bluuebunny/crossref_metadata_2025 huggingface dataset:
Crohn's disease associated strictures
Authors: Chan Webber Pak Wo , Mourad Fadi , Leong Rupert WL
Published: February 2018

Crohn's disease (CD) is a chronic relapsing and remitting disease that can affect any segments of the gastrointestinal tract. More than 50% of patients with CD develop stricturing or penetrating complications within the first 10 years after diagnosis. Strictures can lead to intestinal obstruction, which is a common indication for surgery. Despite significant advances in the understanding of the pathogenesis of intestinal fibrostenosis, imaging and therapeutic armamentarium of CD, the risk of intestinal surgery remained significantly high. Endoscopic balloon dilation is a promising first‐line alternative to surgery as it is less invasive and could preserve intestinal length. In this review, we will evaluate the literature on the mechanism of intestinal fibrosis, emerging imaging techniques, and management strategies for CD associated strictures.
Fecal immunochemical test for predicting mucosal healing in ulcerative colitis patients: A systematic review and meta‐analysis
Authors: Dai Cong , Jiang Min , Sun Ming‐Jun , Cao Qin
Published: February 2018

Background and Aim

Fecal immunochemical test (FIT) is a promising marker for assessment of inflammatory bowel disease activity. However, the utility of FIT for predicting mucosal healing (MH) of ulcerative colitis (UC) patients has yet to be clearly demonstrated. The objective of our study was to perform a diagnostic test accuracy test meta‐analysis evaluating the diagnostic accuracy of FIT in predicting MH of UC patients.

Methods

We systematically searched the databases from inception to November 2017 that evaluated MH in UC. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random‐effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio.

Results

Six studies comprising 625 UC patients were included in the meta‐analysis. The pooled sensitivity and specificity values for predicting MH in UC were 0.77 (95% confidence interval [CI], 0.72–0.81) and 0.81 (95% CI, 0.76–0.85), respectively. The FIT level had a high rule‐in value (positive likelihood ratio, 3.79; 95% CI, 2.85–5.03) and a moderate rule‐out value (negative likelihood ratio, 0.26; 95% CI, 0.16–0.43) for predicting MH in UC. The results of the receiver operating characteristic curve analysis (area under the curve, 0.88; standard error of the mean, 0.02) and diagnostic odds ratio (18.08; 95% CI, 9.57–34.13) also revealed improved discrimination for identifying MH in UC with FIT concentration.

Conclusion

Our meta‐analysis has found that FIT is a simple, reliable non‐invasive marker for predicting MH in UC patients.
Enhanced B‐cell differentiation driven by advanced cirrhosis resulting in hyperglobulinemia
Authors: Doi Hiroyoshi , Hayashi Eiichi , Arai Jun , Tojo Masayuki , Morikawa Kenichi , Eguchi Junichi , Ito Takayoshi , Kanto Tatsuya , Kaplan David E , Yoshida Hitoshi
Published: February 2018

Background and Aim

The mechanism underlying hyperglobulinemia in cirrhosis, a long appreciated phenomenon, has never been clearly understood. The aim of this study is to investigate the basis for changes in humoral immunity observed in cirrhosis.

Methods

We retrospectively reviewed our medical record to analyze serum immunoglobulin (Ig) levels in patients with liver disease. We also prospectively analyzed peripheral blood mononuclear cells and sera from liver disease patients. Peripheral blood mononuclear cell surface marker expressions were measured by flow cytometry and serum B‐cell‐activating factor was measured by enzyme‐linked immunosorbent assay. Expression of specific gene expression in magnetically separated B cells was also analyzed by real‐time polymerase chain reaction.

Results

In retrospective analysis, we found that advancing cirrhosis, irrespective of underlying etiology or hepatocellular carcinoma, resulted in progressively increasing levels of serum IgG and IgA. In prospective analysis using clinical samples, we demonstrated that advancing cirrhosis stage was associated with increased toll‐like‐receptor (TLR)9 expression in CD27+ B cell and serum B‐cell‐activating factor levels but decreased CD27+ memory B‐cell frequency. The remaining CD27+ B cells in peripheral blood exhibited increased activation‐induced cytidine deaminase mRNA expression. Finally, we also demonstrated isolated B cells from advanced cirrhosis were more reactive to TLR9 stimulation that drove antibody secreting cells differentiation leading to hyperimmunoglobulinemia in vitro.

Conclusions

Enhanced TLR9‐induced differentiation into antibody secreting cell may explain peripheral reductions of circulating CD27+ memory B cells as well as increased serum Ig levels in cirrhosis.
Impact of serum carbohydrate antigen 19‐9 level on prognosis and prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma
Authors: Yamada Toru , Nakanishi Yoshitsugu , Okamura Keisuke , Tsuchikawa Takahiro , Nakamura Toru , Noji Takehiro , Asano Toshimichi , Tanaka Kimitaka , Kurashima Yo , Ebihara Yuma , Murakami Soichi , Shichinohe Toshiaki , Mitsuhashi Tomoko , Hirano Satoshi
Published: February 2018

Background and Aim

Lymph node metastasis is an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), but accurate preoperative diagnosis is difficult. The aim of this study was to measure the concentration of serum carbohydrate antigen 19‐9 (s‐CA19‐9) as a preoperative predictor of lymph node metastasis.

