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The high prevalence of obesity is a global concern. However, obesity and inflammatory bowel disease have similarities in epidemiology, diet, and gut microbial dysbiosis. An omnivorous (westernized) diet replacement with a plant-based diet in inflammatory bowel disease achieved better outcomes in both the induction and quiescent phases. Educational hospitalization providing a plant-based diet was found effective in suppressing flare-up in ulcerative colitis. This case report was designed to assess whether a plant-based diet can reduce body weight in patients with obesity during educational hospitalization for a short period of two weeks. Three men with metabolic syndrome (55, 61, and 65 years old) were included in the study with body mass index ranging from 27.0 to 31.2 kg/m2 and visceral fat area between 94.7 and 128 cm2. In Japan, a body mass index of ≥25 is defined as obesity. A lacto-ovo-vegetarian diet with brown rice (1400 or 1100 kcal/day), a plant-based diet, was provided during hospitalization for around two weeks. Patients walked for about 1 h in a park daily during the hospitalization. All three patients showed weight loss: 2.9%, 6.1%, and 6.6% at discharge. A decrease in body mass index, waist circumference, and the visceral fat area was also observed. Restriction in total calories in the form of a plant-based diet and daily 1-hour walks through an educational hospitalization for two weeks effectively reduced body weight and improved obesity-related parameters. Thus, a plant-based diet could be an effective weight-loss diet.

INTRODUCTION: About one-third of patients with severe ulcerative colitis (UC) do not respond to corticosteroid therapy and receive rescue therapy with infliximab or cyclosporine. Up to 20% of such patients fail to respond to rescue therapy and undergo colectomy. OBJECTIVE: We investigated the outcomes of infliximab and a plant-based diet (PBD) as first-line therapy for severe UC. METHODS: Patients with severe UC defined by the Truelove and Witts criteria were admitted and given standard induction therapy with infliximab (5.0 mg/kg-7.5 mg/kg) at 0, 2, and 6 weeks. Additionally, they received a PBD. The primary endpoint was remission or colectomy in the induction phase and 1 year after discharge. Secondary endpoints were changes in inflammatory markers in the induction phase and the PBD score at baseline and follow-up. A higher PBD score indicates greater adherence to a PBD. RESULTS: Infliximab and PBD as first-line therapy was administered in 17 cases. The remission rate was 76% (13/17), and the colectomy rate was 6% (1/17) in the induction phase. C-reactive protein values and the erythrocyte sedimentation rate significantly decreased at week 6 from 9.42 mg/dL to 0.33 mg/dL and from 59 to 17 mm/h, respectively (p < 0.0001). At 1-year follow-up, the cumulative relapse rate was 25%, and there were no additional colectomy cases. Mean PBD scores of 27.7 at 1 year and 23.8 at 4 years were significantly higher than baseline scores of 8.3 and 9.9, respectively (p < 0.0001 and p = 0.0391). CONCLUSION: This new first-line therapy for severe UC demonstrated a higher remission rate and lower colectomy rate than with the current modality.

We describe a scarcely reported case in which ulcerative colitis (UC) occurred in the postpartum period. The aims of this case report are to reinforce the recent assertion that a diet is a ubiquitous environmental factor in inflammatory bowel disease (IBD) and that a plant-based diet (PBD) is recommended for IBD. A 29-year-old woman normally delivered her first child. She first noticed bloody diarrhea 4.5 months after delivery. She was diagnosed with UC (left-sided colitis, moderate severity). Sulfasalazine induced remission. She then experienced and learned about PBD during an educational hospitalization. She resumed breast-feeding and stopped medication. An interview and questionnaire revealed a change in her diet 3 months after delivery, from a sound diet (plant-based diet score: 25) to an unhealthy diet (score: 9). It happened along with a change in residence, from her parent’s home where her mother prepared traditional Japanese meals to her home where she prepared meals by herself. A feeling of release from childbirth prompted her to eat sweets and cheese despite being aware that the quality of the meals deteriorated. We described a scarcely reported case in which UC occurred in the postpartum period. It happened along with a change in her diet, from a sound diet to an unhealthy diet due to a feeling of release from childbirth. She replaced an omnivorous diet by PBD and stopped medication. The critical role of diet is largely ignored by healthcare professionals. We believe that greater appreciation of diet will change and improve management of IBD.

