Kunio Nakane

High Amount of Dietary Fiber Not Harmful But Favorable for Crohn Disease

Current chronic diseases are a reflection of the westernized diet that features a decreased consumption of dietary fiber. Indigestible dietary fiber is metabolized by gut bacteria, including Faecalibacterium prausnitzii, to butyrate, which has a critical role in colonic homeostasis owing to a variety of functions. Dietary fiber intake has been significantly inversely associated with the risk of chronic diseases. Crohn disease (CD) is not an exception. However, even authors who reported the inverse association between dietary fiber and a risk of CD made no recommendation of dietary fiber intake to CD patients. Some correspondence was against advocating high fiber intake in CD. We initiated a semivegetarian diet (SVD), namely a lacto-ovo-vegetarian diet, for patients with inflammatory bowel disease. Our SVD contains 32.4 g of dietary fiber in 2000 kcal. There was no untoward effect of the SVD. The remission rate with combined infliximab and SVD for newly diagnosed CD patients was 100%. Maintenance of remission on SVD without scheduled maintenance therapy with biologic drugs was 92% at 2 years. These excellent short- and long-term results can be explained partly by SVD. The fecal bacterial count of F prausnitzii in patients with CD is significantly lower than in healthy controls. Diet reviews recommend plant-based diets to treat and to prevent a variety of chronic diseases. SVD belongs to plant-based diets that inevitably contain considerable amounts of dietary fiber. Our clinical experience and available data provide a rationale to recommend a high fiber intake to treat CD.

The expression of Fas and Fas ligand, and the effects of interferon in chronic liver diseases with hepatitis C virus

In viral hepatitis, binding of Fas ligand (FasL) with Fas expressed on the surfaces of infected hepatocytes induces apoptosis, removing hepatitis virus along with infected hepatocytes. We measured serum concentrations of soluble Fas (sFas) and FasL (sFasL), expression of membrane-bound FasL, and expression of FasL-mRNA in patients with chronic hepatitis C without cirrhosis (CH-C) and chronic hepatitis C with liver cirrhosis (LC-C). In CH-C, sFasL concentrations were lower and FasL-mRNA expression was significantly less than in volunteers. In LC-C, sFas concentrations were significantly greater than in healthy volunteers, while sFasL, membrane-bound FasL expression, and FasL-mRNA expression did not show significant differences. We also examined these variables over 24 h following the first interferon (IFN) treatment in patients with CH-C. Serum concentrations of sFas and sFasL, and FasL-mRNA expression increased markedly beyond amounts present before IFN injection until 12 h after IFN injection. However, membrane-bound FasL expression decreased until 6 h, followed by an increase until 24 h. Our findings suggest that the ratio of membrane-bound FasL to sFasL may be regulated to remove virally infected cells in CH-C. In addition, apoptosis mediated by the Fas/FasL system may be influenced by IFN injection for treatment of CH-C.

Clinical significance of SEN-virus on interferon response in chronic hepatitis C patients.

Background and Aim:  A novel virus, SEN‐virus (SENV), was recently discovered. It has been reported as a candidate for a non‐A–E hepatitis virus. However, much is still unknown about the clinical significance of SENV. The aim of the present study was to clarify the clinical significance of SENV in patients coinfected with SENV and hepatitis C virus (HCV).

Clinical significance of TT virus in chronic hepatitis C.

Background and Aims: Much is still unknown about the clinical significance of TT virus (TTV), which has been reported as a candidate for non A–G hepatitis virus. The aim of this study was to clarify the clinical significance of TTV in patients coinfected with TTV and hepatitis C virus (HCV).

Crohn's disease successfully treated with infliximab in a patient receiving hemodialysis: case report and review of the literature.

AbstractThere is limited information in the use of antitumor necrosis factor &agr;, infliximab, in patients on hemodialysis. In Crohn’s disease (CD), only 3 cases are reported.A 76-year-old man on hemodialysis for renal failure caused by immunoglobulin A nephropathy developed diarrhea and abdominal pains. A marked edema was observed in the pretibia and ankle. An increase of C-reactive protein (CRP) and erythrocyte sedimentation rate, hypoalbuminemia, hypocholesterolemia, and moderate anemia was found. Ultrasonography and computed tomography (CT) found wall thickness in the left colon. Sigmoidoscopy revealed multiple ulcers in the sigmoid colon and noncaseating epithelioid granuloma was found in the biopsy specimen. Barium enema study exhibited collar button signs and longitudinal ulcers in the left colon.A severe form of CD was diagnosed. Metronidazole seemed to decrease CRP but was ineffective in ameliorating diarrhea. Infliximab rather than steroid hormone was chosen for the treatment. Standard induction therapy with infliximab was initiated. Symptoms rapidly improved then disappeared. CD activity index decreased from 747 to a remission level of 134 after 2 infusions of infliximab. Scheduled maintenance infliximab therapy was administered after the induction therapy. Ultrasonography and CT showed a disappearance of the wall thickness of the colon. Adverse reactions were not observed.Infliximab was effective and safe in a patient with CD on hemodialysis. Our case has added additional literature in accordance with previous reports supporting infliximab as effective and safe in patients on hemodialysis.