Methods

In our department, curative‐intent hepatectomy for ICC has been performed only once the absence of metastases in para‐aortic lymph nodes (PALN) has been confirmed from intraoperative frozen‐section pathological examinations. The present study included 13 non‐resected ICC patients with PALN metastasis (PALN group) and 44 resected ICC patients without PALN metastasis (non‐PALN group). S‐CA19‐9 was examined to evaluate predictive performance for PALN metastasis and regional lymph node metastasis (pN1) from analysis of the receiver operating characteristic curve. In the non‐PALN group, univariate and multivariate analyses for survival were performed on clinicopathological variables.

Results

From receiver operating characteristic curve analysis, s‐CA19‐9 showed good diagnostic accuracy for PALN metastasis (68%; cut‐off, 200 U/mL) and pN1 (77%; cut‐off, 100 U/mL). In univariate analysis, age (<65 years), s‐CA19‐9 (≥100 U/mL), portal vein resection, pN1, and positive resection margin (R1) were all identified as significant negative prognostic factors. Five‐year survival rates of patients with high s‐CA19‐9 and pN1 were 6.9% and 7.3%, respectively. In multivariate analysis, high s‐CA19‐9 and R1 represented independent predictors of poor prognosis.

Conclusions

Preoperative s‐CA19‐9 appears useful as a biomarker in patients with ICC, for predicting not only lymph node metastasis but also prognosis after surgical resection with curative intent.
Managing High‐Cost Healthcare Users: The International Search for Effective Evidence‐Supported Strategies
Authors: Lee Justin Y. , Muratov Sergei , Tarride Jean‐Eric , Holbrook Anne M.
Published: February 2018

High‐cost healthcare users (HCUs) are a small proportion of the population who use a disproportionate amount of healthcare resources. Although the phenomenon occurs across the entire age spectrum, older adults represent the majority of HCUs. HCUs have drawn increasing attention internationally from clinicians, health policy‐makers, and government administrators. Many experts have suggested that the short‐ and long‐term sustainability of the healthcare system is threatened unless current approaches to the care and healthcare costs of this population are modified. Complex case management and care coordination models are being implemented internationally to address HCUs despite a lack of strong evidence to support their effectiveness in improving clinical outcomes or savings in costs of care. We review what is known about HCUs and the available evidence for the effectiveness of interventions designed to manage their high and costly healthcare use.
Frailty Versus Stopping Elderly Accidents, Deaths and Injuries Initiative Fall Risk Score: Ability to Predict Future Falls
Authors: Crow Rebecca S. , Lohman Matthew C. , Pidgeon Dawna , Bruce Martha L. , Bartels Stephen J. , Batsis John A.
Published: February 2018

Objectives

To compare the ability of frailty status to predict fall risk with that of community fall risk screening tools.

Design

Analysis of cross‐sectional and longitudinal data from NHATS.

Setting

National Health and Aging Trend Study (NHATS) 2011‐2015.

Participants

Individuals aged 65 and older (N = 7,392).

Measurements

Fall risk was defined according to the Stopping Elderly Accidents, Deaths and Injuries (STEADI) initiative. Frailty was defined as exhaustion, weight loss, low activity, slow gait speed, and weak grip strength. Robust was defined as meeting 0 criteria, prefrailty as 1 or 2 criteria, and frailty as 3 or more criteria. Falls were self‐reported and ascertained using NHATS subsequent rounds (2012–2015). We compared the ability of frailty to predict future falls with that of STEADI score, adjusting for age, race, sex, education, comorbidities, hearing and vision impairment, and disability.

Results

Of the 7,392 participants (58.5% female), there 3,545 (48.0%) were classified as being at low risk of falling, 2,966 (40.1%) as being at moderate risk, and 881 (11.9%) as being at high risk. The adjusted risk of falling over the 4 subsequent years was 2.5 times as great for the moderate‐risk group (hazard ratio (HR) = 2.50, 95% confidence interval (CI) = 2.16–2.89) and almost 4 times as great (HR = 3.79, 95% CI = 2.76–5.21) for the high‐risk group as for the low‐risk group. Risk of falling was greater for those who were prefrail (HR = 1.34, 95% CI 1.16–1.55) and frail (HR = 1.20, 95% CI = 0.94–1.54) than for those who were robust.

Conclusion

STEADI score is a strong predictor of future falls. Addition of frailty status does not improve the ability of the STEADI measure to predict future falls.
Chronic Physical Conditions, Multimorbidity, and Mild Cognitive Impairment in Low‐ and Middle‐Income Countries
Authors: Koyanagi Ai , Lara Elvira , Stubbs Brendon , Carvalho Andre F. , Oh Hans , Stickley Andrew , Veronese Nicola , Vancampfort Davy
Published: February 2018

Objectives

To assess the association between chronic physical conditions and multimorbidity and mild cognitive impairment (MCI) in low‐ and middle‐income countries (LMICs).

Design

Nationally representative, cross‐sectional, community‐based study.

Setting

Six countries that participated in the World Health Organization Study on Global Ageing and Adult Health.

Participants

Individuals aged 50 and older (N=32,715; mean age 62.1 ± 15.6; 51.7% female).

Measurements

The definition of MCI was based on the recommendations of the National Institute on Ageing and Alzheimer's Association. Ten chronic conditions were assessed (angina pectoris, arthritis, asthma, cataract, chronic lung disease, diabetes mellitus, edentulism, hearing problems, hypertension, stroke). Multivariable logistic regression analysis was conducted to assess the association between chronic physical conditions, multimorbidity (≥2 chronic conditions), and MCI.

