Isolation of OXA-48-like carbapenemase-producing Escherichia coli susceptible to piperacillin/tazobactam in a Japanese patient without a history of travel abroad.

Oxacillinase (OXA)-48-like ß-lactamases are the most common carbapenemases in Enterobacterales in certain regions of the world and are being introduced on a regular basis into regions of non-endemicity. Japan has been characterized by low rates of carbapenemase-producing Enterobacterales, and among them, OXA-48-like carbapenemase-producing isolates are extremely rare. Here we describe a Japanese medical worker, without a history of travel abroad, who was diagnosed as having a community-acquired urinary tract infection, and whose urine sample was found to be positive for OXA-48-like carbapenemase-producing Escherichia coli. None of her close contacts had a history of foreign travel, and the same drug-resistant organism was not observed in other patients who had been hospitalized and undergone environmental culture tests in the same medical institution. This isolate was resistant to penicillins, narrow-spectrum cephalosporins, fluoroquinolones, and cefmetazole, but was susceptible to broad-spectrum cephalosporins, piperacillin/tazobactam, and meropenem and displayed reduced susceptibility to imipenem. The modified carbapenem inactivation test supported carbapenemase production, but inhibitor-based synergistic tests yielded negative results of carbapenemase production. Multiplex polymerase chain reaction revealed the presence of the carbapenemase gene (blaOXA-48) blaTEM and AmpC ß-lactamase gene (blaDHA). Singleplex polymerase chain reaction targeting the blaOXA-48 region amplified a product sequencing to nearly the full length (722 bp) and matching 100% with OXA-48. The present case highlights a new concern regarding OXA-48-like carbapenemase-producing Enterobacterales, which remain challenging to detect for clinical laboratories in regions of non-endemicity, and may already be latent in Japan.

Antenatal mgnesium sulfate and ritodrine increased potassium levels in preterm infants: A cohort study.

BACKGROUND: Ritodrine and magnesium sulfate are administered to prevent preterm labor. Magnesium sulfate is also administered to prevent preeclampsia. These drugs have been reported to increase potassium levels in pregnant women and neonates. The aim of this study was to investigate the relationship between potassium levels in preterm infants and antenatal treatment. METHODS: This prospective cohort study was conducted at Saiseikai Suita Hospital. Preterm infants born at <35 weeks' gestation between October 2012 and September 2014 were recruited and divided into four groups based on the antenatal treatment their mothers received. Serum and urine electrolyte levels at birth and serum potassium levels 1 day after birth were measured. RESULTS: The mothers of 16 infants received no antenatal treatment (condition C); the mothers of 29 infants received antenatal ritodrine (R); the mothers of seven infants received magnesium sulfate (M); and the mothers of 15 infants received both magnesium sulfate and ritodrine (M + R). At birth, potassium levels were similar among the four groups. However, potassium levels a day after birth were significantly higher in the M + R group than in the other groups: median (min.-max.) mEq/L 4.8 (3.8-6.2), 4.8 (3.6-6.0), and 4.4 (3.8-5.9) vs. 5.8 (4.9-7.2), in the C, R, and M groups versus the M + R group, respectively (P < 0.01). Significantly more infants in the M + R group exhibited a fractional excretion of potassium of <10% compared with those in the other groups. CONCLUSION: The increased potassium levels we observe in preterm infants of mothers who received antenatal magnesium sulfate and ritodrine administration on postnatal day 1 warrant monitoring by neonatologists.

Comparison of thrombocytopenia between patients with non-alcoholic fatty liver disease and those with hepatitis C virus-related chronic liver disease.

