Search

Background We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018. Methods The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018. Results NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P = 0.026) and the median platelet count increased (15.1–17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P Conclusions The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

Objective Lusutrombopag is a thrombopoietin receptor agonist that improves thrombocytopenia in patients with chronic liver disease scheduled to undergo invasive procedures. However, information on the efficacy of repeated lusutrombopag treatment and factors associated with the treatment is scarce. We analyzed the efficacy of repeated lusutrombopag treatment and the factors associated with a response to lusutrombopag. Methods Thirty-nine patients with chronic liver disease who received lusutrombopag treatment before undergoing invasive procedures were enrolled in this retrospective study. Of the 39 patients, 10 received lusutrombopag treatment multiple times for a total of 53 regimens of lusutrombopag treatment. Changes in platelet counts, the effects of repeated lusutrombopag treatment, and factors associated with response to lusutrombopag were analyzed. Results The median platelet count increased significantly from 4.5×104/μL before lusutrombopag treatment to 7.2×104/μL before the invasive procedure (p

The current status of Helicobacter pylori infection in Japan has not been investigated. We evaluated the status of H. pylori infection in a Japanese general population using large-scale resident-register-based sampling.All 6069 adults in a rural town and 6000 adults in two urban cities (3000 each), selected by register-based random sampling, were enrolled in our health check-up program. Antibody titers against Helicobacter pylori (cut-off value was 3 U/mL by Eiken E-plate) were evaluated, and subjects with a positive result were encouraged to undergo further examinations.A total of 1586 subjects participated in serum sampling. The overall prevalence of H. pylori infection was 40.0% (634/1586), and it increased with age both in rural and urban areas. Although the overall positive rate was higher in the rural area (49.4%) than in the urban areas (35.6 and 32.3%), there was no difference in H. pylori status of younger subjects between the two areas. Among 634 patients with a positive titer, 374 (59.0%) underwent further examinations including endoscopic examination, and 180/634 (28.4%) patients received eradication therapy. Gastric neoplasms (three adenocarcinomas and one adenoma) were found in our screening program.We clarified population-based random sampling data of H. pylori infection in a Japanese general population. In younger subjects, a decrease in the prevalence of H. pylori infection was confirmed both in rural and urban areas. This provides basic information for establishing a strategy to reduce gastric cancer deaths.

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 772 controls from five European and two East Asian cohorts. [RESULTS] We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, each having key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, Jak-STAT signalling, and differentiation of TH1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some well-established in the treatment of other autoimmune disorders. [CONCLUSIONS] This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. [Lay summary] Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10, 516 people with PBC and 20, 772 healthy individuals recruited in Canada, China, Italy, Japan, UK, or USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these ‘candidate genes’ to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC., 原発性胆汁性胆管炎のゲノムワイド関連解析 --国際メタ解析による新規疾患感受性遺伝子と治療薬候補の同定--. 京都大学プレスリリース. 2021-06-28.

BACKGROUND AND AIM To examine the effect on recurrence and survival of treatment by interferon (IFN)-free direct-acting antivirals (DAA) for patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) who underwent primary curative treatment. METHODS This was a retrospective cohort study of 250 patients with HCV who had received curative treatment for primary HCC. As anti-HCV treatment after HCC treatment, 38 patients received IFN-free DAA therapy (DAA patients) and 94 received IFN-based therapy (IFN patients). The recurrence of HCC and overall survival of the patient groups were compared in a case-control study. RESULTS The cumulative HCC recurrence rates at 1, 3, and 5 years were 5%, 39%, and 39% for DAA patients and 0%, 46%, and 62% for IFN patients, respectively (P = 0.370). Multivariate analysis of the HCC recurrence identified treatment responses (sustained virological response [SVR]: hazard ratio [HR] 2.237; P = 0.003) as an independent predictive factor. The cumulative overall survival rates at 3 and 5 years were 96%, 96% for DAA patients and 93%, 73% for IFN patients, respectively ( P = 0.163). Multivariate analysis identified treatment responses (SVR: HR 8.742; P

Background/Aims: The clinical course and exacerbation of portal hypertensive enteropathy (PHE) are yet to be fully clarified. This study aimed to identify factors related to PHE exacerbation in patients with liver cirrhosis (LC). Methods: Fifty patients with LC (33 male; mean age, 67 years), who underwent capsule endoscopy (CE) at the Hiroshima University Hospital between February 2009 and September 2015, were followed up for >6 months. Exacerbation is defined as the appearance of new lesions or worsening of existing lesions. The association between PHE exacerbation and the clinical factors was evaluated. Results: PHE exacerbation was identified in 24 out of 50 (48%) of cases: erythema (14 cases); angioectasia (11 cases); erosions (9 cases); villous edema (8 cases); and esophageal varices (EVs; 6 cases). The following factors were significantly associated with PHE exacerbation: portosystemic shunts, EVs and portal hypertensive gastropathy (PHG) exacerbation. After therapy, CE findings among the 24 cases were as follows: villous edema (19 cases); erythema (17 cases); angioectasia (16 cases); erosions (12 cases); and EVs (9 cases), and no observable abnormalities in 2 cases. On multivariate analysis, exacerbation of EVs and PHG were independent predictors of PHE exacerbation. Conclusion: EVs and PHG exacerbation may predict PHE exacerbation in patients with LC.

