Hemorrhagic varices around the pancreatojejunostomy site due to left-sided portal hypertension after pancreaticoduodenectomy: A case report.

Pancreaticoduodenectomy (PD) with combined portal vein resection sometimes causes left-sided portal hypertension, which can be a problem. An appropriate treatment strategy for hemorrhagic ectopic varices due to left-sided portal hypertension after PD has not yet been determined. We report a case of repeated variceal rupture around the pancreatojejunostomy site. A 65-year-old woman with a history of PD for pancreatic head cancer was admitted with a chief complaint of bloody stools. She was diagnosed with pancreatojejunostomy variceal rupture, and an endoscopic cyanoacrylate injection was performed. As rebleeding occurred 2 weeks after the first treatment, endoscopic cyanoacrylate injection was repeated, and hemostasis was achieved. Additionally, she had esophageal, colonic, and gastrojejunostomy varices, and the future risk of these variceal ruptures was considered very high. Hence, a splenectomy was performed to prevent rebleeding or other variceal ruptures. Endoscopic cyanoacrylate injection is a useful treatment for hemorrhagic varices around the pancreatojejunostomy site. It is also necessary to understand portal vein hemodynamics and provide appropriate additional treatment in cases of recurrent variceal rupture due to left-sided portal hypertension after PD.

[A case of invasive intraductal papillary mucinous carcinoma arising from jejunal heterotopic pancreas].

Intraductal papillary mucinous carcinoma (IPMC) arising from the heterotopic pancreas is rare. A case of IPMC metastasis from the jejunal heterotopic pancreas was described. The heterotopic pancreas could be the source of the submucosal tumor-like lesion found in the small intestine with an elevated carbohydrate antigen (CA) 19-9 level. A 60-year-old woman was admitted to the hospital with pulmonary thromboembolism and anemia. The level of CA19-9, a tumor marker, was found to be 211.8U/ml. A tumor in the jejunum was discovered using contrast-enhanced computed tomography. There were also a number of hepatic tumors found. A submucosal tumor-like lesion in the jejunum was discovered during an enteroscopy, and a biopsy revealed it to be an adenocarcinoma. Partial resection of the jejunum was performed to control hemorrhage. Histopathology revealed an invasive IPMC arising from a heterotopic pancreas (Heinrich type II) and chemotherapy with gemcitabine and nab-paclitaxel was initiated. There have only been three cases of invasive IPMC from a heterotopic pancreas reported, and this is the first one to include chemotherapeutic treatment of distant metastasis.

Pancreatic hyperechogenicity associated with hypoadiponectinemia and insulin resistance: A Japanese population study.

AIM: To examine the relationship between pancreatic hyperechogenicity and risk factors for metabolic syndrome. METHODS: A general population-based survey of lifestyle-related diseases was conducted from 2005 to 2006 in Japan. The study involved 551 participants older than 40 year of age. Data for 472 non-diabetic adults were included in the analysis. The measures included the demographic factors, blood parameters, results of a 75 g oral glucose tolerance test, and abdominal ultrasonography. The echogenicity of the pancreas and liver was compared, and then the subjects were separated into two groups: cases with pancreatic hyperechogenicity (n = 208) and cases without (controls, n = 264). The differences between both groups were compared using an unpaired t-test or Fisher's exact test. Multiple logistic regression analysis was used to determine the relationship between the pancreatic hyperechogenicity and clinical and biochemical parameters. RESULTS: Subjects with pancreatic hyperechogenicity had decreased serum adiponectin concentration compared to control subjects [8.9 (6.5, 12.8) vs 11.1 (7.8, 15.9), P < 0.001] and more frequently exhibited features of metabolic syndrome. Logistic regression analysis showed that the following variables were significantly and independently associated with pancreatic hyperechogenicity: Presence of hypoadiponectinemia, increased body mass index (BMI), higher homeostasis model assessment of insulin resistance (HOMA-IR) score, and presence of fatty liver. Similar associations were also observed in subjects with pancreatic hyperechogenicity without fatty liver. Multivariate association analysis of data from participants without fatty liver showed that hypoadiponectinemia was significantly associated with pancreatic hyperechogenicity (OR = 0.93, 95%CI: 0.90 - 0.97, P < 0.001). This association was independent of other confounding variables. Additionally, an increased BMI and higher HOMA-IR score were significantly associated with pancreatic hyperechogenicity. CONCLUSION: Pancreatic hyperechogenicity is independently associated with increased BMI, insulin resistance, and hypoadiponectinemia in the general population.

