Summary
Background
The rs738409 GG variant in patatin‐like phospholipase 3 (PNPLA3) is associated with non‐alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if ...it contributes to the development of NAFLD through affecting dietary pattern.
Aim
To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD.
Methods
Liver fat and fibrosis were assessed by proton‐magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food‐frequency questionnaire.
Results
The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern.
Conclusions
The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.
The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine ...aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty‐one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
Summary
Background
Patients with nonalcoholic steatohepatitis (NASH) have gut dysbiosis and intestinal bacterial overgrowth.
Aim
To test the hypothesis that endotoxemia is associated with the ...histological severity of nonalcoholic fatty liver disease (NAFLD) and determine factors associated with endotoxemia.
Methods
The endotoxemia markers lipopolysaccharide‐binding protein (LBP) and endotoxin levels were measured in 237 NAFLD patients 1 day before liver biopsy. Biomarkers of liver injury and transient elastography were performed as additional markers of disease severity.
Results
A total of 114/237 (48%) patients had NASH and 80/237 (34%) had F2‐4 fibrosis. LBP was correlated with lobular inflammation (P=.001), while both LBP (P=.0004) and endotoxin levels (P=0.008) were correlated with fibrosis. LBP was also correlated with cytokeratin‐18 fragments (P=.002) and aspartate aminotransferase‐to‐alanine aminotransferase ratio (P=.006), and both LBP (P=.019) and endotoxin (P=.006) were correlated with liver stiffness measurement by transient elastography. LBP was increased in patients with NASH (15.3±4.6 vs 13.8±3.3 μg/mL; P=.005) and F2‐4 fibrosis (15.4±4.4 vs 14.0±3.7 μg/mL; P=.008). Interestingly, patients harbouring the TM6SF2 rs58542926 T allele that predispose to NAFLD/NASH had higher LBP level. By multivariate analysis, gender, higher body mass index and glycated haemoglobin, and TM6SF2 variants were independent factors associated with increased LBP level.
Conclusions
Endotoxemia is positively associated with NASH and significant fibrosis. The association between TM6SF2 and endotoxemia warrants further investigations. The findings may shed light on the pathogenesis of NASH and inform a novel treatment target.
Linked ContentThis article is linked to Valenti and Romeo paper. To view this article visit https://doi.org/10.1111/apt.14154.
Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear.
We aimed to ...study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB.
We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM.
1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively.
Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.
Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) affects 20%‐40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. ...Electronic medical records facilitate large‐scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases.
Aim
To develop and validate a laboratory parameter‐based machine learning model to detect NAFLD for the general population.
Methods
We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton‐magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver‐operating characteristic curve (AUROC) of models in validation group were compared.
Results
Six predictors including alanine aminotransferase, high‐density lipoprotein cholesterol, triglyceride, haemoglobin A1c, white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83‐0.90) and 0.88 (0.84‐0.91) in the training and validation groups respectively. Using dual cut‐offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%‐96%) sensitivity and 90% (86%‐93%) specificity with corresponding negative and positive predictive values of 96% (91%‐98%) and 69% (59%‐78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate.
Conclusions
NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies.
Linked ContentThis article is linked to Gallacher et al and McPherson and Yip papers. To view these articles visit https://doi.org/10.1111/apt.14217 and https://doi.org/10.1111/apt.14234.
Summary
Background
The accuracy of Enhanced Liver Fibrosis (ELF; ADVIA Centaur, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) in assessing liver fibrosis in chronic hepatitis B (CHB) is to be ...determined.
Aim
To derive and validate a combined ELF‐liver stiffness measurement (LSM) algorithm to predict advanced fibrosis in CHB patients.
Methods
Using the data of a previously reported cohort of 238 CHB patients, an ALT‐based LSM algorithm for liver fibrosis was used as a training cohort to evaluate the performance of ELF against liver histology. The best combined ELF‐LSM algorithm was then validated in new cohort of 85 CHB patients not previously reported.
Results
In the training cohort, LSM has better performance of diagnosing advanced (≥F3) fibrosis (area under the receiver operating characteristics curve AUROC 0.83, 95% confidence interval CI 0.76–0.91 than ELF (AUROC 0.69, 95% CI 0.63–0.75). The optimal cut‐off values of ELF were 8.4 to exclude advanced fibrosis, and 10.8 to confirm advanced fibrosis. In the training cohort, an ELF ≤ 8.4 had a sensitivity of 95% to exclude advanced fibrosis; an ELF > 10.8 had a specificity of 92% to confirm advanced fibrosis. In the combined algorithm, low ELF or low LSM could be used to exclude advanced fibrosis as both of them had high sensitivity (≥90%). To confirm advanced fibrosis, agreement between high ELF and high LSM could improve the negative predictive value specificity (from 65% and 74% to 80%).
