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Introduction: Atezolizumab and bevacizumab (AB) therapy was the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). However, the predictive marker of therapeutic response that can be easily used in clinical practice is still unknown. We prospectively investigated the utility of time-intensity curve (TIC) analysis using contrast-enhanced ultrasound (CEUS) as a predictive indicator of therapeutic response after the start of AB therapy. Methods: Thirty-five patients who received AB therapy for u-HCC were included in this study. TIC analysis was performed in 28 patients who were able to undergo CEUS before and 3–7 days after administration. We analyzed prognostic factors related to the initial therapeutic response and long progression-free survival (PFS). Results: The initial therapeutic response using dynamic computed tomography or Gd-EOB magnetic resonance imaging at 8–12 weeks after administration was partial response/stable disease/progressive disease (PD) in 14/12/9 cases (40/34/26%). Cases with PD (n = 9) had more cases without decreased blood flow in TIC analysis compared with cases with non-PD (100 vs. 18%, p = 0.001). Cases without decreased blood flow in TIC analysis (n = 10) had more cases with PD compared with cases with decreased blood flow (60 vs. 0%, p = 0.001). PFS in patients without decreased blood flow early after the administration was shorter than that in those with decreased blood flow (9.1 vs. 28 weeks, p = 0.0051). Conclusion: Early evaluation by TIC analysis using CEUS may be useful in predicting the therapeutic response in patients treated with AB therapy for u-HCC.

Recently, with the advent of sofosbuvir/velpatasvir therapy, sustained virological response (SVR) can now be achieved even in patients with decompensated cirrhosis (dLC). However, the prognosis after SVR does not always improve in dLC, and appropriate indicators enabling prediction of prognosis is desired.Serum IP-10/CXCL10 levels were measured in 47 patients (15 chronic hepatitis [CH], 17 compensated cirrhosis [cLC], and 15 dLC) receiving direct acting antiviral (DAA) therapy, and their changes during the therapy were examined.All the patients achieved SVR. In patients with CH, the average IP-10 level was 367, 102, and 68 pg/ml respectively at baseline, at the end of therapy and at 12 weeks after SVR (SVR12), and was decreased upon DAA therapy (P 0.001). In patients with cLC, IP-10 was respectively 215, 91, and 77 pg/ml, and was decreased upon DAA therapy (P 0.001) while it was 283, 131, and 182 pg/ml in patients with dLC and there was no evident decrease (P = 0.55). When patients with dLC were further classified depending on the difference in Child-Pugh (CP) score improvement at SVR12, a significant decrease in IP-10 was observed after treatment in those with improvement (P = 0.023) while a significant increase was observed in those without improvement (P = 0.016).While serum IP-10 level was decreased in patients with CH/cLC and dLC with post-SVR-CP improvement following SVR, it was increased in patients with dLC without post-SVR CP improvement. The result indicates that IP-10 dynamics may be useful for predicting liver function after DAA therapy.

The damping ratio (DR) and the loss modulus (G″) obtained by 3D MR elastography complex modulus analysis has been reported recently to reflect early intrahepatic inflammation, and is expected to be a noninvasive biomarker of inflammation in nonalcoholic fatty liver disease (NAFLD). However, the role of the DR and the G″ in Japanese NAFLD patients remains unclear.We enrolled 39 Japanese patients with NAFLD who underwent liver biopsy and 3D MR elastography within 1 month and analyzed the association between DR, G″, and histological activity.Regarding DR, no evident correlation was observed between the DR and histological activity (p = 0.14) when patients with all fibrosis stages were included. However, when patients were restricted up to stage F2 fibrosis, the association of the DR and inflammation became significant, the DR increasing with the degree of activity (p = 0.02). Among the constituents of fibrosis activity, ballooning correlated with the DR (p 0.01) while lobular inflammation did not. Regarding G″, it was correlated with histological activity (p 0.01), ballooning (p 0.01), and lobular inflammation (p 0.01) in patients with all fibrosis stages and in patients up to F2 fibrosis (p = 0.03 for activity and p = 0.04 for ballooning). The best cutoff value of DR for hepatitis activity in patients within the F2 stage was 0.094 (area under the receiver operating characteristic curve 0.775, 95% CI: 0.529-1.000) and G″ was 0.402 (area under the receiver operating characteristic curve 0.825, 95% CI: 0.628-1.000).The DR and G″ reflected the histological activity in Japanese patients with NAFLD during the early stage, indicating these values for noninvasive diagnosis of inflammation in Japanese patients with NAFLD.

