A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis.

BACKGROUND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-non-specific) and non-shared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC. APPROACH RESULTS: Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was identified as a novel PBC susceptibility gene locus through a GWAS and subsequent genome-wide meta-analysis involving 2,181 cases and 2,699 controls from the Japanese population (GWAS-lead variant: rs8098858, p=2.6×10-8). In-silico and in-vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells (Tfh) and plasmacytoid dendritic cells (pDCs). Infiltration of PTPN2-positive T-cells and pDCs were confirmed in the portal area of the PBC-liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in-vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758. CONCLUSIONS: PTPN2, a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC via an insufficient negative feedback loop caused by the PTPN2 risk allele of rs2292758 in IFN signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment.

Prognosis of patients with liver cirrhosis: A multi-center retrospective observational study.

AIM: Despite advances in the management of liver diseases and changes in the etiology of cirrhosis, few studies have updated the prognosis of cirrhosis. This study aimed to clarify the recent prognosis of cirrhosis and identify risk factors for death. METHODS: In this retrospective observational study by the Hepatic Disease Network of the National Hospital Organization in Japan, chart reviews were performed to follow patients with cirrhosis beginning in 2011. We conducted Kaplan-Meier survival time analyses stratified by Child-Pugh classification and albumin-bilirubin grade. Cox regression analysis was used to identify risk factors for death. RESULTS: We identified 444 eligible patients from 25 hospitals, including 303 (68%), 110 (25%), and 31 (7%) patients with Child-Pugh classes A, B, and C, respectively. Hepatitis C virus infection was the cause of cirrhosis for 63% of the patients. The 1-year and 5-year cumulative survival rates of patients with Child-Pugh classes A, B, and C were 90% and 61%, 78% and 42%, and 65% and 25%, respectively. The 1-year and 5-year cumulative survival rates of patients with albumin-bilirubin grades 1, 2, and 3 were 98% and 80%, 91% and 56%, and 58% and 23%, respectively. Cirrhosis classification (Child-Pugh and albumin-bilirubin), age, liver cancer, and untreated esophageal varices were associated with increased hazard of death. CONCLUSIONS: Little improvement was observed in the prognosis of cirrhosis compared with previous reports, and the prognosis of Child-Pugh class C cirrhosis remained poor. Untreated esophageal varices were identified as a risk factor for death.

Reducing the risk of developing walled-off necrosis in patients with acute necrotic collection using recombinant human soluble thrombomodulin.

BACKGROUND/PURPOSE: The purpose of the present study was to investigate the possibility of reducing clinical impacts of acute necrotic collection (ANC) on patients with acute pancreatitis (AP) using recombinant human soluble thrombomodulin (rTM). METHODS: In this retrospective multicenter study, 233 consecutive AP patients with ANC and acute peripancreatic fluid collection (APFC) from 2012 to 2016 were enrolled. To assess clinical impacts of ANC, severity on admission (JPN score, JPN CT grade, and Modified CT severity index), development of walled-off necrosis (WON), imaging costs for follow-up, and mortality were recorded. Finally, we investigated whether rTM could reduce the clinical impacts, adjusting the severity using propensity analysis with Inverse probability of treatment weighting. RESULTS: Patients with ANC developed WON with higher ratio than APFC (58/98 [59.2%] vs 20/135 [14.8%], OR = 8.3, P < .01]. Severity on admission and imaging costs for follow-up in ANC patients were significantly higher than those in APFC (P < .01). However, regarding mortality, there was no significant difference between patients with ANC and APFC (P = .41). Adjusting severity, it was revealed that rTM administration significantly reduced the risk of ANC developed WON (OR = 0.23, P = .01). CONCLUSIONS: While ANC had a higher clinical impact than that of APFC, we found that early administration of rTM may reduce the impact.

A Phase 1 Study of KHK4083: A Single-Blind, Randomized, Placebo-Controlled Single-Ascending-Dose Study in Healthy Adults and an Open-Label Multiple-Dose Study in Patients With Ulcerative Colitis.

