AimWe comprehensively analyzed how hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting-antiviral-agents (DAAs) affects liver steatosis and atherogenic risk.MethodsPatients treated with IFN-free-DAAs who underwent transient elastography before and at 24-weeks post-treatment, including controlled attenuation parameter (CAP), and achieved sustained viral response (SVR) were enrolled. The association between changes in liver steatosis, lipid-metabolism, and genetic and clinical factors was analyzed.ResultsA total of 117 patients were included. The mean CAP and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated at SVR24. However, baseline LDL-C and CAP values were significantly negatively correlated with changes in these values after HCV eradication, indicating that in patients with high baseline values, the values generally decreased after HCV eradication. Mean small-dense LDL-C (sdLDL-C), which has greater atherogenic potential, was significantly elevated only in patients with both dyslipidemia (LDL-C >140 mg/dL) and liver steatosis (CAP >248 dB/m) at SVR24. Those patients had significant higher baseline BMI, LDL-C, and total-cholesterol levels.ConclusionsGenerally, successful HCV eradication by IFN-free-DAAs decreases CAP and LDL-C in patients with high baseline values. However, elevated LDL-C was accompanied with elevated sdLDL-C only in patients with liver steatosis and dyslipidemia at SVR24; therefore, those patients may require closer monitoring.

Aim Factors associated with improvement of liver fibrosis after successful hepatitis C virus (HCV) eradication by interferon (IFN)‐free direct‐acting antiviral agents (DAAs) have been not clarified well. Angiopoietin‐2 (Ang2) is reported to be associated with vascular leak and inflammation observed in patients with advanced liver fibrosis. Methods In this retrospective study, patients treated with IFN‐free DAAs who underwent transient elastography before and at 24‐weeks post‐treatment and achieved sustained viral response were enrolled. Baseline serum Ang2 was measured, and its relationship with other clinical factors was analyzed. Liver fibrosis stage was defined based on liver stiffness according to a previous report. Predictive factors for regression of liver fibrosis stage after DAA therapy were evaluated. Results Overall, 116 patients were analyzed. Baseline serum Ang2 levels were significantly associated with liver stiffness, spleen index, and liver stiffness‐based liver fibrosis stage. Moreover, 75% of patients experienced regression of liver fibrosis stage after DAA therapy. Multivariate analysis revealed that advanced liver fibrosis stage and Ang2 levels were significantly associated with regression of liver fibrosis stage after DAA therapy. In patients with advanced liver fibrosis (F3/4), baseline Ang2 level alone could predict regression of liver fibrosis stage. A baseline Ang2 cut‐off value (354 pg/ML) could predict regression of liver fibrosis stage after DAA therapy with high accuracy (sensitivity 0.882, specificity 0.733). Conclusions Evaluation of serum Ang2 levels before DAA therapy is important. Our results provide a novel mechanistic insight into non‐regression of liver stiffness after DAA therapy. Long‐term and larger studies are required.

Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a well-documented complication after hematopoietic stem cell transplantation (HSCT). Transabdominal ultrasonography (US) enables the visualization of blood flow abnormalities and is therefore useful for the diagnosis of SOS/VOD. We herein prospectively evaluated accuracy of a novel US diagnostic scoring system of SOS/VOD based on US findings. We carried out US in 106 patients on day 14 and when SOS/VOD was suspected after allogeneic HSCT. Among 106 patients, 10 patients (9.4%) were diagnosed as SOS/VOD by Baltimore or Seattle criteria. According to univariate analysis of 17 US findings (US-17 screening), we established a novel scoring system (HokUS-10) consisting of 10 parameters, such as gallbladder wall thickening, ascites, and blood flow signal in the paraumbilical vein. The sensitivity and specificity were 100% and 95.8%, respectively. Diagnostic performance of the HokUS-10 was significantly better than US-17 screening. In 4 of 10 patients US detection of SOS/VOD preceded to clinical diagnosis. The HokUS-10 scoring system is useful in the diagnosis of SOS/VOD; however, our results should be validated in other cohorts.

