The prediction of microvascular invasion of hepatocellular carcinoma using multiple imaging modalities

To implement an adequate treatment strategy for solitary hepatocellular carcinoma (HCC), the prediction of microvascular invasion (MVI) is crucial. Metastatic recurrences after curative treatments can result from occult metastasis derived from invisible MVI. For predicting MVI, poorly differentiated or non-singular nodular HCC with a high risk of MVI should be evaluated by common imaging modalities such as ultrasound, contrast enhanced computed tomography (CECT), or magnetic resonance imaging (MRI). Summarizing these predictabilities in previous reports, the accuracies for predicting MVI were 78% in contrast enhanced ultrasonography (CEUS), 76%-89% in CECT, and 62%-77% in MRI. Those for predicting poor differentiation were 69%-92% in CEUS, 52%-90% in CECT, and 71%-75% in MRI. Those for predicting non-singular nodular type were 92%-95% in CEUS, 81%-89% in MRI, and 91%-93% in the combination of MRI and CECT. Among common imaging modalities, MRI can provide tissue characterization of the HCC using signal intensity. Gadolinium-ethoxybenzyl diethylenetriamine penta-acetic acid-enhanced MRI including diffusion imaging is the most informative imaging modality to predict MVI. Combination of MRI with other imaging modalities or tumor markers may provide a more accurate predicting for MVI. HCC with a high risk of MVI should be treated as advanced HCC even after curative treatment

Measurements of Serum Mac-2-Binding Protein Glycosylation Isomer and Shear Wave Velocity in Health Checkups Are Useful in Screening for Non-Alcoholic Steatohepatitis

Liver-related mortality rates in patients with non-alcoholic steatohepatitis (NASH) increase with advancing liver fibrosis stage. The present study aimed to elucidate whether adding non-invasive liver fibrosis tests to a comprehensive health checkup system is useful for NASH screening. Both serum Mac-2-binding protein glycosylation isomer (M2BPGi) and point shear wave elastography (pSWE) using ultrasonography were performed for 483 health checkup subjects who consented to participate in this prospective study. Outcomes in positive subjects were surveyed 1 year later. Eighty-eight subjects (18%) showed positive results for at least one liver fibrosis test, with 63 subjects positive for pSWE, 33 subjects positive for M2BPGi, and 72 subjects showing no significant elevation of liver enzymes. The secondary consultation rate for positive subjects was 52% (46/88). However, as 15 of those 46 subjects visited a non-liver-specialist and could not undergo detailed examination, the secondary examination rate was only 35% (31/88). For the 31 subjects who received secondary examination, NASH was diagnosed in 14 subjects, other chronic liver disease (CLD) in 6 subjects, and no CLD in 11 subjects. Additional liver fibrosis tests using M2BPGi and pSWE appear useful in health checkups when screening for CLD, especially for NASH

Risk Factors of Glecaprevir/Pibrentasvir-Induced Liver Injury and Efficacy of Ursodeoxycholic Acid

Although glecaprevir/pibrentasvir (GP) therapy is recommended as a first-line treatment for hepatitis C virus (HCV) infection, serious drug-induced liver injury occasionally develops. The present study aimed to elucidate real-world risk factors for GP-induced liver injury and to evaluate the efficacy of add-on ursodeoxycholic acid (UDCA) for liver injury. We analyzed 236 HCV patients who received GP therapy. GP-induced liver injury was defined as any elevation to grade ≥ 1 in total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), or γ-glutamyl transferase (γ-GT) during treatment without other cause. The frequency of GP-induced liver injury was 61.9% (146/236). Serious elevation to grade ≥ 3 in TB, AST, ALT, ALP, and γ-GT was identified in 3.8% (9/236), 0%, 0%, 0%, and 0.4% (1/209), respectively. Therapy discontinuation and dose reduction were seen in one patient each. Multivariate analysis revealed age and TB as independent risk factors for GP-induced liver injury. In patients with grade ≥ 2 hyperbilirubinemia, TB after onset significantly decreased in the add-on UDCA group but not in the no UDCA group. Careful attention to GP-induced liver injury is warranted for elderly patients with cirrhosis. Add-on UDCA could suppress the aggravation of GP-induced liver injury

Proteomic analysis in usual and nonspecific interstitial pneumonia

Differentiating nonspecific interstitial pneumonia (NSIP) from usual interstitial pneumonia (UIP) is important for the determination of both treatment and prognosis. Using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), we examined 8 UIPs, 8 NSIPs, and 30 normal lung tissues. Comparisons with control in 2D-DIGE showed that (a) in UIP, nine protein spots were significantly upregulated and seven were significantly downregulated, (b) in NSIP, four protein spots were significantly upregulated and nine were significantly downregulated. The detected proteins were analyzed by MALDI-TOF mass spectrometry, allowing qualitative differences in vimentin subtypes to be characterized. One vimentin subtype was upregulated in UIP, while another one was downregulated in NSIP (vs. control). These different characteristics were partially supported by the results of Western blot analysis. Our immunohistochemistry revealed vimentin expression within fibroblasts (a) in fibroblastic foci in UIP and (b) in fibrotic alveolar walls in NSIP. Differences in vimentin subtypes may provide useful biomarkers for separating NSIP from UIP, alongside differences in histological characteristics

Effects of soil nutrient availability and ozone on container-grown Japanese larch seedlings and role of soil microbes

The interactive effects of ozone, soil nutrient availability and root microorganisms on physiological, growth, and productivity traits were studied for the first time for Japanese larch (Larix kaempferi) seedlings grown in containers over a growing season, using a free air ozone-concentration enrichment exposure system. High nutrient availability altered leaf and root nutrient dynamics and enhanced plant growth; however, it also enhanced seedling susceptibility to damping-off disease compared to low nutrient availability. Negative effects of elevated ozone, as compared with ambient ozone, on leaf gas exchange and plant stem form were neither offset nor exacerbated by soil nutrient availability and root colonizers. Such negative effects suggest that elevated ozone may have implications for ecological health even when plant vigor is limited by factors other than ozone. Inoculation of roots with ectomycorrhizae had negligible influence on the effects of either soil nutrient availability or ozone. However, this lack of effect may be upon impeded formation of complete mycorrhizal root tips due to factors other than the manipulated variables. B and Na appeared to have an important role in stress responses, so further studies to examine their link with physiological mechanisms as a function of time. This study provides an important perspective for designing forestry practices to enhance seedling health