AIM: Thrombocytopenia is widely recognized as a simple surrogate marker of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Thrombocytopenia of NAFLD has not been compared with that of hepatitis C virus-related chronic liver disease (CLD-C). Here, we examined whether there is any difference in the platelet counts between patients with NAFLD and CLD-C and investigated the underlying mechanisms. METHODS: A total of 760 biopsy-confirmed NAFLD and 1171 CLD-C patients were enrolled. After stratification according to the liver fibrosis stage, platelet counts between NAFLD and CLD-C patients were compared. The platelet count, spleen size, serum albumin level, serum thrombopoietin level, and immature platelet fraction (IPF) value were also compared after covariate adjustment using propensity score (PS) matching. RESULTS: The median platelet counts (×104 /µL) of NAFLD and CLD-C patients were 20.2 and 18.7 (p = 2.4 × 10-5 ) in F1; 20.0 and 14.5 (p = 2.1 × 10-12 ) in F2; 16.9 and 12.3 (p = 8.1 × 10-10 ) in F3; and 11.1 and 8.1 (p = 0.02) in F4, respectively. In the F3 group, NAFLD patients had a significantly higher platelet count and significantly smaller spleen volume than CLD-C patients. Although the serum thrombopoietin levels were comparable between NAFLD and CLD-C patients, the IPF value of NAFLD patients was significantly higher than that of CLD-C patients. CONCLUSIONS: NAFLD patients had a significantly higher platelet count than CLD-C patients following stratification according to the liver fibrosis stage. The milder hypersplenism and higher platelet production in NAFLD than CLD-C may have contributed to this difference.

Catechins in green tea powder (matcha) are heat-stable scavengers of acrolein, a lipid peroxide-derived reactive carbonyl species.

Lipid peroxidation-derived reactive carbonyl species (RCS) such as acrolein and 4-hydroxynonenal pose health risks. We characterized the RCS-scavenging reactions of tea catechins in an aqueous solution and in baked cake. Acrolein's reaction with each of the major tea catechins (epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate) resulted in the formation of mono-, di-, and tri-acrolein conjugates of each catechin as revealed by our LC-linear ion trap MS analysis. The formation of the acrolein-conjugates of the four catechins was confirmed in the reaction of acrolein with green tea powder (matcha) extract. The addition of matcha tea powder to cake dough significantly suppressed the accumulation of RCS during cake baking. The mono-acrolein conjugates of the four major catechins were detected in the baked cake. The RCS-scavenging capability of tea catechins offers a new functionality of matcha tea powder, and its heat stability demonstrates the usefulness of matcha as a food additive.

Diagnostic accuracy of combined biomarker measurements and vibration-controlled transient elastography (VCTE) for predicting fibrosis stage of non-alcoholic fatty liver disease.

BACKGROUND: Numerous biomarkers have been developed for assessing the presence and severity of liver fibrosis associated with non-alcoholic fatty liver disease (NAFLD). Fibrosis can be assessed by liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE). Here we examined whether diagnostic accuracy and applicability can be further improved by combining various biomarker measurements with LSM. METHODS: A total of 278 patients with biopsy-confirmed Japanese NAFLD patients were enrolled. Area under the receiver operator characteristic curve (AUROC) was evaluated for obtaining the optimum interpretation criteria for LSM by VCTE and comparing various biomarkers alone and in combination with LSM. RESULTS: Liver stiffness measurements including cases with interquartile range (IQR)/median (M) < 30% or LSM ≤ 7.1 kPa demonstrated high applicability (90% of patients with NAFLD) and accuracy (AUROC: 0.891) for predicting stage ≥ 3 fibrosis. For all biomarkers tested, the AUROC values for predicting stage ≥ 3 fibrosis were increased when combined with LSM [platelet count, 0.734 vs. 0.912; type-4 collagen 7s (T4C7s), 0.894 vs. 0.921; aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), 0.774 vs. 0.906; AST to platelet ratio index, 0.789 vs. 0.902; FIB-4 index, 0.828 vs. 0.922; NAFLD fibrosis score, 0.800 vs. 0.906; CA index-fibrosis, 0.884 vs. 0.913; FM-fibro index, 0.920 vs. 0.943; FIB-4 index + T4C7s, 0.901 vs. 0.930], demonstrating the advantage of concurrent LSM. CONCLUSIONS: While VCTE has slightly limited applicability (90%) for patients with NAFLD, concurrent measurement with certain biomarkers (especially FM-fibro, T4C7s, and FIB-4) greatly improves the diagnostic accuracy.

Updates to and quality of clinical practice guidelines for high-priority diseases in Japan.