Relationship between tumor necrosis factor-α release and granulocyte and monocyte adsorption to cellulose acetate beads.

Tumor necrosis factor-α, (TNF)-α, a proinflammatory cytokine, is produced by activated granulocytes and monocytes (GMs) and implicated as a major factor in inflammatory bowel disease (IBD) pathogenesis. Reduction of TNF-α should improve IBD pathology. GM adsorptive apheresis (GMA) is an effective therapy for inflammatory disorders including IBD. GM adsorption to cellulose acetate (CA) beads induces anti-inflammatory cytokine release, although these effects on TNF-α release are not clarified. We hypothesized that GMA may inhibit TNF-α release. The aim of the present study was to clarify the effects of GM adsorption to CA beads on TNF-α release in vitro. Peripheral blood was incubated with and without CA beads and TNF-α was measured. For comparison, TNF-α was measured in another lipopolysaccharide (LPS)-containing peripheral blood sample incubated similarly. The amount of TNF-α in blood samples incubated with CA beads was significantly higher than in those incubated without beads, although it was significantly lower than TNF-α incubated with LPS-containing sample without beads. The amount of TNF-α after incubation with CA beads positively correlated with GM adsorption ratio. GM adsorption to CA beads induced a small amount of TNF-α release. This is the first report on TNF-α release induced via GM adsorption stimuli. The biological effects of TNF-α release during GM adsorption need to be clarified.

Epiregulin promotes the emergence and proliferation of adult liver progenitor cells.

We have previously reported that epiregulin is a growth factor that seems to act on liver progenitor cells (LPCs) during liver regeneration. However, the relationship between epiregulin and LPCs has remained unclear. The aim of the present study was to clarify the role of epiregulin during liver regeneration. The serum levels of epiregulin in patients with acute liver failure were examined. A liver injury model was developed using mice fed a diet containing 0.1% 3.5-diethoxycarbonyl-1.4-dihydrocollidine (DDC) to induce LPCs. We then evaluated the expression of epiregulin and LPCs in these mice. The proliferation of epithelial cell adhesion molecule + LPCs cultured with epiregulin was examined in vitro, and finally epiregulin was overexpressed in mouse liver. In patients with acute liver failure, serum epiregulin levels were elevated significantly. In DDC mice, LPCs emerged around the portal area. Epiregulin was also detected around the portal area during the course of DDC-induced liver injury and was partially coexpressed with Thy1. Serum epiregulin levels in DDC mice were also significantly elevated. Recombinant epiregulin augmented the proliferative capacity of the LPCs in a dose-dependent manner. In mice showing overexpression of epiregulin, the expression of PCNA on hepatocytes was increased significantly. Finally, LPCs emerged around the portal area after epiregulin gene delivery. We concluded that epiregulin promotes the proliferation of LPCs and DNA synthesis by hepatocytes and is upregulated in the serum of patients with liver injury. Furthermore, induction of epiregulin leads to the appearance of LPCs. Epiregulin would be a useful biomarker of liver regeneration.

Clinical manifestations of liver injury in patients with anorexia nervosa.

AIM: The number of Japanese patients with anorexia nervosa (AN) is increasing as society changes. Mild liver injury is a complication of AN in around 30% of cases. In some rare instances, patients present with severe liver injury similar to acute liver failure. However, there are numerous uncertainties over the clinical characteristics of this condition. The objective of the present study was to clarify the clinical characteristics of AN complicated by liver injury and to investigate the factors related to hepatic complications. METHODS: Thirty-seven patients hospitalized at our institution with a diagnosis of AN were enrolled as the study subjects. The study used clinical data obtained at the time of hospitalization. The enrolled patients underwent subgroup analysis and were categorized into three groups: (i) normal alanine aminotransferase (ALT), (ii) moderately elevated ALT, and (iii) highly elevated ALT. RESULTS: All of the study subjects were female with a median age of 24 years and presenting with marked weight loss (mean body mass index, 13 kg/m(2) ). Thirteen of the subjects had liver injury. We found that patients in the highly elevated ALT group had a significantly high blood urea nitrogen (BUN)/creatinine ratio, and a low blood sugar level. CONCLUSIONS: Our present findings indicate that AN patients with highly elevated ALT have a severe dehydration. This suggests that dysfunction of hepatic circulation accompanying severe dehydration due to malnutrition may be an important factor in the development of liver injury in AN patients.