Background and Aims: A retrospective study was to analyze the association of plasma renin activity (PRA) with overall survival and liver disease-related events in decompensated liver cirrhosis with ascites treated by tolvaptan. Methods: We included 196 patients with decompensated cirrhosis treated with tolvaptan and for whom hepatic ascites had remained uncontrolled by conventional diuretics. Factors associated with prognosis and appearance of liver disease-related events were investigated, including vasopressin, sympathetic nervous system hormones (adrenaline, noradrenaline, and dopamine), and the renin-angiotensin system (PRA and aldosterone) at the beginning of tolvaptan treatment. Results: Age, history of hepatocellular carcinoma (HCC), and PRA were identified as independent factors for prognosis after tolvaptan treatment. The median survival time in patients with PRA ≥9.5 ng/mL/h at the beginning of tolvaptan treatment was significantly shorter than in patients with PRA p < 0.001). PRA and a history of HCC were independent factors for the occurrence of liver disease-related events. The median event-free period in patients with PRA ≥3.2 ng/mL/h was significantly shorter than that of patients with PRA p < 0.001). Conclusions: PRA is an independent predictor of prognosis and appearance of liver disease-related events in patients with decompensated cirrhosis who have started tolvaptan treatment.

Presarcopenia is a prognostic factor in patients with hepatocellular carcinoma (HCC). The Japan integrated staging (JIS) score is a prognostic method that combines the Child–Turcotte–Pugh classification and the tumor-node-metastasis (TNM) staging for HCC. We investigated the relationship between presarcopenia, the JIS score, and prognosis in patients with primary HCC. This retrospective study included 153 patients with primary HCC who were hospitalized from October 2011 to March 2018 at Municipal Hospital of Kofu. The skeletal muscle mass was measured using simplified psoas muscle mass index (PMI) based on CT imaging, and PMI using the volume analyzer SYNAPSE VINCENT ver3.0. We diagnosed presarcopenia based on the cut off value according to the assessment criteria for sarcopenia in liver disease defined by the Japan Society of Hepatology. Forty-three patients (28%) were diagnosed with presarcopenia. The median event-free survival was significantly worse in patients with presarcopenia than those without presarcopenia (P = 0.016). In multivariate analysis, presence of presarcopenia, JIS score ≥3, alpha-fetoprotein ≥200 ng/ml, and prothrombin induced by vitamin K absence-II ≥ 200 mAU/ml were significant prognostic factors. Among the patients with JIS scores ≥3, there was no difference in the event occurrence rate with presence of presarcopenia (P = 0.96). Among the patients with JIS scores ≤2, the median event-free-survival was significantly shorter in those with presarcopenia than those without presarcopenia (P = 0.045). Presarcopenia was an independent prognostic factor in patients with primary HCC. In patients with JIS scores ≤2, the median event-free survival was significantly shorter in those with presarcopenia compared to those without presarcopenia. In the patients with JIS scores ≥3, there was no difference in the event occurrence rates in those with and without presarcopenia.

