Clinical Features of Hepatitis C Virus Carriers With Persistently Normal Alanine Aminotransferase Levels

Hepatitis C virus (HCV) infection causes chronic hepatitis, which frequently leads to hepatic fibrosis and hepatocellular carcinoma (HCC). Alanine aminotransferase (ALT) is a biomarker of hepatocyte injury and is associated with the progression of hepatic fibrosis. Advanced hepatic fibrosis also predisposes HCV carriers to a risk of HCC. In contrast, some cases with persistent HCV infection have normal ALT levels that persist for a long time, and these HCV carriers have no or mild hepatitis and hepatic fibrosis. These HCV carriers are defined as persistent normal ALT (PNALT) cases and their risk of HCC is low compared to HCV carriers with abnormal ALT. However, there are various definitions of normal ALT and PNALT, and advanced hepatic fibrosis may be missed without a liver biopsy. In addition, there is also a risk of ALT elevation in HCV carriers with PNALT, which increases the risk of progression to hepatic fibrosis and HCC. Most HCV carriers with PNALT have asymptomatic or nonspecific symptoms. HCV carriers with PNALT are also considered to be responsive to interferon-based treatment. Thus, assessment of hepatic fibrosis is important in HCV carriers, and the eradication of HCV infection is more likely in HCV carriers with evidence of hepatic fibrosis, regardless of their ALT levels

Resection of positive tissue on methionine‐PET is associated with improved survival in glioblastomas

Abstract Background and purpose The volume of excised tumor in contrast‐enhanced areas evaluated via magnetic resonance imaging is known to have a strong influence on the survival of patients with glioblastoma (GBM). In this study, we investigated the effect of tumor resection on the survival of patients with GBM in the 11C‐methionine (MET) accumulation area using MET‐positron emission tomography (MET‐PET). Methods A total of 26 patients (median age, 69 years; 15 males) who had undergone tumor resection and MET‐PET before and after surgery, after being newly diagnosed with GBM, were included in the study. MET‐PET before and after tumor resection were compared. The association between the decrease in the maximum standardized uptake value (SUV) of the tumor divided by the normal cortical mean SUV (%; ΔT/N), the MET extent of resection (MET‐EOR) from the % reduction in the MET accumulation area (%), and residual MET accumulation area (in cm3; MET‐residual tumor volume [RTV]), as well as the survival time of patients with GBM, were evaluated via univariate analysis. Results ΔT/N were positively associated with survival (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.97–0.99], p = .02). MET‐RTV revealed a negative association with survival (HR, 1.02 [95% CI, 1.01–1.04], p = .04). Additionally, MET‐EOR showed a strong trend with survival (HR, 0.99 [95% CI, 0.97–1.01], p = .06). Conclusions Surgical resection of MET‐accumulated areas in GBM significantly prolongs the survival of patients with GBM. However, a prospective large‐scale multicenter study is needed to confirm our findings

Enterohepatic Transcription Factor CREB3L3 Protects Atherosclerosis via SREBP Competitive Inhibition

動脈硬化発症を制御する転写因子の相互作用を発見. 京都大学プレスリリース. 2020-12-09.Background and Aims: cAMP responsive element-binding protein 3 like 3 (CREB3L3) is a membrane-bound transcription factor involved in the maintenance of lipid metabolism in the liver and small intestine. CREB3L3 controls hepatic triglyceride and glucose metabolism by activating plasma fibroblast growth factor 21 (FGF21) and lipoprotein lipase. In this study, we intended to clarify its effect on atherosclerosis. Methods: CREB3L3-deficifient, liver-specific CREB3L3 knockout, intestine-specific CREB3L3 knockout, both liver- and intestine-specific CREB3L3 knockout, and liver CREB3L3 transgenic mice were crossed with LDLR−/− mice. These mice were fed with a Western diet to develop atherosclerosis. Results: CREB3L3 ablation in LDLR−/− mice exacerbated hyperlipidemia with accumulation of remnant APOB-containing lipoprotein. This led to the development of enhanced aortic atheroma formation, the extent of which was additive between liver- and intestine-specific deletion. Conversely, hepatic nuclear CREB3L3 overexpression markedly suppressed atherosclerosis with amelioration of hyperlipidemia. CREB3L3 directly upregulates anti-atherogenic FGF21 and APOA4. In contrast, it antagonizes hepatic sterol regulatory element-binding protein (SREBP)-mediated lipogenic and cholesterogenic genes, and regulates intestinal liver X receptor-regulated genes involved in the transport of cholesterol. CREB3L3 deficiency results in the accumulation of nuclear SREBP proteins. Because both transcriptional factors share the cleavage system for nuclear transactivation, full-length CREB3L3 and SREBPs in the endoplasmic reticulum (ER) functionally inhibit each other. CREB3L3 promotes the formation of the SREBP-insulin induced gene 1 (SREBP-INSIG1) complex to suppress SREBPs for ER-Golgi transport, resulting in ER retention and inhibition of proteolytic activation at the Golgi, and vice versa. Conclusions: CREB3L3 has multi-potent protective effects against atherosclerosis owing to new mechanistic interaction between CREB3L3 and SREBPs under atherogenic conditions

Serum manganese superoxide dismutase and thioredoxin are potential prognostic markers for hepatitis C virus-related hepatocellular carcinoma

AIM: To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)

Association of parity with the prevalence of hypertension in Japan: The Tohoku Medical Megabank Community‐based cohort study

Abstract This study investigated the association of parity with hypertension prevalence in Japanese women while considering a clinical history of hypertensive disorders of pregnancy (HDP) and menopausal status. This cross‐sectional study included 30,530 Japanese women (6700 premenopausal; 23 830 postmenopausal). The association between parity and the prevalence of hypertension was evaluated using a multiple logistic regression model with possible confounders. In premenopausal women, no statistically significant association between parity and hypertension prevalence was found. When not adjusted for current body mass index (BMI), a linear graded association was observed between parity and the prevalence of hypertension in postmenopausal women. However, the association between parity and hypertension prevalence in postmenopausal women was attenuated after adjustment for current BMI. Both current BMI and a clinical history of HDP were significantly associated with a high risk of hypertension in both premenopausal and postmenopausal women. Our results also suggest that continuous surveillance and preventive measures for hypertension should be provided for women with HDP and high parity