OX40 plays an essential role in maintaining late T-cell proliferation and survival by suppressing apoptosis and by inducing T-cell memory formation. Here, we report the results of the phase 1 study of KHK4083, a fully human antimonoclonal antibody specific for OX40. In this study, we aimed to assess the safety and tolerability of a single intravenous or subcutaneous administration of KHK4083 compared with placebo in healthy Japanese and Caucasian subjects and determined the pharmacokinetics (PK) and immunogenicity. Also, we assessed the preliminary efficacy and pharmacodynamics of multiple intravenous doses in Japanese patients with moderate to severe ulcerative colitis (UC). Drug-related treatment emergent adverse events occurred in 21 healthy subjects (58.3%) and 5 patients with UC (62.5%) after administration of KHK4083. There were no serious adverse events. The PK profile of a single intravenous dose of 10 mg/kg KHK4083 was similar in healthy Japanese and Caucasian subjects. Of 8 UC patients, a clinical response was observed in 3 patients (37.5%) and clinical remission in 2 patients (25.0%) in week 6. Our study demonstrated the safety and tolerability of single and multiple administrations of KHK4083 in healthy Japanese and Caucasian subjects and Japanese patients with moderate to severe UC. It also indicated favorable pharmacological properties of the drug.

Risk Factors for Delayed Bleeding after Therapeutic Gastrointestinal Endoscopy in Patients Receiving Oral Anticoagulants: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. METHODS: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. RESULTS: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. CONCLUSION: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

Long-term safety and efficacy of lanreotide autogel in Japanese patients with neuroendocrine tumors: Final results of a phase II open-label extension study.

AIM: The aim of this study was to describe the long-term safety and efficacy of lanreotide in Japanese patients with neuroendocrine tumors. METHODS: The final analyses of a 48-week open-label phase II study (n = 32) and its extension study (n = 17) were conducted. Patients received 4-weekly subcutaneous injections of lanreotide autogel 120 mg. Safety was evaluated by adverse events. Efficacy endpoints included tumor response by RECIST and change in tumor size. Post hoc analyses including tumor growth rate were performed. RESULTS: The median (range) of lanreotide exposure in the safety analysis set (n = 17) and efficacy analysis set (n = 28) were 151.4 (52-181) and 52.7 (12-181) weeks, respectively. Sixteen patients developed adverse drug reaction; of these, upper abdominal pain and urticaria were not reported before 48 weeks. No patient discontinued lanreotide or died from an adverse event. Two serious events of bile duct stones in one patient were drug-related. Partial response was observed in 2 patients (7.1%; at 60 and 108 weeks), stable disease in 20 (71.4%) and progressive disease in 6 (21.4%). The mean of the greatest change from baseline in the sum of diameters of target lesions was -5.5%. The mean (standard deviation) tumor growth rate before treatment and from baseline to last observation was 25.3% (35.7%)/month and 6.4% (9.6%)/month, respectively. CONCLUSION: Lanreotide treatment had an acceptable safety profile and was effective over long-term treatment in Japanese patients with neuroendocrine tumors. No unexpected serious adverse events developed during prolonged use of lanreotide.

[Prediction of pancreatitis following endoscopic retrograde cholangiopancreatography].

OBJECTIVE: The aim of this study was to determine if the difference in serum amylase levels prior to, and two hours following, an endoscopic retrograde cholangiopancreatography (ERCP), or the ratio of the two-hour post-ERCP amylase level to the pre-ERCP amylase level was a better predictor of post-ERCP pancreatitis (PEP). METHODS: This was a retrospective, single-center study of consecutive patients, who underwent ERCP between April 2015 and August 2018. Serum amylase was measured before and two hours following ERCP. We compared the difference and the ratio of the two levels in predicting PEP using a receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 1029 patients underwent ERCP, with PEP occurring in 118 (11.5%). Multivariate analysis revealed that an elevated two-hour post-ERCP serum amylase level was a significant predictor of PEP. ROC analysis of the difference and the ratio of the two levels found good performance for both parameters, with an area under the curve (AUC) of 0.861 (95% confidence interval [CI], 0.823-0.900) and 0.847 (95% CI, 0.809-0.886), respectively. The difference between the values was a significantly more effective predictor of PEP, based on the AUC analysis (P = 0.011). CONCLUSION: The difference between pre and two-hour post-ERCP amylase levels is a better predictor of PEP than the ratio of the two.

Integrated GWAS and mRNA Microarray Analysis Identified IFNG and CD40L as the Central Upstream Regulators in Primary Biliary Cholangitis.