The risk factors in the progression of nonalcoholic fatty liver disease (NAFLD) have not been fully clarified. Porphyromonas gingivalis (P.g) has been considered to be a confounding risk factor for systemic diseases. We aimed to evaluate the effect of P.g infection on risk of progression to NASH. (1) Serum IgG antibody titers against P.g fimbriae (fimA) in 200 biopsy-proven NAFLD patients were measured by ELISA and compared with histological findings. (2) C57BL/6J mice were fed a control diet (CD) or high-fat diet (HFD) with or without P.g-odontogenic infection and analyzed histologically. Mouse livers were analyzed using CE–TOFMS and LC–TOFMS. (1) A significant correlation between fibrosis progression and antibody titers against P.g possessing fimA type 4 was identified (P = 0.0081). Multivariate analysis identified older age and type 4 P.g-positivity as risk factors for advanced fibrosis. (2) Fibrosis and steatosis were more severe in HFD P.g(+) mice compared with HFD P.g(−) mice. In metabolome analysis, fatty acid metabolism was significantly disrupted with HFD in P.g-infected mouse livers. Monounsaturated/saturated fatty acid ratios were significantly higher in the HFD P.g(+) group than in the HFD P.g(−) group (P

The urea cycle converts ammonia and produces urea. One form of urea cycle abnormality is ornithine transcarbamylase (OTC) deficiency. This hereditary disorder is associated with hyperammonemia. OTC deficiency commonly appears during neonatal and early childhood life and is rare in adults. We report a 69-year-old man who presented at the local hospital with 3-day loss of appetite, early morning vomiting, and state of confusion. Blood ammonia was 293 μg/dl. At 2-3 h after admission, the patient went into a deep coma. He was intubated and admitted immediately to the intensive care unit. Treatment, including sustained hemodialysis, failed to lower blood ammonia level. His grandchild died of OTC deficiency at 6 year of age. Computed tomography, magnetic resonance imaging and esophagogastroduodenoscopy showed no abnormalities. On admission to our hospital, he complained of vomiting and disturbance of consciousness, hyperammonemia, and normal anion gap. Genetic analysis showed A208T mutation. The deceased grandchild with OTC deficiency also had the same mutation. Long-term hemodialysis coupled with administration of L-arginine and lactulose resulted in improvement of blood ammonia level. Early diagnosis and treatment of adult-onset OTC deficiency are essential to avoid serious complications.

Objective: To evaluate the impact of hepatitis C virus (HCV) eradication on the clinical outcome of patients with HCV-related advanced hepatocellular carcinoma (HCC) treated with sorafenib. Methods: A total of 58 HCV-related advanced HCC patients with Child-Pugh grade A disease who were treated with sorafenib were enrolled in this retrospective cohort study. Of these, 27 patients were HCV RNA negative as a result of previous antiviral therapy (sustained viral response [SVR] group), while the remaining 31 were HCV RNA positive (non-SVR group). Results: The response rate, disease control rate and median time to progression in the SVR group (6, 46.0%, and 3.8 months, respectively) were similar to those in the non-SVR group (3, 51.5%, and 2.7 months, respectively). On the other hand, the median time to treatment failure (TTTF), post-progression survival (PPS), and overall survival (OS) were significantly longer in the SVR group than in the non-SVR group (9.7, 8.5, and 15 months vs. 5.9, 5.2, and 9.3 months; p = 0.023, 0.02, and 0.014, respectively). On multivariate analysis, SVR was identified as a significant and independent determinant of PPS (p = 0.009), TTTF (p = 0.028), and OS (p = 0.01). Conclusion: HCV eradication before sorafenib treatment for HCV-related advanced HCC could prolong PPS and TTTF and improve OS.

Introduction: Portal hypertensive enteropathy (PHE) is a well-known small-bowel lesion that occurs with liver cirrhosis (LC) and is associated with increased hepatic venous pressure. However, it is unclear how esophageal varices (EV) treatment actually affects PHE. We aimed to analyze the effects of EV treatment on PHE. Methods: Among LC patients who underwent capsule endoscopy (CE) more than twice to confirm PHE at our hospital from February 2009 to September 2018, we targeted those with no change in the Child-Pugh classification after EV treatment for the prevention of bleeding. Patients were assigned to groups based on the EV treatment method (endoscopic injection sclerotherapy [EIS] group or endoscopic variceal ligation [EVL] group). We analyzed the PHE findings before and after treatment, and we investigated changes in the collateral vein using computed tomography imaging. Results: We analyzed 42 LC patients (27 men; mean age, 65.3 years); 20 were in the EIS group and 22 were in the EVL group. Exacerbation of PHE was significantly prevalent in the EIS group (90%) compared to that in the EVL group (50%). CE of PHE showed significantly prevalent exacerbation of villous edema in the EIS group (65%) compared to that in the EVL group (23%). Stenosis or disappearance of the feeding vessel (55%) and exacerbation of the hepatofugal collateral vein (35%) were significantly prevalent in the EIS group. Conclusions: EIS exacerbates PHE, especially villous edema, in LC patients with changes in collateral circulation.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Polymorphisms in the inosine triphosphatase (ITPA) gene is associated with anemia induced by peg-interferon (PEG-IFN) plus ribavirin (RBV) treatment for patients with chronic hepatitis C virus (HCV) infection. However, the effect of ITPA polymorphism on sofosbuvir plus RBV treatment is unknown. Two hundred and forty-four patients with chronic HCV genotype 2 infection without decompensated liver cirrhosis were treated with sofosbuvir plus RBV for 12 weeks. The effects of ITPA polymorphism on hemoglobin levels and RBV dose reduction and treatment response were analyzed. ITPA (rs1127354) was genotyped using the Invader assay. Multivariate regression analysis was performed to identify factors associated with sustained virological response (SVR). Overall, SVR12 was achieved in 231 (94.7%) patients, based on intention to treat analysis. During the therapy, reduction of hemoglobin levels was significantly greater in ITPA genotype CC patients than CA/AA patients. Therefore, the cumulative proportion of patients with RBV dose reduction was significantly higher and total dose of RBV was significantly lower in patients with CC genotype compared to CA/AA genotypes. SVR12 rates were similar between ITPA genotypes CC and CA/AA (94.7 and 94.4%, respectively, P = 0.933). Multivariate logistic regression analysis identified FIB4 index

