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Reports on the association between idiopathic thrombocytopenic purpura (ITP) and hepatitis C virus infection. Patterns of virus associated ITP; Possible reasons for ITP.

Aim Various loci and genes that confer susceptibility to coronary artery disease ( CAD) have been identified in Caucasian populations by genome-wide association studies ( GWASs). The aim of the present study was to examine a possible association of chronic kidney disease ( CKD) with 29 polymorphisms previously identified as susceptibility loci for CAD by meta-analyses of GWASs. Methods The study population comprised 2247 Japanese individuals, including 1588 subjects with CKD [estimated glomerular filtration rate ( eGFR) of <60 mL min−1 1.73 m−2] and 659 controls ( eGFR of ≥90 mL min−1 1.73 m−2). The genotypes for 29 polymorphisms of 28 candidate genes were determined. Results The χ2 test revealed that rs4845625 ( T→ C) of IL6R, rs4773144 ( A→ G) of COL4A1, rs9319428 ( G→A) of FLT1, and rs46522 ( T→ C) of UBE2Z were significantly ( P < 0.05) related to CKD. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidaemia revealed that rs4845625 of IL6R ( P = 0.0008; dominant model; odds ratio, 1.49), rs4773144 of COL4A1 ( P = 0.0252; dominant model; odds ratio, 1.28), and rs9319428 of FLT1 ( P = 0.0260: additive model; odds ratio, 0.77) were significantly associated with CKD. The serum concentration of creatinine was significantly ( P = 0.0065) greater and eGFR was significantly ( P = 0.0009) lower in individuals with the TC or CC genotype of IL6R than in those with the TT genotype. Conclusion The rs4845625 of IL6R may be a susceptibility locus for CKD in Japanese individuals. [ABSTRACT FROM AUTHOR]

Invasive species and anthropogenic habitat alteration are major drivers of biodiversity loss. When multiple invasive species occupy different trophic levels, removing an invasive predator might cause unexpected outcomes owing to complex interactions among native and non-native prey. Moreover, external factors such as habitat alteration and resource availability can affect such dynamics. We hypothesized that native and non-native prey respond differently to an invasive predator, habitat alteration and bottom-up effects. To test the hypothesis, we used Bayesian state-space modelling to analyse 8-year data on the spatio-temporal patterns of two endemic rat species and the non-native black rat in response to the continual removal of the invasive small Indian mongoose on Amami Island, Japan. Despite low reproductive potentials, the endemic rats recovered better after mongoose removal than did the black rat. The endemic species appeared to be vulnerable to predation by mongooses, whose eradication increased the abundances of the endemic rats, but not of the black rat. Habitat alteration increased the black rat�s carrying capacity, but decreased those of the endemic species. We propose that spatio-temporal monitoring data from eradication programmes will clarify the underlying ecological impacts of land-use change and invasive species, and will be useful for future habitat management. [ABSTRACT FROM AUTHOR]

An understanding of the underlying processes and comprehensive history of invasive species is necessary to assess the long-term effectiveness of invasive species management. However, continuous, long-term labour-intensive population surveys on invasive species are often not feasible. Thus, it is important to learn about their dynamics through management action and its consequences., Amami Island, Japan, has an ongoing large-scale and long-term eradication programme of invasive small Indian mongooses. To estimate the long-term pattern of population size and the parameters determining the dynamics, including anthropogenic removal, we applied a surplus-production model within a Bayesian state-space formulation incorporating the initial population size, number of captures and capture effort. Using the estimated process model directly, we conducted stochastic simulations to evaluate the feasibility of eradication., Estimated 32-year annual capture probability of mongooses has increased since their introduction. The population size started to decline in 2001; mean population size in 2000 was 6141 (95% CI: 5415-6817), and declined to 169 (95% CI: 42-408) by 2011. Parameter estimates of a Weibull catchability model indicated that there was large individual heterogeneity in the probability of being captured, and per-effort capture probability declined with an increase in annual capture effort., The simulation study indicated that the eradication feasibility in 2023 would be over 90% if the same annual capture effort is upheld as in 2010 (2 075 760 corrected trap-days). However, increasing annual capture effort would have little effect on shortening the time to eradication., Synthesis and applications. A hierarchical model that incorporates multiple types of data to reveal long-term population dynamics has the potential to be updated with the outcomes of control efforts, and will enhance adaptive management of invasive species. This approach will offer valuable information about trade-offs between time to eradication success and effort per unit time in a long-term eradication project, and the length of time needed to continue management actions to achieve eradication success. [ABSTRACT FROM AUTHOR]

A 56-year-old woman was referred to our hospital due to fever and cholestatic liver dysfunction. Her eosinophil count was normal and she had no abdominal pain or neurological manifestations. We performed a liver biopsy and found fibrinoid necrosis of the hepatic artery with granulomatous reaction and eosinophilic infiltration in the portal area in the liver. Later, sensory abnormalities of the arms and legs appeared and the eosinophil count increased. Serum immunoglobulin E and immunoglobulin G4 were elevated and rheumatoid factor was strongly positive. Endoscopic retrograde cholangiopancreatography revealed no abnormality of the bile duct and pancreatic duct. We made a diagnosis of Churg-Strauss syndrome and began corticosteroid treatment. Fever and liver function immediately improved. In the present patient, Churg-Strauss syndrome manifested first in the liver, before hypereosinophilia and neural manifestations. We believe that Churg-Strauss syndrome is an autoimmune liver disease, and it is important to recognize that the liver may be involved in Churg-Strauss syndrome. [ABSTRACT FROM AUTHOR]

A 50-year-old woman was referred to our hospital due to liver dysfunction and progressive neurological symptoms. She had previously been diagnosed with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) had effectively normalized her serum aminotransferase levels, however, she presented with loss of balance, dysarthria and difficulty in handwriting. Autoantibodies and hepatitis virus markers were negative. Serum ceruloplasmin and copper levels were noted to be 9 mg/dL and 32 µg/dL, respectively. The 24-h urinary copper excretion was 331.8 µg/day. Kayser-Fleischer ring was demonstrated. Histological examination of the liver revealed inflammatory infiltrate and fibrosis, and the hepatic copper concentration was 444.4 µg/g dry weight. We diagnosed her as having Wilson disease and started treatment with trientine. Immuohistochemistry for keratin 8 and p62 demonstrated Mallory-Denk bodies. Many of the p62-expressing cells were positive for 4-Hydroxy-2-nonenal (HNE). Few Ki-67-positive hepatocytes were present in the liver. Wilson disease is one of the causes of NASH and UDCA may be a supportive therapeutic agent for Wilson disease. Cell proliferation is suppressed under copper-loaded conditions and this phenomenon may be associated with the clinical course of Wilson disease. [ABSTRACT FROM AUTHOR]