PURPOSE: To examine the update status of clinical practice guidelines (CPGs) for 24 main diseases in Japan, and to clarify the quality of and issues pertaining to the most recent versions of CPGs for each disease. DATA SOURCES: CPGs were searched in two Japanese guideline databases. STUDY SELECTION: All relevant Japanese CPGs published between January 1999 and July 2016 were selected. DATA EXTRACTION: The developer and issue date were extracted for all target CPGs. The most recent CPGs were assessed using the Appraisal of Guidelines for Research and Evaluation-II (AGREE II) instrument. RESULTS OF DATA SYNTHESIS: Among 106 target CPGs, 24 most recent CPGs were subjected to assessment using the AGREE II instrument. CPGs for 11 diseases (46%) had a mean time interval for update of ≥5 years. Among the 24 CPGs subjected to AGREE II assessment, median domain scores were 74% for "Domain 1: Scope and Purpose," 43% for "Domain 2: Stakeholder Involvement," 46% for "Domain 3: Rigor of Development," 69% for "Domain 4: Clarity of Presentation," 24% for "Domain 5: Applicability" and 27% for "Domain 6: Editorial Independence." CONCLUSIONS: The systematic assessment of CPGs for 24 major diseases in Japan revealed a trend for a delay in timing of update for many CPGs. Moreover, the 24 most recent CPGs had low domain scores for domains 2, 3, 5 and 6. In the future, concrete measures will need to be considered in order to improve the quality of CPGs.

Hepatocellular carcinoma as a leading cause of cancer-related deaths in Japanese type 2 diabetes mellitus patients.

BACKGROUND: We reported a cross-sectional study on causes of liver injury in Japanese type 2 diabetes mellitus (T2D) patients (JG 2013). We assessed overall and cause-specific mortality risk during follow-up of patients enrolled in JG 2013. METHODS: This was a longitudinal, multicenter cohort study. Of the 5642 Japanese T2D patients who visited T2D clinics of nine hospitals in the original study, 3,999 patients were followed up for an average of 4.5 years. Expected deaths in T2D patients were estimated using age-specific mortality rates in the general population (GP) of Japan. Standardized mortality ratios (SMRs) were calculated to compare mortality between T2D patients and GP. RESULTS: All-cancer mortality was significantly higher in T2D patients than in the GP [SMR 1.58, 95% confidence interval (CI) 1.33-1.87]. Among malignancies, hepatocellular carcinoma (HCC) conferred the highest mortality risk in T2D patients (SMR 3.57, 95% CI 2.41-5.10). HCC-associated mortality risk in T2D patients remained significantly high (SMR 2.56, 95% CI 1.64-3.97) after adjusting for high positivity rates of hepatitis B surface antigen (1.7%) and anti-hepatitis C virus (5.3%). In T2D patients with platelet counts < 200 × 103/µl, SMR of HCC increased from 3.57 to 6.58 (95% CI 4.34-9.58). T2D patients with platelet count > 200 × 103/µl showed no increase in mortality risk (SMR 0.68) of HCC. CONCLUSIONS: HCC-associated mortality risk was the highest among all cancers in Japanese T2D patients. Regular follow-up may be important for T2D patients with platelet counts < 200 × 103/µl for early detection of HCC.

[The impact of direct-acting antiviral therapy on the diagnosis of hepatitis-C virus-associated hepatocellular carcinoma].

Since the introduction of direct-acting antiviral (DAA)-based combination therapies in September 2014 for patients with chronic hepatitis-C (CH-C), numerous patients have been diagnosed with hepatitis-C virus (HCV)-associated hepatocellular carcinomas (HCCs) during the screening performed prior to DAA therapy. The present study was conducted on the antiviral therapy for CH-C in two phases:i) the interferon (IFN) phase between January 2011 and August 2014 and ii) the DAA phase between September 2014 and September 2016. During the DAA phase, HCCs were detected in eight patients who were referred to our hospital for anti-HCV therapy. In contrast, HCCs were detected in only two patients during the IFN phase. The number of patients with newly detected HCC in the DAA phase (20.5%) who were referred for the anti-HCV therapy was significantly higher than that in the IFN phase (1.7%). Owing to the high efficacy and safety of the DAA therapy, the number of patients referred to our hospital for anti-HCV therapy increased from 40.5 persons/year in the IFN phase to 80.3 persons/year in the DAA phase. The average ages of patients in the DAA and IFN phases were 68 and 61 years, respectively. The increase in the number of patients with newly detected HCC referred for the anti-HCV therapy in the DAA phase could be attributed to the increase in the number of referred patients for anti-HCV therapy and the aging of these patients in the DAA phase. All the eight patients with newly detected HCC who were referred for anti-HCV therapy in the DAA phase received curative treatments. The median age, rate of liver cirrhosis, and median tumor size of the patients were 69 years, 13%, and 16mm. Therefore, the findings of this study indicate that DAA therapies not only eradicate HCV infection but also contribute to the early diagnosis of HCC by encouraging the HCV-infected patients to visit hospitals and by promoting active network between hepatologists and family physicians.

