Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication

AIM To clarify the association between aldo-keto reductase family 1 member B10(AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication.METHODS In this study,we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response(SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios(HRs) of AKR1B10 expression for hepatocellular carcinoma(HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test.RESULTS Of the 303 chronic hepatitis C patients,153(50.5%) showed scarce hepatic AKR1B10 expression,quantified as 0%,which was similar to the expression in control normal liver tissues. However,the remaining 150 patients(49.5%) exhibited various degrees of AKR1B10 expression in the liver,with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years(range 1.0-10.0 years),8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression(≥ 8%) was an independent risk factor for HCC development(HR = 15.4,95%CI: 1. 8- 1 3 2. 5,P = 0. 0 1 2). T h e 5- y e a r c u m u l a t i v e incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression,respectively(P 0.001). During the follow-up period after viral eradication,patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression.CONCLUSION Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.     

Effect of Low‐Density Lipoprotein Apheresis for Nephrotic Idiopathic Membranous Nephropathy as Initial Induction Therapy

Low‐density lipoprotein apheresis (LDL‐A) has been used for nephrotic syndrome (NS) caused by focal segmental glomerulosclerosis in Japan. Idiopathic membranous nephropathy (iMN) can also cause treatment‐resistant NS. Therefore, we investigated the effect of LDL‐A during initial induction for it. This retrospective, observational, and single‐center study enrolled consecutive iMN patients who received steroids from March 2000 to May 2015. We compared data between 11 patients treated with LDL‐A (LDL‐A group) and 27 patients without (non‐LDL‐A group) at baseline and 4 and 8 weeks later. Reduction rate of proteinuria and increase rate of serum albumin in LDL‐A group were significantly higher than the other after 4 weeks (P = 0.036 and 0.030) and 8 weeks (P = 0.030 and <0.001), respectively. There was no adverse event caused by LDL‐A and immunosuppressant dose was not significantly different. In conclusion, LDL‐A may be an effective choice for initial induction of nephrotic iMN.     

DHMEQ, a novel nuclear factor-kappaB inhibitor, induces selective depletion of alloreactive or phytohaemagglutinin-stimulated peripheral blood mononuclear cells, decreases production of T helper type 1 cytokines, and blocks maturation of dendritic cells

Dehydroxymethylepoxyquinomicin (DHMEQ), a novel nuclear factor κB (NF-κB) inhibitor, has been shown to be active against variety types of solid tumours as well as haematological malignant cells. This study explored the anti-inflammatory effects of DHMEQ in vitro. DHMEQ inhibited the proliferation of phytohaemagglutinin (PHA)-stimulated or alloreactive peripheral blood mononuclear cells (PBMC) in mixed lymphocyte cultures as measured using a 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. In contrast, DHMEQ did not affect the viability of resting PBMC. In addition, real-time polymerase chain reaction showed that DHMEQ decreased PHA-stimulated expression of T helper type 1 (Th1) cytokines, including interleukin-2, interferon-γ, and tumour necrosis factor α, in PBMC as well as Jurkat T-lymphoblastic leukaemia cells, and also decreased levels of p65 isoforms of NF-κB in the nucleus. Furthermore, we found that DHMEQ inhibited the endocytic capacity of dendritic cells (DCs) and down-regulated the expression of cell surface antigen CD40, suggesting that DHMEQ blocked the maturation as well as the function of DCs. Taken together, the results suggest that DHMEQ may be useful for treatment of inflammatory diseases, including graft-versus-host disease after allogenic haematopoietic stem cell transplantation.     

Tuberculous pleuroperitonitis

An 83‐year‐old man was diagnosed with tuberculous pleuroperitonitis on a thoracoscopic pleural biopsy. It may be due to endogenous reactivation of the foci in the pleura and peritoneum. Thoracoscopy, which can be performed under local anesthesia, should be considered when both pleural effusion and ascites are present.     

Risk factors and prediction of bleeding after gastric endoscopic submucosal dissection in patients on antithrombotic therapy: newly developed bleeding prediction application software,SAMURAI model

Bleeding after gastric endoscopic submucosal dissection (ESD) remains problematic, especially in patients receiving antithrombotic therapy. Therefore, this study aimed to identify the risk factors. In this retrospective study, patients (n = 1,207) who underwent gastric ESD while receiving antithrombotic therapy were enrolled at Osaka Medical and Pharmaceutical University Hospital and 18 other referral hospitals in Japan. Risks of post-ESD bleeding were calculated using multivariable logistic regression. The dataset was divided into a derivation cohort and a validation cohort. We created a prediction model using the derivation cohort. The accuracy of the model was evaluated using the validation cohort. Post-ESD bleeding occurred in 142 (11.8%) participants. Multivariable analysis yielded an odds ratio of 2.33 for aspirin, 4.90 for P2Y12 receptor antagonist, 1.79 for cilostazol, 0.95 for other antithrombotic agents, 6.53 for warfarin, 5.65 for dabigatran, 7.84 for apixaban, 10.45 for edoxaban, 6.02 for rivaroxaban, and 1.46 for heparin bridging. The created prediction model was called safe ESD management using the risk analysis of post-bleeding in patients with antithrombotic therapy (SAMURAI). This model had good predictability, with a C-statistic of 0.77. In conclusion, use of the SAMURAI model will allow proactive management of post-ESD bleeding risk in patients receiving antithrombotic therapy.