Possible autoimmune hepatitis induced after chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus infection (CAEBV) can be manifested in a variety of systemic conditions, including interstitial pneumonia, malignant lymphoma, and coronary aneurysm. Sometimes it may be associated with hepatic failure, although the mechanism underlying CAEBV-related hepatotoxicity remains unclear. We encountered a case of autoimmune hepatitis (AIH) associated with CAEBV. A 61-year-old male was referred to our hospital because of abnormal liver enzyme levels after initial diagnosis of CAEBV had been made by laboratory tests and liver biopsy. On admission, positivity for anti-nuclear antibody was evident, and examination of the liver biopsy specimen showed findings compatible with AIH. Steroid administration was initiated, and the liver function parameters subsequently improved. Although phenotypic changes in liver biopsy specimens are rare in this condition, the present case could provide clues to the possible pathogenesis of AIH.

A case of adult type 1 Gaucher disease complicated by temporal intestinal hemorrhage.

A 21-year-old man with a history of sudden rectal hemorrhage was referred to our hospital. Examination disclosed thrombocytopenia and hepatosplenomegaly. A liver biopsy specimen demonstrated Gaucher cells in Glisson's capsule. Additional investigations revealed a low level of leukocyte ß-glucosidase activity and common mutations of the glucocerebrosidase gene, L444P/D409H. We diagnosed the patient with Gaucher disease type 1. He underwent enzyme replacement therapy. Thrombocytopenia and hepatosplenomegaly improved at a rate of approximately 50 and 20%, respectively, within 6 months. This case suggests that we must pay attention to adult Gaucher disease as a differential diagnosis for cryptogenic thrombocytopenia.

Dynamics of serum metabolites in patients with chronic hepatitis C receiving pegylated interferon plus ribavirin: a metabolomics analysis.

OBJECTIVES: Serum samples from patients with chronic hepatitis C were subjected to metabolomics analysis to clarify the pretreatment characteristics of their metabolites and also changes in specific metabolites resulting from antiviral therapy with pegylated interferon plus ribavirin (PegIFN/RBV). MATERIALS/METHODS: The serum levels of low-molecular-weight metabolites in the twenty patients before and 24weeks after completion of PegIFN/RBV therapy were analyzed using capillary electrophoresis and liquid chromatography-mass spectrometry. RESULTS: Ten patients showed a non-virological response (NVR) and 10 achieved a sustained virological response (SVR) with eradication of viremia. The pretreatment levels of tryptophan were significantly higher in the patients of SVR than in those of NVR (p=0.010). The area under the curve (AUC) value of tryptophan calculated from the receiver operating characteristic (ROC) curve for discriminating SVR from NVR was 0.84 (95% confidential interval, 0.66-1.02, p=0.010). The ROC curve of multiple logistic regression model incorporating the pretreatment levels of tryptophan and γ-glutamate-arginine showed that the AUC value was highly significant (AUC=0.92, 95% confidential interval, 0.79-1.05, p=0.002). Twenty four weeks after completion of treatment, the levels of γ-glutamyl dipeptides, glutamic acid, 5-oxoproline, glucosamine and methionine sulfoxide were decreased, whereas those of 5-methoxy-3-indoleacetate, glutamine, kynurenine and lysine were increased significantly (p<0.05) in both the NVR and SVR patients. CONCLUSIONS: The pretreatment serum levels of certain metabolites including tryptophan are associated with the response to PegIFN/RBV therapy. PegIFN/RBV therapy can ameliorate the oxidative stress responsible for glutathione metabolism.

Serum prolactin levels and prolactin mRNA expression in peripheral blood mononuclear cells in hepatitis C virus infection.