Background: This study investigated the impact of serum cytokeratin 19 fragment (CYFRA21-1) level on the clinical outcomes of patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib (SOR) or lenvatinib (LEN). Methods: A total of 71 cases with unresectable HCC taking SOR or LEN were included. Univariate and multivariate analyses were performed to identify the prognostic factors in patients taking SOR or LEN. Results: Among the 71 patients taking SOR or LEN, the frequency of cases showing high CYFRA21-1 levels after administration increased compared to before the administration. There was no association between the CYFRA21-1 level and the result of treatment response using modified Response Evaluation Criteria in Solid Tumors (mRECIST) 12 weeks after the administration. Univariate analysis identified a maximum intrahepatic tumor diameter of 70 mm or more, extrahepatic metastasis, baseline alpha-fetoprotein (AFP) ≥ 2000 ng/mL, baseline AFP-L3 index ≥ 15%, baseline des-gamma-carboxy prothrombin (DCP) ≥ 1000 mAU/mL, baseline CYFRA21-1 &gt, 3.5 ng/mL, 12-week mRECIST progressive disease (PD), 12-week DCP ratio ≥ 4, 12-week CYFRA21-1 ratio ≥ 2, administration period less than 12 weeks, ALBI grade 3 at PD, and no additional treatment after discontinuation of SOR/LEN as prognostic factors. Multivariate analysis revealed that AFP-L3 index ≥ 15%, 12-week mRECIST PD, 12-week DCP ratio ≥ 4, 12-week CYFRA21-1 ratio ≥ 2, administration period less than 12 weeks, and no additional treatment after discontinuation of SOR/LEN were independent factors. Conclusions: Patients with a high CYFRA21-1 level at baseline tend to have poor prognosis, and patients with a high CYFRA21-1 ratio 12 weeks after administration have poor prognosis. Serum CYFRA21-1 measurement may have additional effects on prognostic prediction, and it may be necessary to pay close attention to the transition to the next HCC treatment in cases whose CYFRA21-1 level is high.

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.

Objective: Protein–energy malnutrition (PEM) is an important prognostic factor in patients with cirrhosis. Energy malnutrition (EM) is defined by the Japanese Society of Gastroenterology Guidelines for cirrhosis as a non-protein respiratory quotient 660 μEq/L. The parameters associated with EM are difficult to measure in all patients. In this study, we evaluated simple indicators of EM.Methods: This retrospective study included 295 patients with chronic liver diseases (CLDs) in whom serum FFA values or %AC were measured at the Department of Gastroenterology at the Municipal Hospital of Kofu. We examined the characteristics of the patients with EM. Results: EM was observed in 36% of patients with CLDs without a late-evening snack (LES). The frequency of EM was high in patients with Child–Pugh grade B or C, γ-GTP level ≥100 U/ml, AST level ≥27 IU/l, and ALT level ≥27 IU/l in males, and Child–Pugh grade B or C, γ-GTP ≥84 U/ml, AST ≥24 IU/l, and ALT ≥28IU/l in females. Among the three indicators of Child–Pugh grade B or C, increased γ-GTP levels, and increased transaminase values, EM was observed in 16%, 35%, 59%, and 57% of patients who were positive for 0, 1, 2, or 3 of the indicators. The frequency of EM in patients with Child-Pugh grade A was high for increased γ-GTP, AST, and ALT levels. Among the two indicators of increased γ-GTP, and transaminase levels, 16%, 32%, and 67% of patients were positive for 0, 1, or 2 of the indicators.Conclusion: Child-Pugh grade, transaminase values, and γ-GTP levels were useful indicators of EM in patients with CLDs. We should evaluate positively the presence of EM in cases with poor liver function, high transaminase concentrations, or high γ-GTP levels.

Identification of high-risk patients for hepatocellular carcinoma (HCC) after sustained virological responses (SVR) is necessary to define candidates for long-term surveillance. In this study, we examined whether serum markers after 1 year of SVR could predict subsequent HCC development. Total 734 chronic hepatitis C patients without a history of HCC who achieved SVR with direct-acting antivirals were included. The regular surveillance for HCC started from 24 weeks after the end of treatment (SVR24). Factors at SVR24 and 1 year after SVR24 were analyzed for predicting HCC development. During the mean observation period of 19.7 &plusmn, 10 months, 24 patients developed HCC. At SVR24, Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA&plusmn, M2BP) &ge, 1.85 and &alpha, fetoprotein (AFP) &ge, 6.0 ng/mL were independent factors of HCC development. However, at 1 year after SVR24, WFA&plusmn, M2BP &ge, 1.85 was associated with subsequent HCC development (hazard ratio: 23.5, 95% confidence interval: 2.68&ndash, 205) but not AFP. Among patients with WFA&plusmn, 1.85 at SVR24, 42% had WFA&plusmn, M2BP &lt, 1.85 at 1 year after SVR24 (WFA&plusmn, M2BP declined group). Subsequent HCC development was significantly lower in the declined group than in the non-declined group (1 year HCC rate: 0% vs. 9.4%, p = 0.04). In conclusion, WFA&plusmn, M2BP but not AFP could identify high and no-risk cases of HCC at 1 year after SVR. Therefore, it was useful as a real-time monitoring tool to identify the candidates for continuous surveillance for HCC.