Abstract: To reveal a subsurface structure beneath the southern part of the Boso Peninsula, Japan, where the Philippine Sea plate is subducting and great interplate earthquakes associated with the subduction occur repeatedly, we conducted a new seismic reflection survey from March to April 2005 (Boso05). We also reanalyzed old multi-channel seismic (MCS) survey data that had been collected off the Boso Peninsula in 1978 (SK78). We found clear strong reflectors beneath the southern coast of the Boso Peninsula. Since common mid points (CMPs) were distributed widely beneath the study area owing to the design of the receiver and shot lines of Boso05, we selected appropriate directions of stacking lines to get the best image of the dipping reflectors by optimum azimuth search (OAS) processing. We carefully checked the seismic profiles at the intersections of the survey lines to confirm the NNE-dipping configuration of the strong reflectors. These strong reflectors were interpreted as the upper surface of the subducting PHS plate from their locations and the estimated velocities beneath the reflectors. Furthermore, these reflectors revealed a topographic high (bump) beneath the southern coast of the Boso Peninsula where the source fault of the Genroku earthquake of 1703 is thought to be located. [Copyright &y& Elsevier]

Abstract: Concentrations of 22 elements (Mg, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Ag, Cd, Sb, Cs, Ba, Tl, total Hg (T-Hg), Pb) and organic Hg (O-Hg) were examined in the liver, kidney and brain of the Javan mongoose (Herpestes javanicus) and in liver of the Amami rabbit (Pentalagus furnessi) from Amamioshima Island in Japan. Relatively high levels of T-Hg levels (from 1.75 to 55.5μgg−1 wet wt.) were found in the Javan mongoose. As for a comparison of hepatic T-Hg concentrations between the two areas, there was no significant difference between the Javan mongoose in Amamioshima and those in the Okinawa islands. In addition, T-Hg levels in the livers of the Amami rabbit were the same as in the livers of other herbivorous mammals. Taken together, it suggested that T-Hg accumulation in the livers of the Javan mongoose was not affected by the environment but by a specific physiological mechanism. The comparison of Hg and other heavy metal accumulations between terrestrial mammals (13 species, 61 individuals) including the Javan mongoose and marine mammals (18 species, 508 individuals) were also discussed. [Copyright &y& Elsevier]

BACKGROUND AND AIMS: The efficacy of interferon (IFN)-based antiviral therapy for chronic hepatitis C (CHC) varies depending on predictive factors such as hepatitis C virus (HCV) genotype and viral load. For patients with good predictive factors, a low dose and short course of IFN-based therapy may be adequate. However, there is no evidence about the optimal duration of IFN-based therapy for these patients. The aim of this study was to clarify whether the duration of IFN therapy could be shortened to less than the conventional treatment period for patients with good predictive factors.METHODS: A total of 25 treatment-naive CHC patients with genotype 2a were randomized to receive either IFN monotherapy for 24 wks (group A: long-term IFN therapy, n= 13) or for 6 wks (group B: short-term IFN therapy, n= 12). Patients were monitored for HCV RNA and routine liver function tests during and following treatment, and data were examined according to intention-to-treat analysis.RESULTS: Eleven of 13 patients in group A and all patients in group B completed IFN therapy according to the original planned schedule. At the end of the treatment, viral clearance occurred in all patients. However, 4 patients in group A and 5 in group B relapsed within 6 months of follow-up. There was no significant difference of sustained response rate between group A (53.8%) and group B (58.3%). Among patients who had HCV viral load of<100 kIU/ml, the sustained response rate was 83.3% (5/6) in group A and 100% (5/5) in group B.CONCLUSIONS: In this study, our results suggest that the duration of IFN therapy can be shortened to less than 24 wks in patients with good predictive factors. Further studies, however, should examine the optimal regimen of IFN therapy based on the backgrounds of patients.(Am J Gastroenterol 2005;100:1-6) [ABSTRACT FROM AUTHOR]

A rare autopsy case of hepatocellular carcinoma (HCC) presenting as extrahepatic bile duct obstruction is reported. A 54-year-old man who had been treated at another hospital for obstructive jaundice was referred to our hospital and admitted on March 1, 1998, because of progressive jaundice. On hospital day 94, he died of bleeding esophageal varices. At autopsy, a bile duct tumor, measuring 3.0 x 3.5 cm and adhering to the wall of the left hepatic duct, occluded the common hepatic duct at the hilus. A tumor measuring 2.0 x 2.0 cm was found in the parenchyma of the left liver lobe. The parenchymal tumor was not continuous with the extrahepatic bile duct tumor. Histologically, the bile duct tumor and the parenchymal tumor of the left lobe were diagnosed as HCC. The bile duct tumor was attached to the mucosa of the bile duct with a thin stalk. No invasive growth into the submucosa was observed. The tumor may have been an intrabiliary transplantation from the HCC in the left lobe via the bile duct. [ABSTRACT FROM AUTHOR]

Abstract Background and Aims: Troglitazone is a newly developed antidiabetic drug and is indicated to be useful for the treatment of patients with type II diabetes mellitus. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. In addition, a relationship between the activation of the peroxisome proliferator-activated receptor gamma receptor by troglitazone and colon tumorigenesis has been suggested. The present study was undertaken to examine the effects of long-term administration of troglitazone on the liver and intestine in genetically obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) and control Long-Evans Tokushima Otsuka (LETO) rats. Methods: A troglitazone-rich diet (200 mg/100 g normal chow) or a standard rat chow, free of troglitazone (control), was given to OLETF and LETO rats from 12 or 28 weeks of age until 72 weeks of age. Serum levels of glucose, insulin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined at several time points. In addition, histology of the liver and intestine and serum levels of cholesterol and triglycerides were examined at 72 weeks of age. Results: Troglitazone prevented age-related increases in fasting glucose and insulin concentrations in OLETF rats, but had no significant influences on serum levels of AST and ALT in both strains of rats. The liver weights in the control OLETF rats were significantly heavier than in the LETO rats. Troglitazone significantly reduced serum cholesterol and triglyceride levels and the liver weight. However, it had no influence on the large intestine weight and the number of colonic polyps in both OLETF and LETO rats. Sections of the liver from the untreated OLETF rats showed mild fatty changes in the central zone of the hepatic lobule, whereas those from the troglitazone-treated OLETF rats appeared normal with no fat deposition in the hepatocytes. Troglitazone in LETO rats also caused no significant histopathologic changes of the liver tissue. Conclusion: Our present study demonstrated that long-term administration of troglitazone prevents the progress of the metabolic derangement and fatty changes of the liver in genetically determined obese diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Two cases of Cronkhite-Canada syndrome are reported. In the first case, a 56-year-old woman had an adenoma of the colon, arising within the Cronkhite-Canada polyps, which was removed by endoscopic polypectomy. This suggests possible neoplastic transformation of polyps in this syndrome. She achieved remission with corticosteroids, but the polyposis recurred (only in the stomach) 7 months after the remission. In the recurrent polyposis, corticosteroid therapy resulted again in complete remission, which has lasted for 5 years. In the second case, a 69-year-old man developed typical manifestations of the syndrome while under emotional stress. He had a past history of chronic pityriasis lichenoides, and serum antinuclear antibody was positive. These findings suggested a possible role of autoimmune response in the pathogenesis of the syndrome. Corticosteroids were also effective in this patient. [ABSTRACT FROM AUTHOR]