Genome-wide association studies (GWASs) in European and East Asian populations have identified more than 40 disease-susceptibility genes in primary biliary cholangitis (PBC). The aim of this study is to computationally identify disease pathways, upstream regulators, and therapeutic targets in PBC through integrated GWAS and messenger RNA (mRNA) microarray analysis. Disease pathways and upstream regulators were analyzed with ingenuity pathway analysis in data set 1 for GWASs (1,920 patients with PBC and 1,770 controls), which included 261 annotated genes derived from 6,760 single-nucleotide polymorphisms (P < 0.00001), and data set 2 for mRNA microarray analysis of liver biopsy specimens (36 patients with PBC and 5 normal controls), which included 1,574 genes with fold change >2 versus controls (P < 0.05). Hierarchical cluster analysis and categorization of cell type-specific genes were performed for data set 2. There were 27 genes, 10 pathways, and 149 upstream regulators that overlapped between data sets 1 and 2. All 10 pathways were immune-related. The most significant common upstream regulators associated with PBC disease susceptibility identified were interferon-gamma (IFNG) and CD40 ligand (CD40L). Hierarchical cluster analysis of data set 2 revealed two distinct groups of patients with PBC by disease activity. The most significant upstream regulators associated with disease activity were IFNG and CD40L. Several molecules expressed in B cells, T cells, Kupffer cells, and natural killer-like cells were identified as potential therapeutic targets in PBC with reference to a recently reported list of cell type-specific gene expression in the liver. Conclusion: Our integrated analysis using GWAS and mRNA microarray data sets predicted that IFNG and CD40L are the central upstream regulators in both disease susceptibility and activity of PBC and identified potential downstream therapeutic targets.

POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33.

Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls). A susceptibility locus on chromosome 3q13.33 (including ARHGAP31, TMEM39A, POGLUT1, TIMMDC1, and CD80) was previously identified both in the European and Chinese populations and was replicated in the Japanese population (OR = 0.7241, P = 3.5 × 10-9). Subsequent in silico and in vitro functional analyses identified rs2293370, previously reported as the top-hit SNP in this locus in the European population, as the primary functional SNP. Moreover, e-QTL analysis indicated that the effector gene of rs2293370 was Protein O-Glucosyltransferase 1 (POGLUT1) (P = 3.4 × 10-8). This is the first study to demonstrate that POGLUT1 and not CD80 is the effector gene regulated by the primary functional SNP rs2293370, and that increased expression of POGLUT1 might be involved in the pathogenesis of PBC.

Antithrombin III for portal vein thrombosis in patients with liver disease: A randomized, double-blind, controlled trial.

AIM: Portal vein thrombosis (PVT) is one of the most critical disorders in liver disease patients. These patients have the imbalance of coagulation and coagulation inhibition resulting from decreased levels of coagulation inhibitory factors, such as protein C, protein S, and antithrombin III (AT-III). We designed this randomized, double-blind, placebo-controlled trial comparing the safety and efficacy of AT-III for PVT in liver disease patients with those who received no treatment. METHODS: Eligible patients were diagnosed with the association of thrombus, without tumor thrombus, and thrombus in more than 50% of the cross-sectional lumen of the portal vein. Patients with 70% or less serum level of AT-III were included. The study drug was given up to three times in a 5-day consecutive infusion interval if the thrombus decreased in size. Efficacy was evaluated by contrast enhanced computed tomography using a five-grade scale (complete response, partial response, slight response, no response, and progression). From October 2014 through to March 2016, 36 patients were randomly assigned to the AT-III group and 37 patients to the placebo group. RESULTS: The proportion of patients with complete response or partial response of PVT was significantly higher in the AT-III group (55.6%; 20/36 patients; 95% confidence interval, 38.1-72.1) than in the placebo group (19.4%; 7/36 patients, 95% confidence interval, 8.2-36.0) (P = 0.003). The overall incidence of adverse events and adverse drug reactions did not differ significantly between the two groups. CONCLUSION: Antithrombin III is one of the essential therapies for patients with PVT in cases with lower concentration levels of AT-III.

Serum IFN-λ3 Levels Correlate with Serum Hepatitis C Virus RNA Levels in Symptomatic Patients with Acute Hepatitis C.