Background: A test to narrow down patients who require esophagogastroduodenoscopy (EGD) with a high probability of having gastroesophageal varices (GEV) and a high-risk of liver-related events is an unmet need. Methods: The measurement of serum fibrosis markers and EGD was performed in 166 consecutive chronic hepatitis C patients. The correlation between the grades of GEV and fibrosis markers and the subsequent occurrence of liver-related and fibrosis markers were examined. Results: Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+&ndash, M2BP) levels increased according to the grade of GEV (3.4 (0.2&ndash, 18.6) for no GEV, 7.9 (1.8&ndash, 20.0) for small GEV, and 11.4 (4.0&ndash, 20.0) for large GEV, p &lt, 0.001). The diagnostic accuracy of the WFA+&ndash, M2BP was superior compared to other serum fibrosis markers, and WFA+&ndash, M2BP was an independent predictor of GEV in the multivariate analysis. Furthermore, the cumulative incidence of liver-related events at one year was 2.3% in patients with WFA+&ndash, M2BP levels &le, 7.0 and 37.5% in patients with WFA+&ndash, M2BP levels &gt, 7.0 (p &lt, 0.001). WFA+&ndash, M2BP &gt, 7.0 was a significant predictive factor for liver-related events (Hazard ratio 6.7, p = 0.004) independent of Child&ndash, Pughclass. Conclusions: WFA+&ndash, M2BP could be used to estimate the presence and grade of GEV and is linked to liver-related events in chronic hepatitis C patients.

Sarcopenia is an important prognostic factor in patients with gastrointestinal and chronic liver diseases. Computed tomography and bioelectrical impedance analysis are the gold standards for measuring skeletal muscle mass for the diagnosis of decreased muscle mass, but there are some institutions where BIA and CT cannot be carried out. We evaluated the utility of simplified methods for measuring muscle mass; the psoas muscle mass index (PMI) method, simple PMI method, and arm muscle area (AMA) method. This retrospective study included 331 patients with gastrointestinal diseases and 81 patients with chronic liver diseases who were admitted from June 2018 to December 2019 at Municipal Hospital of Kofu. The skeletal muscle mass was measured using the PMI via the volume analyzer SYNAPSE VINCENT ver3.0, simple PMI based on CT imaging, and AMA method. Positive correlations were found between muscle mass measured by PMI and simple PMI, PMI and AMA, and simple PMI and AMA in patients with gastrointestinal diseases (correlation coefficients = 0.76, 0.57, 0.47, respectively, p

Brown adipocyte activation or beige adipocyte emergence in white adipose tissue (WAT) increases energy expenditure, leading to a reduction in body fat mass and improved glucose metabolism. We found that activin E functions as a hepatokine that enhances thermogenesis in response to cold exposure through beige adipocyte emergence in inguinal WAT (ingWAT). Hepatic activin E overexpression activated thermogenesis through Ucp1 upregulation in ingWAT and other adipose tissues including interscapular brown adipose tissue and mesenteric WAT. Hepatic activin E-transgenic mice exhibited improved insulin sensitivity. Inhibin βE gene silencing inhibited cold-induced Ucp1 induction in ingWAT. Furthermore, in vitro experiments suggested that activin E directly stimulated expression of Ucp1 and Fgf21, which was mediated by transforming growth factor-β or activin type I receptors. We uncovered a function of activin E to stimulate energy expenditure through brown and beige adipocyte activation, suggesting a possible preventive or therapeutic target for obesity., アクチビンEが脂肪燃焼細胞の増加を促進することを解明 --肥満解消の新たなプレイヤーを発見--. 京都大学プレスリリース. 2018-11-02.