• Rabbit hepatitis E virus (HEV) circulates among feral rabbits in Japan. • Persistent HEV infection was observed in a rabbit experimentally infected with the HEV isolate JP-59. • Further studies are required to determine the zoonotic risk of rabbit HEV. Rabbit hepatitis E virus (HEV) has been detected among rabbits and recently isolated from immunocompromised patients, suggesting zoonotic transmission. In this study, HEV infection among feral rabbits (Oryctolagus cuniculus) was assessed by detection of anti-HEV antibodies and HEV RNA. The prevalence of anti-HEV antibodies in sera was of 33 % (20/60) and HEV RNA was detected from only one of fecal swabs (1.7 %, 1/58). Furthermore, one naïve rabbit was intravenously inoculated with the suspension of the HEV-positive fecal specimen, exhibiting persistent HEV shedding in feces, intermittent viremia, seroconversion to anti-HEV IgM and IgG, and high alanine aminotransferase (ALT) values, indicating persistent HEV infection. The isolate JP-59 had a length of 7,282 bp excluding a poly (A) tail and possessed the characteristic 93 bp-insertion in ORF1. Phylogenetic analysis indicated that JP-59 formed a cluster with other rabbit HEV isolates from rabbits and human origin. The JP-59 shared the nucleotide sequence identities less than 87 % with other rabbit HEVs, suggesting that a novel rabbit HEV strain was circulating in Japan. [ABSTRACT FROM AUTHOR]

A 54-year-old man was diagnosed as having pancreatic cancer and disseminated intravascular coagulation. His plasma tissue factor level on the 11th hospital day was 996 pg/ml (normal range, 120–270 pg/ml). He was treated with gabexate mesilate, antithrombin III, and low-molecular-weight heparin. However, he died of multiple organ failure on the 17th hospital day. The histological finding was poorly differentiated ductal adenocarcinoma of the pancreas, and the production of tissue factor in this lesion was revealed. Tissue factor is a factor that initiates blood coagulation; thus, its expression in pancreatic cancer is one of the causes of coagulation abnormalities in this disease. Although one report has demonstrated immunoreactivity for tissue factor in pancreatic cancer, the patient's detailed clinical course was not mentioned in that report. This is the first report to prove that pancreatic cancer produced tissue factor in a patient with disseminated intravascular coagulation. [ABSTRACT FROM AUTHOR]

Obesity is a major contributor to insulin resistance and nonalcoholic fatty liver disease, which is the most common cause of chronic liver diseases. Nonalcoholic steatohepatitis (NASH) can progress to liver cirrhosis and end-stage liver diseases. Some cases already show severe liver fibrosis at the time of diagnosis. We present the case of a 44-year-old male with overt obesity who was admitted with hematemesis due to the rupture of gastric varices. We diagnosed him with NASH with severe liver fibrosis. This case shows that we should be concerned about the progression of liver fibrosis due to NASH associated with severe obesity even in young patients. [ABSTRACT FROM AUTHOR]

Proves that the duration of the interferon (IFN) therapy can be shortened, and that the total dose of IFN can be reduced for IFN-sensitive patients with chronic hepatitis C in Japan. Association between high dosage of interferon and severe general fatigue and neutropenia; Effectiveness of interferon therapy for patients with a low viral load than those with a high viral load.

Asymptomatic splenic nodules were detected incidentally in two middle-aged women at an annual checkup. They showed no abnormalities on laboratory tests, but imaging studies revealed splenic nodules. No other localized lesions were found. Splenic nodules were hypoechoic on ultrasonography (US), hypovascular on contrast-enhanced computed tomography, and showed a low intensity on T2-weighted magnetic resonance imaging. We performed US-guided percutaneous aspiration biopsies using 21-gauge needles without complications, including bleeding. Pathological specimens showed noncaseating granulomas, so both patients were diagnosed with isolated splenic sarcoidosis. A US-guided fine-needle aspiration biopsy is a safe and useful method for diagnosing splenic nodules.

A 72-year-old woman with advanced lung cancer had received systemic chemotherapy including atezolizumab. About three months after the initial administration of atezolizumab, her liver enzyme levels increased. The histopathological findings of the initial liver biopsy revealed acute inflammatory infiltrate, predominantly CD3 + , CD4 + and CD8 + T lymphocytes, in the hepatic lobules. We diagnosed her with atezolizumab-induced immune-related acute hepatitis. Oral corticosteroid therapy successfully improved the elevation of serum aminotransferases. A sequential liver biopsy demonstrated the rapid progression of liver fibrosis. Because hepatocellular carcinoma occurs most often in advanced cases of chronic liver disease, we should pay close attention to immune-related acute hepatic injury when treating patients with advanced liver diseases using atezolizumab.

A 75-year-old-man experienced liver dysfunction and was diagnosed with decompensated liver cirrhosis. His serum hepatocyte growth factor (HGF) was very high (16.24 ng/ml). Because the etiology was unclear, we considered the possibility of amyloidosis. Biopsy of the mucosa of the stomach, duodenum and rectum demonstrated amyloid deposition. From the findings of Congo red staining and immunohistochemical analyses, we made a diagnosis of systemic amyloid light-chain amyloidosis. Unfortunately, the patient died one month after the diagnosis. We considered that serum HGF was useful for the diagnosis and prediction of prognosis of primary systemic amyloidosis.

Prevalence of antibodies to Toxoplasm gondii was studied using the latex agglutination (LA) method, followed by sucrose density gradient centrifugation (SDGC) method on the small Indian mongoose (Herpestes auropunctatus), which inhabits Amami-Oshima Island. Of the 362 samples, 38 (10.5%) revealed positive. Single or double peaks in the 7-8 and/or 12-14 fraction to LA titer by SDGC indicated the early stage of T. gondii infection. It is suggested that domestic/feral cats play an important role for spreading this zoonotic pathogen to the mongoose as well as other species that are endemic to this island. Future studies are warranted to prevent the transmission of T. gondii among cats and wild animals in order to maintain the ecosystem health.

