Diagnostic performance of shear wave measurement in the detection of hepatic fibrosis: A multicenter prospective study

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Diagnostic performance of shear wave measurement in the detection of hepatic fibrosis: A multicenter prospective study

The correlation coefficient between shear wave measurement and magnetic resonance elastography values was 0.793 (95% confidence interval 0.761–0.821), indicating a strong correlation. The correlation coefficients between shear wave measurement and magnetic resonance elastography values decreased significantly with increasing body mass index and skin capsular distance, and skin–capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. We established shear wave measurement cut-off values for different degrees of fibrosis in chronic liver diseases using magnetic resonance elastography as a reference standard.


Abstract

Aim

This study aimed to establish the shear wave measurement (SWM) cut-off value for each fibrosis stage using magnetic resonance (MR) elastography values as a reference standard.

Methods

We prospectively analyzed 594 patients with chronic liver disease who underwent SWM and MR elastography. Correlation coefficients (were analyzed, and the diagnostic value was evaluated by the area under the receiver operating characteristic curve. Liver stiffness was categorized by MR elastography as F0 (<2.61 kPa), F1 (≥2.61 kPa, <2.97 kPa, any fibrosis), F2 (≥2.97 kPa, <3.62 kPa, significant fibrosis), F3 (≥3.62 kPa, <4.62 kPa, advanced fibrosis), or F4 (≥4.62 kPa, cirrhosis).

Results

The median SWM values increased significantly with increasing fibrosis stage (p < 0.001). The correlation coefficient between SWM and MR elastography values was 0.793 (95% confidence interval 0.761–0.821). The correlation coefficients between SWM and MR elastography values significantly decreased with increasing body mass index and skin–capsular distance; skin–capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. The best cut-off values for any fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis were 6.18, 7.09, 8.05, and 10.89 kPa, respectively.

Conclusions

This multicenter study in a large number of patients established SWM cut-off values for different degrees of fibrosis in chronic liver diseases using MR elastography as a reference standard. It is expected that these cut-off values will be applied to liver diseases in the future.

A unifying mechanism for seipin‐mediated lipid droplet formation

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A unifying mechanism for seipin-mediated lipid droplet formation

Seipin is a key factor in the assembly of lipid droplets at the endoplasmic reticulum. Here, we review recent advances provided by structural, biochemical, and in silico analyses that provided mechanistic insights into seipin function in lipid droplet formation.


Lipid droplets (LDs) are dynamic organelles essential for cellular lipid homeostasis. Assembly of LDs occurs in the endoplasmic reticulum (ER), and the conserved ER membrane protein seipin emerged as a key player in this process. Here, we review recent advances provided by structural, biochemical, and in silico analysis that revealed mechanistic insights into the molecular role of the seipin complexes and led to an updated model for LD biogenesis. We further discuss how other ER components cooperate with seipin during LD biogenesis. Understanding the molecular mechanisms underlying seipin-mediated LD assembly is important to uncover the fundamental aspects of lipid homeostasis and organelle biogenesis and to provide hints on the pathogenesis of lipid storage disorders.

Lipid Droplets in Virus Replication

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Lipid Droplets in Virus Replication

Viruses rely on host lipid metabolic pathways for multiplication. Lipid droplets are the cellular storage organelles of neutral lipids and central hubs of lipid metabolism. Viruses exploit host lipid droplets as source for membrane lipids that form replication organelles or the envelope of virions or for energy to fulfil their replicative cycle. These findings are summarized in this Graphical Review.


Intracellular pathogens rely on host metabolic networks for multiplication. Enveloped viruses need lipids for formation of the viral envelope and positive sense RNA viruses that replicate in membranous inclusions require lipids for formation of the replication compartments. In addition, all intracellular pathogens need energy for their replicative cycle. As triglycerides in lipid droplets are the main energy storage unit of cells and major source of membrane lipids, it is not surprising that viruses have evolved various strategies to exploit different aspects of lipid droplet biology.

Lipid sensing nuclear receptors involved in the pathogenesis of fatty liver disease

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Lipid sensing nuclear receptors involved in the pathogenesis of fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation and progresses toward inflammation and fibrosis. Nuclear receptors (NRs), like the Peroxisome Proliferator-Activated Receptors alpha and gamma (PPARα and PPARy), the Farnesoid X Receptor (FXR), and the Liver X receptor (LXR), regulate genes by heterodimerizing with Retinoid X receptor (RXR). These receptors are emerging targets for pharmaceutical intervention for metabolic diseases.


