Clinical and histologic factors associated with discordance between steatosis grade derived from histology vs. MRI-PDFF in NAFLD.

BACKGROUND: Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is an excellent biomarker for the non-invasive quantification of hepatic steatosis. AIM: To examine clinical and histologic factors associated with discordance between steatosis grade determined by histology and MRI-PDFF in patients with non-alcoholic fatty liver disease (NAFLD) METHODS: We included 728 patients with biopsy-proven NAFLD from UC San Diego (n = 414) and Yokohama City University (n = 314) who underwent MRI-PDFF and liver biopsy. Patients were stratified by steatosis, and matched with MRI-PDFF cut-points for each steatosis grade: 0 (MRI-PDFF < 6.4%), 1 (MRI-PDFF: 6.4%-17.4%), 2 (MRI-PDFF: 17.4%-22.1%), 3 (MRI-PDFF ≥ 22.1%). Primary outcome was major discordance defined as ≥2 steatosis grade difference determined by histology and MRI-PDFF. RESULTS: Mean (±SD) age and BMI were 55.3 (±13.8) years and 29.9 (±4.9) kg/m2 , respectively. The distributions of histology and MRI-PDFF-determined steatosis were 5.5% grade 0 (n = 40), 44.8% 1 (n = 326, 44.8%), 33.9% 2 (n = 247), and 15.8% 3 (n = 115) vs. 23.5% grade 0 (n = 171), 49.7% 1 (n = 362), 12.9% 2 (n = 94), and 13.9% 3 (n = 101). Major discordance rate was 6.6% (n = 48). Most cases with major discordance had greater histology-determined steatosis grade (n = 40, 88.3%), higher serum AST and liver stiffness, and greater likelihood of fibrosis ≥2, ballooning ≥1 and lobular inflammation ≥2 (all p < 0.05). CONCLUSION: Histology overestimates steatosis grade compared to MRI-PDFF. Patients with advanced NASH are likely to be upgraded on steatosis grade by histology. These data have important implications for steatosis estimation and reporting on histology in clinical practice and trials, especially in patients with stage 2 fibrosis.

Two-Step Strategy, FIB-4 Followed by Magnetic Resonance Elastography, for Detecting Advanced Fibrosis in NAFLD.

BACKGROUND & AIMS: A two-step strategy combining a serum marker and magnetic resonance elastography (MRE) for detecting advanced fibrosis (stage 3-4) among patients with nonalcoholic fatty liver disease (NAFLD) has been proposed, but its diagnostic accuracy has not been evaluated. In this multicenter study, we aimed to investigate the diagnostic accuracy of a two-step strategy including Fibrosis-4 (FIB-4) followed by MRE. METHODS: In this multicenter study, 806 patients with biopsy-proven NAFLD who underwent contemporaneous MRE were enrolled and randomly assigned to training and validation cohorts. As a first step, patients with FIB-4 <1.3 were defined as test negative regardless of MRE. As a second step, among patients with FIB-4 ≥1.3, MRE <3.6 and ≥3.6 kPa were defined as test negative and positive. The primary outcome was the diagnostic accuracy for advanced fibrosis comparing MRE alone versus the two-step strategy. RESULTS: Area under the receiver characteristic curves of MRE alone and the two-step strategy were 0.840 and 0.853 in the training cohort (P = .4) and 0.867 and 0.834 in the validation cohort (P = .2), respectively, and the diagnostic accuracy was comparable between the 2 methods. In the entire cohort, negative predictive value (NPV) and positive predictive value (PPV) of MRE for advanced fibrosis were 92.2% and 73.7%, respectively, whereas NPV at the first and second step and PPV at the second step were 90.9%, 84.4%, and 77.0%, respectively. CONCLUSIONS: The diagnostic accuracy of the two-step strategy was comparable to MRE and could reduce cost by reducing excessive MRE. Therefore, the two-step strategy could be used as a screening method in a large population.