Efficacy of interferon therapy to GBV-C/HGV in patients with GBV-C/HGV and HCV coinfection

Abstract GB virus C (GBV-C) and hepatitis G virus (HGV) seemed to be the cause of hepatic injury in a setting of both acute and chronic infection. Some patients with hepatitis C virus (HCV) infection were coinfected with GBV-C/HGV. In the present study, we examined the effect of interferon on the GBV-C/HGV in chronic hepatitis C patients who were coinfected with GBV-C/HGV, in order to clarify the clinical significance of GBV-C/HGV infection. For GBV-C/HGV-RNA detection, the reverse transcription-nested polymerase chain reaction (RT-PCR) with primers from the 5′ untranslated subgenomic region was used. For GBV-C/HGV-RNA quantitative analysis, competitive RT-PCR was employed. Polymerase chain reaction products were directly sequenced. During IFN therapy, serum GBV-C/HGV-RNA became negative in nine patients (90%). However, a breakthrough of GBV-C/HGV was seen in two patients (20%), a virological relapse was seen after the cessation of IFN therapy in four patients (40%), and only three patients (30%) were sustained as negative. The changes in serum alanine aminotransferase levels after the cessation of IFN therapy correlated well with the changes in HCV-RNA. However, the correlation with GBV-C/HGV-RNA was poor. These results suggest that [1] GBV-C/HGV is sensitive to IFN therapy; and [2] In chronic hepatitis C patients coinfected with GBV-C/HGV and HCV, HCV appears to be involved with hepatocellular injury. It is less likely that GBV-C/HGV is directly involved in the initiation and progression of hepatic injury.

Development and Application of a Plant-Based Diet Scoring System for Japanese Patients with Inflammatory Bowel Disease.

CONTEXT Plant-based diets (PBDs) are a healthy alternative to westernized diets. A semivegetarian diet, a PBD, has been shown to prevent a relapse in Crohn disease. However, there is no way to measure adherence to PBDs. OBJECTIVE To develop a simple way of evaluating adherence to a PBD for Japanese patients with inflammatory bowel disease (IBD). DESIGN PBD scores were assigned according to the frequency of consumption provided on a food-frequency questionnaire, obtained on hospitalization for 159 patients with ulcerative colitis and 70 patients with Crohn disease. Eight items considered to be preventive factors for IBD were scored positively, and 8 items considered to be IBD risk factors were scored negatively. The PBD score was calculated from the sum of plus and minus scores. Higher PBD scores indicated greater adherence to a PBD. The PBD scores were evaluated on hospitalization and 2 years after discharge for 22 patients with Crohn disease whose dietary pattern and prognosis were established. MAIN OUTCOME MEASURE Plant-Based Diet score. RESULTS The PBD scores differed significantly, in descending order, by dietary type: pro-Japanese diet, mixed type, and pro-westernized diet (Wilcoxon/Kruskal-Wallis test). The PBD scores in the ulcerative colitis and Crohn disease groups were 10.9 ± 9.5 and 8.2 ± 8.2, respectively. For patients with Crohn disease, those with long-term remission and normal C-reactive protein concentration were significantly more likely to have PBD scores of 25 or greater than below 25 (χ2). CONCLUSION The PBD score is a valid assessment of PBD dietary adherence.