Estimation of genetic parameters for reproductive indices in sheep

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Abstract

This study aimed to estimate two reproductive efficiency indices in sheep based on the ratio between litter weight (at birth and weaning) and dam weight, as well as their genetic parameters. Phenotypic and pedigree data comprising the period from 1990 to 2018 were obtained from the Santa Inês sheep database of Embrapa Tabuleiros Costeiros. For estimation of the genetic parameters of the indices, a repeatability model was applied in single- and two-trait analyses by a Bayesian approach. The mean reproductive efficiency index was 0.069 ± 0.0163 and 0.43 ± 0.0955 at birth and weaning, respectively. These values indicate that, on average, ewes give birth to 69 g of lamb per kg body weight and wean 430 g of lamb per kg body weight. Described here for the first time, the heritability estimate obtained in single- and two-trait analyses was 0.24 for the index based on birth weights and ranged from 0.13 to 0.15 for the index based on weaning weights. The estimates indicate the possibility of genetic gain by selection and are similar to those reported for reproductive traits in sheep, representing an option for selection criterion. The genetic correlation between indices was positive and moderate (0.26). The repeatability estimates were high (0.49 for the birth weight index and 0.71 for the weaning weight index). These values indicate good prediction of future performance with few observations. The weaning weight index might be a good culling criterion of females.

Genetic correlation estimates between calving ease in primiparous cows and economically important traits in Nellore cattle

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Abstract

This study aimed to estimate (co)variance components and genetic parameters for calving ease (CE) and their genetic correlations with growth, reproductive, carcass, and feed efficiency traits in Nellore cattle. Phenotypes for CE are scored in two categories: normal calving and assisted calving. The traits considered were probability of precocious calving, age at first calving, stayability, adjusted scrotal circumference at 365 days of age, accumulated cow productivity, age at puberty of males, gestation length, birth weight, adjusted weights at 210 and 450 days of age, adult cow weight, frame score, hip height, rib eye area, subcutaneous backfat thickness, rump fat thickness, intramuscular fat percentage, residual feed intake and dry matter intake. The estimation of genetic parameters was performed using a two-trait threshold-linear animal model, except for CE, stayability, and probability of precocious calving, which were evaluated through a two-trait threshold animal model. The direct (0.27) and maternal (0.19) heritability estimates for CE in heifers primiparous Nellore indicated that selecting for this trait is feasible. The selection to improve the female sexual precocity should consider CE during the selection and mating decisions to reduce calving problems. Genetic correlation estimates between CE and BW suggest that selecting low birth weight to reduce calving problems is not an appropriate strategy to improve calving ease in heifers Nellore. Therefore, adopting a multi-trait selection model with CE and BW in the Nellore breed would reduce calving difficulties, particularly in sexually precocious heifers, without impairing the growth, reproductive, feed efficiency conversion, and carcass indicator traits.

Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy

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Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy

The baseline platelet count and on-treatment hepatitis B surface antigen glycan isomer/hepatitis B surface antigen (HBsAgGi/HBsAg) ratio were useful predictors of hepatocellular carcinoma (HCC) development during nucleoside/nucleotide analog (NA) therapy. In addition, it suggests that a combination of on-treatment HBsAgGi and HBsAg may lead to an increase in the accuracy of predictions of the development of HCC during NA therapy compared with HBsAg alone.


Abstract

Aim

A recombinant monoclonal antibody against the hepatitis B surface antigen glycan isomer (HBsAgGi) was newly developed using the O-glycosylated PreS2 peptide in M-HBsAg of hepatitis B virus (HBV) genotype C. However, the association between HBsAgGi and the development of hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy remains unknown.

Methods

A total of 112 HBV genotype C-infected patients who were treated with NA were included in this study. We assessed the association between HBV markers, including HBsAgGi and other conventional markers, and the development of HCC during NA therapy.

Results

Ten patients developed HCC during the follow-up period. Of the HBV markers, HBsAg (≤3.53 log IU/mL; p = 0.047), HBsAgGi/HBsAg ratio (≥1.10; p = 0.035), and HBV DNA (≤6.3 log copies/mL; p = 0.012) at baseline and HBsAg (≤3.19 log IU/mL; p = 0.033) and HBsAgGi/HBsAg ratio (≥1.09; p = 0.003) at 48 weeks after NA therapy were significantly associated with the development of HCC according to the log rank test. In contrast, no significant association was observed between HBsAgGi and the development of HCC. Multivariate analysis revealed that a platelet count at baseline ≤88 × 103/mm3 (p = 0.026; hazard ratio [HR], 10.577) and an HBsAgGi/HBsAg ratio at 48 weeks after NA therapy ≥1.09 (p = 0.040; HR, 10.099) were independently and significantly associated with the development of HCC.

Conclusions

Our findings suggest that a combination of on-treatment HBsAgGi and HBsAg predicts the development of HCC during NA therapy.