A 37-year-old Wilson disease patient treated with D-penicillamine visited our hospital for the evaluation of his liver function. Laboratory data showed a low serum copper level and ceruloplasmin. The ratio of urinary copper to urinary creatinine in a spot urinary analysis after 4 days' cessation of D-penicillamine was under 0.1. We concluded that the copper chelation was excessive and changed D-penicillamine to zinc acetate. However, his liver function test results did not normalize. We performed a liver biopsy and discovered a high copper content. The liver dysfunction was improved after resuming chelating therapy. Accurate measurement of the hepatic copper content via a biopsy is important for the adequate management of this disease.

Pathological studies have suggested the different process of in-stent restenosis (ISR) of bare-metal stents (BMS) and drug-eluting stents (DES). Here, we evaluated the components of neointimal tissue using integrated backscatter intravascular ultrasound (IB-IVUS) and focused on the time course after stent implantation and tissue signal distribution. We evaluated 125 lesions of 125 patients who underwent target lesion revascularization for ISR (BMS: n = 73, DES: n = 52). Volume analysis of a 4-mm length centered on a minimum lumen area in every 1-mm cross-sectional area was performed. For IB-IVUS analysis, color-coded maps were constructed from the default setting based on the integrated backscatter (IB) values (middle-IB value, green: fibrous and low-IB value, blue: lipid pool). For the neointimal tissue volume, we evaluated the ratios of the green (%G) and blue (%B) areas. Tissue signal distribution (TD) was also obtained from the default setting based on IB values in each pixel of IB-IVUS imaging. We compared values of neointimal tissues measured by IB-IVUS between the DES and BMS and time course. The observed period was longer after BMS implantation than after DES implantation (BMS: 2545 days, DES: 1233 days, p < 0.001). Overall, %G and %B were similar between the BMS and DES groups (%G: 55% and 51%, respectively, p = 0.10; %B: 36% and 38%, respectively, p = 0.51); however, TD was significantly higher in the DES group than in the BMS group (1091 vs. 1367, p < 0.001). TD in the DES group remained high during the follow-up periods. However, TD in the BMS group was low in the early phase and significantly increased over time (r = 0.56, p < 0.001). When analyzing the ISR within 2 years after stent implantation, the BMS was distinguished with a sensitivity of 66% and a specificity of 90% (cut-off value: TD = 1135, area under the curve 0.83, 95% confidence interval 0.74-0.92). TD could differentiate neointimal tissue after BMS implantation in the early phase. TD can be a useful index in the observation of neoatherosclerosis.

Introduction: Two opening methods are used for injection needle products: the "peel-apart method" where the adhesive surface of the packaging mount is peeled off, and the "push-off top method," where the needle hub is pressed against the mount to break it. However, the risks of bacterial contamination as a result of opening method remain unknown. The aim of our study was to evaluate the bacterial contamination of needle hubs upon the opening of injection needles by the peel-apart or push-off top method under various conditions., Methods: Bacterial contamination upon the opening of injection needles was examined in two materials, paper and plastic. Various concentrations of Staphylococcus aureus were applied to the mount and were maintained under wet or dry conditions. Injection needles were opened using the peel-apart or push-off top method. Needle hub contamination was examined using agar medium colony counting. Clinically assumed conditions (the hands and saliva of anesthesiologists) were also evaluated. Data were statistically examined using the Cochran-Mantel-Haenszel, Jonckheere, and Fisher's exact tests., Results: The lateral surfaces of needle hubs were contaminated using the push-off top method, but not by the peel-apart method, in a manner that was dependent on S. aureus concentrations. No significant differences were observed between mount materials. Needle hub contamination was significantly more severe for the wet than for the dry opening portion. The clinically assumed condition study revealed that the lateral and bottom surfaces of the needle hub were contaminated significantly more in the saliva contamination group than in the dry and wet hand groups., Conclusions: The bacterial contamination of needle hubs may occur upon the opening of injection needles when the push-off top method is used and may be affected by hands contaminated with saliva under clinical conditions.

A 49-year-old woman with a history of heavy alcohol drinking was admitted to our hospital due to jaundice and abdominal distention. A blood test showed leukophilia, mild hypoalbuminemia, hyperbilirubinemia, hepatobiliary injury and coagulopathy. Image studies showed an extremely enlarged fatty liver and splenomegaly. The Japan alcoholic hepatitis score and Maddrey's discriminant function were 10 and 54 points, respectively. We diagnosed her with severe alcoholic hepatitis and treated her with corticosteroids, but her liver function did not improve. We therefore administered the vitamin E product tochopheryl acetate (150 mg/day) as an add-on therapy, after which her leukophilia, liver enzymes and coagulopathy improved immediately.

Staphylococcus spp. is a major cause of device-related infections. However, the mechanisms of deep-tissue infection by staphylococci from the skin surface remain unclear. We performed in vitro experiments to determine how staphylococci are transferred from the surface to the deeper layers of agar along the catheter for different strains of Staphylococcus aureus with respect to bacterial concentrations, catheter movements, and biofilm formation. We found that when 5-mm reciprocal movements of the catheter were repeated every 8h, all catheter samples of S. aureus penetrated the typical distance of 50mm from the skin to the epidural space. The number of reciprocal catheter movements and the depth of bacterial growth were correlated. A greater regression coefficient for different strains implied faster bacterial growth. Enhanced biofilm formation by different strains implied larger regression coefficients. Increased biofilm formation ability may accelerate S. aureus transport along a catheter due to physical movements by patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A 68-year-old man with occult hepatitis B virus (HBV) infection was diagnosed with malignant lymphoma and achieved complete remission after treatment with a chemotherapy regimen including rituximab for 5 months. Entecavir (ETV) was also used during and after chemotherapy and was ended at 14 months after chemotherapy. However, reactivation of HBV was observed in blood tests, which showed not only elevation of HBV-DNA but also HBsAg and HBeAg, at 27 months after the end of chemotherapy. After restarting ETV, the HBV-DNA levels immediately subsided. In addition, anti-HBs became and remained positive at 31 months after chemotherapy. ETV was re-discontinued at 36 months after chemotherapy.

A 70-year-old woman with chronic hepatitis C was admitted to our hospital due to liver injury, cholecystitis, and disseminated intravascular coagulation with a fever and skin rash. She had been on a combination regimen of daclatasvir and asunaprevir for 2 weeks of a 24-week regimen. Because of the symptoms, laboratory findings, results of a drug-induced lymphocyte stimulation test, and pathological findings of liver biopsy, we diagnosed her with drug-induced liver injury. Although daclatasvir and asunaprevir combination therapy is generally well-tolerated, some serious adverse effects have been reported. Our findings indicate that immunoallergic mechanisms were associated with daclatasvir and asunaprevir-induced liver injury.