Objectives This study aimed to assess the value of preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) for predicting microvascular invasion (MVI) in small hepatocellular carcinoma (HCC). Methods We retrospectively examined 60 patients who received F-FDG PET-CT prior to hepatic resection for small HCC (≤30 mm) with subsequent MVI confirmation by histopathology. The associations between PET-positive status and tumor factors were assessed. Furthermore, independent predictors for MVI and diagnostic utility of each MVI predictor were assessed. Results Multivariate analysis revealed the presence of MVI as an independent predictor of PET-positive status (P = 0.023). Maximum standardized uptake value (SUVmax) of 3.2 or greater (P = 0.017) and lens culinaris agglutinin a-reactive α-fetoprotein (AFP-L3) 19% or greater (P = 0.010) were independent predictors of MVI. Areas under the receiver operating characteristic curves for SUVmax of 3.2 or greater, AFP-L3 19% or greater, and both factors combined for predicting MVI were 0.712 (0.493-0.932), 0.755 (0.563-0.947), and 0.856 (0.721-0.991), respectively. The sensitivity and specificity for predicting MVI were 77.8% and 74.5% for SUVmax of 3.2 or greater, 66.7% and 84.3% for AFP-L3 19% or greater, and 88.9% and 82.4% for the combination. Conclusions F-FDG PET-CT and AFP-L3 may be useful for predicting MVI in small HCC, and the combination of the 2 factors provided reliable assessment for selection of suitable hepatic resection and liver transplantation candidates.

To assess the outcome of stable disease (SD) patients with advanced hepatocellular carcinoma (HCC) by tumor markers after the first course of hepatic arterial infusion chemotherapy (HAIC). The study subjects were 156 HCC patients treated with HAIC and classified as Child Pugh A, with no extrahepatic metastasis, and no history of sorafenib treatment. In the study and validation cohorts, the AFP and DCP ratios of patients who were considered SD to the first course of HAIC were analyzed by AUROC for a prediction of response to the second course of HAIC. The imaging response to the first course of HAIC was classified as partial response (PR), SD and progressive disease (PD) in 29 (18.8%), 80 (51.9%), and 44 (28.6%) patients respectively. For SD patients, the a-fetoprotein (AFP) and des-y-carboxy prothrombin (DCP) ratios of patients who were considered SD to the first course of HAIC were analyzed by the receiver operating characteristic curve for prediction of response to the second course of HAIC in the study cohorts. The area under the curve of AFP ratio was 0.743. The area under the curve of DCP ratio was 0.695. The cut-off values of AFP and DCP ratios were 1.3 and 1.0, respectively. In the validation cohort, the accuracy of the prediction of response in this validation cohort (71.4%) showed no significant difference compared to that in the study cohort (72.4%) (p = 1.0). The results suggested that patients with a high tumor marker ratio could be switched to alternative therapeutic regimens despite the SD response to HAIC.

Background In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib. Methods Fifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events. Results Of the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively. Conclusion Given the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.

The relationship between the presence of villous edema (VE) in portal hypertensive enteropathy and clinical factors remains unclear. The aim of this study was to reveal the clinical factors related to VE in patients with liver cirrhosis (LC), and investigate the clinical significance of VE.Between February 2009 and September 2016, 363 consecutive patients with LC underwent capsule endoscopy for diagnosing portal hypertensive enteropathy at Hiroshima University Hospital. We evaluated the relationship between the presence of VE and patients' clinical characteristics, findings of esophagogastroduodenoscopy and computed tomography, and survival time.Villous edema was observed in 131 patients (36%), and severe lesions were found in 71 (20%). The presence of VE was significantly greater in patients with Child-Pugh classification B or C, esophageal varices, portal hypertensive gastropathy (PHG), ascites, portal vein thrombosis (PVT), and splenomegaly. In multivariate analysis, Child-Pugh class B or C, esophageal varices, PVT, and splenomegaly were significant predictive factors for the presence of VE. Severe VE was significantly greater in patients with Child-Pugh class B or C, serum albumin level ≤ 3.2 mg/dL, PHG, and PVT. In multivariate analysis, PHG, Child-Pugh class B or C, PVT, were significant predictive factors for severe VE.Clinical factors related to portal hypertension were significantly correlated with VE. In particular PVT was correlated with the appearance and exacerbation of VE. Periodic capsule endoscopy in LC patients may lead to early detection of portal hypertension and PVT.

The risk of hepatocellular carcinoma (HCC) development is reduced following viral elimination by interferon therapy in chronic hepatitis C patients. However, the risk in patients treated with interferon-free direct-acting antivirals (DAAs) is unknown. We evaluated chronic hepatitis C patients who achieved viral eradication by pegylated-interferon plus ribavirin (PEG-IFN/RBV, n = 244) or daclatasvir plus asunaprevir (DCV/ASV, n = 154) therapy. None of the patients had prior history of HCC or antiviral therapy. The median observation period after the end of treatment for the PEG-IFN/RBV and DCV/ASV groups were 96 (range 10-196) and 23 (range 4-78) months, respectively. During the observation period, HCC developed in 13 (5.3%) and 7 (4.5%) patients in the PEG-IFN/RBV and DCV/ASV groups, respectively. The cumulative HCC development rate after 1-, 3- and 5-years (0.4%, 3% and 5% for the PEG-IFN/RBV group and 0.6%, 9% and 9% for the DAA group, respectively) were similar between the two groups. Propensity score matching analysis also showed no significant difference in HCC development rates between the two groups. Serum AFP levels decreased to similar levels between PEG-IFN/RBV and DCV/ASV groups following the achievement of viral eradication. The risk for HCC development following viral eradication by IFN-free DAA therapy may be similar to that in IFN-based therapy.