GB Virus C Infection: Clinical Significance

GB virus C (GBV-C) RNA positivity rates were examined in serum specimens from 231 patients with liver disease (23 patients with hepatitis B, 175 patients with hepatitis C, five patients with hepatitis B virus plus hepatitis C virus coinfection, and 28 patients with non-A, non-B, non-C hepatitis) to clarify the clinical significance of this virus. GBV-C RNA was detected in none of 12 patients with fulminant hepatitis, one of two patients with acute hepatitis positive for hepatitis B surface antigen and one of four patients with acute non-A, non-B, non-C hepatitis. Pathogenetic involvement of GBV-C was suspected in some patients in the latter group. Among patients with the non-B, non-C type of chronic disease, one of seven with cirrhosis (14%) and none with chronic hepatitis or hepatocellular carcinoma were GBV-C-positive. In chronic hepatitis C patients who had received interferon treatment, no difference was found in clinical findings, alanine aminotransferase (ALT) concentrations, histology or response to interferon between 11 patients who were GBV-C RNA-positive and 101 patients who were GBV-C RNA-negative. Moreover, changes in ALT after interferon therapy showed no relation to positivity for GBV-C RNA. On the basis of these findings, GBV-C appears to be an unlikely cause of initiation or progression of chronic hepatic diseases.

Prevalence of TTV in an area endemic for hepatitis C virus and in patients with non a to G hepatitis

Background: TT virus (TTV), a non-enveloped single stranded DNA virus, was identified as candidate for a new hepatitis virus. Little is known about its pathogenicity and routes of transmission. In this study, we investigated TTV infection in inhabitants of an area endemic for hepatitis C virus (HCV) and in patients with non A to G hepatitis and in healthy blood donors, and analyzed prevalence and transmission routes of TTY infection. Materials and methods: TTV infection was studied in 290 inhabitants, including 41 couples, who participated in a mass screening in HCV hyper-endemic area, furthermore in 45 patients with non A to G hepatitis, and in 50 healthy blood donors. TTV DNA was determined by polymerase chain reaction (PCR) with the set of primer reported by Okamoto et al. TTV DNA sequences were determined by dideoxy chain termination method and were analyzed by phylogenetic analysis. Result: TTY DNA was detected in 166 of 290 (57.2%) inhabitants in HCV hyper-endemic area, 20 of 45 (44.4%) patients with non A to G hepatitis, 11 of 50 (22%) healthy blood donors by Okamotos primer set. In inhabitants in HCV hyper-endemic area, TTV infection was not related to the positive rate of other hepatitis virus markers (anti-HBc, HCV RNA, HGV RNA, antiHGV). The prevalence of TTV tended to be higher in inhabitants who had blood transfusion (P<0,07). In only TTV positive inhabitants, 7 cases had elevations of ALT level, although its degree is not severe. Among TTV positive inhabitants, there were no specific aminoacid sequences between patients of liver diseases and asymptomatic carriers, and also in phylogenetic analysis, no specific difference exists among two groups. In 41 couples, 15 couples (36.6%) were both positive for TTV DNA, 18 couples (43.9%) were either positive, 8 couples (19.5%) were neither positive. There was no couple that the genetic distance between husband and wife was close. Conclusion: The prevalence of TTV DNA showed high rate (57.2%) in HCV endemic area. The prevalence of TTY tends to be higher in inhabitants who had blood transfusion, however these strains reported here are distinct phylogenically. This raises the possibility that the TTV spreading in the study area originated from multiple locations. And we consider that TTV infection is rarely associated with liver diseases, because most of TTV positive inhabitants reveal normal ALT level. In transmission route, our results indicated that TTV is not likely to transmit sexually.

Effect of dibutyryl cyclic AMP on phagocytosis and production of nitric oxide and tumor necrosis factor-α in cultured rat Kupffer cells

Abstract Dibutyryl cyclic AMP (DBcAMP) is an analogue of cAMP. DBcAMP has many effects on hepatocellular carcinoma, liver cirrhosis, ischemic liver failure and endotoxin-induced inflammatory liver injury. However, little is known about the mechanism of DBcAMP action in Kupffer cells. We examined the effects of DBcAMP on phagocytic activity and production of nitric oxide (NO) and tumor necrosis factor- α (TNF- α ) in cultured rat Kupffer cells treated with lipopolysaccharide (LPS). NO concentrations in culture supernatants were measured using an NO analyzer and TNF- α levels were measured with ELISA. Immunofluorescent staining for nuclear factor- κ B (NF- κ B) was visualized using an anti-NF- κ B p65 antibody. DBcAMP premedication had no effect on LPS-stimulated phagocytic activity of Kupffer cells but increased NO production and inhibited TNF- α production in a dose-dependent manner. Genistein did not block, but H-89 did block, the inhibitory effect of DBcAMP on LPS-stimulated TNF- α production in Kupffer cells. We conclude that DBcAMP inhibits LPS-stimulated TNF- α production by activating cyclic AMP-dependent protein kinase. Using immunofluorescent staining for NF- κ B, we demonstrate that the effect of DBcAMP does not involve signal transduction through NF- κ B.