We conducted a survey on the recognition of infection, status of outpatient treatment, and treatment history in hepatitis virus-associated hepatocellular carcinoma patients admitted to our department between 2005 and 2014. We compared these parameters in 75 patients with primary hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and 307 patients with hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC). Based on the presence or absence of outpatient treatment in medical institutions at the time of HCC diagnosis, the patients were divided into an outpatient treatment-free group or an outpatient treated group. In addition, the latter group was divided into three subgroups depending on the department consulted:the Department of Internal Medicine group, the Department of Gastroenterology group, and a hepatologist-treated group. Patients in the outpatient treatment-free group accounted for 40.0% of patients with HBV-HCC. In the outpatient treated group (60.0%), 21.3% were treated in the Department of Internal Medicine, 22.7% in the Department of Gastroenterology, and 16.0% were treated by a hepatologist. The percentage of HBV-HCC patients in the outpatient treatment-free group was 1.9 times higher than that in the HCV-HCC group and 0.6-fold higher in the hepatologist-treated group. Of the HBV-HCC patients, non-recognizers who were not diagnosed with a viral infection accounted for 21.3%, and non-outpatients who had not consulted a hospital despite the recognition of infection accounted for 33.3%. These percentages were approximately 2 times higher than in HCV-HCC patients. Of the HBV-HCC patients, 66.7% in the hepatologist-treated group had received nucleic acid analogue preparations. On the other hand, one patient in each of the Department of Internal Medicine and Department of Gastroenterology groups (approximately 6.0%) had received a nucleic acid analogue, lamivudine, despite the appearance of a resistant strain. In the HBV-HCC patients, the proportions of "non-recognizers" and "non-outpatients" were higher than in the HCV-HCC patients, suggesting a lack of appropriate treatment.

A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

Various loci and genes that confer susceptibility to coronary heart disease (CHD) have been identified in Caucasian populations by genome-wide association studies (GWASs). As type 2 diabetes mellitus (DM) is an important risk factor for CHD, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to CHD through affecting the susceptibility to type 2 DM. The purpose of the present study was to examine a possible association of type 2 DM in Japanese individuals with 29 polymorphisms identified as susceptibility loci for CHD by meta-analyses of the GWASs. The study subjects comprised of 3,757 individuals (1,444 subjects with type 2 DM and 2,313 controls). The polymorphism genotypes were determined by the multiplex bead-based Luminex assay, which combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. To compensate for multiple comparisons of genotypes, the criterion of a false discovery rate (FDR) ≤0.05 was adopted for testing the statistical significance of the association. The comparisons of allele frequencies by the χ 2 test revealed that the rs964184 (C→G) of the ZPR1 zinc finger gene ( ZPR1 ) was significantly associated (P=0.0017; FDR=0.050) with type 2 DM. Multivariable logistic regression analysis with adjustment for age, gender and body mass index revealed that rs964184 of ZPR1 was significantly associated (P=0.0012; odds ratio, 1.25; dominant model) with type 2 DM with the minor G allele representing a risk factor for this condition. Fasting plasma glucose levels (P=0.0076) and blood glycosylated hemoglobin contents (P=0.0132) significantly differed among ZPR1 genotypes with the G allele associated with increases in these parameters. ZPR1 may thus be a susceptibility locus for type 2 DM in Japanese individuals.

Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously identified by meta-analyses of GWASs as susceptibility loci for CAD. Study subjects comprised of 5,460 individuals (3,348 subjects with hypertension and 2,112 controls). The genotypes of SNPs were determined by the multiplex bead-based Luminex assay. The χ 2 test revealed that genotype distributions and allele frequencies for rs12190287 of the transcription factor 21 gene ( TCF21 ) and rs1122608 of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 gene ( SMARCA4 ) were significantly (P<0.05) associated with hypertension. Allele frequencies for rs9369640 of the phosphatase and actin regulator 1 gene ( PHACTR1 ) and genotype distributions for rs599839 of the proline/serine-rich coiled-coil 1 gene ( PSRC1 ) were also significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that rs12190287 of TCF21 (P=0.0014; recessive model; odds ratio, 1.21) was significantly associated with hypertension, and the C allele represented a risk factor for this condition. Similar analyses revealed that rs1122608 of SMARCA4 (P=0.0305; dominant model; odds ratio, 0.86), rs9369640 of PHACTR1 (P=0.0119; dominant model; odds ratio, 0.82) and rs599839 of PSRC1 (P=0.0248; dominant model; odds ratio, 0.84) were also related to hypertension, with the minor T, C and G alleles, respectively, being protective against this condition. Thus, the present results indicate that rs12190287 ( G → C ) of TCF21 is a susceptibility locus for hypertension.

The present study established a primary hepatocyte culture for the small Indian mongoose (Herpestes auropunctatus). To determine the suitable medium for growing the primary hepatic cells of this species, we compared the condition of cells cultured in three media that are frequently used for mammalian cell culture: Dulbecco's Modified Eagle's Medium, RPMI-1640, and William's E. Of these, William's E medium was best suited for culturing the hepatic cells of this species. Using periodic acid-Schiff staining and ultrastructural observations, we demonstrated the cells collected from mongoose livers were hepatocytes. To evaluate the distribution of mercury (Hg) in the liver tissue, we carried out autometallography staining. Most of the Hg compounds were found in the central region of hepatic lobules. Smooth endoplasmic reticulum, which plays a role inxenobiotic metabolism, lipid/cholesterol metabolism, and the digestion and detoxification of lipophilic substances is grown in this area. This suggested that Hg colocalized with smooth endoplasmic reticulum. The results of the present study could be useful to identify the detoxification systems of wildlife with high Hg content in the body, and to evaluate the susceptibility of wildlife to Hg toxicity.

Nematodes of the family Heligmonellidae (Heligmosomoidea; Trichostrongylina) reside in the digestive tracts of rodents and lagomorphs. Although this family contains large numbers of genera and species, genetic information on the Heligmonellidae is very limited. We collected and isolated adult worms of three species in Japan that belong to the family Heligmonellidae, namely Heligmonoides speciosus (Konno, 1963) Durette-Desset, 1970 (Hs) from Apodemus argenteus, Orientostrongylus ezoensis Tada, 1975 (Oe) from Rattus norvegicus and Lagostrongylus leporis (Schulz, 1931) (Ll) from Pentalagus furnessi, and sequenced the entire internal transcribed spacer regions, ITS-1 and ITS-2 of ribosomal DNA. ITS-1 of Hs, Oe and Ll was 426, 468 and 449 bp in length, and had a G+C content of about 41, 41 and 37 %, respectively. ITS-2 of Hs, Oe and Ll was 297, 319 and 276 bp in length and had a G+C content of about 38, 40 and 28%, respectively. The data of Hs, Oe and Ll were compared with those of two other known species within the family Heligmonellidae, Calorinensis minutus (Dujardin, 1845) (Cm) and Nippostrogylus brasiliensis (Travassos, 1914) (Nb), and with those of two species of Heligmosomidae (Heligmosomoidea), Heligmosomoides polygyrus bakeri and Ohbayashinema erbaevae. Phylogenetic analysis placed Hs, Oe and Ll in the same clade with Cm and Nb, forming a Heligmonellidae branch in both ITS-1 and ITS-2, separate from the Heligmosomoidea branch. These results demonstrated that the ITS-1 and ITS-2 sequences are useful for differentiating the Heligmonellidae nematode species. This study is the first to describe the ITS-1 and ITS-2 sequences of Hs, Oe and Ll.