Prolactin is not only a pituitary hormone but an immunoregulatory hormone secreted from lymphocytes. Prolactin induction in relation to hepatitis C virus (HCV) infection has not been elucidated. The serum levels of prolactin were examined in 232 HCV-infected subjects positive for anti-HCV antibody and 65 healthy controls negative for it, who were recruited in the cohort study. The prolactin mRNAs were measured in peripheral blood mononuclear cells (PBMCs) of eleven healthy volunteers including five men and six women before and after stimulation by HCV in vitro. The serum level of prolactin and prolactin mRNA in PBMCs were measured by chemiluminescence immunoassay and real-time PCR, respectively. The serum levels of prolactin were significantly higher in the HCV-infected subjects (median: 7.5, IQR: 5.7-10.9 ng/ml) than in the controls (median: 5.6, IQR: 4.4-8.3 ng/ml) (P < 0.01). They were significantly higher in HCV-infected males (median: 8.0, IQR: 5.9-11.8 ng/ml) than in the controls (median: 4.8, IQR: 4.2-5.9 ng/ml) (P < 0.001), however, the difference was not significant between HCV-infected females (median: 7.3, IQR: 5.6-10.5 ng/ml) and the controls (median: 6.4, IQR: 5.3-9.8 ng/ml). The mRNA expression of prolactin was induced in PBMCs of all males, but it was induced in PBMCs of the two of six females examined in vitro. These results suggest that the serum level of prolactin is higher in HCV-infected males than in healthy males, and that HCV infection induces the mRNA expression of prolactin in PBMCs that is more apparent in male than in females.

Impaired mitochondrial ß-oxidation in patients with chronic hepatitis C: relation with viral load and insulin resistance.

BACKGROUND: Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial ß-oxidation. In this study we assessed mitochondrial ß-oxidation in CH-C patients by investigating ketogenesis during fasting. METHODS: This study consisted of thirty patients with CH-C. Serum levels of insulin and hepatitis C virus (HCV) core protein were measured by chemiluminescence enzyme immunoassay. The subjects were then fasted, and venous blood samples were drawn 12 h and 15 h after the start of fasting. The levels of blood ketone bodies were measured by an enzymatic cycling method. The rate of change in total ketone body concentration was compared with that in eight healthy volunteers. RESULTS: The rate of change in total ketone body concentration between 12 h and 15 h after the start of fasting was significantly lower in CH-C patients than in healthy volunteers (129.9% (8.5-577.3%) vs. 321.6% (139.6-405.4%); P <0.01). The rate of change in total ketone body concentration in patients with a serum level of HCV core protein of 10000 fmol/L or higher was significantly lower than in patients with a level of less than 10000 fmol/L (54.8% (8.5-304.3%) vs. 153.6% (17.1-577.3%); P <0.05). The rate of change in total ketone body concentration in patients with a homeostasis model assessment of insulin resistance (HOMA-IR) of 2.5 or higher was significantly lower than in patients with a HOMA-IR of less than 2.5 (56.7% (8.5-186.7%) vs. 156.4% (33.3-577.3%); P <0.01). CONCLUSIONS: These results suggest that mitochondrial ß-oxidation is impaired, possibly due to HCV infection in patients with CH-C.

Production of interleukin-10 by combining a granulocyte and monocyte adsorption carrier with ulinastatin.

Interleukin (IL)-10 is an anti-inflammatory cytokine mainly produced by monocytes and is essential for the induction of anti-inflammatory intestinal macrophages with macrophage colony-stimulating factor (M-CSF). Thus, IL-10- and M-CSF-rich conditions in colonic tissues seem to contribute to the improvement of pathological conditions in patients with inflammatory bowel diseases (IBD). We have already reported that ulinastatin, a serine protease inhibitor, increases M-CSF production during granulocyte/monocyte (GM) adsorption to cellulose acetate (CA) beads (carriers for Adacolumn therapy). However, the effects of ulinastatin on IL-10 production have not been clarified. The aim of the present study was to clarify the effects of ulinastatin on IL-10 production during GM adsorption by in vitro experiments. Peripheral blood was divided into four groups: (Control) no ulinastatin added, no contact with CA beads; (1) no ulinastatin added, contact with CA beads; (2) ulinastatin added, no contact with CA beads; and (3) ulinastatin added, contact with CA beads. After incubation, IL-10 in the plasma was measured. Compared with the level in the Control group, plasma IL-10 was significantly higher only in group 3, in which ulinastatin was added in the presence of CA beads, but did not increase in the absence of CA beads. These results suggest that ulinastatin synergistically increases IL-10 production with monocyte adsorption stimuli. By increasing not only M-CSF but also IL-10, a combination of ulinastatin and Adacolumn therapy may improve clinical efficacy for the treatment of IBD in terms of the induction of anti-inflammatory intestinal macrophages.