Hepatocellular Carcinoma Incidence in Alcohol-Associated Cirrhosis: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Alcohol is one of the leading causes of hepatocellular carcinoma (HCC). However, pooled estimates of HCC incidence in alcohol-associated cirrhosis have not been evaluated systematically. We performed a pooled analysis of time-to-event data to provide robust estimates for the incidence of HCC in alcohol-associated cirrhosis. METHODS: Medline, Embase, Cochrane Central Register, Scopus, and Web of Science were searched from inception to August 2021. Individual patient data were reconstructed from published Kaplan-Meier curves, and a pooled analysis of cumulative HCC incidence was performed using a random-effects model. RESULTS: We screened 5022 articles and included 18 studies (148,333 patients). In the pooled analysis, the cumulative incidence of HCC in alcohol-associated cirrhosis at 1, 5, and 10 years among studies that accounted for the competing risk of death without HCC was 1%, 3%, and 9%, respectively. A secondary analysis by traditional meta-analysis determined that the HCC incidence rate was higher in cohorts enrolled in a HCC surveillance program (18.6 vs 4.8 per 1000 person-years; P = .001) vs those who were not enrolled in a surveillance program. Meta-regression showed that diabetes, smoking, variceal bleeding, and hepatic decompensation were associated with a higher risk of HCC. CONCLUSIONS: Our analysis determined that the 5- and 10- year cumulative risk of HCC in alcohol-associated cirrhosis was 3% and 9%, respectively, with a higher incidence in cohorts that were enrolled in a HCC surveillance program. These data should be validated further in large prospective studies, and may have important implications for HCC screening and surveillance among patients with alcohol-associated cirrhosis.

Head-to-head comparison between MEFIB, MAST, and FAST for detecting stage 2 fibrosis or higher among patients with NAFLD.

BACKGROUND & AIMS: Patients with non-alcoholic fatty liver disease (NAFLD) and significant fibrosis (fibrosis stage ≥2) are candidates for pharmacological trials. The aim of this study was to perform a head-to-head comparison of the diagnostic test characteristics of three non-invasive stiffness-based models including MEFIB (magnetic resonance elastography [MRE] plus FIB-4), MAST (magnetic resonance imaging [MRI]-aspartate aminotransferase [AST]), and FAST (FibroScan-AST) for detecting significant fibrosis. METHODS: This prospective study included 563 patients with biopsy-proven NAFLD undergoing contemporaneous MRE, MRI proton density fat fraction (MRI-PDFF) and FibroScan from two prospective cohorts derived from Southern California and Japan. Diagnostic performances of models were evaluated by area under the receiver-operating characteristic curve (AUC). RESULTS: The mean age of the cohort was 56.5 years (51% were women). Significant fibrosis was observed in 51.2%. To detect significant fibrosis, MEFIB outperformed both MAST and FAST (both p <0.001); AUCs for MEFIB, MAST, and FAST were 0.901 (95% CI 0.875-0.928), 0.770 (95% CI 0.730-0.810), and 0.725 (95% CI 0.683-0.767), respectively. Using rule-in criteria, the positive predictive value of MEFIB (95.3%) was significantly higher than that of FAST (83.5%, p = 0.001) and numerically but not statistically greater than that of MAST (90.0%, p = 0.056). Notably, MEFIB's rule-in criteria covered more of the study population than MAST (34.1% vs. 26.6%; p = 0.006). Using rule-out criteria, the negative predictive value of MEFIB (90.1%) was significantly higher than that of either MAST (69.6%) or FAST (71.8%) (both p <0.001). Furthermore, to diagnose "at risk" non-alcoholic steatohepatitis defined as NAFLD activity score ≥4 and fibrosis stage ≥2, MEFIB outperformed both MAST and FAST (both p <0.05); AUCs for MEFIB, MAST, and FAST were 0.768 (95% CI 0.728-0.808), 0.719 (95% CI 0.671-0.766), and 0.687 (95% CI 0.640-0.733), respectively. CONCLUSIONS: MEFIB was better than MAST and FAST for detection of significant fibrosis as well as "at risk" NASH. All three models provide utility for the risk stratification of NAFLD. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) affects over 25% of the general population worldwide and is one of the main causes of chronic liver disease. Because so many individuals have NAFLD, it is not practical to perform liver biopsies to identify those with more severe disease who may require pharmacological interventions. Therefore, accurate non-invasive tests are crucial. Herein, we compared three such tests and found that a test called MEFIB was the best at detecting patients who might require treatment.