Tokudaia osimensis (the Amami spiny rat) and Tokudaia tokunoshimensis (the Tokunoshima spiny rat) have a sex chromosome composition of XO/XO, no Y chromosome. The mammalian sex-determining gene, SRY, is also absent in these species, which indicates that these spiny rats exhibit a novel sex-determining mechanism that is independent of SRY. To identify a candidate gene that controls this mechanism, the copy numbers and chromosomal locations of 10 genes with important functions in gonadal differentiation were determined: ATRX, CBX2 (M33), DMRT1, FGF9, NR0B1 (DAX1), NR5A1 (Ad4BP/SF1), RSPO1, SOX9, WNT4, and WT1. Multiple bands were detected for NR0B1 in Southern blot analysis, which suggested the presence of multiple copies of the gene in the genomes of these two species. CBX2 was localized to two loci in both sexes of the two species by fluorescence in situ hybridization mapping: 3q24 and 6p11.2 in T. osimensis and 10q25-q26 and 14q12-q13.1 in T. tokunoshimensis. Quantification of copy numbers in the two species by quantitative real-time PCR indicated that there were two or three more copies of CBX2 per haploid genome in males (T. osimensis, n = 3; T. tokunoshimensis, n = 2) than in females (T. osimensis, n = 4; T. tokunoshimensis, n = 2), whereas NR0B1 was present as a single copy in both. The results suggest that additional copies of CBX2 in males might be involved in a novel sex-determining mechanism in species that lack SRY.

A 71-year-old male patient was diagnosed with rheumatoid arthritis (RA) in 2000. Various disease-modifying anti-rheumatic drugs (DMARDs) and an anti-tumor necrosis factor biologic etanercept were administrated, but were unable to control the disease activity of RA. He was then diagnosed with rheumatoid vasculitis and received a total of 3 courses of an anti-interleukin-6 receptor antibody, tocilizumab. After the 3 courses of tocilizumab therapy, ascites and renal dysfunction gradually appeared and he was admitted to our hospital. Biochemical data suggested that he had developed decompensated liver cirrhosis. His renal function deteriorated rapidly, and he died 9 days after the admission. Serum aminotransferase levels had been relatively low during the treatment with tocilizumab, however, autopsy showed marked atrophy of the liver. Immunohistochemical analysis revealed that the hepatocytes had fallen into apoptosis and that hepatic regeneration had been extremely suppressed. Although molecular target drugs such as tocilizumab are being widely used and are important emerging treatment options in adult patients with moderate to severe RA, these drugs could induce liver failure by inhibiting liver regeneration as in this case. Physicians need to stay alert to the impact of these drugs on liver regeneration and should follow up with ultrasonography or computed tomography., (© 2011 The Japan Society of Hepatology.)

Metastatic malignant melanoma (MM) of the liver evolving into acute hepatic failure is a rare occurrence. We describe the case of an 82-year-old man with a history of MM on the left thumb treated with amputation and chemotherapy 40 months previously. On admission, he had abdominal pain, weight loss, lethargy and jaundice. Radiologic investigations such as enhanced computed tomography and abdominal ultrasound failed to establish an etiologic diagnosis. A liver biopsy revealed amelanotic melanoma cells diffusely infiltrating the hepatic parenchyma. His liver injury progressed and the patient died of hepatic failure on the 13th hospital day. Autopsy revealed >70% infiltration by metastatic amelanotic melanoma in the liver.

A 59-year-old male patient underwent surgical treatment for non-Hodgkin's lymphoma of the right scrotum in October 2007. He received a total of 4 courses of two different adjuvant chemotherapy regimens including rituximab from January to April 2008. In June 2008 he was hospitalized due to severe liver dysfunction with an alanine aminotransferase of 2039 IU/l and a prothrombin time of 23.3%. He was diagnosed with acute hepatitis C by the detection of hepatitis C virus (HCV) RNA and negative anti-HCV antibody, and his hepatic function improved with bed rest during hospitalization; however, the production of anti-HCV antibodies was not detected until January 2009. Severe liver dysfunction is uncommon among patients with acute hepatitis C, and the long window (8 months) between HCV infection and the development of anti-HCV antibodies observed in the present case may have been due, at least in part, to a B cell disorder caused by rituximab therapy. In addition to the well-known risk of reactivation of hepatitis B virus infection in patients undergoing chemotherapy, physicians should be aware of the potential effects of chemotherapy on the clinical course of HCV infection.

We report three cases with unresectable locally advanced pancreatic cancer (PC) treated with a combination of chemoradiotherapy (CRT) and systemic chemotherapy, using gemcitabine (GEM) and/or S-1. All three cases were diagnosed as having locally advanced unresectable PC without distant metastatic lesions based on computed tomography, endoscopic retrograde pancreatography and/or blushing cytology. In Cases 1 and 2, we applied a so-called sandwich therapy, which consisted of induction chemotherapy before CRT and maintenance chemotherapy after CRT. The induction and maintenance chemotherapy in Cases 1 and 2 used a combination of GEM and S-1, whereas maintenance therapy with GEM or S-1 was applied in Case 3. S-1-based CRT was performed in Cases 1 and 2, and GEM-based CRT in Case 3. Survivals were 27 and 65 months, respectively, in two cases, and the disease remained stable in the other case 30 months after diagnosis. We show three cases with unresectable locally advanced PC who achieved long-term survival (27-65 months) after treatment with a combination of CRT and systemic chemotherapy, using GEM and/or S-1. Our findings indicate that sandwich therapy might be particularly effective for locally advanced PC.