BACKGROUND: Recent genome-wide association studies demonstrated that 2 single nucleotide polymorphisms (SNPs), upstream of the interferon-λ (IFNL) 3 gene, are associated with the spontaneous clearance of hepatitis C virus (HCV) in symptomatic patients with acute hepatitis C (AHC). Although these 2 SNPs, rs8099917 and rs12979860, have established their significant roles in the innate immunity response to spontaneously clear HCV in patients with AHC, the detailed mechanisms of their roles remain largely unknown. AIM: This study is aimed at clarifying the factors affecting IFNL3 production and assessing the roles of IFNL3 in AHC. MATERIALS AND METHODS: A total of 21 AHC patients who visited the hospital within 10 days after symptom onset were assessed. As controls, 23 healthy volunteers (HVs) were examined. Serum IFNL3 levels were quantified using an in-house, IFNL3-specific chemiluminescence enzyme immunoassay (CLEIA) kit. Serum IFNL1, IFN-α, IFN-ß, and IFN-γ induced protein-10 (IP-10) levels were assayed using commercial enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: At baseline, serum IFNL3 levels were higher in AHC patients than in HVs (p < 0.0001). The higher levels in AHC patients did not differ between patients with the rs8099917 TT genotype and those with the non-TT (TG/GG) genotype (p = 0.546). Serial measurement of serum IFNL3 levels did not predict the outcome of conventional AHC. However, serum IFNL3 levels at baseline correlated positively with the HCV RNA levels (p = 0.005). Following HCV eradication, serum IFNL3 levels reduced to within the range obtained for HVs. Baseline serum IFNL1 levels did not differ significantly between AHC patients and HVs (p = 0.284). Serum levels of IFNL1 and IFNL3 at baseline also showed no correlative power (p = 0.288). Serum IFN-α and IFN-ß were detected together with remarkably high serum IFNL3 levels in only one patient who progressed to acute liver failure (ALF). CONCLUSION: These findings indicate that serum IFNL3 levels at baseline are higher in AHC patients regardless of the rs8099917 polymorphism, and primary HCV infection triggers the production of IFNL3. As a first line of defense in the innate immune system against invading HCV, increased IFNL3 levels play an important role, but serum IFNL3 levels are not the principal determinant of the clinical course of conventional AHC.

Selection of regimens for patients with hepatitis C virus genotype/serotype discrepancy.

In the present study, the usefulness of the resistance-associated variant (RAV) analysis to select direct acting antiviral (DAA) drugs for patients with hepatitis C virus (HCV) genotype/serotype discrepancy was evaluated. The core-genotype and serotype were determined in the 559 patients recruited in the study. The RAV analysis and NS5B-genotype determination were performed in the eight patients who exhibited a genotype/serotype discrepancy. One of these patients exhibited a core-genotype 1b/serotype 2, and detection by RAV analysis was possible in this patient. The other seven patients demonstrated a core-genotype 2/serotype 1, and detection using the RAV analysis was possible in four of them. The NS5B-genotype was 1b in all patients in whom detection using the RAV analysis was possible and was other than 1b in patients in whom detection using the RAV analysis was impossible. The RAV analysis could detect RNA sequences specific to genotype 1b in the NS5A region. Therefore, in patients with genotype/serotype discrepancy in whom detection using the RAV analysis is possible, the treatment regimens should be selected based on the assumption that HCV with genome that is highly homologous to genotype 1b is present in the NS5A region.

Early diagnosis of pancreatic necrosis based on perfusion CT to predict the severity of acute pancreatitis.

BACKGROUND: Perfusion CT can diagnose pancreatic necrosis in early stage of severe acute pancreatitis, accurately. However, no study to date has examined whether early diagnosis of pancreatic necrosis is useful in predicting persistent organ failure (POF). METHODS: We performed a multi-center prospective observational cohort study to investigate whether perfusion CT can predict the development of POF in the early stage of AP, based on early diagnosis of the development of pancreatic necrosis (PN). From 2009 to 2012, we examined patients showing potential early signs of severe AP (n = 78) on admission. Diagnoses for the development of PN were made prospectively by on-site physicians on the admission based on perfusion CT (diagnosis 1). Blinded retrospective reviews were performed by radiologists A and B, having 8 and 13 years of experience as radiologists (diagnosis 2 and 3), respectively. Positive diagnosis for the development of PN were assumed equivalent to positive predictions for the development of POF. We then calculated the area under the curve (AUC) of the receiver operating characteristic for POF predictions. RESULTS: Fourteen (17.9%) and 23 patients (29.5%) developed PN and POF, respectively. For diagnoses 1, 2, and 3, AUCs for POF predictions were 74, 68, and 73, respectively. CONCLUSIONS: Perfusion CT diagnoses pancreatic necrosis and on that basis predicts the development of POF; http://www.umin.ac.jp/ctr/index-j.htm,UMIN000001926 .

