Diagnostic accuracy of enhanced liver fibrosis test for nonalcoholic steatohepatitis-related fibrosis: Multicenter study

Aim

The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan.

Methods

We analyzed 371 Japanese patients with biopsy-proven NAFLD. We constructed area under the receiver operator characteristic curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac-2-binding protein glycosylation isomer (M2BPGi), the Fibrosis-4 (FIB-4) index, and combinations of these indices.

Results

In patients with F0/F1/F2/F3/F4 fibrosis, the median values of the ELF test were 8.98/9.56/10.39/10.92/11.41, respectively. The AUROCs of the ELF test for patients with F0 versus F1–4, F0–1 versus F2–4, F0–2 versus F3–4, and F0–3 versus F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB-4 index and M2BPGi at each fibrosis stage. Respective low and high cut-off values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8%, and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB-4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%.

Conclusions

In Japan, the ELF test predicts NAFLD-related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate.     

Increased frequency of HLA DR13 in hepatitis C virus carriers with persistently normal ALT levels

The aim of this study was to clarify the relationship between human leukocyte antigen DR allele distribution and the degree of liver cell injury of hepatitis C virus (HCV) carriers in Japan. The subjects, 68 HCV carriers, were divided into two groups according to the laboratory data and liver histology. Those in the asymptomatic carrier group (n = 19) had normal ALT levels persistently for 8–153 months (mean 25.7 months) and were diagnosed histologically as normal liver, nonspecific reactive hepatitis or chronic persistent hepatitis. Those in the chronic active hepatitis group (n = 49) had elevated ALT levels and were diagnosed histologically with chronic active hepatitis. The human leukocyte antigen DR alleles of all subjects were defined using the polymerase chain reaction restriction fragment length polymorphism method. The expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane were also examined in 14 patients from each group using an indirect immunohistochemical method. The frequency of DR13 (42.1%) in the asymptomatic carrier group was significantly higher (Pc < 0.003) than that of the chronic active hepatitis group (4.1%). There were no significant differences for the other DR alleles. The frequencies of expression of human leukocyte antigen class I antigen and intercellular adhesion molecule 1 on the hepatocyte membrane of the asymptomatic carrier group were significantly less than those of the chronic hepatitis group (64% vs. 100% P < 0.05, 29%; vs. 71% P < 0.05, respectively), although there was no significant difference in the serum HCV-RNA titer between the two groups (10^6.4±1.1 vs. 10^6.5±0.7 copies/mL). These results demonstrate that the cellular immune response of the asymptomatic carrier group is less activated than the response of the chronic active hepatitis group and that HLA DR13 may be closely associated with this low activity of hepatitis among HCV carriers. © 1996 Wiley-Liss, Inc.     

Helicobacter pylori heat shock protein 60 antibodies are associated with gastric cancer

Helicobacter pylori infection causes atrophic gastritis, peptic ulcer, and gastric cancer. The host immune response plays an important role in the pathogenesis of H. pylori-related diseases. Heat shock proteins are antigens involved in various diseases. This study evaluated seropositivity for antibodies to H. pylori heat shock protein 60 in patients with gastric cancer.     

Endothelin synthesis and receptors in human endometrium throughout the normal menstrual cycle

This study was undertaken to investigate the presence of messengerRNA (mRNA) for prepro-endothelin-I (ET-1) and the known receptorsubtypes (ETA and ETB) in human endometrium at different stagesof the menstrual cycle obtained at hysterectomy. Northern blotanalysis revealed expression of ET-1 mRNA in human endometriumduring the normal menstrual cycle. The concentration of ET-1mRNA in endometrial tissue was greater during the menstrualand proliferative phases than during the ovulatory and secretoryphases. Immunoreactive ET-1 was secreted into the medium ofisolated endometrial stromal cells. Oestradiol and progesteronesignificantly attenuated ET-1 release in endometrial stromalcells cultured for 6 days. ETA and ETB mRNA were also presentin endometrial tissue of the normal cycle. The concentrationof ETA receptor mRNA was greater in the proliferative phasethan in the secretory phase, whereas expression of ETB mRNAincreased in menstrual phase. ET-1 significantly increased extracellularaccumulation of cyclic AMP (cAMP), intracellular generationof inositol phosphates and significantly enhanced DNA synthesisin cultured endometrial stromal cells from the proliferativephase. Our results showed that human endometrial cells synthesizedand released ET-1, and contained ETA and ETB receptors whichwere functionally coupled to phosphoinositide breakdown andto adenylate cyclase with the increase of cAMP by ET-1 stimulation.Our findings suggest that ET-1 may have a potential autocrineand/or paracrine function in human endometrial stromal cells.     