AIM The aim of this study is to clarify the value of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) for predicting hepatocellular carcinoma (HCC) in chronic hepatitis C patients who achieved sustained virologic response (SVR) by therapy with interferon-free, direct-acting antivirals (DAAs). METHODS This is a retrospective cohort study that included 567 patients who underwent antiviral therapy with an interferon-free DAA regimen and achieved SVR. Serum WFA+ -M2BP was measured after SVR. Factors predictive of HCC occurrence and recurrence were analyzed in the patients after stratification by previous treatment history of HCC. RESULTS Among 518 patients who had no history of HCC, 13 developed HCC. Post-SVR WFA+ -M2BP ≥1.75 cut-off index (C.O.I., P

Chronic changes following radiotherapy include alterations in tissue-resident stem cells and vasculatures, which can lead to impaired wound healing. In this study, novel recombinant human collagen peptide (rhCP) scaffolds were evaluated as a biomaterial carrier for cellular regenerative therapy. Human adipose-derived stem cells (hASCs) were successfully cultured on rhCP scaffolds. By hASC culture on rhCP, microarray assay indicated that expression of genes related to cell proliferation and extracellular matrix production was upregulated. Pathway analyses revealed that signaling pathways related to inflammatory suppression and cell growth promotion were activated as well as signaling pathways consistent with some growth factors including vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor beta, although gene expression of these growth factors was not upregulated. These findings suggest the rhCP scaffold showed similar biological actions to cytokines regulating cell growth and immunity. In subsequent impaired wound healing experiments using a locally irradiated (20 Gray) mouse, wound treatment with rhCP sponges combined with cultured hASCs and human umbilical vein endothelial cells accelerated wound closure compared with wounds treated with rhCP with hASCs alone, rhCP only, and control (dressing alone), with better healing observed according to this order. These results indicating the therapeutic value of rhCP scaffolds as a topical biomaterial dressing and a biocarrier of stem cells and vascular endothelial cells for regenerating therapies. The combination of rhCP and functional cells was suggested to be a potential tool for revitalizing stem cell-depleted conditions such as radiation tissue damage.

Aim Intermediate-stage hepatocellular carcinoma varies widely in tumor burden and liver function. This study aimed to clarify the importance of subclassification by the up-to-seven criteria in both clinical course and liver function deterioration in such patients. Methods We retrospectively analyzed 224 patients with Child-Pugh grade A who underwent initial transarterial chemoembolization (TACE) for hepatocellular carcinoma. Tumor downstaging to within the Milan criteria within 1 year and liver function worsening as Child-Pugh grade deterioration from A to B were analyzed. Results The median survival time was 35.8 months. Forty-five patients had no recurrence within 1 year after initial TACE. Of the 179 patients with at least one recurrence within a year, 44 (25%) achieved tumor downstaging to within the Milan criteria and showed significantly longer survival than non-downstaged ones (P = 0.02). Logistic regression univariate analysis revealed that up-to-seven criteria fulfillment was associated with tumor downstaging to within the Milan criteria (odds ratio 2.6; P = 0.007). The median deterioration time was 26.7 months. Multivariate analysis revealed that beyond the up-to-seven criteria (hazard ratio [HR] 1.9; P = 0.005) was an independent factor associated with Child-Pugh grade deterioration, along with serum albumin (HR 1.54; P = 0.01), serum bilirubin (HR 1.49; P = 0.02), and prothrombin time (HR 1.54; P = 0.04). Conclusions The up-to-seven criteria had prognostic value and could predict non-critical recurrence and maintenance of Child-Pugh grade in patients who underwent initial conventional TACE.