Results

The prevalence of multimorbidity was 49.8% (95% confidence interval (CI)=48.1–51.5%) and of MCI was 15.3% (95% CI=14.4–16.3%). After adjustment for potential confounders, edentulism (odds ratio (OR)=1.24), arthritis (OR=1.24), chronic lung disease (OR=1.29), cataract (OR=1.33), stroke (OR=1.94), hearing problems (OR=2.27), and multimorbidity (OR=1.40) were significantly associated with MCI. There was a gradual increase in the likelihood of MCI (1 condition: OR=1.21, 95% CI=1.03–1.42; ≥4 conditions: OR=2.07, 95% CI=1.70–2.52).

Conclusion

These results highlight the need to investigate the underlying mechanisms linking chronic conditions and MCI and whether prevention or treatment of chronic conditions or multimorbidity can reduce the onset of cognitive decline and subsequent dementia, especially in LMICs.
UHP metamorphism recorded by phengite eclogite from the Caledonides of northern Sweden: P–T path and tectonic implications
Authors: Bukała Michał , Klonowska Iwona , Barnes Christopher , Majka Jarosław , Kośmińska Karolina , Janák Marian , Fassmer Kathrin , Broman Curt , Luptáková Jarmila
Published: February 2018

The Seve Nappe Complex (SNC) of the Scandinavian Caledonides records a well‐documented history of high pressure (HP) and ultra‐high pressure (UHP) metamorphism. Eclogites of the SNC occur in two areas in Sweden, namely Jämtland and Norrbotten. The Jämtland eclogites and associated rocks are well‐studied and provide evidence for late Ordovician UHP metamorphism, whereas the Norrbotten eclogites, formed during the late Cambrian (Furongian)/Early Ordovician, have not been studied in such detail, especially in terms of the P–T conditions of their formation. Within the studied eclogite, clinopyroxene contains a high‐Na core and two rims: inner, medium‐Na and outer, low‐Na. Garnet consists of a high‐Ca euhedral core, low‐Ca inner rim and medium‐Ca outer rim. A similar pattern occurs within phengite, where high‐Si cores are enveloped by medium and low‐Si rims. The compositions of the mineral cores, inner rims and outer rims reflect three stages in the metamorphic evolution of the eclogite. Applied Quartz‐in‐Garnet geobarometry, coupled with Zr‐in‐rutile geothermometry reveal that garnet nucleation (E0 stage) took place at 1.5–1.6 GPa and 620–660°C. The eclogite peak‐pressure assemblage developed during the E1 stage, it consists of garnet+omphacite+phengite+rutile+coesite? and yields P–T conditions of 2.8–3.1 GPa and 660–780°C as constrained by conventional geothermobarometry and thermodynamic modelling in the NCKFMMnASHT system. Later, lower‐pressure stages E2 and E3 record conditions of 2.2–2.8 GPa, 680–780°C and 2.1 GPa, 735°C, respectively. The prograde metamorphic evolution of the eclogite is inferred from inclusions of epidote, amphibole and clinopyroxene within garnet. The presence of amphibole–quartz–plagioclase symplectites, secondary epidote/zoisite and titanite replacing rutile record the later retrograde changes taking place at <1.5 GPa (referred as E4 stage). The obtained P–T conditions indicate that the Norrbotten eclogites underwent a metamorphic evolution characterized by a clockwise P–T path with peak metamorphism reaching up to coesite stability field within a relatively cold subduction regime (7.8°C/km). The obtained results provide the first evidence for UHP metamorphism in the SNC above the Arctic Circle and document cold subduction regime and multistage exhumation of the deeply subducted Baltican margin at early stage of the Caledonian Orogeny.
Glucosensing capacity of rainbow trout telencephalon
Authors: Otero‐Rodiño C. , Rocha A. , Álvarez‐Otero R. , Ceinos R. M. , López‐Patiño M. A. , Míguez J. M. , Cerdá‐Reverter J. M. , Soengas J. L.
Published: February 2018

To assess the hypothesis of glucosensing systems present in fish telencephalon, we first demonstrated in rainbow trout, by in situ hybridisation, the presence of glucokinase (GK). Then, we assessed the response of glucosensing markers in rainbow trout telencephalon 6 hours after i.c.v. treatment with glucose or 2‐deoxyglucose (inducing glucoprivation). We evaluated the response of parameters related to the mechanisms dependent on GK, liver X receptor (LXR), mitochondrial activity, sweet taste receptor and sodium‐glucose linked transporter 1 (SGLT‐1). We also assessed mRNA abundance of neuropeptides involved in the metabolic control of food intake (agouti‐related protein, neuropeptide Y, pro‐opiomelanocortin, and cocaine‐ and amphetamine‐related transcript), as well as the abundance and phosphorylation status of proteins possibly involved in linking glucosensing with neuropeptide expression, such as protein kinase B (AkT), AMP‐activated protein kinase (AMPK), mechanistic target of rapamycin and cAMP response element‐binding protein (CREB). The responses obtained support the presence in the telencephalon of a glucosensing mechanism based on GK and maybe one based on LXR, although they do not support the presence of mechanisms dependent on mitochondrial activity and SGLT‐1. The mechanism based on sweet taste receptor responded to glucose but in a converse way to that characterised previously in the hypothalamus. In general, systems responded only to glucose but not to glucoprivation. Neuropeptides did not respond to glucose or glucoprivation. By contrast, the presence of glucose activates Akt and inhibits AMPK, CREB and forkhead box01. This is the first study in any vertebrate species in which the response to glucose of putative glucosensing mechanisms is demonstrated in the telencephalon. Their role might relate to processes other than homeostatic control of food intake, such as the hedonic and reward system.
Feed and water deprivation has a negative but transient effect on the rumen kinetics of Bos indicus steers
Authors: Leo‐Penu C. L. O. , Picard J. , Fitzpatrick L. A. , Parker A. J.
Published: February 2018