Molecular diversity of Scutellonema bradys populations from Benin, based on ITS1 rDNA and COI mtDNA.

In Benin, yam production continues to face numerous production constraints, including yield and quality reduction by Scutellonema bradys. Implementation of efficient management techniques against this pest requires an improved understanding, including at the molecular level, of the pest. The current study aimed at identifying the Scutellonema spp. associated with yam in Benin and investigating the phylogenetic relationships between populations. Nematodes of the genus Scutellonema were obtained from tubers exhibiting external dry rot symptoms. DNA was extracted from nematodes belonging to 138 populations collected from 49 fields from 29 villages. For 51 of these populations, both the ITS1 and COI regions could be amplified via PCR, sequenced, compared with available sequences in the NCBI database and were identified as S. bradys. Maximum likelihood was used to construct 60% consensus phylogenetic trees based on 51 sequences. This phylogenetic analysis did not reveal any genetic separation between populations by cultivar, village, cropping system nor by agroecological zone. Neither could any subgroups within S. bradys be separated, indicating that no subspecies were present. An earlier published species-specific primer set was verified with the DNA of the 51 sequences and was considered a reliable and rapid method for S. bradys identification.

Diversity of Root-knot Nematodes Associated with Tubers of Yam (Dioscorea spp.) Established Using Isozyme Analysis and Mitochondrial DNA-based Identification.

The root-knot nematodes (RKN), Meloidogyne spp., represent an important threat to yam (Dioscorea spp.) production in West Africa. With the aim to establish the diversity of RKN species affecting yam tubers, for control and resistance screening purposes, surveys were conducted in the main yam producing areas of Nigeria. Galled tubers (N = 48) were collected from farmers' stores and markets in nine states in Nigeria and in one district in Ghana. RKN isolated from yam tubers were identified using enzyme phenotyping (esterase and malate dehydrogenase) and mitochondrial DNA (mtDNA) NADH dehydrogenase subunit 5 (Nad5) barcoding. Examination of 48 populations revealed that yam tubers were infested by Meloidogyne incognita (69%), followed by M. javanica (13%), M. enterolobii (2%), and M. arenaria (2%). Most of the tubers sampled (86%) were infected by a single species, and multiple species of RKN were detected in 14% of the samples. Results of both identification methods revealed the same species, confirming their accuracy for the identification of these tropical RKN species. In addition to M. incognita, M. javanica, and M. enterolobii, we report for the first time M. arenaria infecting yam tubers in Nigeria. This finding extends the list of yam pests and calls for caution when developing practices for yam pest management.

Species of Heterodera cysts in cereal fields in Flanders.

Heterodera is a genus of cyst-forming nematodes, including the cereal cysts which can provoke yield reductions in grain crops. As little is known about the occurrence of these cysts in Belgian grain fields, a survey was organized, starting in Flanders. Soil samples were taken from 50 fields where cereals are grown in rotation with mainly beet, potato and vegetables. Cysts were extracted from the 112 samples and 10 individuals per sample were identified up to species level by morphometrical and morphological observations. The beet cyst nematode, Heterodera schachtii, was found in 34 fields (56%) at infestation levels varying from 0.6 to 1322 cysts/kg soil. Other Heterodera species (e.g. H. trifolii, H. mani) were found in low numbers and sometimes in mixtures with H. schachtii, but no cereal cysts were detected. This survey confirms that beet cyst nematodes are a problem in Flanders. The few cereal cysts that might be present were perhaps not detected due to the few individuals that were identified. For this reason, molecular identification tools which allow fast and accurate identification of Heterodera species would be very useful. It could be interesting to find out why cereal cysts are suppressed in our regions and to expand the survey to the Walloon region where more cereals are grown.

Effect of several centrifugal pump passages on the viability and activity of Steinernema carpocapsae, a biopesticide.

The effect of several passages through a centrifugal pump on the viability and activity of Steinernema corpocapsoe was investigated. A tendency of reduced viability was detected after 10 passages through the centrifugal pump, but the difference was not statistically significant. Activity decreased significantly from 91.9% to 83.6%. The experimental set-up was chosen to eliminate temperature increase. Therefore, the results prove that mechanical pump damage cannot be excluded as the cause of EPN damage during spray application.