Combination of sofosbuvir plus ledipasvir therapy has been expected to enhance sustained virological response (SVR) rates in hepatitis C virus (HCV) genotype 1 chronic infected patients. We analyzed the emergence of drug resistance-associated variants (RAVs) in treatment failure and changes in lipid profiles in sofosbuvir/ledipasvir-treated patients. A total of 176 patients with chronic HCV genotype 1 infection without decompensated liver cirrhosis were treated with sofosbuvir/ledipasvir for 12 weeks. NS5A and NS5B RAVs were determined by either Invader assay or direct sequencing. Serum lipid-related markers were measured at the start of treatment and at week 4 in patients who received sofosbuvir/ledipasvir and ombitasvir/paritaprevir/ritonavir therapies. SVR was achieved in 94.9% (167 out of 176) of patients. SVR12 rate was 97.1% for patietns with low frequncy (25%) of baseline NS5A RAVs, but 82.8% for patients with high frequency (75%) of NS5A RAVs. In multivariate regression analysis, higher albumin (odds ratio [OR] = 0.020 for presence; P = 0.007), and NS5A-L31/Y93 RAVs with a population frequency75% (OR = 29.860 for presence; P = 0.023) were identified as significant independent predictors for SVR12. NS5A-Y93H substitutions were detected in all nine treatment failures at HCV relapse, and three out of six patients with NS5A inhibitor-naïve patients achieved additional NS5A RAVs. Serum low-density lipoprotein cholesterol and apolipoprotein B levels were significantly elevated at week 4 in sofosbuvir/ledipasvir-treated patients. These elevations were greater than in ombitasvir/paritaprevir/ritonavir-treated patients. In conclusion, NS5A multi-RAVs are likely to develop in patients who fail to respond to sofosbuvir/ledipasvir therapy. Inhibition of HCV replication with sofosbuvir might affect lipid metabolism.

Wisteria floribunda agglutinin positive human Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker for liver fibrosis. However, it is not known whether or not M2BPGi reflects only liver fibrosis. We measured serum M2BPGi levels in patients with acute liver injury.Fifty-one patients with acute liver injury were enrolled. M2BPGi levels were measured at the initial visit and at achievement of recovery. The relationship between M2BPGi values at the initial visit and clinical outcomes was analyzed.Serum M2BPGi levels at the initial visit were elevated in 47 of 51 acute liver injury patients (8.33 ± 7.56 cutoff index). M2BPGi values were associated with prothrombin activity (r = -0.600, P = 0.001), total bilirubin level (r = 0.588, P = 0.001), and Model for End-Stage Liver Disease score (r = 0.490, P = 0.001) but not with aspartate aminotransferase (r = -0.070) and alanine aminotransferase (r = -0.073) levels. M2BPGi values at the initial visit were significantly higher in patients with acute liver failure (diagnosed by prothrombin activity of 40% or less; P 0.001), subsequent development of hepatic coma (P = 0.036), and subsequent requirement of liver transplant (P = 0.014), and in a patient who died (P = 0.045). M2BPGi values decreased after aminotransferase level normalization in patients who recovered from acute liver injury; however, M2BPGi level was not a predictive factor for recovery with medical therapy.Serum M2BPGi values increased in patients with acute liver injury and decreased following recovery. The marker seems to reflect not only liver fibrosis but also other factors, such as liver inflammation, liver damage, and hepatocyte regeneration.

Older patients with chronic hepatitis C have a lower virological response to interferon (IFN) treatment compared to younger patients. The efficacy of telaprevir (TVR) and PEG-IFN plus ribavirin combination therapy and the predictive value of recently identified IFN lambda (IFNL) 4 polymorphisms on the outcome of therapy for older patients have not been addressed.We assessed predictive factors for sustained virological response (SVR) to triple therapy in 226 younger (≤65 years) and 87 older (65 years) Japanese patients with chronic genotype 1 hepatitis C. IFNL4 polymorphism ss469415590 was analyzed by Invader assay.The SVR rate for older patients was slightly lower than for younger patients (69 vs. 82%, P = 0.043). In the older group, the SVR rate for patients with the IFNL4 TT/TT genotype was significantly higher than patients with TT/ΔG or ΔG/ΔG genotypes (81.8 and 42.9%, P = 0.003). In multivariate regression analysis, rapid virological response (OR 36.601, P = 0.002) and IFNL4 TT/TT genotype (OR 19.502, P = 0.009) were identified as significant independent predictors for SVR in older patients. Treatment-related decreases in hemoglobin and increases in serum creatinine were higher in older patients than younger patients. Reduction of initial TVR dose to 1,500 mg per day alleviated these adverse events without compromising SVR rate in older patients.Analysis of IFNL4 polymorphisms is a valuable predictor in older patients receiving TVR triple therapy. 1,500 mg per day is a suitable initial TVR dose for older Japanese patients.

Chronic hepatitis C virus (HCV) infection is associated with renal dysfunction. Daclatasvir and asunaprevir combination therapy showed a high virological response for genotype 1 chronic HCV-infected patients with renal dysfunction on hemodialysis. However, the safety and efficacy of the therapy for patients with renal dysfunction who are not on hemodialysis are not well-known. In total, 147 patients with chronic HCV genotype 1 infection were treated with 24 weeks of daclatasvir plus asunaprevir therapy. Among these patients, 126 had normal renal function (estimated glomerular filtration rate [eGFR] ≥ 50 ml/min/1.73 m2) and 21 had renal dysfunction (eGFR