This paper proposes an automatic classification method based on machine learning in contrast-enhanced ultrasonography (CEUS) of focal liver lesions using the contrast agent Sonazoid. This method yields spatial and temporal features in the arterial phase, portal phase, and post-vascular phase, as well as max-hold images. The lesions are classified as benign or malignant and again as benign, hepatocellular carcinoma (HCC), or metastatic liver tumor using support vector machines (SVM) with a combination of selected optimal features. Experimental results using 98 subjects indicated that the benign and malignant classification has 94.0% sensitivity, 87.1% specificity, and 91.8% accuracy, and the accuracy of the benign, HCC, and metastatic liver tumor classifications are 84.4%, 87.7%, and 85.7%, respectively. The selected features in the SVM indicate that combining features from the three phases are important for classifying FLLs, especially, for the benign and malignant classifications. The experimental results are consistent with CEUS guidelines for diagnosing FLLs. This research can be considered to be a validation study, that confirms the importance of using features from these phases of the examination in a quantitative manner. In addition, the experimental results indicate that for the benign and malignant classifications, the specificity without the post-vascular phase features is significantly lower than the specificity with the post-vascular phase features. We also conducted an experiment on the operator dependency of setting regions of interest and observed that the intra-operator and inter-operator kappa coefficients were 0.45 and 0.77, respectively.

Summary:Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen. Bone Marrow Transplantation (2001) 27, 1315-1317. Keywords: hemorrhagic cystitis; hyperbaric oxygen; allogeneic bone marrow transplantation; children Hemorrhagic cystitis (HC) is a major complication following hematopoietic stem cell transplantation. Severe cystitis has been reported to occur in about 5% of bone marrow transplant (BMT) patients. Allogeneic BMT, grade II-IV graft-versus-host disease (GVHD), use of busulfan (Bu), age at transplantation and adenovirus infection increase the risk of severe HC. 1 Many therapeutic approaches have been tried to control pain and bleeding due to HC; despite this, HC can lead to bladder tamponade requiring surgical intervention, and can contribute to death. Hyperbaric oxygen (HBO) therapy has been used extensively in hypoxic tissue in an attempt to stimulate angiogenesis and prompt healing. HBO has been used successfully in the treatment of radiation or cyclophosphamide (CY)-induced HC. 2,3 This is the first report in patients with intractable HC after allogeneic BMT who were controlled by HBO. Case histories Case 1An eight-year-old boy with acute lymphocytic leukemia in third remission underwent BMT from an HLA-matched unrelated donor in June 1998. He received a conditioning regimen of Bu 4 mg/kg/day for 4 days, CY 60 mg/kg/day for 2 days, and etoposide 60 mg/kg/day for 1 day. Cyclosporine A (CsA) and prednisolone were administered for GVHD prophylaxis. The clinical course after BMT is shown in Figure 1. By the fifth week after BMT, trilineage engraftment was confirmed. The patient did not develop acute GVHD. At day +4 he had developed dysuria, suprapubic pain and macrohematuria. On day +70 he developed gross hematuria with clots and an abundant residue of bladder mucus. Adenovirus was not cultured from the urine, and HC was not attributed to polyomavirus infection because characteristic morphologic changes in the urinary sediment were not seen in conjunction with the urine culture being negative for other pathogens. During the next 9 weeks, gross hematuria continued, and the patient required seven transfusions of packed red blood cells and 33 transfusion of platelets. Despite conservative treatment with continuous bladder irrigation and intravesicular maalox and prostaglandin E1 (PGE1), he developed bladder tamponade on days +78 and +118 after BMT requiring emergency cystostomy and evacuation of hematomas. Post-renal failure developed, and he was referred for HBO therapy after bilateral tympanostomies. The patient was ...