Transgene-free induced pluripotent stem cells (iPSCs) are valuable for both basic research and potential clinical applications. We previously reported that a replication-defective and persistent Sendai virus (SeVdp) vector harboring four reprogramming factors (SeVdp-iPS) can efficiently induce generation of transgene-free iPSCs. This vector can express all four factors stably and simultaneously without chromosomal integration and can be eliminated completely from reprogrammed cells by suppressing vector-derived RNA-dependent RNA polymerase. Here, we describe an improved SeVdp-iPS vector (SeVdp(KOSM)302L) that is automatically erased in response to microRNA-302 (miR-302), uniquely expressed in pluripotent stem cells (PSCs). Gene expression and genome replication of the SeVdp-302L vector, which contains miRNA-302a target sequences at the 3' untranslated region of L mRNA, are strongly suppressed in PSCs. Consequently, SeVdp(KOSM)302L induces expression of reprogramming factors in somatic cells, while it is automatically erased from cells successfully reprogrammed to express miR-302. As this vector can reprogram somatic cells into transgene-free iPSCs without the aid of exogenous short interfering RNA (siRNA), the results we present here demonstrate that this vector may become an invaluable tool for the generation of human iPSCs for future clinical applications.

Objective We evaluated the characteristics of patients with diverticular bleeding in whom emergency endoscopy should be proactively performed and those in whom it is unnecessary for spontaneous hemostasis following conservative treatment. Methods This study involved 132 patients in whom diverticular bleeding was diagnosed on lower gastrointestinal endoscopy. We evaluated the rate of identification of the bleeding diverticulum during endoscopy and the rate of spontaneous hemostasis following conservative treatment. Results In 26 patients (20%), bleeding diverticulum was identified during endoscopy. Extravasation or fluid collection on CT imaging was an important factor of successful identification of the bleeding source on endoscopy. Of the 104 patients in the conservative treatment group, 91 (87%) were able to be discharged after spontaneous hemostasis. Univariate analysis revealed a high rate of spontaneous hemostasis in patients without extravasation and fluid collection on CT imaging, those without adhesion of blood during endoscopy, those without diabetes, and those with a hemoglobin level ≥10 g/dL. Conclusion In patients with colonic diverticular bleeding, extravasation or fluid collection on CT is an important factor related to the identification of the bleeding diverticulum. Patients without characteristic CT findings had a high rate of spontaneous hemostasis after conservative treatment. Background Diverticular bleeding is the most frequent cause of lower gastrointestinal bleeding accounting for 20%-40% of all cases in Japan and 20%-48% of all those in the Western countries[1, 2]. The prevalence of colonic diverticula tends to increase with age; thus, the overall prevalence of diverticular bleeding is expected to increase in the future. In Japan, the Japanese Gastroenterological Association published guidelines on colonic diverticulitis in 2017; these guidelines recommend the performance of lower gastrointestinal endoscopic examination within 24 h in patients with lower gastrointestinal bleeding suspected to be diverticular bleeding[3]. It has been reported that, for patients with lower gastrointestinal bleeding, urgent endoscopy helps avoid embolotherapy, colectomy, massive blood transfusion, and repeat bleeding[1, 4, 5]. However, it is often difficult to identify the bleeding point [6]; further, there are many challenging cases wherein it is difficult to decide whether urgent endoscopy should be performed in situations where there is insufficient medical staff, such as during nighttime and on holidays. Bleeding is reported to stop spontaneously with conservative treatment alone in 70% of diverticular bleeding cases[7, 8]. In particular, when determining the treatment policy for diverticular bleeding and in the case of patients at high risk of complications following endoscopy, such as older patients, those with poor performance status or cardiovascular disease, and those in whom spontaneous hemostasis can be expected, urgent endoscopy should be avoided, and elective endoscopy should be selected. Therefore, the type of cases wherein urgent endoscopy is effective and the type wherein it is unnecessary need to be clarified. Thus far, there have been very few reports of the characteristics of patients with diverticular bleeding in whom spontaneous hemostasis was achieved. We aimed to assess the characteristics of patients in whom emergency endoscopy should be proactively performed and those for whom it is unnecessary. Thus, we retrospectively analyzed the identification rate for the responsible diverticulum in patients with diverticular bleeding and the rate of spontaneous hemostasis following conservative treatment.