Biomarkers predicting the response to the anticancer treatment and prognosis in patients with advanced hepatocellular carcinoma (HCC) are required. Recently, high mobility group box 1 (HMGB1) was reported to promote HCC progression and be associated with poor prognosis for patients with HCC. The purpose of this study was to assess serum HMGB1 concentrations before and during sorafenib treatment or hepatic arterial infusion chemotherapy (HAIC) and to explore the ability of serum HMGB1 concentrations to predict prognosis. Serum HMGB1 concentrations were measured in 71 and 72 patients with advanced HCC treated with sorafenib and HAIC, respectively, to assess their usefulness for prediction of the response to the treatment and prognosis. Multivariate analysis identified high HMGB1 at 4 weeks (P = 0.001), high α-fetoprotein (AFP) at baseline (P = 0.025), tumor liver occupying rate (P = 0.009) and modified RECIST (mRECIST, P

Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV) infected-patients. However, the real-world efficacy and safety of the therapy for patients with cirrhosis are unknown.A total of 252 patients with genotype 1 HCV infection (158 with chronic hepatitis and 94 with compensated liver cirrhosis) were treated with 24 weeks of daclatasvir and asunaprevir combination therapy. Plasma concentrations of daclatasvir and asunaprevir at day 5 of treatment, end-of-treatment response, sustained virological response (SVR), and the frequencies of adverse events were analyzed.Plasma asunaprevir concentration was significantly higher, and daclatasvir concentration tended to be higher, in cirrhosis patients compared with chronic hepatitis patients. End-of-treatment response was achieved in 95.6% and 94.7% of chronic hepatitis and cirrhosis patients, respectively, and SVR was achieved in 94.3% and 92.6%. Although pre-treatment NS5A drug resistant-associated variants were detected, a high SVR rate was achieved when the population frequency of the variant was low. The frequencies of treatment-related adverse events in cirrhosis patients were similar to those in chronic hepatitis patients. Treatment discontinuation due to adverse events occurred in three and two patients in chronic hepatitis and cirrhosis groups, respectively; however, four out of five patients with treatment discontinuation nonetheless achieved SVR.Patients with compensated liver cirrhosis have similar virological response and tolerance for daclatasvir plus asunaprevir therapy to patients with chronic hepatitis. This combination therapy might offer a safe and effective treatment for chronic HCV infected-patients with compensated cirrhosis.

Previous studies have demonstrated that afternoon naps can have a negative effect on subsequent nighttime sleep in children. These studies have mainly been based on sleep questionnaires completed by parents. To investigate the effect of napping on such aspects of sleep quality, we performed a study in which child activity and sleep levels were recorded using actigraphy. The parents were asked to attach actigraphy units to their child’s waist by an adjustable elastic belt and complete a sleep diary for 7 consecutive days. 50 healthy young toddlers of approximately 1.5 years of age were recruited. There was a significant negative correlation between nap duration and both nighttime sleep duration and sleep onset time, suggesting that long nap sleep induces short nighttime sleep duration and late sleep onset time. We also found a significant negative correlation between nap timing and nighttime sleep duration and also a significant positive correlation between nap timing and sleep onset time, suggesting that naps in the late afternoon also lead to short nighttime sleep duration and late sleep onset. Our findings suggest that duration-controlled naps starting early in the afternoon can induce a longer nighttime sleep in full-term infants of approximately 1.5 years of age.

Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV)-infected patients. However, the safety and efficacy of the therapy for older patients are unknown. One hundred seventy patients younger than 75 years and 139 patients aged 75 years or older with genotype 1 HCV infection were treated for 24 weeks with daclatasvir plus asunaprevir. Pretreatment drug-resistance-associated variants at NS5A-L31 and NS5A-Y93 were determined by the Invader assay. Virological response and adverse events according to age were analyzed. The sustained virological response (SVR) rate for older patients was similar to that for younger patients (97.1 and 92.4 % respectively). In multivariate regression analysis, prior simeprevir treatment (odds ratio 56.6 for absence; P

We report a case in which sustained viral response was achieved after switching treatment from pegylated interferon (PEG-IFN) α-2b to α-2a and ribavirin (RBV) in patients with recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation. The patient was a 62-year-old man with liver cirrhosis due to HCV genotype 1b infection. The patient had 8 amino acid (aa) substitutions in the interferon sensitivity-determining region, and had substitutions for mutant and wild-type at aa70 and aa91, respectively, in the core region. The patient had minor genotype (GG) IL28B single nucleotide polymorphisms (rs8099917). He had initially received interferon α-2b and RBV for 2 years, and later developed hepatocellular carcinoma (HCC). After surgical resection of HCC, he subsequently received PEG-IFN α-2b and RBV for 1.5 years, without undetectable viremia during the treatment course. Due to recurrence of HCC, the patient received a living donor liver transplantation. Later on, hepatitis C relapsed. For the management of relapse, he received another course of PEG-IFN α-2b and RBV. However, breakthrough viremia occurred. PEG-IFN was thus switched from α-2b to α-2a and RBV for another 17 months. The patient eventually achieved a sustained viral response.

We evaluated the clinical features and the prognostic factors of hepatocellular carcinoma (HCC) developed after hepatitis C virus (HCV) eradication with interferon (IFN) therapy. Forty-one consecutive patients who developed HCC after HCV eradication with IFN therapy were enrolled. Clinical features were reviewed, and overall survival and associated factors were analyzed. The recurrence rate in 26 patients receiving radical therapy was also analyzed. Twenty patients developed HCC within 5 years after the end of IFN therapy, 9 patients developed the disease from 5 to 10 years after the end of the therapy, 9 patients developed the disease from 10 to 15 years after the end of the therapy, and 3 patients developed the disease from 15 years after the end of the therapy. Multivariate analysis of independent variables for the development of HCC within 5 years identified age >55 years at HCV eradication (P = 0.007) and heavy alcohol intake (P = 0.009). The 5-year survival rate was 64%. On multivariate analysis of overall survival for the 41 patients, the only risk factor with prognostic influence was radical therapy (P = 0.010), which was associated with a cumulative 5-year survival rate of 91%. The only independent factor for the receipt of radical therapy was regular surveillance for HCC (P = 0.004). Among patients receiving radical therapy, the 3- and 5-year recurrence rates were 18 and 18%, respectively. We found that, despite HCV eradication, patients with the risk factors of high age at HCV eradication and heavy alcohol intake might be at heightened risk for the development of HCC within 5 years after HCV eradication. In contrast, risk factors for the development of HCC more than 10 years after HCV eradication were uncertain. These findings indicate the need for long-term surveillance for HCC after HCV eradication.