Conclusions
An Enhanced Liver Fibrosis ‐ liver stiffness measurement algorithm could improve the accuracy of prediction of either ELF or LSM alone. Liver biopsy could be correctly avoided in approximately 60% of patients.
Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of ...an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.
Summary
Background
The diagnosis of non‐alcoholic fatty liver disease (NAFLD), non‐alcoholic steatohepatitis (NASH) and fibrosis relies on liver biopsy. Non‐invasive assessments are urgently needed.
...Aim
To evaluate cell apoptotic marker cytokeratin‐18 M30 and total cell death markers cytokeratin‐18 M65/M65ED for the assessment and monitoring of NAFLD.
Methods
A cohort of 147 patients with biopsy‐proven NAFLD and 73 controls were enroled, including 51 patients who received paired liver biopsies 36 months apart. Biomarkers were determined by enzyme‐linked immunosorbent assay.
Results
M30, M65 and M65ED increased in a stepwise fashion in control subjects, patients with non‐NASH, NAFLD and NASH (all P < 0.001). All biomarkers had similarly high accuracy over 0.9 in predicting NAFLD and moderate accuracy around 0.7 in predicting NASH. Among patients with paired liver biopsies, changes in M30, M65 and M65ED positively correlated with disease progression (rho = 0.42, 0.32 and 0.39; P = 0.002, 0.023 and 0.005 respectively), and only changes in M65 and M65ED correlated with fibrosis progression (rho = 0.29, 0.34; P = 0.038, 0.015 respectively). Both M30 and M65 had area under receiver‐operating characteristics curve above 0.8 in predicting disease progression. At cut‐off of 236 U/L, changes of M65ED had 88% NPV and 59% PPV to exclude and predict fibrosis progression.
Conclusions
Cytokeratin‐18 M30 and M65/M65ED have moderate accuracy in detecting non‐alcoholic steatohepatitis. Changes in the biomarkers also correlate with histological progression. However, development of new biomarkers is still required to improve the diagnostic accuracy.
In this paper, a new dance training system based on the motion capture and virtual reality (VR) technologies is proposed. Our system is inspired by the traditional way to learn new ...movements-imitating the teacher's movements and listening to the teacher's feedback. A prototype of our proposed system is implemented, in which a student can imitate the motion demonstrated by a virtual teacher projected on the wall screen. Meanwhile, the student's motions will be captured and analyzed by the system based on which feedback is given back to them. The result of user studies showed that our system can successfully guide students to improve their skills. The subjects agreed that the system is interesting and can motivate them to learn.
Background and Objective: Short‐chain fatty acids, such as butyric acid and propionic acid, are metabolic by‐products generated by periodontal microflora such as Porphyromonas gingivalis, and ...contribute to the pathogenesis of periodontitis. However, the effects of butyrate on the biological activities of gingival fibroblasts (GFs) are not well elucidated.
Material and Methods: Human GFs were exposed to various concentrations of butyrate (0.5–16 mm) for 24 h. Viable cells that excluded trypan blue were counted. Cell cycle distribution of GFs was analyzed by propidium iodide‐staining flow cytometry. Cellular reactive oxygen species (ROS) production was measured by flow cytometry using 2’,7’‐dichlorofluorescein (DCF). Total RNA and protein lysates were isolated and subjected to RT‐PCR using specific primers or to western blotting using specific antibodies, respectively.
Results: Butyrate inhibited the growth of GFs, as indicated by a decrease in the number of viable cells. This event was associated with an induction of G0/G1 and G2/M cell cycle arrest by butyrate (4–16 mm) in GFs. However, no marked apoptosis of GFs was noted in this experimental condition. Butyrate (> 2 mm) inhibited the expression of cdc2, cdc25C and cyclinB1 mRNAs and reduced the levels of Cdc2, Cdc25C and cyclinB1 proteins in GFs, as determined using RT‐PCR and western blotting, respectively. This toxic effect of butyrate was associated with the production of ROS.
Conclusion: These results suggest that butyrate generated by periodontal pathogens may be involved in the pathogenesis of periodontal diseases via the induction of ROS production and the impairment of cell growth, cell cycle progression and expression of cell cycle‐related genes in GFs. These events are important in the initiation and prolongation of inflammatory processes in periodontal diseases.
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