Antibody Responses to the BNT162b2 mRNA Vaccine in Healthcare Workers in a General Hospital in Japan: A Comparison of Two Assays for Anti-spike Protein Immunoglobulin G

Objective This study assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses to the BNT162b2 mRNA vaccine in Japanese healthcare workers. Methods In this prospective cohort study, participants received two doses of the BNT162b2 mRNA vaccine on days 0 and 21 and provided blood for anti-SARS-CoV-2 antibody testing before the first vaccine and on days 21 and 35 after vaccination. Anti-spike protein immunoglobulin G (S-IgG) was measured using Abbott and Fujirebio chemiluminescent immunoassays. Patients One hundred healthcare workers (median age: 39 years old, interquartile range: 30-48 years old), including 6 who had been previously infected with SARS-CoV-2 and 3 individuals taking immunosuppressive drugs, participated in the study. Results The S-IgG antibody titers (AU/mL) measured using both the Abbott and Fujirebio assays increased significantly (p＜0.001) over time, both with a prevalence of 100% at 35 days after the first vaccination. The multivariate log-normal linear regression analysis indicated the effect of immunosuppressant medication using both the Abbott (p=0.013) and Fujirebio (p=0.039) assays on S-IgG levels after complete vaccination. Pearson''s correlation coefficient between the Abbott and Fujirebio S-IgG results in all 300 samples collected before and after vaccination and 50 positive controls from patients with coronavirus disease 2019 were 0.963 [95% confidence interval (CI): 0.954-0.970, p＜0.001] and 0.909 (95% CI: 0.845-0.948, p＜0.001), respectively. Conclusion The BNT162b2 mRNA vaccine was effective at increasing S-IgG levels in Japanese immunocompetent healthcare workers. The Fujirebio S-IgG assay showed high diagnostic accuracy, using the Abbott S-IgG assay as the reference test.     

Biochemical activities of lysosomal acid hydrolases in leukemic cells

The biochemical activities of 8 lysosomal acid hydrolases in leukemic cells from 48 patients were examined. Characteristic alterations were found in α-mannosidase, β-galactosidase and N-acetyl-β-glucosaminidase activities of leukemic cells. The level of α-mannosidase activity was much higher in myelo(mono)genous leukemias (AML, AMoL, AMMoL, CML and CMMoL) than in lymphogenous ones (ALL, T-cell leukemia, hairy cell leukemia and CLL) without exception. The β-galactosidase activity also differed as a result of α-mannosidase, except in T-cell leukemia. In T-cell leukemia it was within the range of normal lymphocytes, but in the other lymphogenous leukemias it was significantly below normal. N-acetyl-β-glucosaminidase activity in myelo(mono)genous leukemic cells was above the range of normal granulocytes. The changes in these enzyme levels were consistent. The lymphocytic or myelocytic nature of three cases of acute undifferentiated leukemia could be determined by enzyme studies. In two cases it was lymphocytic and in one it was myelocytic. The enzymatic abnormalities were also found in morphologically mature neutrophils from patients with not only chronic types (CML, CMMoL) but also acute types (AMoL, AMMoL) of leukemias, and were similar to those of their respective leukemic cells. Analysis of lysosomal enzymes (at least three of those mentioned above), can elucidate one of the biochemical properties of leukemic cells and may be valuable in the differentiation of leukemias.     

