibitor-based triple therapy is more efficacious than PEG-IFN and RBV in nontransplant genotype 1 patients, so sustained virologic response rates are predicted to be higher in waitlisted candidates and transplant recipients treated with protease inhibitor-triple therapy. Because of the need to use a backbone of PEG-IFN and RBV, tolerability of therapy will remain a major challenge. Anemia, a well recognized side-effect with PEG-IFN and RBV, will be especially common with protease inhibitor-triple therapy. Both protease inhibitors can modify the levels of drugs metabolized by the CYP3A/4 pathway, and in posttransplant patients, the protease inhibitors increase the levels of cyclosporine and tacrolimus, with the magnitude of the drug-drug interactions varying with protease inhibitor and type of calcineurin inhibitor (CNI). SUMMARY: Given the complexities of treatment, it is best undertaken by experienced clinicians and only after a detailed discussion of risks-benefits with the patient. To maximize the benefit while minimizing risk, only Child-Turcott-Pugh A (CPT-A) cirrhotics should be considered for pretransplant protease inhibitor-triple therapy. For transplant recipients, very close monitoring and adjustment of CNI levels is critical during protease inhibitor-triple therapy. Cytopenias, especially anemia, will require aggressive management.

Microstructural, electrical and biological activity in [Formula: see text] ceramic composites designed for tissue engineering applications.

The article investigates electrically active ceramic composite of [Formula: see text] (HAP) and [Formula: see text] (BST) for biomedical applications. The study is a systematic blend of the materials science aspect of composites with a special focus on the dielectric and biological properties and their relationships. The article emphasized primarily extracting the dielectric constant ([Formula: see text] of the specimens (that lay in the range of 3-65) and related them to microstructural properties like the grain size and at.% of BST. A broad outlook on the importance of [Formula: see text] in determining the suitability of bioceramics for clinical applications is presented. Bioactivity analysis of the specimens led to probing the surface charges (that were negative), and it was found crucial to the growth of dense apatite layers. Furthermore, the cytocompatibility of the specimens displayed cell viability above 100% for Day 1, which increased substantially for Day 3. To reveal other biological properties of the composites, protein adsorption studies using bovine serum albumin (BSA) and fetal bovine serum (FBS) was carried out. Electrostatic interactions govern the adsorption, and the mathematical dependence on surface charges is linear. The protein adsorption is also linearly correlated with the [Formula: see text], intrinsic to the biomaterials. We delve deeper into protein-biomaterials interactions by considering the evolution of the secondary structure of BSA adsorbed into the specimens. Based on the investigations, 20 at.% HAP-80 at.% BST (20H-80B) was established as a suitable composite comprising the desired features of HAP and BST. Such explorations of electrical and biological properties are interesting for modulating the behavior of bioceramic composites. The results project the suitability of 20H-80B for designing electrically active smart scaffolds for the proposed biomedical applications and are expected to incite further clinical trials.

Cancer in People with and without Hepatitis C Virus Infection: Comparison of Risk Before and After Introduction of Direct-Acting Antivirals.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a leading cause of liver cancer. The association of HCV infection with extrahepatic cancers, and the impact of direct-acting antiviral (DAA) treatment on these cancers, is less well known. METHODS: We conducted a cohort study in a healthcare delivery system. Using electronic health record data from 2007 to 2017, we determined cancer incidence, overall and by type, in people with HCV infection and by DAA treatment status. All analyses included comparisons with a reference population of people without HCV infection. Covariate-adjusted Poisson models were used to estimate incidence rate ratios. RESULTS: 2,451 people with HCV and 173,548 people without HCV were diagnosed with at least one type of cancer. Compared with people without HCV, those with HCV were at higher risk for liver cancer [adjusted incidence rate ratio (aIRR) = 31.4, 95% confidence interval (CI) = 28.9-34.0], hematologic cancer (aIRR = 1.3, 95% CI = 1.1-1.5), lung cancer (aIRR = 1.3, 95% CI = 1.2-1.5), pancreatic cancer (aIRR = 2.0, 95% CI = 1.6-2.5), oral/oropharynx cancer (aIRR = 1.4, 95% CI = 1.1-1.8), and anal cancer (aIRR = 1.6, 95% CI = 1.1-2.4). Compared with people without HCV, the aIRR for liver cancer was 31.9 (95% CI = 27.9-36.4) among DAA-untreated and 21.2 (95% CI = 16.8-26.6) among DAA-treated, and the aIRR for hematologic cancer was 1.5 (95% CI = 1.1-2.0) among DAA-untreated and 0.6 (95% CI = 0.3-1.2) among DAA-treated. CONCLUSIONS: People with HCV infection were at increased risk of liver cancer, hematologic cancer, and some other extrahepatic cancers. DAA treatment was associated with reduced risk of liver cancers and hematologic cancers. IMPACT: DAA treatment is important for reducing cancer incidence among people with HCV infection.