Two species of Ryukyu spiny rat, Tokudaia osimensis and Tokudaia tokunoshimensis, have an XO/XO sex chromosome constitution with no cytogenetically visible Y chromosome in both sexes. The single X chromosomes of T. osimensis and T. tokunoshimensis are submetacentric and subtelocentric, respectively. It was therefore suggested that a pericentric inversion event occurred in the X chromosome of either species. To identify X chromosome rearrangements that have occurred between the two species, we mapped 22 mouse cDNA clones of the X-linked genes on the chromosomes of the two species by direct R-banding FISH. The gene orders of the X chromosomes were conserved in the two species, whereas the position of the centromere on the X chromosome was different. This result indicates that the rearrangement which occurred in either of the X chromosomes after the two species diverged from a common ancestor involved not pericentric inversion but centromere repositioning.

Objectives: Liver steatosis is frequently observed in patients with chronic hepatitis C (CHC) and is an identified risk factor for progression of liver fibrosis. This study aimed to evaluate the relationship between steatosis and host/viral factors, and the correlation between steatosis and insulin secretion in CHC patients with normal glucose tolerance (NGT)., Methods: A total of 212 CHC patients were enrolled in this study. Insulin resistance and insulin secretion were determined in response to oral loading of 75 g glucose. Liver fibrosis and steatosis were quantified by the image analysis., Results: Of the 212 CHC patients, 165 (78%) had steatosis, mostly of a mild degree. Multiple ordinal regression analysis revealed body mass index (BMI) (P= 0.011) as the main factor associated with severe steatosis. Of the 212 CHC patients, 148 (61%) showed NGT, and the serum insulin response to oral glucose loading in these NGT patients with steatosis was significantly different from that in patients with NGT but no steatosis. The peak insulin response occurred at 60 min in cases of mild steatosis, and at 90 min in patients with moderate or severe steatosis. The insulin level at 120 min in patients with severe steatosis was higher than that in those without steatosis. The total area under the response curve of insulin during OGTT in the patients with steatosis is higher than that in those without steatosis., Conclusion: Exaggerated insulin secretion was observed even in CHC patients with mild steatosis and NGT, suggesting the presence of insulin resistance. Exaggerated insulin secretion may accelerate the progression of liver fibrosis in CHC patients.

Although many workers suffer from chronic hepatitis, the influence of labor on its clinical course is not clear. We prospectively followed 89 workers with chronic hepatitis for 3 years, and examined the relationship between job-related factors, such as job class, job type, working hours and work effort, and the liver function test. There were no job-related factors that had any influence on the activity of hepatitis. Moreover, no significant relationship was found between job-related factors, including tiredness, and the acute exacerbation of hepatitis. No significant changes of aminotransferase levels and of platelet counts divided by each job-related factor were found during the observation period, but the platelet counts decreased in workers with acute exacerbation, but without clinical significance. These results suggest that job-related factors have little influence on the clinical course of chronic hepatitis during a relatively short observation period.

The Ryukyu spiny rats (genus Tokudaia) inhabit only three islands in the Nansei Shoto archipelago in Japan, and have the variations of karyotype among the islands. The chromosome number of T. osimensis in Amami-Oshima Island is 2n = 25, and T. tokunoshimensis in Tokunoshima Island is 2n = 45, and the two species have X0 sex chromosome constitution with no cytogenetically visible Y chromosome in both sexes. We constructed the standard ideograms for these species at the 100 and 200 band levels. Comparing the banding patterns between these species, it was suggested that at least 10 times the number of Robertsonian fusions occurred in T. osimensis chromosomes. However, no karyotypic differences were observed between sexes in each species. To detect the sex-specific chromosomal region of these X0 species we applied the comparative genomic hybridization (CGH) method. Although the male- and female-derived gains and losses were detected in several chromosome regions, all of them were located in the heterochromatic and/or telomeric regions. This result suggested that the differences detected by CGH might be caused by the polymorphism on the copy numbers of repeated sequences in the heterochromatic and telomeric regions. Our result indicated that the sex-specific region, where the key to sex determination lies, is very minute in X0 species of Tokudaia.

Background and Aim: The aim of the present study was to determine whether a 24-week course of combination therapy with ribavirin and high-dose interferon-alpha2b (IFN-alpha2b) could provide an acceptable treatment efficacy in chronic hepatitis C (CHC)., Methods: Seventy-six patients with CHC whose serum hepatitis C virus (HCV) RNA levels were more than 100 kIU/mL on quantitative polymerase chain reaction (PCR) assay were included. The patients were assigned to two different dose groups of IFN-alpha2b: group A (n = 39) received 6 MU and group B (n = 37) received 10 MU. Each group received the dose daily for 14 days then three times per week for a total of 24 weeks. In addition, HCV genotype 1b patients in group A and group B were classified into group C (n = 20) and D (n = 29), respectively. All patients received 600 or 800 mg ribavirin per day., Results: Sustained response rates in group A were significantly higher than those in group B (66.7%vs 35.1%, intent-to-treat, P = 0.0060). However, sustained response rates in group C were not different from those in group D (45.0%vs 20.7%, intent-to-treat, P = 0.0696). The proportion of patients who discontinued the treatment or reduced drug dosage because of adverse events was significantly higher in group B than in group A (27.0%vs 7.69%, P = 0.0224)., Conclusion: A 24-week course of combination therapy with ribavirin and 6 MU IFN-alpha2b had an acceptable efficacy with fewer adverse events than that with ribavirin and 10 MU IFN-alpha2b in CHC.

A 62-year-old male was referred to our hospital because of liver dysfunction, diffuse pancreatic swelling, and trachelophyma. At admission, the patient was free of pain. Physical examination showed enlarged and palpable bilateral submandibular masses, but no palpable mass or organomegaly in the abdomen. Laboratory findings were as follows: total protein 90 g/L with gamma-globulin of 37.3% (33 g/L), total bilirubin 4 mg/L, aspartate aminotransferase 39 IU/L, alanine aminotransferase 67 IU/L, gamma-glutamyl transpeptidase 1 647 IU/L, and amylase 135 IU/L. Autoantibodies were negative, and tumor markers were within the normal range. Serum IgG4 level was markedly elevated (18 900 mg/L). Computed tomography (CT) showed diffuse swelling of the pancreas and dilatation of both common and intra-hepatic bile ducts. Endoscopic retrograde pancreatography (ERP) revealed diffuse irregular and narrow main pancreatic duct and stenosis of the lower common bile duct. Biopsy specimens from the pancreas, salivary gland and liver showed marked periductal IgG4-positive plasma cell infiltration with fibrosis. We considered this patient to be autoimmune pancreatitis (AIP) with fibrosclerosis of the salivary gland and biliary tract, prescribed prednisolone at an initial dose of 40 mg/d. Three months later, the laboratory data improved almost to normal. Abdominal CT reflected prominent improvement in the pancreatic lesion. Swelling of the salivary gland also improved. At present, the patient is on 10 mg/d of prednisolone without recurrence of the pancreatitis. We present here a case of AIP with fibrosclerosis of salivary gland and biliary tract.