The effects on rumen kinetics after feed and water had been deprived for 72 hr were studied using four fistulated Bos indicus steers. The animals were assigned in a 2 × 4 crossover design with two treatments: feed and water ad libitum (control) and no feed and water for 72 hr (deprived) with four steers per treatment over two time periods. Feed and water deprivation caused decreases in the numbers of cellulolytic bacteria (1.4 vs. 0.4 cfu × 106/ml; p = .001), live (23.7 vs. 0.8 × 109/ml; p = .001), dead (12.7 vs. 0.5 × 109/ml; p = .001) and total bacterial counts (36.4 vs. 1.4 × 109/ml; p = .001) at day 0, compared with the control treatment. However, the deprived group had greater numbers of cellulolytic bacteria (2.7 vs. 50.1 cfu × 106/ml; p = .001), live (18.3 vs. 42.2 × 109/ml; p = .001), dead (6. 5 vs. 19.1 × 109/ml; p = .001) and total bacterial counts (24.8 vs. 61.3 × 109/ml; p = .001) from rumen fluid on day 4, compared with the control treatment. The numbers of protozoa in rumen fluid from the deprived group were less than (551.2 vs. 2.4 × 103/ml; p = .001) the control group on day 0. However, the deprived treatment had fewer protozoa in rumen fluid than the control treatment on day 4 (p = .001) and day 9 (p = .001). Volatile fatty acids and in vitro gas production as functional measurements of rumen fluid followed the same trend as the bacterial and protozoa populations. These results indicate that feed and water deprivation would have a negative but transient effect on the rumen kinetics of Bos indicus steers.
Utilization of a biomedical device (VeinViewer®) to assist with peripheral intravenous catheter (PIV) insertion for pediatric nurses
Authors: McNeely Heidi L. , Ream Theresa L. , Thrasher Jodi M. , Dziadkowiec Oliwier , Callahan Tiffany J.
Published: February 2018

Purpose

Vascular access in pediatric patients can be challenging even with the currently available technological resources. This nurse‐driven research study explored time, cost, and resources for intravenous access to determine if a biomedical device, VeinViewer® Vision, would facilitate improvements in pediatric access. In addition, this study looked at nurse perceptions of skills and confidence around intravenous insertion and if the use of the VeinViewer® impacted these perceptions. Literature examining pediatric intravenous access success rates compared with nurse perceived skills and confidence is lacking.

Design

Nonblinded randomized control trial of pediatric nurses working in an acute care hospital setting.

Methods

A preliminary needs assessment solicited feedback from nurses regarding their practice, perceived skills, and confidence with placing peripheral intravenous catheters (PIVs). Due to the results of the preliminary needs assessment, a research study was designed and 40 nurses were recruited to participate. The nurses were randomized into either a VeinViewer® or standard practice group. Nurse participants placed intravenous catheters on hospitalized pediatric patients using established procedures while tracking data for the study.

Results

Needs assessment showed a majority of nurses felt a biomedical device would be helpful in building their intravenous insertion skills and their confidence. The study results did not demonstrate any clinically significant differences between VeinViewer® use and standard practice for intravenous catheter insertion in pediatric patients for success of placement, number of attempts, or overall cost. In addition, no difference was noted between nurses in either group on perceived skills or confidence with insertion of PIVs.

Practice implications

The ongoing need for resources focused on building nurse skills and confidence for PIV insertion was highlighted and organizations should continue to direct efforts toward developing skills and competency for staff that are responsible for pediatric vascular access. This study illustrates the importance of data‐driven decision‐making for expensive hospital‐funded equipment purchases. This nursing led research study highlights how perceptions do not always align with outcomes. The lessons gleaned from this study may aid in decision‐making around pediatric intravenous access practice.
Pediatric nurses’ perceived knowledge and beliefs of evidence‐based practice in the care of children and adolescents with moderate‐to‐severe traumatic brain injury
Authors: Oyesanya Tolu O. , Snedden Traci R.
Published: February 2018

Purpose

Pediatric nurses play a significant role in all phases of traumatic brain injury (TBI) recovery, particularly during the hospital stay. Although evidence‐based nursing practice is known to improve patient outcomes, limited research exists on nurses’ evidence‐based perceived knowledge and beliefs specific to TBI care. As nurses’ perceived knowledge and beliefs are known to guide their practice behaviors, this assessment is important to overall TBI outcomes. The purpose of this study was to evaluate pediatric nurses’ evidence‐based perceived knowledge and beliefs in providing care for children and adolescents with moderate‐to‐severe TBI.