Risk factors for developing colorectal cancer in Japanese patients with ulcerative colitis: a retrospective observational study-CAPITAL (Cohort and Practice for IBD total management in Kyoto-Shiga Links) study I.

BACKGROUND AND AIMS: Patients with ulcerative colitis (UC) are at risk for developing colorectal cancer (CRC), despite the development of new therapeutic agents. Stratification of the individual UC-patient's risk would be helpful to validate the risk factors for CRC. The aim of this study was to evaluate the risk factors for the development of CRC in a large cohort of patients with UC. METHODS: Data were obtained from 12 hospitals in the Kyoto-Shiga region during 2003-2013. We performed a retrospective cohort study of 2137 patients with UC. RESULTS: In total, 60 lesions of CRC were detected in 43 (2.0%) of 2137 patients. 30 of the 43 patients were male. The median age was 53 years. The median duration of disease was 13 years, and 67.4% of these patients had a disease duration >10 years. Of the 43 patients, 34 (79.1%) had extensive colitis. Primary sclerosing cholangitis was detected in 2 patients (4.7%). The median corticosteroids (CS) dose was 6.4 g, and 4 patients were treated with a total of more than 10 g of CS. 18 of these patients underwent more than 1 year CS treatment. Of all 60 CRC lesions, 43 (71.7%) were located in the distal colon and 35 (58.3%) were of the superficial type. Moreover, the stage of CRC was stage 0 or I in 55.8% of the 43 patients with CRC. Multivariate analysis suggested that extensive colitis could be a risk factor for the development of advanced CRC in patients with UC. CONCLUSIONS: Our findings indicated that male, extensive colitis, long-term duration of UC and family history of CRC, but not concomitant primary sclerosing cholangitis, are important factors for predicting CRC in Japanese patients with UC. Moreover, long-standing extensive colitis might contribute to the progression of CRC. Further studies are required to establish CRC surveillance in Japanese patients with UC.

Inhibition of hepatocellular carcinoma by PegIFNα-2a in patients with chronic hepatitis C: a nationwide multicenter cooperative study.

BACKGROUND: We investigated whether the administration of maintenance doses of interferon prevented hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. METHODS: Study 1: A multicenter, retrospective, cooperative study was carried out to determine whether long-term administration of low-dose peginterferon alpha-2a (PegIFNα-2a) prevented HCC development in patients with chronic hepatitis C. In total, 594 chronic hepatitis C patients without a history of HCC were enrolled and treated with 90 µg PegIFNα-2a administered weekly or bi-weekly for at least 1 year. Study 2: HCC developed in 16 of 99 additional patients without PegIFNα-2a treatment during 3.8 years of observation. A propensity-matched control study was then carried out to compare the incidence of HCC between the 59 patients who received low-dose PegIFNα-2a (PegIFNα-2a group) and 59 patients who did not receive PegIFNα-2a treatment (control group), matched for sex, age, platelet count, and total bilirubin levels. RESULTS: Study 1: HCC developed in 49 patients. The risk of HCC was lower in patients with undetectable hepatitis C virus RNA, ≤40 IU/L alanine aminotransferase (ALT), or ≤10 ng/L alpha-fetoprotein (AFP) 24 weeks after the start of therapy. Study 2: The incidence of HCC was significantly lower in the PegIFNα-2a group than in the control group. CONCLUSIONS: Low-dose and long-term maintenance administration of PegIFNα-2a decreased the incidence of HCC in patients with normalized ALT and AFP levels at 24 weeks compared with patients without normal ALT and AFP levels.

Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction.

We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the ¹³C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.

[A case of epithelioid hemangioendothelioma of the liver: detection by FDG-PET].

A 57 year-old woman was admitted for focal accumulation of 18F-fluorodeoxyglucose (FDG) in the liver detected by positron emission tomography (PET). A 25- mm hypovascular tumor was detected by computed tomography. Tumor biopsy revealed many atypical cells with positive staining for factor VIII-related-antigen in sinusoids. Right lobectomy was performed and the tumor was diagnosed as epithelioid hemangioendothelioma (EHE) pathologically. We demonstrated that FDG-PET was useful for the diagnosis of EHE and making deciding on therapeutic strategy.