CONTEXT: No known previous study has focused on plant-based diet (PBD) to prevent relapse of ulcerative colitis (UC) except our previous educational hospitalization study. OBJECTIVE: To describe the relapse rate in a large case series of UC after incorporation of PBD into induction therapy. DESIGN: All patients with UC between 2003 and 2017 were admitted for induction therapy. Patients receiving educational hospitalization or treated with infliximab were excluded. A lacto-ovo-semivegetarian diet (PBD) together with medication prescribed according to UC guidelines was provided during hospitalization. MAIN OUTCOME MEASURES: The primary endpoint was relapse during follow-up. The secondary endpoint was change over time in the plant-based diet score (PBDS), which evaluated adherence to the PBD. RESULTS: Ninety-two cases were studied, of which 51 were initial episodes and 41 were relapses. Cases varied in severity (31 mild, 48 moderate, 13 severe) and extent (15 proctitis, 22 left-sided colitis, 55 extensive colitis). More severe cases existed among the relapse cases than among the initial episode cases. Cumulative relapse rates at 1- and 5-year follow-up (Kaplan-Meier analysis) were 14% and 27%, respectively, for the initial episode cases, and 36% and 53%, respectively, for relapse cases. At long-term follow-up (6 years 4 months), PBDS was significantly higher than baseline PBDS (p < 0.0001). CONCLUSION: Relapse rates in UC after induction therapy with PBD were far lower than those previously reported with conventional therapy. Adherence to PBD was significantly higher than baseline even at 6-year follow-up. We conclude PBD is effective for preventing UC relapse. (Study identification no.: UMIN000019061: Registration: www.umin.ac.jp)

The incidence of inflammatory bowel disease (IBD), a collective term for Crohn’s disease (CD) and ulcerative colitis (UC), has been increasing over time and expanding to different regions around the world, indicating that IBD is a global disease. IBD is a polygenic disease thought to be triggered by environmental factors. IBD may represent dysregulated mucosal inflammation in response to gut microbiota. A Western or westernized lifestyle is thought to be a major driver of the growing incidence of IBD. Currently, however, the key environmental factor for IBD is unidentified.

Inflammatory bowel disease (IBD), a collective term for Crohn disease and ulcerative colitis, is a polygenic disease thought to be triggered by environmental factors. A Western or westernized lifestyle may be a major driver of the growing incidence of IBD. IBD may represent dysregulated mucosal inflammation to gut microbiota. Despite many review articles on environmental factors in IBD, no consensus exists regarding which factor contributes most to trigger the onset of IBD. Identification and recognition of major environmental factors are prerequisite for effective disease treatment and prevention. Representative environmental factors such as smoking, breastfeeding, nonsteroidal anti-inflammatory drugs, antibiotic use in childhood, oral contraceptives, and appendectomy do not correlate with disease onset in most patients with IBD. In contrast, diet appears to be important in most cases of IBD. Diets rich in animal protein (risk factor) and deficient in dietary fiber (preventive factor) are characteristic of westernized diets in affluent societies. Recent research shows that westernized diets are associated with a reduced gut microbial diversity (dysbiosis), which may result in increased susceptibility to IBD and other common chronic diseases. Plant-based diets rich in dietary fiber are associated with increased microbial diversity. Recent reports on IBD therapy that replaced westernized diets with plant-based diets achieved far better outcomes than those previously reported in the literature. We believe that westernized diet-associated gut dysbiosis is the most ubiquitous environmental factor in IBD. Adoption of this concept may have the potential to provide a better quality of life for patients with IBD.

Overweight and obesity are global health concerns. Various effective weight-loss diets have been developed, including the Atkins diet. The Atkins diet is known as an extreme low-carbohydrate diet. This diet reduces body weight and has gained widespread popularity. However, the metabolite profiles of such a diet have been shown to be detrimental to colonic health. Therefore, a concern for the long-term health effects of this diet exists. We encountered a case in which ulcerative colitis developed while the patient was following the Atkins diet.A man, 172 cm in height and weighing 72 kg, at age 36 years followed a low-carbohydrate weight-loss diet. His weight decreased to 66 kg as desired. Thereafter he noticed bloody stool. Colonoscopy revealed diffuse inflammation limited to the rectum, and he was diagnosed with ulcerative colitis. He underwent an educational hospitalization for ulcerative colitis. A plant-based/semivegetarian diet was provided during hospitalization. Bloody stool disappeared during hospitalization and he achieved remission without medication for inflammatory bowel disease.This case indicates that an onset of ulcerative colitis can be an adverse event to a low-carbohydrate weight-loss diet.