Design and methods

Data for this study were obtained from a larger parent study on nurses’ perceptions of caring for patients of all ages with moderate‐to‐severe TBI. The parent study was an exploratory, cross‐sectional electronic survey of registered nurses across all hospital departments within a large Midwestern health system. Only data specific to pediatric nurses (n = 330) were analyzed for this study. Descriptive statistics and latent class analysis (LCA) were performed.

Results

Pediatric nurses, on average, were 38.79 years, female (90.37%), had over a decade of nursing experience (13.55 years), and practiced as a staff nurse (80.07%) on an inpatient unit (45.51%). Findings indicated pediatric nurses reported overall low levels of evidence‐based perceived knowledge and had inaccurate beliefs about caring for patients with TBI. LCA indicated two distinct homogenous subgroups specific to evidence‐based perceived knowledge: low (41%) and high (59%). Nurses in the low evidence‐based perceived knowledge group were younger, had less nursing experience, worked primarily on an inpatient unit, and cared for patients with TBI at a higher frequency compared to high evidence‐based perceived knowledge nurses. Additionally, there were significant differences in beliefs about sex‐based patient differences after TBI and the role of nurses in caring for patients with TBI based on level of evidence‐based perceived knowledge.

Practice implications

Assessing nurses’ perceived knowledge and beliefs of evidence‐based practice is a foundational step toward implementing evidence‐based care for patients with moderate‐to‐severe TBI. Implications of these findings indicate the need to provide additional education to increase pediatric nurses’ perceived knowledge and ensure accurate beliefs about evidence‐based TBI care.
How to control highly endemic hepatitis B in Asia
Authors: Shan Shan , Cui Fuqian , Jia Jidong
Published: February 2018

Chronic hepatitis B virus (HBV) infection is an enormous economic and social burden. Asian countries such as Vietnam, Mongolia, Laos, China, the Philippines, South Korea, Singapore and Cambodia have high or high‐intermediate HBsAg prevalence. Most of the chronic HBV carriers in this region acquire their infection during early childhood or through mother‐to‐child transmission (MTCT). Asia has been highly successful in controlling HBV in the last 2 decades. For example, China has adopted a comprehensive strategy to control HBV and has offered universal HBV vaccination to infants since 1992. With increasing coverage and a timely birth dose of the HBV vaccine, the prevalence of HBsAg in that general population decreased from 9.75% in 1992 to 7.18% in 2006. The prevalence of HBsAg in the population <30 years old decreased from 10.1% in 1992 to 2.6% in 2014. In addition, passive and active immunization has been increased and has successfully interrupted MTCT in recent years. Recent studies in China show that maternal antiviral therapy in the late trimesters of pregnancy could further reduce MTCT in mothers with a high viral load. First‐line treatments such as entecavir and tenofovir as well as pegylated interferon alpha are recommended in Chinese guidelines and are on the Basic Medical Insurance reimbursement list. Increased awareness, access to and affordability of antiviral therapy will reduce HBV‐related morbidity and mortality. The combined efforts of the government, the medical community, industry, civil society and the public should eliminate hepatitis B as a public threat by 2030.
Treatment of hepatitis C: the use of the new pangenotypic direct‐acting antivirals in “special populations”
Authors: Pol Stanislas , Parlati Lucia
Published: February 2018

Background & Aims

The recommended combination of pangenotypic direct‐acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) associates the co‐formulation of 2 or 3 second‐generation DAAs. In the so‐called “special populations” defined as patients with chronic kidney disease (CKD), HCV/HIV co‐infection, HCV/HBV co‐infection and an unsuccessful previous DAA regimen, these combinations have a high antiviral potency (sustained virologic response (SVR) > 95%), fair tolerance and a reduced pill burden.

Methods

We have taken into account the scientific evidence on the treatment of “special populations”, in particular from the RUBY 1‐2 trials, EXPEDITION 2‐4 study, C‐WORTHY trial, ASTRAL 5, POLARIS 1‐4 studies, MAGELLAN 1 and REVENGE study.

Results

CKD and HCV/HIV co‐infection are not predictors of a non‐viral response. The glecaprevir/pibentrasvir (Maviret) combination appears to be the first‐line therapy for CKD patients while the sofosbuvir/vlpatasvir/voxaliprevir (Sovesi) combination is the first‐line option for DAAs failures. Both are effective in patients with HIV‐or HBV‐HCV co‐infection and should be chosen according to the potential drug‐drug interaction profile.

Conclusions

The notion of “special populations” is no longer pertinent with pangenotypic DAAs combinations. International guidelines recommend treating all infected patients and the next challenge is not the therapeutic choice, but to improve the limitations for screening and access to care in HCV infection.
Treatment of hepatitis B: Is there still a role for interferon?
Authors: Viganò Mauro , Grossi Glenda , Loglio Alessandro , Lampertico Pietro
Published: February 2018