Ethanol Stimulates Immunoreactive Endothelin-1 and -2 Release from Cultured Human Umbilical Vein Endothelial Cells

The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome.     

Evaluation of duodenal hypersensitivity induced by duodenal acidification using transnasal endoscopy

Background and Aim: Although duodenal hypersensitivity has been suggested as one of the causes of functional dyspepsia (FD), a practical method to clarify this has not yet been established. The aim of this study was to evaluate whether patients with FD have duodenal hypersensitivity to acid, using transnasal endoscopy. Methods: In all, 44 patients with FD and 16 healthy volunteers were enrolled, and all the subjects received transnasal endoscopy in the morning after overnight fasting. After ordinary transnasal endoscopy, an infusion tube was introduced into the duodenal bulb by transnasal endoscopy and acid (20 mL, 0.1 N HCl, 20 mL/min, 36.5°C) was injected via the infusion tube. The severity of 12 symptoms was assessed by each subject using a 100‐mm visual analogue scale. The maximum severity scale was defined as the maximum score of the symptom severity scale. The total score was defined as the aggregate score of the maximum severity scale of the 12 symptoms. The maximum severity scales and the total scores between patients with FD and healthy volunteers were evaluated. Results: The maximum severity scales of nine symptoms increased significantly more after acid infusion in patients with FD than in healthy volunteers (P < 0.05). There were significant differences in the total scores (patients with FD vs healthy volunteers 233.8 ± 37.8 vs 63.9 ± 14.6, mean ± standard error of the mean, P < 0.001). Conclusions: Duodenal acidification using transnasal endoscopy enabled the evaluation of duodenal hypersensitivity to acid in healthy volunteers and patients with FD.     

Asymptomatic hyperglycaemia is associated with increased intimal plus medial thickness of the carotid artery

Summary Atherosclerotic changes have not been demonstrated directly in asymptomatic hyperglycaemic non-diabetic subjects, although high mortality due to coronary heart disease has been reported. We measured arterial wall thickness non-invasively, in order to directly demonstrate atherosclerosis of the carotid arteries of hyperglycaemic non-diabetic subjects and to evaluate its risk factors.The thicknesses of the intimal plus medial complex (IMT) of the carotid arteries of 112 asymptomatic hyperglycaemic non-diabetic subjects (aged 22–81, 95 males and 17 females) were compared with those of 55 healthy male subjects and 211 non-insulin-dependent NIDDM male diabetic patients. The subjects were subgrouped into impaired glucose-tolerant (IGT) subjects who had a 2-h glycaemic level of more than 7.8 mmol/l, and non-IGT subjects whose 2-h glycaemic levels were within 6.7–7.7 mmol/l.Non-IGT and IGT subjects showed significantly greater IMTs than age-matched healthy males and showed no significant differences compared to age-matched NIDDM patients. Multivariate analysis demonstrated that the risk factors for IMT of non-IGT and IGT subjects were age and systolic blood pressure. According to data on the accumulation of atherogenic risks (hypertension, dyslipidaemia, and smoking), IMT increased linearly in non-IGT and IGT subjects. However, non-IGT and IGT subjects without hyperlipidaemia, hypertension, or smoking risk still had significantly greater IMT than age-matched normal males (1.019±0.063 vs 0.770±0.111 mm, p<0.05). Prevalence of ECG-indicated coronary heart disease was significantly higher in hyperglycaemic non-diabetic subjects and NIDDM with increased carotid arterial wall thickness (IMT 1.1 mm) than in those without increased thickness (IMT<1.1 mm). Asymptomatic hyperglycaemic non-diabetic subjects have increased thickness of their carotid arteries compared to age-matched male NIDDM patients. As one of several independent risk factors, mild hyperglycaemia advances atherosclerosis, which leads to coronary heart disease.Abbreviations IMT Intimal plus medial complex - NIDDM non-insulin-dependent diabetes mellitus - IGT impaired glucose tolerance - CHD coronary heart disease - T-Chol serum total cholesterol - HDL-C high-density lipoprotein cholesterol - TG serum triglycerides