Background: Recent advances in the development of tyrosine kinase inhibitors (TKIs) have enabled patients with unresectable hepatocellular carcinoma (HCC) to receive multiple TKIs in sequence. The aim of this study was to identify predictors of good candidates for second-line treatment after disease progression during sorafenib treatment. Methods: This is a retrospective cohort study of 190 consecutive HCC patients who were treated with sorafenib in our hospital. Three criteria of good candidates for second-line TKI at the time of disease progression during sorafenib treatment were defined as follows: criterion 1 was the same as the inclusion criteria of the regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE) study, criterion 2 was the inclusion criteria of the RESORCE study plus Child–Pugh score 5, and criterion 3 was the inclusion criteria of the RESORCE study plus albumin–bilirubin (ALBI) grade 1. Factors at baseline and at week 4 during sorafenib treatment were used to predict patients fulfilling each of these three criteria. Results: The distribution of patients was 29%, 13%, and 6% in criteria 1, 2, and 3, respectively. Significant factors for meeting criterion 1 was the combination of baseline albumin &gt, 3.7 g/dL (odds ratio (OR) 2.7) plus degree of decrease in albumin (Δalbumin) at week 4 &lt, 0.2 g/dL (OR 2.6), or the combination of baseline ALBI score &lt, −2.33 (OR 2.5) and ΔALBI at week 4 &lt, 0.255 (OR 4.9). For criterion 2, the value of baseline albumin and ALBI score was identical to criterion 1, however, Δalbumin (&lt, 0.1 g/dL) and ΔALBI score (&lt, 0.19) became stricter. For criterion 3, the value of baseline albumin (&gt, 3.8 g/dL) and ALBI (&lt, −2.55) became stricter, as did Δalbumin (&lt, 0.1 g/dL) and ΔALBI (&lt, 0.085). Furthermore, tumor burden (&gt, 11) was selected as an additional predictor (OR 5.4). Conclusion: Predictors to satisfy the RESORCE study inclusion criteria were as follows: preserved liver function at baseline, as reflected by albumin or ALBI score, and small deterioration of liver function early during sorafenib therapy, as reflected by Δalbumin or ΔALBI at week 4. Liver function at baseline and degree of change in liver function during sorafenib treatment need to be stricter for better outcomes of liver function with disease progression.

The assessment of liver fibrosis is essential because it correlates with mortality risk in nonalcoholic fatty liver disease (NAFLD). This study aims to examine whether serum fibrosis markers could identify candidate patients likely to have advanced fibrosis. We enrolled 352 patients with NAFLD and performed liver biopsies in 97 patients. The area under the receiver operating characteristic curve (AUROC) of liver stiffness by magnetic resonance elastography for histological advanced fibrosis was 0.910, and the optimal cutoff value was 4.07 kPa. To predict severe liver stiffness (≥4.07 kPa), the AUROC for Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) and FIB-4 were 0.897 (cutoff value, 1.08) and 0.880 (cutoff value, 2.53), respectively. After stratification of patients into four age groups as quartile, the optimal cutoff values of WFA+-M2BP for predicting severe liver stiffness were similar in each group (1.09, 1.08, 1.10, and 1.12). On the other hand, those of FIB-4 increased in parallel with age (1.47, 2.19, 2.99, and 3.88). In conclusion, WFA+-M2BP was precise for estimating severe liver stiffness in NAFLD with single cutoff value independent of age. Hence, identifying high-risk cases using WFA+-M2BP from a large number of NAFLD patients is clinically significant.

For patients receiving palliative care, information about prognosis is important to help them set priorities and expectations for care and to assist clinicians in decision-making. The purpose of this study was to investigate prognostic models applicable to the terminal stage of gastrointestinal cancer, especially in terms of accuracy of prediction regarding 3-week survival. We validated retrospectively the accuracy of a prognosis prediction model for 354 end-stage gastrointestinal cancer patients who underwent palliative care at our hospital. Using receiver operating characteristic analysis and the area under the curve (AUC), we selected the cut-off value for 3-week survival and evaluated the predictive ability using sensitivity, specificity, positive predictive value, negative predictive value, and accurate diagnosis rate. In our analysis of various models, Palliative Prognostic Index (PPI) and Biological Prognostic Score (BPS) version 3 showed excellent predictive performance with AUCs of 0.85 and 0.83, respectively, and accurate diagnosis rates of 80.0 and 79.0, respectively. BPS version 2 showed fair predictive performance with an AUC of 0.76 and an accurate diagnosis rate of 72.0. Using these models, stratification of prognostic prediction was possible. PPI and BPS were found to be accurate prediction models for short-term survival of terminal gastrointestinal cancer patients.