The treatment of chronic hepatitis B (CHB) patients is based on monotherapy with pegylated‐interferon (Peg‐IFN) or with one of the three most potent nucleot(s)ide analogues (NUCs) with the best resistance profiles, i.e. entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). Long‐term NUCs treatment can achieve virological suppression in almost all patients. However, this requires lifelong therapy, is costly and the rate of hepatitis B surface antigen (HBsAg) seroclearance is low. A one‐year course of Peg‐IFN has the advantage of providing immune‐mediated control of the hepatitis B virus (HBV) infection, the possibility of achieving a sustained off‐treatment response in nearly 30% of the patients and ultimately, HBsAg loss in approximately 30%‐50% of the latter patients during long‐term off treatment follow‐up. However, the major limitations to the extensive use of this treatment are the need for parenteral therapy and clinical and laboratory monitoring, the side‐effects profile and contraindications in certain patients and the limited effectiveness in a large proportion of patients. Nevertheless, the cost‐effectiveness of Peg‐IFN can be significantly increased by careful patient selection based upon baseline alanine aminotransferase (ALT), HBV DNA levels, viral genotype, host genetic variants and especially by applying early on‐treatment stopping rules based upon HBsAg kinetics. Recently, because of the different mechanisms of action of Peg‐IFN and NUCs, the strategy of “adding‐on” or “switching to” Peg‐IFN in patients being treated with NUCs to accelerate the decline in HBsAg and enhance HBsAg seroclearance rates, has provided interesting results.
Managing hepatitis C in patients with the complications of cirrhosis
Authors: Mücke Marcus M. , Mücke Victoria T. , Lange Christian M. , Zeuzem Stefan
Published: February 2018

Direct acting antivirals (DAA) have revolutionized the treatment of hepatitis C virus (HCV). Sustained virological response rates of nearly 100% have become common in the general population. However, physicians face the growing problem of managing HCV in patients with the complications of cirrhosis, eg hepatic decompensation or hepatocellular carcinoma (HCC). Safety and efficacy remain a clinical challenge in these difficult‐to‐treat patients. This review focuses on the current state of knowledge and treatment regimens in patients with decompensated cirrhosis as well as the potential risk of the development of HCC following DAA therapy.
Management of patients with non‐alcoholic steatohepatitis (NASH) in real life
Authors: Serfaty Lawrence
Published: February 2018

Non‐alcoholic fatty liver disease (NAFLD)/non‐alcoholic steatohepatitis (NASH) is a prevalent condition that is associated with the development of cirrhosis and hepatocellular carcinoma and with no approved treatment options except for lifestyle changes. Guidelines have been drafted for the management of NAFLD patients in this setting. Because of the lack of real‐life cohort data, we will focus on practice surveys on the management of patients with NAFLD/NASH, which included primary care practitioners, gastroenterologists/hepatologists and other specialists from various countries. Practice patterns have been collected from interviews with practitioners or reviews of patient's files. This review discusses the screening, diagnosis and therapeutic management of NAFLD/NASH patients in real life practice, as well as adherence to guidelines.
Treatment of hepatitis C: Results in real life
Authors: Hézode Christophe
Published: February 2018

Direct‐acting antivirals (DAAs) have transformed traditional treatment options for hepatitis C virus (HCV) infection. DAA combinations have been shown to be highly effective in reducing the burden of chronic HCV infection in clinical trials and have been recommended by the European Association for the Study of the Liver (EASL) treatment guidelines. This review examines the results of second‐generation DAA combinations in real‐life clinical practice in patients with genotypes 1‐3 and in those co‐infected with HIV (real‐world data in genotypes 4‐6 are rare). Second generation DAAs (sofosbuvir plus daclatasvir, sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, sofosbuvir plus velpatasvir, glecaprevir plus pibrentasvir, grazoprevir plus elbasvir) have very high SVR rates and good safety profiles, higher resistance barriers and are more convenient. Real‐world data in all 3 genotypes generally support the EASL guidelines and high overall sustained virological response rates are reported with recommended regimens. However, real‐world data are only available for sofosbuvir plus daclatasvir, sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir. Furthermore, because of the existing level of evidence, it is difficult to define optimal regimens based on real‐world data (ie, treatment duration, when to include ribavirin and options for patients with cirrhosis). The real‐life challenges of managing HIV‐coinfected patients are also discussed showing the additional burden of avoiding drug–drug interactions between DAAs and antiretrovirals.
Global epidemiology of non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis: What we need in the future
Authors: Araújo Ana Ruth , Rosso Natalia , Bedogni Giorgio , Tiribelli Claudio , Bellentani Stefano
Published: February 2018

The estimated prevalence of non‐alcoholic fatty liver disease (NAFLD) worldwide is approximately 25%. However, the real prevalence of NAFLD and the associated disorders is unknown mainly because reliable and applicable diagnostic tests are lacking. This is further complicated by the lack of consensus on the terminology of different entities such as NAFLD or nonalcoholic steatohepatitis (NASH). Although assessing fatty infiltration in the liver is simple by ultrasound, the gold standard for the assessment of fibrosis, the only marker of progression towards more severe liver disease is still liver biopsy. Although other non‐invasive tests have been proposed, they must still be validated in large series. Because NAFL/NAFLD/NASH and related metabolic diseases represent an economic burden, finding an inexpensive method to diagnose and stage fatty liver is a priority. A translational approach with the use of cell and/or animal models could help to reach this goal.
Towards HBV curative therapies
Authors: Schinazi Raymond F. , Ehteshami Maryam , Bassit Leda , Asselah Tarik
Published: February 2018