Effectiveness of Helicobacter pylori eradication in the prevention of primary gastric cancer in healthy asymptomatic people: A systematic review and meta-analysis comparing risk ratio with risk difference.

BACKGROUND: Helicobacter pylori infection is strongly associated with gastric cancer occurrence. However, it is unclear whether eradication therapy reduces the risk of gastric cancer occurrence. We evaluated whether H. pylori eradication reduces the risk of primary gastric cancer by using both risk ratio (RR) and risk difference (RD). METHODS: Searches of PubMed, EMBASE, Google scholar, the Cochrane Library, and the Japan Medical Abstracts Society as well as those registered in databases of the Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, ClinicalTrials.gov, controlled-trials.com, UMIN-CTR, JMACCT-CTR, and JAPIC-CTI between January 1965 and March 2017, supplemented with manual screening. Randomized controlled trials (RCTs) in which eradication therapy were implemented for the interventional group but not for the control group, and assessed the subsequent occurrence of primary gastric cancer as the main outcome. Two authors independently reviewed articles and extracted data. Integrated results for all data were presented as RR and RD. RESULTS: Seven studies met inclusion criteria. The reductions in risk of primary gastric cancer occurrence in terms of overall RR and RD were 0.67 (95% CI: 0.48 to 0.95) and -0.00 ([95% CI: -0.01 to 0.00]; number needed to treat: 125.5 [95% CI: 70.0 to 800.9]), respectively. CONCLUSIONS: The effectiveness of H. pylori eradication therapy in suppressing the occurrence of primary gastric cancer was significant and comparable to that of previous studies in terms of the estimated RR. However, the estimated RD was slight and not statistically significant.

Classification of patients with non-alcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with liver histology and other fibrosis markers.

AIM: Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). We investigated the association among serum type IV collagen level, liver histology, and other fibrosis markers in NAFLD progression. METHODS: We evaluated 184 patients diagnosed with NAFLD following biopsy, including 89 males and 95 females with an average age of 52.6 and 62.6 years, respectively. Non-alcoholic fatty liver disease was classified as NAFL or NASH using Matteoni's classification, and the grade and stage of NASH were assessed using Brunt's classification. Serum type IV collagen was measured by a rapid and sensitive latex particle-enhanced turbidimetric immunoassay. RESULTS: Forty-two patients with NAFL and 142 patients with NASH were included in this study. Compared with patients with NAFL, patients with NASH showed more significant liver function disorder and increased expression of fibrosis markers including type IV collagen, collagen 7S, Mac2-binding protein (M2BP), and hyaluronic acid (HA). Expression of type IV collagen and collagen 7S, but not M2BP and HA, was more significantly elevated in patients with stage 1 NASH than in patients with NAFL, indicating that type IV collagen and collagen 7S may be better discriminators of NASH and NAFL than M2BP and HA at an early stage of fibrosis. When patients were stratified by NAFLD activity score, type IV collagen and collagen 7S were significantly elevated as NAFLD activity score progressed, whereas M2BP and HA expression were not significantly elevated. CONCLUSION: Type IV collagen may be a useful measure of NASH severity as latex particle-enhanced turbidimetric immunoassay-based rapid type IV collagen assay can be carried out routinely.

Long-term (>=2 yr) efficacy of vitamin E for non-alcoholic steatohepatitis.