The aim of the present retrospective study was to evaluate the therapeutic efficacy and predictive factors of prolongation of treatment with peginterferon (PEGIFN) combined with ribavirin (RBV) for recurrent hepatitis C after living donor liver transplantation (LDLT).Fifty-three patients underwent LDLT due to HCV-related end-stage liver disease. Sixteen patients were removed from the study as a result of early death (n=14), no recurrence of HCV (n=1) and refusal of antiviral therapy (n=1). Therapy is ongoing in another 10 patients. The remaining 27 patients were available to establish the efficacy of IFN therapy. HCV genotype was 1b in 24 patients. All patients with genotype 1b were treated with IFN therapy for at least 48 weeks after HCV RNA levels had become undetectable. Amino acid substitutions in the HCV core region and NS5A region were analyzed by direct sequencing before LDLT.The rate of sustained virological response (SVR) was 37.0% (10/27). SVR rate in patients with genotype 1 was 29.2% (7/24) and 100% (3/3) in patients with genotype 2. Most patients with genotype 1b whose HCV RNA reached undetectable levels achieved SVR (87.5%; 7/8). However, mutation of the HCV core region and number of ISDR mutations were not associated with SVR rate in LDLT in our study.Prolonged IFN therapy for more than 48 weeks after HCV RNA reached undetectable levels might prevent virological relapse of HCV.

Background and aims The feature of blood glucose dynamics in patients with chronic liver disease (CLD) is marked blood glucose fluctuations. However, the detail of blood glucose dynamics is not well known. The aim of the present study was to evaluate glycemic fluctuations by continuous glucose monitoring (CGM). Materials and methods A total of 105 CLD patients with type 2 diabetes mellitus (T2DM) were enrolled in this study. Various parameters of glycemic variability were evaluated. The association of these parameters with liver functional reserve was examined. The parameters were also evaluated according to glycated hemoglobin A1c (HbA1c) levels. Results and discussion Data of all patients showed that mean blood glucose (MBG) levels and the difference between highest and lowest blood glucose (ΔBG) increased significantly with worsening of liver functional reserve (P < 0.001 and P = 0.005, respectively). Although many of the cases were being treated for diabetes, postprandial hyperglycemia was seen in 92% of patients. Nocturnal hypoglycemia was seen in 22% of patients. In non-anemic patients with HbA1c levels of < 7.0%, the percentage of patients with mean amplitude of glycemic excursion (MAGE) of ≥ 77.4 mg/dL and that of MBG levels of > 145 mg/dL were higher in liver cirrhosis (LC) patients than in chronic hepatitis (CH) patients. In them, homeostasis model assessment for insulin resistance (HOMA-IR) of > 2.5 and LC were significantly associated with the increase in MAGE. LC was also significantly associated with increased MBG levels. Conclusion The CGM systems were useful in finding hidden abnormalities of blood glucose fluctuations in CLD patients with T2DM, especially in non-anemic CLD patients with HbA1c levels of < 7.0%.

We present the cases of 3 children with huge undifferentiated sarcoma of the liver who were treated with surgical excision including liver transplantation as an option and adjuvant chemotherapy. All 3 patients were males aged 10, 13, and 15 years old. The size of the tumor was 10, 15, and 20 cm in diameter, respectively. The youngest patient is disease free and doing well 43 months after resection. The 13-year-old patient presented with tumor rupture and underwent operation. The primary tumor and the ruptured tissue fragments were removed and he was given postoperative chemotherapy. The patient is disease free and doing well 52 months after surgery. The oldest patient had an unresectable tumor in the hilar region. Preoperative chemotherapy was given but later discontinued owing to severe side effects. He underwent living donor liver transplantation followed by postoperative chemotherapy. The patient had recurrent tumor 24 months after transplantation that was excised at reoperation. He is doing well and is disease free 18 months after the second procedure. Complete removal of the tumor including total hepatectomy and transplantation when indicated and suitable pre- and/or postoperative chemotherapy is an effective treatment for children with undifferentiated sarcoma of the liver.

We assessed the risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon (IFN) therapy in a long-term, large-scale cohort study.We reviewed 1094 consecutive patients with HCV who achieved sustained virological response (SVR) following IFN therapy between January 1995 and September 2013.During the observation period (median 50 months: range 13-224), 36 (3%) of 1094 patients developed HCC after SVR. The median period from SVR to diagnosis of HCC was 37 months (range 17-141), and the cumulative rates of HCC at 5, 10, and 15 years were 4%, 6%, and 12%, respectively. Multivariate analysis identified old age (≥60 years, HR, 3.1: 95%CI, 1.3-6.6: P = 0.009), male sex (HR, 12.0: 95%CI, 2.8-50.0: P 0.0001), advanced fibrosis stage (F3/4, HR, 3.2: 95%CI, 1.6-7.2: P 0.0001), and alpha-fetoprotein ≥10 ng/mL at 1 year after SVR (HR, 7.8: 95%CI, 2.9-16.8: P 0.0001) as significant and independent risk factors for post-SVR HCC.Older age and male sex (host factors), advanced fibrosis stage (pre-IFN treatment factor), and higher alpha-fetoprotein values (post-treatment factor) were significantly associated with HCC development after HCV eradication.