Background/aims: Diabetes mellitus (DM) is frequently observed in patients with chronic hepatitis caused by hepatitis C virus infection (CHC). The present study was designed to determine the pathogenic factors responsible for glucose intolerance in CHC patients., Methods: A total of 131 patients with CHC were enrolled in this study. Insulin resistance and beta-cell function were determined after 75 g oral glucose tolerance tests., Results: Glucose intolerance was detected in 27.5% (36/131) of CHC patients; 10 had DM and 26 impaired glucose tolerance. HOMA-R [insulin 0xglucose 0/22.5] was greater in patients with both impaired glucose tolerance and DM than in those with normal glucose tolerance (P<0.01). Matsuda index [10(4)/ (square root) (mean insulinxmean glucosexglucose 0xinsulin 0)] was lower in diabetic patients than in those with normal glucose tolerance (P<0.05). The insulinogenic index [Deltainsulin 30-0/Deltaglucose 30-0] and DeltaC-peptide 30 [DeltaC-peptide 30-0/Deltaglucose 30-0] were significantly lower even in patients with impaired glucose tolerance than in patients with normal glucose tolerance (P<0.01)., Conclusions: Both insulin resistance and beta-cell dysfunction contribute to glucose intolerance in CHC patients.

Background: We evaluated whether early changes in serum levels of fibrogenic markers during interferon (IFN) treatment can predict long-term anti-fibrogenic effects in patients with chronic hepatitis C (CHC)., Methods: We retrospectively examined the serum levels of N-terminal peptide of type III procollagen (P-III-NP) and 7S domain of type IV collagen (IV-7S) in 56 patients with CHC who were revealed to be IFN-nonresponders. We measured these markers before (T0) and 1 month (T1) after the commencement of IFN therapy, at the end of 24 weeks' IFN therapy (T24), and 1 year (T24-1) and more than 2 years (T24-2) after the cessation of IFN therapy. We also measured these markers twice, at intervals of more than 2 years, in 43 IFN-untreated patients with CHC as controls., Results: In nonresponders, both P-III-NP and IV-7S levels at T24-2 were significantly decreased compared with those at T0. P-III-NP levels at T1 were significantly decreased compared with those at T0, and remained at significantly low levels until the end of the observation period. IV-7S levels at T1 were not significantly different from those at T0. In patients whose IV-7S levels at T24-2 were decreased compared with those at T0, IV-7S levels at T1 were significantly lower than those at T0. In patients whose IV-7S levels at T24-2 were elevated or unchanged compared with those at T0, IV-7S levels at T1 were significantly higher than those at T0. In untreated patients, both P-III-NP and IV-7S levels at more than 2 years after the initial time were significantly increased compared with those at the initial time., Conclusions: An early decrease in IV-7S levels after IFN treatment is a useful indicator of anti-fibrogenic effects in nonresponders.

We examined the levels of serum N-terminal peptide of type III procollagen (P-III-NP) and the 7S domain of type IV collagen (IV-7S) as fibrogenesis markers in patients with chronic hepatitis C to clarify whether high-dose interferon-alpha (IFN-alpha) therapy has a suppressive effect on hepatic fibrogenesis for a long period (over 5 years) after the cessation of IFN therapy. Eighty patients with CHC were given 10 million units of IFN-alpha2b daily for 14 days followed by three times per week for a total of 24 weeks. Patients were divided into the following three groups according to the highest serum alanine aminotransferase levels during 1 year observation after the end of IFN therapy: complete responders (CR), partial responders (PR), and nonresponders (NR). We measured serum fibrogenesis markers before and at the end of IFN therapy, and again 1 year and more than 5 years after the end of IFN therapy. Liver biopsies were performed before IFN therapy in all patients and again over long-term observation in 10 patients (PR; 5 and NR; 5). Serum P-III-NP levels significantly decreased after IFN therapy in all three groups of patients, and further decreased in CR and PR over long-term observation. Serum IV-7S levels in CR significantly decreased after IFN therapy and further decreased over long-term observation. Serum IV-7S levels over long-term observation were significantly lower than those at the end of IFN therapy in CR and PR and significantly lower than the initial values in all three groups of patients. The progression of fibrosis was not significant over long-term observation in liver biopsy specimens of 10 patients. The results of the present study suggest that high-dose IFN-alpha therapy for 6 months suppresses the progression of hepatic fibrosis for more than 5 years not only in CR but also in PR.

A variety of treatments have recently been introduced to improve the prognosis of hepatocellular carcinoma (HCC). These anticancer therapies include the oily carcinostatic agent styrene maleic acid neocarzinostatin (SMANCS). SMANCS is a chemical conjugate of a synthetic copolymer of styrene maleic acid (SMA) and the proteinaceous anti-cancer agent neocarzinostatin (NCS), which dissolves in organic solvents such as pyridine and acetone, and particularly in Lipiodol. NCS is a simple protein capable of inhibiting DNA synthesis and inducing DNA degradation. Lipiodol is an ethyl ester of iodinated poppy seed oil in which most of the unsaturated double bonds in oleic, linoleic and linolenic acid are almost completely iodinated. When a homogeneous suspension of SMANCS with Lipiodol (SMANCS/Lipiodol) is administered intra-arterially, Lipiodol acts as a carrier of SMANCS. Many studies have demonstrated the clinical efficacy of SMANCS/Lipiodol in the treatment of HCC. We have shown that transcatheter arterial infusion (TAI) with SMANCS/Lipiodol has a more favorable focal therapeutic effect than does epirubicin in Lipiodol in the initial treatment of HCC. However, recent clinical studies have indicated that SMANCS causes severe adverse reactions and complications. We have also reported a case of HCC in which multifocal hepatic infarction developed after TAI with SMANCS/Lipiodol. Arterial administration of SMANCS/Lipiodol, therefore, should be given as peripherally as possible via the tumor feeding arteries, to enhance the efficacy of the agent and to reduce the adverse effects.

Ischemic colitis is typically limited to elderly patients who have concomitant disorders such as cardiovascular disease and chronic renal failure, but rarely affects a young person. The patient was an 18-year-old Japanese female who started dieting to obtain a slim figure three months before admission and presented with a two-month history of constipation and a sudden onset of lower abdominal pain and bloody diarrhea. She underwent colonoscopy, which revealed edema, hemorrhages, and several longitudinal shallow ulcers in the descending colon. Stool and blood culture results were negative for pathogens. She improved rapidly within five days without any specific therapies except intravenous hydration and anticholinergic agents, under the diagnosis of ischemic colitis. In this case constipation and dehydration associated with dieting seemed to be responsible for the development of ischemic colitis. We recommend that ischemic colitis should be included in the differential diagnosis of colitis with bleeding, even in patients younger than age 20 who do not have any predisposing factors.