Prediction of hepatocellular carcinoma (HCC) development after sustained virological response (SVR) is clinically important, and the usefulness of noninvasive markers for prediction HCC have been reported. The aim of this study was to compare the prediction accuracy for HCC development by noninvasive markers. A total of 346 patients with chronic hepatitis C without history of HCC who achieved SVR through direct-acting antivirals were included. Magnetic resonance elastography (MRE) and serum fibrosis markers were measured 12 weeks after the end of treatment, and the subsequent HCC development was examined. The mean observation period was 26.4 ± 7.9 months, and 24 patients developed HCC. Area under the receiver operating characteristic curve of liver stiffness by MRE, Wisteria floribunda agglutinin-positive mac-2 binding protein and FIB-4 for predicting HCC within 3 years was 0.743, 0.697 and 0.647, respectively. The 1/2/3-year rates of HCC development in patients with liver stiffness ≥3.75 KPa were 6.6%, 11.9% and 14.5%, whereas they were 1.4%, 2.5% and 2.5% in patients with liver stiffness

Background and aimsThe present study aimed to report our real-life experience of the TPO receptor agonist lusutrombopag for cirrhotic patients with low platelet counts.MethodsWe studied platelet counts in 1,760 cirrhotic patients undergoing invasive procedures at our hospital between January 2014 and December 2017. In addition, we studied 25 patients who were administered lusutrombopag before invasive procedures between June 2017 and January 2018. Effectiveness of lusutrombopag to raise platelet counts and to avoid transfusion and treatment-related adverse events were analyzed.ResultsIn 1,760 cirrhotic patients without lusutrombopag prior to invasive procedures, proportion of patients whose platelet counts 30,000/μL (n = 17) (50,000 ± 20,000 vs 86,000 ± 26,000/μL, p = 0.002). Patients with a baseline platelet count ≤30,000/μL with spleen index (calculated by multiplying the transverse diameter by the vertical diameter measured by ultrasonography) ≥40 cm2 (n = 3) had a lower response rate to lusutrombopag compared to those with spleen index ConclusionsLusutrombopag is an effective and safe drug for thrombocytopenia in cirrhotic patients, and can reduce the frequency of platelet transfusions.

Radiofrequency ablation (RFA) is considered the most effective treatment for early‐stage hepatocellular carcinoma (HCC) patients unsuitable for resection. However, poor outcome after RFA has occasionally been reported worldwide. To predict such an outcome, we investigated imaging findings using contrast‐enhanced ultrasonography (CEUS) with Sonazoid and serum tumor markers before RFA. This study included 176 early‐stage HCC patients who had initially achieved successful RFA. Patients were examined using CEUS; their levels of alpha‐fetoprotein (AFP), Lens culinaris agglutinin‐reactive fraction of AFP (AFP‐L3), and des‐gamma‐carboxy prothrombin before RFA were measured. Sonazoid provided parenchyma‐specific contrast imaging and facilitated tumor vascular architecture imaging through maximum intensity projection (MIP). Kaplan–Meier analysis examined cumulative rates of local tumor progression, intrasubsegmental recurrence, and survival; factors associated with these were determined with Cox proportional hazards analysis. Local tumor progression (n = 15), intrasubsegmental recurrence (n = 46), and death (n = 18) were observed. Irregular pattern in MIP classification and serum AFP‐L3 level (>10%) before RFA were identified as independent risk factors for local tumor progression and intrasubsegmental recurrence. These two factors were independently associated with poor survival after RFA (irregular pattern in MIP: hazard ratio, (HR) = 8.26; 95% confidence interval, (CI) = 2.24–30.3; P = 0.002 and AFP‐L3 > 10%: HR = 2.94; 95% CI = 1.09–7.94; P = 0.033). Irregular MIP pattern by CEUS and high level of serum AFP‐L3 were independent risk factors for poor outcome after successful RFA. The Patients with these findings should be considered as special high‐risk group in early‐stage HCC.