BACKGROUND/AIMS: Vitamin E is one of the most promising treatments for non-alcoholic steatohepatitis (NASH). However, the long-term efficacy of this treatment remains unknown. METHODOLOGY: We retrospectively examined 17 patients with biopsy-proven NASH who received vitamin E at a dose of 300 mg/day for >=2 yr, and underwent second liver biopsies after treatment. Variables were compared between patients with (group R) and without (group NR) fibrosis regression. RESULTS: The median interval between basal and second liver biopsies was 2.4 yr (range, 2.0-5.8 yr). Overall, transaminase activities, insulin resistance index, and hepatic fibrosis markers were significantly improved. Although histological steatosis, inflammation, and fibrosis did not change after treatment, liver fibrosis improved in seven patients (41.2%), progressed in five (29.4%), and remained unchanged in five (29.4%). At baseline, subjects in group R (n = 7) were more likely to have diabetes, insulin resistance, and severe fibrosis compared to those in group NR (n = 10). Lower NAFLD activity score and larger decrease of ALT and insulin resistance after treatment were observed in group R compared with group NR. CONCLUSIONS: Two years or longer treatment can be expected to ameliorate NASH fibrosis, especially in those whose serum transaminase activities and insulin resistance can be improved.

A large-scale nationwide multicenter prospective observational study of triple therapy using rabeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in Japan.

BACKGROUND: In recent years in Japan, the rate of clarithromycin (CAM) resistance in Helicobacter pylori has risen to around 30%, and the eradication rate with triple therapy [proton pump inhibitor + amoxicillin (AMPC) + CAM] has been trending downward to around 70%. In 2007, rabeprazole (RPZ)-based triple therapy (RPZ + AMPC + CAM: RAC therapy) was approved in Japan, and a large-scale nationwide study was therefore initiated to evaluate the efficacy and safety of RAC therapy in clinical practice. METHODS: Patients with H. pylori-positive gastric/duodenal ulcer (including ulcer scars) were administered triple therapy comprising RPZ 10 mg, AMPC 750 mg, and CAM 200 mg (or 400 mg), twice daily for 7 days. RESULTS: The eradication rate was 80.7% (2,551/3,162). The results of multivariate analysis indicated the following as factors affecting the eradication rate: sex, treatment compliance, history of H. pylori treatment, presence of urologic disease, presence of respiratory disease, and year of starting treatment. The incidence of adverse drug reactions (such as diarrhea and dysgeusia) was 4.4% (166/3,789). The results of multivariate analysis indicated the following as factors affecting the incidence of adverse drug reactions: sex, daily CAM dose, and history of allergies. CONCLUSION: In a large-scale nationwide study of use in clinical practice, RAC therapy was confirmed to be effective and safe.

Impact of amino acid substitutions in hepatitis C virus genotype 1b core region on liver steatosis and glucose tolerance in non-cirrhotic patients without overt diabetes.

BACKGROUND AND AIM: The hepatitis C virus (HCV) core protein induces hepatic steatosis and glucose intolerance in transgenic mice. The aim of this study was to clarify the impact of mutations in the HCV core region on hepatic steatosis and glucose tolerance in patients with chronic hepatitis C. METHODS: Seventy-four Japanese patients (27 men, 47 women; mean age, 61.9 years) infected with HCV 1b with high viral load (>5 log IU/ml), without cirrhosis and overt diabetes, were enrolled. Substitutions in amino acids 70 and 91 of the HCV genotype 1b core region, the percentage of hepatic steatosis by liver histology, and glucose tolerance evaluated by the oral glucose tolerance test were investigated in all patients. RESULTS: Steatosis was observed in 40 patients (54%). Transaminase activities, γ-glutamyl-transpeptidase, serum ferritin levels, homeostasis model assessment of insulin resistance index, and substitutions of amino acid 70 were significantly associated with the presence of steatosis, upon univariate analysis. Glucose intolerance was more prevalent in patients with steatosis (63%) than in those without steatosis (32%, P = 0.012). Multivariate analysis showed that substitution of amino acid 70 (odds ratio: 4.924; 95% confidence interval: 1.442-16.815; P = 0.014) and glucose intolerance (odds ratio: 3.369; 95% confidence interval: 1.076-10.544; P = 0.040) were independent factors related to liver steatosis. Levels of plasma glucose and serum insulin after glucose load were similar between patients with and without substitutions of amino acids 70 and 91. CONCLUSIONS: Amino acid substitutions in the HCV genotype 1b core region are associated with hepatic steatosis in patients with chronic hepatitis C, independent of glucose intolerance.

Lower circulating levels of dehydroepiandrosterone, independent of insulin resistance, is an important determinant of severity of non-alcoholic steatohepatitis in Japanese patients.