Evaluation of the effect of ulinastatin on the production of macrophage colony-stimulating factor in vitro for potential combination therapy with leukocyte adsorption.

Macrophage colony-stimulating factor (M-CSF) induces normal intestinal macrophages that have anti-inflammatory effects. Thus, M-CSF-rich conditions in colonic tissues seem to contribute to the improvement of pathological conditions in patients with inflammatory bowel diseases (IBD). However, it has not been clarified whether current therapies for IBD, including granulocyte/monocyte adsorptive apheresis using an Adacolumn, and ulinastatin, a serine protease inhibitor, affect the production of M-CSF. To clarify the effects of these therapies on M-CSF production, we investigated whether monocyte adsorption to cellulose acetate (CA) beads (carriers for Adacolumn therapy) and ulinastatin augmented M-CSF production in in vitro experiments. Peripheral blood was incubated with and without CA beads, and then M-CSF production was measured. Additionally, peripheral blood containing serial dilutions of ulinastatin was incubated with CA beads followed by measurement of M-CSF production. Monocyte adsorption to CA beads did not affect M-CSF production. A high concentration of ulinastatin augmented M-CSF production without inhibiting monocyte adsorption to CA beads, although a low concentration of ulinastatin conversely suppressed M-CSF production. The present study found that a high concentration of ulinastatin, which was administrated with CA beads, increased the production of M-CSF. Our results suggest that a combination of ulinastatin and Adacolumn therapy may provide more clinical efficacy for the treatment of IBD in terms of the production of M-CSF.

(99m)Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C.

We describe a 62-year-old woman with advanced chronic hepatitis C who showed no response to low-dose long-term interferon-beta monotherapy (3 MU, three times a week). The interferon monotherapy was continued for 2 years and 9 months. Despite this lack of response to interferon, the patient's clinical course was good and liver function assessed by (99m)Tc-galactosyl human serum albumin single photon emission computed tomography ((99m)Tc-GSA SPECT) analysis improved significantly. Improvement of the data obtained by (99m)Tc-GSA SPECT analysis justified continuation of the treatment. (99m)Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C, despite a lack of reduction of the ALT level and HCV-RNA titer.

Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.

The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.

A case of monocular blindness as the initial presentation of hepatocellular carcinoma with skull metastasis.

A 52-year-old man suffering from monocular blindness, with light perception only, was admitted to our hospital. The symptom had begun as low vision and developed rapidly within 3 weeks into monocular blindness in the right eye, with no other systemic manifestations. Imaging examinations revealed multiple hepatocellular carcinomas in the cirrhotic liver, and tumors at the skull base and vertebra. A pathological and immunochemical study of specimens obtained by endoscopic transnasal tumor biopsy and laminectomy revealed them to be metastatic hepatocellular carcinomas (HCCs). Although the patient underwent radiation therapy and chemotherapy, he died 5 months after admission to our hospital. The cranial HCC, involving only the optic canal, may have disturbed the optic nerve in preference to the other cranial nerves. This is the first report of a HCC patient with monocular blindness as the initial presentation of the disease.

Enhanced expression of fibroblast growth factor 2 in bone marrow cells and its potential role in the differentiation of hepatic epithelial stem-like cells into the hepatocyte lineage.

The transplantation of bone marrow cells (BMCs) has been applied in liver regenerative cell therapy. However, details of the interaction between the transplanted BMCs and hepatic stem cells have not been elucidated. The aim of the present study was to investigate the interaction of BMCs with hepatic stem-like cells (HSLCs) and to determine the BMC factor that steers HSLC differentiation into the hepatocyte lineage. Both BMCs and HSLCs were obtained from an adult Sprague-Dawley rat, and a co-culture system was established. Cell proliferation was analyzed by a proliferation assay, and the differentiation of HSLCs into the hepatocyte lineage was evaluated by the detection of cellular mRNA for liver-specific proteins. DNA microarray analysis was applied to BMCs co-cultured with HSLCs to determine the genes upregulated by their interaction. The proliferation of HSLCs co-cultured with BMCs was significantly higher than that of HSLCs cultured alone, and the expression of mRNAs for both albumin and tryptophan-2,3-dioxygenase was detectable in the co-cultured HSLCs. DNA microarray analysis showed the upregulated expression of fibroblast growth factor 2 (FGF2) mRNA in BMCs co-cultured with HSLCs, and the expression of mRNAs for both albumin and tyrosine aminotransferase became detectable in HSLCs cultured with FGF2. Thus, BMCs stimulate both the proliferation of HSLCs and their differentiation into the hepatocyte lineage. FGF2 is one of the factors that is produced by the interacting BMCs and that stimulates this differentiation.