We retrospectively evaluated the local tumor control and safety of transcatheter arterial chemoembolization (TACE) followed by stereotactic body radiation therapy (SBRT) for small hepatocellular carcinoma (HCC) in this pilot study.Twenty-eight patients not for the indication of hepatectomy or ablation procedures were enrolled in this study. Eligible criteria was as followed: i) less than 3 hypervascular HCC nodules, each up to 30 mm in diameter; ii) not suitable for the hepatic resection or ablative therapy; iii) Child-Turcotte-Pugh (CTP) scoreor = 7. SBRT was performed within 1-2 months after TACE. Treatment efficacy was evaluated, according to the Response Evaluation Criteria in Cancer of the Liver (RECICL).The median local tumor control time was not reached. The 1-year cumulative local tumor control rate was 96.3%. The median disease-free survival time was 18 months. The 1- year cumulative overall survival rate was 92.6%. One patient (3.6%) died due to intrahepatic ectopic multiple recurrence and systemic metastasis and one (3.6%) due to cerebral hemorrhage. No patients experienced severe acute hematologic or physical toxicity or radiation induced liver damage.Our study demonstrated SBRT combined with TACE is a safe and effective modality of the locoregional therapy for small primary HCC.

Delay of umbilical cord clamping by at least 1 min is recommended for newborns not requiring resuscitation in the International Liaison Committee On Resuscitation-Consensus on Science with Treatment Recommendations (ILCOR-CoSTR) 2010 guidelines. The delay in clamping improves iron status through early infancy but may increase the likelihood of jaundice requiring phototherapy. The present study investigated the relationship between umbilical cord hemoglobin and the rate of jaundice requiring phototherapy in healthy Japanese newborns.Cord hemoglobin was measured in healthy newborns and the rate of infants receiving phototherapy for jaundice and other data were obtained from medical records.Jaundice requiring phototherapy mostly occurred in association with high cord blood hemoglobin, which is increased by delayed cord clamping.Higher cord hemoglobin may increase neonatal jaundice in newborns in Japan, therefore the present results support the Japan Resuscitation Council guideline 2010, which does not recommend delay of umbilical cord clamping by at least 1 min, in contrast to the ILCOR guidelines.

The aim of this study was to evaluate the birth and discharge dates of neonates and analyze their distribution over days of the week and the old lunar calendar.A retrospective study of the neonates discharged in the years 1990, 2000, 2005, and 2010 was conducted in a general hospital in Tokyo, Japan. Data are represented as odds ratios (OR) of the total number of discharges per day divided by the expected number of days per year, for each day of the week as well as each 6 day cycle of the lunar calendar.The timing of discharge has an uneven distribution across the days of the week, with weekday discharge rates significantly lower than weekend discharge rates. This uneven distribution is particularly significant in the preterm subgroup. In contrast, there is a minor uneven distribution of births across the days of the week and that of discharges across the 6 day cycle of the lunar calendar. Logistic regression analysis for 2005 and 2010 identified admission fee paid by insurance and prematurity as significant factors associated with weekend/holiday discharge (OR, 1.84; 95% confidence interval [CI]: 1.23-2.75; OR, 1.71; 95% CI: 1.15-2.55, respectively). The average length of stay of neonates discharged on the weekend was longer than that for those discharged on a weekday, in both term and preterm infants.Japanese parents prefer the convenience of weekends over old superstitions about using the lunar calendar to determine the discharge date.

A 61-year-old man was admitted to our hospital for examination of the cause of rapid growth of a liver cyst. We found a slight dilatation of bile duct in the vicinity of the liver cyst. Then, we underwent ERCP and found a communication between the bile duct and liver cyst. Bile cytodiagnosis revealed a large quantity of clonorchis eggs. The patient like to do eat raw freshwater fish and we suspected that the acute expansion of the cyst was due to clonorchiasis. Following administration of 40mg/kg praziquantel, the blood clonorchis antibody disappeared and the liver cyst also disappeared after 6 months. We encountered a case of clonorchiasis complicated with growth of a liver cyst. Medical interviews should be conducted carefully along with meticulous examinations.

To compare the tumor control and safety of stereotactic body radiation therapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) for small, solitary, and hypervascular hepatocellular carcinoma (HCC) with TACE alone.Three hundred and sixty-five HCC patients who had solitary, ≤ 3 cm, and hypervascular nodule were treated with TACE. Among them, 30 patients followed by SBRT (SBRT group) and 38 patients without additional therapy and previous HCC treatment (control group) were enrolled in this retrospective cohort study. Local tumor progression, complication, and disease-free survival were compared between these groups.There was no difference in clinical background between these groups. Complete response to therapy was noted in 29 (96.3%) patients of the SBRT group, and in only one (3.3%) patient of the TACE group (P 0.001). None of the patients developed acute hematologic toxicity of more than Common Terminology Criteria for Adverse Events Grade 3 during and after the treatment. Furthermore, none of the SBRT group developed radiation-induced liver damage. Disease-free survival of the 12 patients without previous HCC treatments in SBRT group was significantly superior to that in control group (15.7 months vs 4.2 months; P = 0.029).The results indicated that SBRT combined with TACE is a safe and effective modality for locoregional treatment of small solitary primary HCC, and could be potentially a suitable option.

A 30-year-old man underwent a left lobectomy and S5/6 partial hepatectomy in August 2001 for hepatocellular carcinoma (HCC). A lung tumor was detected by positron emission tomography (PET-CT) 8 years after the surgery. In May 2010, he received pulmonary tumor resection and the histopathological findings revealed metastasis of HCC. However a metastatic brain tumor was detected by computed tomography (CT) in September 2010, therefore surgery and radiation therapy were subsequently performed. Thereafter, metastatic hilar lymph node appeared in December 2010, therefore we performed systemic chemotherapy using S-1/cisplatin combined with radiation therapy for the metastatic tumor. The tumor was markedly decreased and no shadow was detected by PET-CT. He has been followed up in the outpatient clinic with no recurrence.