AIM: The biological basis of variability in histological progression of non-alcoholic fatty liver disease (NAFLD) remains unknown. Dehydroepiandrosterone (DHEA), the most abundant steroid hormone, has been shown to influence sensitivity to reactive oxygen species, insulin sensitivity and expression of peroxisome proliferator-activated receptor-α. Our aim was to determine whether more histologically advanced NAFLD is associated with low circulating levels of DHEA in Japanese patients. METHODS: Serum samples were obtained in 133 Japanese patients with biopsy-proven NAFLD and in 399 sex- and age-matched healthy people undergoing health checkups. Serum levels of sulfated DHEA (DHEA-S) were measured by chemiluminescent enzyme immunoassay. RESULTS: Serum DHEA-S levels in NAFLD patients were similar to those in the control group. Of 133 patients, 90 patients were diagnosed as non-alcoholic steatohepatitis (NASH): 73 patients had stage 0-2, and 17 had stage 3 or 4. Patients with advanced NAFLD (NASH with fibrosis stage 3 or 4) had lower plasma levels of DHEA-S than patients with mild NAFLD (simple steatosis or NASH with fibrosis stage 0-2). The area under the receiver operating characteristic curve for DHEA in separating patients with and without advanced fibrosis was 0.788. A "dose effect" of lower DHEA-S and incremental fibrosis stage was observed with a mean DHEA-S of 170.4 ± 129.2, 137.6 ± 110.5, 96.2 ± 79.3, 61.2 ± 46.3 and 30.0 ± 32.0 µg/dL for fibrosis stages 0, 1, 2, 3, and 4, respectively. The association between DHEA-S and severity of NAFLD persisted after adjusting for age, sex and insulin resistance. CONCLUSION: Low circulating DHEA-S might have a role in the development of advanced NASH.

Outcome of endoscopic submucosal dissection for colorectal tumors in elderly people.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been reported to be effective for the en bloc resection of large colorectal tumors. Our study investigated whether ESD was suitable for elderly people with large colorectal tumors in terms of its invasiveness. PATIENTS AND METHODS: We studied 119 colorectal tumors that were treated with ESD at Kyoto Prefectural University of Medicine or Nara City Hospital between 2006 and 2009. We classified each patient as either elderly, i.e., more than 75 years old, or non-elderly, i.e., less than 75 years old. Thirty-two of the cases were classified as elderly. Performance status, tumor size, operation time, rate of en bloc resection, histopathological diagnosis, complications, and hospital stay after ESD were analyzed retrospectively in both groups. RESULTS: In the elderly group, the average tumor size was 32.6 mm; the average operation time, 96 min; the rate of en bloc resection, 81.2%; the rate of perforation, 3.1%; and hospital stay after ESD, 5.1 days. Histopathological diagnosis for 16 tumors was adenoma; for 13, carcinoma with invasion into the mucosa; and for three, carcinoma with invasion into the submucosa. There were no statistical differences between the two groups in any of these data. The case with perforation was treated conservatively without urgent surgery in the elderly group. CONCLUSIONS: ESD for colorectal tumors resulted in favorable rates of en bloc resection in elderly people. Perforation occurred in elderly people, but these patients were cured with conservative treatment. ESD is a safe and minimally invasive treatment for elderly people with colorectal tumors.

Prevalence of Helicobacter pylori infection in long-term hemodialysis patients.

Patients on hemodialysis often have gastrointestinal complications; however, it is unclear if Helicobacter pylori infection is present in these patients. Here we determined the prevalence of H. pylori infection in 539 Japanese hemodialysis patients by measuring serum anti-H. pylori IgG antibodies. Endoscopy was performed on 299 of these patients and the results were compared to 400 patients with normal renal function who had also undergone endoscopy and sero-testing. A second cohort of 478 dialysis patients, within the original group, was checked serologically for H. pylori infection three times over a four-year observation period. The prevalence of infection in these patients was significantly lower than in those patients with normal renal function, irrespective of the clinical outcomes. The prevalence of H. pylori infection significantly decreased as the duration of dialysis increased, particularly within the first four years following initiation of dialysis. About one-third of patients on dialysis for less than four years became serologically negative for H. pylori infection within this observation period. Our study suggests that although long-term dialysis patients have low prevalence of H. pylori, they still have significant gastroduodenal diseases, such as peptic ulcers, that require endoscopic follow-up.

Levels of interleukin-18 are markedly increased in Helicobacter pylori-infected gastric mucosa among patients with specific IL18 genotypes.