Tremendous progress has been made over the last 2 decades to discover and develop approaches to control hepatitis B virus (HBV) infections and to prevent the development of hepatocellular carcinoma using various interferons and small molecules as antiviral agents. However, none of these agents have significant impact on eliminating HBV from infected cells. Currently the emphasis is on silencing or eliminating cccDNA, which could lead to a cure for HBV. Various approaches are being developed including the development of capsid effectors, CRISPR/Cas9, TALENS, siRNA, entry and secretion inhibitors, as well as immunological approaches. It is very likely that a combination of these modalities will need to be employed to successfully eliminate HBV or prevent virus rebound on discontinuation of therapy. In the next 5 years clinical data will emerge which will provide insight on the safety and feasibility of these approaches and if they can be applied to eradicate HBV infections globally. In this review, we summarize current treatments and we highlight and examine recent therapeutic strategies that are currently being evaluated at the preclinical and clinical stage.
Diagnosis of non‐alcoholic fatty liver disease/non‐alcoholic steatohepatitis: Non‐invasive tests are enough
Authors: Castera Laurent
Published: February 2018

Non‐alcoholic fatty liver disease is a major cause of liver disease worldwide and the most common liver disorder in Western countries, affecting around 25% of the general population. Fibrosis is the major long‐term histological prognostic criteria of this disease. Liver biopsy cannot be realistically performed in such a huge population and, moreover, has well‐known limitations (invasiveness, rare but potentially life‐threatening complications and sampling variability). Over the past decade, there has been a growing interest in alternative novel strategies for the non‐invasive evaluation of fibrosis. These tests rely on two different but complementary approaches: either measuring the levels of serum biomarkers, or liver stiffness, using ultrasound‐based elastography techniques. In non‐alcoholic fatty liver disease patients, transient elastography, FIB‐4 and the non‐alcoholic fatty liver disease fibrosis score are the best validated tests, with summary area under the ROC curve values for diagnosing severe fibrosis‐cirrhosis of 0.88, 0.84 and 0.84 respectively. They can also identify the subgroup of non‐alcoholic fatty liver disease patients at high risk of developing liver‐related complications and death. As a result, non‐invasive tests are now widely used in routine clinical practice and included in national and international guidelines. The next step is the use of non‐invasive tests as first‐line tools for screening non‐alcoholic fatty liver disease in the general population to identify patients who should be referred to specialized centres.
Is global elimination of HCV realistic?
Authors: Calvaruso Vincenza , Petta Salvatore , Craxì Antonio
Published: February 2018

The elimination of hepatitis C virus (HCV) has been made possible through the availability of new antiviral drugs which may now be administered to all patients with HCV infection, even those with decompensated cirrhosis. The goal of the World Health Organization (WHO) is to reduce the incidence of chronic hepatitis infection from the current 6‐10 million to 0.9 million cases of chronic infections by 2030, and annual deaths from 1.4 million to fewer than 0.5 million. Achieving these targets will require full implementation of epidemiological knowledge of HCV infection, screening and testing practices and strategies to link HCV patients to care. This review will focus on the current state of knowledge in the epidemiology of HCV and what can be done to increase patient awareness and reduce the barriers to treatment. Furthermore, we will discuss the role of HCV clearance on the control of HCV‐related outcomes.
Treatment of hepatitis C virus infection with direct‐acting antiviral agents: 100% cure?
Authors: Asselah Tarik , Marcellin Patrick , Schinazi Raymond F.
Published: February 2018

Around 71 million people are chronically infected with HCV worldwide. HCV antiviral drug development has been remarkable. The availability of pangenotypic direct‐acting antivirals with excellent efficacy and good tolerability profiles offer a unique opportunity to achieve HCV elimination worldwide. IFN‐free DAA combinations can now cure HCV in more than 95% of patients with HCV infection after 8‐12 weeks of treatment. Programmes to eliminate HCV must include increased screening (risk‐based and universal), linkage to care, as well as increased access to treatment worldwide. In this paper, we will review the available data on recently approved direct‐acting antiviral agents, with sustained virological response that reaches almost 100%.
Future therapy for non‐alcoholic fatty liver disease
Authors: Issa Danny , Patel Vaishali , Sanyal Arun J.
Published: February 2018

Non‐alcoholic fatty liver disease is a leading cause of chronic liver disease and can lead to cirrhosis, hepatocellular cancer and end stage liver disease. It is also associated with increased cardiovascular and cancer related morbidity and mortality. The pathogenesis of non‐alcoholic fatty liver disease includes metabolic stress to the liver associated with insulin resistance with downstream cell stress from reactive oxygen species and unfolded protein response with activation of inflammatory and fibrotic pathways. There are currently no approved therapies for non‐alcoholic fatty liver disease. This review summarizes ongoing efforts to establish the treatment of non‐alcoholic steatohepatitis the progressive form of non‐alcoholic fatty liver disease. Therapies are currently directed towards improving the metabolic status of the liver, cell stress, apoptosis, inflammation or fibrosis. Several agents are now in pivotal trials and it is expected that the first therapies will be approved in 2‐3 years.
Liver diseases: A major, neglected global public health problem requiring urgent actions and large‐scale screening
Authors: Marcellin Patrick , Kutala Blaise K.
Published: February 2018