Release of interleukin-1 receptor antagonist by combining a leukocyte adsorption carrier with ulinastatin.

Both granulocyte/monocyte adsorptive apheresis (GMA) and ulinastatin, a serine protease inhibitor, are reported to be effective in patients with ulcerative colitis; however, combination therapy with GMA and ulinastatin has not been attempted. Investigating the effect of ulinastatin on GMA is required for combination therapy since the inhibition of serine protease suppresses the reaction of GMA. To clarify the effects of ulinastatin on GMA, we investigated whether granulocyte adsorption to cellulose acetate beads (carriers for GMA) and interleukin-1 receptor antagonist (IL-1ra) release were inhibited by ulinastatin. Peripheral blood containing ulinastatin, a different serine protease inhibitor (gabexate mesilate), or signal-transduction inhibitors was incubated with cellulose acetate beads in vitro, and the ratios of adsorbed granulocytes and IL-1ra release were measured. Granulocyte adsorption and IL-1ra release were significantly suppressed with increasing gabexate mesilate concentrations; however, the adsorption was not significantly inhibited by ulinastatin. Furthermore, IL-1ra release was augmented by the addition of a high dose of ulinastatin or PD98059 as compared to a low dose. The activation levels of extracellular signal-regulated protein kinase may regulate IL-1ra release induced by the carrier, because both ulinastatin and PD98059 inhibit extracellular signal-regulated protein kinase. High concentrations of ulinastatin increased IL-1ra release without inhibiting granulocyte adsorption to cellulose acetate beads. This result warrants clinical trials of a combination of ulinastatin and GMA for the treatment of ulcerative colitis.

Secondary structure of the amino-terminal region of HCV NS3 and virological response to pegylated interferon plus ribavirin therapy for chronic hepatitis C.

The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B. The association between HCV NS3 protein polymorphism and virological response was analyzed in patients infected with group A (n = 28) and B (n = 40) isolates who had good adherence to both pegylated interferon and ribavirin administration (>95% of the scheduled dosage) for 48 weeks. A sustained virological response (SVR) representing successful HCV eradication occurred in 33 (49%) in the 68 patients. Of the 28 patients infected with the group A isolate, 18 (64%) were SVR, whereas of the 40 patients infected with the group B isolate only 15 (38%) were SVR. The proportion of virological responses differed significantly between the two groups (P < 0.05). These results suggest that polymorphism in the secondary structure of the HCV-1b NS3 amino-terminal region influences the virological response to pegylated interferon plus ribavirin therapy, and that virus grouping based on this polymorphism can contribute to prediction of the outcome of this therapy.

Relationship between alcohol consumption and serum adiponectin levels: the Takahata study--a cross-sectional study of a healthy Japanese population.

CONTEXT: The relationship between alcohol consumption and serum adiponectin levels has not been fully explored in an Asian population. OBJECTIVE: Our goal was to determine whether alcohol consumption is associated with a change in adiponectin levels in a healthy Japanese population. DESIGN: This was a cross-sectional study. SETTING: Subjects were recruited from participants in a health check-up program. PARTICIPANTS: This study included 2932 subjects (1306 men and 1626 women). MAIN OUTCOME MEASURES: The effects of total weekly or daily volume of ethanol intake on serum adiponectin levels were evaluated. In addition, the correlation of clinical traits with serum adiponectin levels was examined. A multivariate regression model was used to control for possible confounding factors. RESULTS: Alcohol consumption was weakly correlated with decreased serum adiponectin levels in men [Spearman's ordered correlation coefficient (rs=-0.141; P<0.001]; an even weaker correlation was seen in women (rs=-0.055; P=0.025). Multivariate analysis demonstrated that alcohol consumption was independently associated with hypoadiponectinemia. CONCLUSION: In contrast to reports from the United States and Europe among White and Black subjects, our study demonstrated an inverse association between alcohol intake and serum adiponectin levels in Asian subjects, suggesting ethnic differences in the effects of alcohol consumption on serum adiponectin levels.