BACKGROUND: The cellular immune response in gastric mucosa infected with Helicobacter pylori is proposed to be predominantly of the T helper cell type 1 type. METHODS: Interleukin (IL)-18, IL-12, and interferon (IFN)-gamma levels were measured in gastric mucosal biopsy specimens by reverse-transcription polymerase chain reaction (PCR) and by enzyme-linked immunosorbent assay; IL18 polymorphisms were determined by PCR. RESULTS: Biopsy specimens from 128 patients (56 with nonulcer dyspepsia, 28 with gastric ulcers, 28 with duodenal ulcers, and 16 with gastric cancer) were examined; 96 patients had H. pylori infection. IL-18 levels were markedly up-regulated in mucosa infected with H. pylori (P < .001), whereas IL-12 and IFN-gamma levels were independent of H. pylori status. IL-18 levels correlated with IFN-gamma levels only in infected patients (R = 0.31 to R = 0.51). IL-18 levels were the determining factor for monocyte infiltration in H. pylori-infected mucosa (P < .001). H. pylori-infected patients displaying IL18 -607C/C and -137G/G had higher IL-18 levels than did those with other genotypes and were more likely to experience treatment failure. CONCLUSION: H. pylori infection induces IL-18 in the gastric mucosa. H. pylori-infected patients with IL18 -607C/C and -137G/G have higher IL-18 levels, which causes severe gastric inflammation. IL18 genotype might be a marker for predicting the effects of eradication therapy.

[A case of adult-onset type II citrullinemia having a liver histology of nonalcoholic steatohepatitis (NASH)].

A 47-year man was hospitalized to our hospital because of consciousness disturbance. He had been abnormally fond of soy bean products since childhood. His plasma levels of ammonia and citrulline were elevated, and we suspected of adult-onset type II citrullinemia (CTLN2). Gene examination demonstrated abnormality in the SLC25A13 gene, confirming CTLN2. Serum levels of hepatobiliary enzymes were increased and his liver biopsy revealed nonalcoholic steatohepatitis. Although we considered that living donor liver transplantation was suitable for the treatment, unfortunately, there was no appropriate donor candidate in his family. He has received conservative treatments, showing a symptom-free course.

Hepatic iron accumulation may be associated with insulin resistance in patients with chronic hepatitis C.

BACKGROUND/AIM: Insulin resistance and hepatic iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases. We investigated the relationship between insulin resistance and hepatic iron deposition in patients with chronic HCV infection. METHODS: Insulin resistance was evaluated using the homeostasis model assessments for insulin resistance (HOMA-IR) in 56 non-diabetic non-obese patients with biopsy proven chronic hepatitis C. The relationship between insulin resistance and serum ferritin levels or the grade of hepatic iron deposition was assessed. RESULTS: The levels of plasma immunoreactive insulin (IRI) and HOMA-IR were significantly correlated with serum ferritin levels and the grade of hepatic iron deposition (P = 0.003).Although IRI and HOMA-IR increased in parallel with the development of hepatic fibrosis, insulin resistance (HOMA-IR > 2) was observed in 11 (26.2%) of 42 patients even without severe fibrosis (F0-2). Among patients without severe fibrosis, IRI and HOMA-IR were significantly higher in patients with iron deposits than in those without iron deposits. CONCLUSION: Hepatic iron overload may be associated with insulin resistance in patients with chronic hepatitis C, especially in patients with mild to moderate fibrosis.

[Utility of a little phlebotomy intermittently just before intravenous injection of glycyrrhizin for patients with chronic hepatitis C].

We performed a small phlebotomy (50 ml) intermittently just before intravenous injection of glycyrrhizin (GL) in eight patients with chronic hepatitis C and continued this therapy until their serum ferritin levels dropped below 20 ng/ml without any changes of GL dosage. No patients had complications but one patient holded treatment according to their wishing. In seven patients who completed this therapy, the average amount of phlebotomized blood was 1221 +/- 1055 ml, their serum ferritin value significantly fell from 253 +/- 233 ng/ml to 18+/-5 ng/ml (p=0.038). Serum ALT levels also significantly decreased from 74 +/- 22 IU/L to 41 +/- 12 IU/L (p=0.001). Small intermittent phlebotomies before GL injection may be a effective treatment for hepatitis C.