CLDs represent an important, and certainly underestimated, global public health problem. CLDs are highly prevalent and silent, related to different, sometimes associated causes. The distribution of the causes of these diseases is slowly changing, and within the next decade, the proportion of virus‐induced CLDs will certainly decrease significantly while the proportion of NASH will increase. There is an urgent need for effective global actions including education, prevention and early diagnosis to manage and treat CLDs, thus preventing cirrhosis‐related morbidity and mortality. Our role is to increase the awareness of the public, healthcare professionals and public health authorities to encourage active policies for early management that will decrease the short‐ and long‐term public health burden of these diseases. Because necroinflammation is the key mechanism in the progression of CLDs, it should be detected early. Thus, large‐scale screening for CLDs is needed. ALT levels are an easy and inexpensive marker of liver necroinflammation and could be the first‐line tool in this process.
ALT flares during nucleotide analogue therapy are associated with HBsAg loss in genotype A HBeAg‐positive chronic hepatitis B
Authors: Wong Darren , Littlejohn Margaret , Edwards Rosalind , Jackson Kathy , Revill Peter , Gaggar Anuj , Kitrinos Kathryn , Subramanian Mani , Marcellin Patrick , Buti‐Ferret Maria , Janssen Harry , Gane Ed , Locarnini Stephen , Thompson Alexander
Published: February 2018

Background

Alanine aminotransferase (ALT) flares during NA therapy are uncommon but occur. Evaluation of ALT flares during nucleos(t)ide analogue (NA) therapy is important as new immunomodulatory therapies for hepatitis B virus (HBV) are developed. We evaluated the association between ALT flares and HBsAg loss during long‐term therapy for genotype A CHB.

Methods

This analysis included genotype A subjects from a phase III study of tenofovir vs adefovir in HBeAg‐positive HBV. ALT flare was defined as (i) a rise in ALT >2x ULN from normal ALT levels; or (ii) a rise in ALT >2x baseline ALT level. HBsAg response at week 384 was recorded as one of HBsAg loss vs HBsAg decline (≥1 log10 IU/mL decline) vs non‐response. The primary analysis evaluated the association between ALT flare and HBsAg response.

Results

54 subjects were included. 23/54 (43%) subjects experienced an on‐treatment ALT flare. 45% achieved an HBsAg reduction ≥1 log10 IU/mL, and of these 67% achieved HBsAg loss at a median of 102 weeks [IQR: 64‐156]. Flare was associated with HBsAg decline vs non‐response (67% vs 23%, P = .002), and were more common in subjects who achieved HBsAg loss vs non‐response (56% vs 23%), P = .049). There was a median delay of 56 weeks [IQR: 40‐80] between a flare and HBsAg loss.

Conclusion

In genotype A subjects undergoing long‐term NA therapy, ALT flares predict for HBsAg response. The delay between ALT flare and HBsAg loss has implications for clinical trial design for early phase development of immunomodulatory strategies aiming for HBsAg loss.
The ecosystem services of animal microbiomes
Authors: McKenney E. A. , Koelle K. , Dunn R. R. , Yoder A. D.
Published: February 2018

Microbiologists often evaluate microbial community dynamics by formulating functional hypotheses based on ecological processes. Indeed, many of the methods and terms currently used to describe animal microbiomes derive from ecology and evolutionary biology. As our understanding of the composition and functional dynamics of “the microbiome” grows, we increasingly refer to the host as an ecosystem within which microbial processes play out. Even so, an ecosystem service framework that extends to the context of the host has thus far been lacking. Here, we argue that ecosystem services are a useful framework with which to consider the value of microbes to their hosts. We discuss those “microbiome services” in the specific context of the mammalian gut, providing a context from which to develop new hypotheses and to evaluate microbial functions in future studies and novel systems.
Zebularine treatment is associated with deletion of FT‐B1 leading to an increase in spikelet number in bread wheat
Authors: Finnegan E. Jean , Ford Brett , Wallace Xiaomei , Pettolino Filomena , Griffin Patrick T. , Schmitz Robert J. , Zhang Peng , Barrero Jose M. , Hayden Matthew J. , Boden Scott A. , Cavanagh Colin A. , Swain Steve M. , Trevaskis Ben
Published: February 2018

The number of rachis nodes (spikelets) on a wheat spike is a component of grain yield that correlates with flowering time. The genetic basis regulating flowering in cereals is well understood, but there are reports that flowering time can be modified at a high frequency by selective breeding, suggesting that it may be regulated by both epigenetic and genetic mechanisms. We investigated the role of DNA methylation in regulating spikelet number and flowering time by treating a semi‐spring wheat with the demethylating agent, Zebularine. Three lines with a heritable increase in spikelet number were identified. The molecular basis for increased spikelet number was not determined in 2 lines, but the phenotype showed non‐Mendelian inheritance, suggesting that it could have an epigenetic basis. In the remaining line, the increased spikelet phenotype behaved as a Mendelian recessive trait and late flowering was associated with a deletion encompassing the floral promoter, FT‐B1. Deletion of FT‐B1 delayed the transition to reproductive growth, extended the duration of spike development, and increased spikelet number under different temperature regimes and photoperiod. Transiently disrupting DNA methylation can generate novel flowering behaviour in wheat, but these changes may not be sufficiently stable for use in breeding programs.
Permissivism and the Value of Rationality: A Challenge to the Uniqueness Thesis
Authors: Schoenfield Miriam
Published: February 2018

In recent years, permissivism—the claim that a body of evidence can rationalize more than one response—has enjoyed somewhat of a revival. But it is once again being threatened, this time by a host of new and interesting arguments that, at their core, are challenging the permissivist to explain why rationality matters. A version of the challenge that I am especially interested in is this: if permissivism is true, why should we expect the rational credences to be more accurate than the irrational ones? My aim is to turn this challenge on its head and argue that, actually, those who deny permissivism will have a harder time responding to such a challenge than those who accept it.