We aimed to identify risk factors contributing to the exacerbation of esophageal varices (EV) or portosystemic encephalopathy after hepatitis C virus (HCV) eradication with interferon (IFN) therapy in patients with compensated cirrhosis. Also, the prognosis after HCV eradication was analyzed. Fifty-two patients with sustained virological response to IFN treatment for HCV-related compensated cirrhosis were enrolled in this retrospective cohort study. At the achievement of HCV eradication, in 31 of the 52 patients (60 %), feeding vessels for EVs (left gastric vein, posterior gastric vein, short gastric vein) were shown, and in 18 patients (35 %) there were extrahepatic portosystemic shunts (paraesophageal vein, paraumbilical vein, and splenorenal shunt). Although the HCV eradication was successful, significant improvements were not observed in portosystemic collateral vessels 1 year after HCV eradication, and EVs were exacerbated in 19 (36 %) patients. The cumulative 1- and 3-year rates of EV exacerbation were 13 % and 49 %, respectively. By multivariate analysis, the existence of feeding vessels for EVs at HCV eradication was an independent predictive factor for the exacerbation of EVs (P = 0.009). Seven patients who had an extrahepatic portosystemic shunt at HCV eradication developed portosystemic encephalopathy during follow up. The 1-, 3-, and 5-year incidences of portosystemic encephalopathy were 6, 21, and 34 %, respectively. The cumulative 5-year survival rate of the cohort was 81 %. Two patients died of hepatocellular carcinoma (HCC). Our findings suggest that the existence of radical portosystemic collateral vessels at successful HCV eradication increases the risk of the exacerbation of EVs and the incidence of portosystemic encephalopathy in patients with HCV-related cirrhosis.

Objective: To compare the assessment of response and prognosis of patients to sorafenib treatment by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP). Methods: Sixty-six patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib were enrolled in this retrospective study. The response to treatment was evaluated by RECIST, mRECIST and changes in AFP and DCP. Results: The median survival time of all patients was 8.6 months. The median time to radiological progression was 3.3 months. The response rates [complete response (CR) + partial response (PR)] by RECIST and mRECIST were 3.0 and 9.0%, respectively, while the disease control rates [CR + PR + stable disease (SD)] were 50 and 50%, respectively. Assessment by mRECIST of overall survival provided a better stratification of the patients according to the response to treatment (p = 0.009) than RECIST (p = 0.09). Assessment of overall survival by a change in AFP ratio of ≤1 at 8 weeks was better than that of >1 at 8 weeks (p = 0.002). The DCP ratio was not useful for assessment of overall survival. Multivariate analysis identified mRECIST response (CR + PR + SD; p = 0.001), AFP ratio at 8 weeks (≤1; p = 0.046) and Child-Pugh A before treatment (p = 0.012) as significant and independent determinants of survival. The combination of AFP ratio at 8 weeks, assessment by mRECIST and Child-Pugh score before treatment allows stratification of prognosis of patients treated with sorafenib. Conclusion: The combination of mRECIST and AFP ratio is useful for the assessment of prognosis of patients with advanced HCC treated with sorafenib.

A 60 year-old woman was admitted to our hospital because of management of multiple liver tumors. According to image findings and liver biopsy, she was diagnosed as having epithelioid hemangioendothelioma of the liver accompanied by metastases in the spleen, lungs and bones. Based on the spread of the liver tumors and the extensive systemic metastases, she was considered inoperable. Instead, she received hepatic arterial infusion therapy using recombinant interleukin-2. However, she died due to liver failure about two months after admission. Autopsy revealed that the liver tumor was angiosarcoma. It is difficult to differentiate angiosarcoma from epithelioid hemangioendothelioma based on the image findings and pathological findings of percutaneous liver biopsy. Many cases are diagnosed as angiosarcoma at autopsy. There is no established effective treatment for hepatic angiosarcoma, because the tumor stage at the time of diagnosis is often progressive. To date, immunotherapy with recombinant interleukin-2 has been reported to be effective clinically for cutaneous angiosarcoma, such as of the scalp and facial skin. To our knowledge, there have been no reported cases of hepatic angiosarcoma treated with recombinant interleukin-2. Our case is important should recombinant interleukin-2 be considered effective for hepatic angiosarcoma in the future.

A sixties woman was found to have diagnosed by abdominal ultrasonography with a tumor in the left lobe of the liver and was referred to our institution in 1998. Abdominal magnetic resonance imaging (MRI) showed a typical, 70×45 mm cavernous hemangioma, which was followed up by annual MRI. In 2006, 8 years after the initial diagnosis, the MRI showed that the tumor had reduced to 30×15 mm. Although atypical of hemangioma, review of the annual observations indicated a diagnosis of regressive hemangioma, which also accorded with clinical observations. In 2009, a liver biopsy was performed by laparotomy during gastrectomy for gastric cancer. Pathological examination of the biopsy revealed sclerosed hemangioma tissue, confirming the diagnosis of regression of a cavernous hemangioma to a sclerosed hemangioma over 12 years.

A 55-year-old man with advanced gastric cancer underwent total gastrectomy (T3N0M0, stage II , por, sig) in the USA. Following his return to Japan, the patient then suffered from a recurrence with ileus, bilateral hydronephrosis and ascites caused by peritoneal dissemination. Systemic chemotherapy of paclitaxel combined with 5-FU was performed, and after four cycles, ileus, bilateral hydronephrosis and ascites disappeared. S-1 monotherapy was started to maintain his QOL, but after five cycles, ileus of the transverse colon recurred. Colostomy was performed and systemic chemotherapy of paclitaxel combined with S-1 was performed. For 13 months, the patient's condition remained stable and he returned to society, but died 30 months after the first recurrence. This case suggests that paclitaxel-based chemotherapy is a promising treatment for gastric cancer with peritoneal dissemination.