Context No known published study has focused on a plant-based diet (PBD) in the treatment of ulcerative colitis (UC). Objective To investigate relapse prevention in UC after consumption of a PBD during educational hospitalization in Japan. Design Prospective study of patients with mild UC or UC in remission who did not need immediate treatment. A PBD and dietary guidance were provided during a two-week hospitalization. Main outcome measures The primary end point was relapse (a flare-up that required more aggressive treatment) during the follow-up period. Kaplan-Meier analysis was used to calculate the cumulative relapse rate. Secondary end points were immediate improvement in symptoms or laboratory data during hospitalization and a chronologic change in the PBD score, which evaluated adherence to the PBD. Results Sixty cases were studied: 29 initial episode cases and 31 relapse cases. Of these, 31 involved proctitis; 7, left-sided colitis; and 22, extensive colitis. Thirty-seven patients were receiving medication; 23 were not. The median age was 34 years; median follow-up was 3 years 6 months. Eight cases relapsed during follow-up. The cumulative relapse rates at 1, 2, 3, 4, and 5 years of follow-up were 2%, 4%, 7%, 19%, and 19%, respectively. Most patients (77%) experienced some improvement such as disappearance or decrease of bloody stool during hospitalization. The short- and long-term PBD scores after the hospitalization were higher than baseline PBD scores. Conclusion Relapse rates after educational hospitalization providing a PBD were far lower than those reported with medication. Educational hospitalization is effective at inducing habitual dietary changes.

BACKGROUND: The aim of the study was to examine dietary patterns and risk of adverse pregnancy outcomes among mothers with inflammatory bowel disease (IBD) in the Norwegian Mother and Child Cohort Study (MoBa). METHOD: MoBa enrolled participants from all over Norway between 1999 and 2008, and the study comprised 83,988 mothers, of whom there were 183 mothers with Crohn’s disease (CD) and 240 with ulcerative colitis (UC). An additional questionnaire was submitted to mothers with IBD in 2013. We extracted three exploratory dietary patterns: a “Prudent,” a “Western,” and a “Traditional” pattern. We explored the relationship between dietary patterns and IBD and dietary patterns and adverse pregnancy outcomes: small for gestational age (SGA) and preterm delivery (PTD). RESULTS: IBD mothers had a significantly lower adherence to the Traditional dietary pattern [mean score -0.10 (95% CI: - 0.2 - - 0.01)] than non-IBD mothers. In IBD mothers, middle and high adherence to the Traditional dietary pattern was associated with lower risk of SGA [OR tertile 2 vs. tertile 1: 0.44 (95% CI: 0.20 - 0.97) and OR tertile 3 vs. tertile 1: 0.23 (95% CI: 0.08–0.61)] than in IBD and non-IBD mothers with low adherence. In the IBD-subset analyses, similar results were demonstrated for UC mothers [OR tertile 2 vs. tertile 1: 0.21 (95% CI: 0.05 – 0.80) and OR tertile 3 vs. tertile 1: 0.16 (95% CI: 0.04 – 0.60)]. CONCLUSION: In IBD mothers, higher adherence to a Traditional dietary pattern, characterized by high consumption of lean fish, fish products, potatoes, rice porridge, cooked vegetables, and gravy, was associated with lower risk of SGA.

Nonalcoholic fatty liver disease (NAFLD) develops in ulcerative colitis (UC) and Crohn’s disease. However, there is scarce reporting on the onset of UC in patients with NAFLD.A 44-year-old man was diagnosed with UC and referred to us in 2019. His height was 166.0 cm, and body weight was 86.3 kg. The waist circumference was 93.7 cm (normal range He underwent 12 days of educational hospitalization for UC. A lacto-ovo-semi-vegetarian diet (1400 kcal/day), a kind of plant-based diet (PBD), was provided. He lost 4 kg, which was 4.6% of his base body weight. Triglyceride and total cholesterol decreased to the normal ranges. Transaminases and γ-glutamyl transpeptidase also decreased. His body weight decreased further after discharge. Follow-up ultrasonography indicated an improvement in hepatic enlargement. The shear wave velocity decreased from 1.11 to 0.88 m/s. His soft stool became normal stool by 2 months after discharge.Records of his health checkups revealed the presence of metabolic syndrome and abnormal liver function tests already in 2015. Thus, it was concluded that UC developed in a patient with NAFLD in this case. Plant-based diet has already been shown to be effective in inflammatory bowel disease (IBD). In the present case, NAFLD parameters were dramatically improved by PBD. Whether the improvement was due to weight loss per se or due to weight loss with PBD is to be clarified.

BACKGROUND Approximately 30% of patients with Crohn disease (CD) are unresponsive to biologics. No previous study has focused on a plant-based diet in an induction phase of CD treatment. OBJECTIVE To investigate the remission rate of infliximab combined with a plant-based diet as first-line (IPF) therapy for CD. METHODS This was a prospective single-group trial conducted at tertiary hospitals. Subjects included consecutive adults with a new diagnosis (n = 26), children with a new diagnosis (n = 11), and relapsing adults (n = 9) with CD who were naive to treatment with biologics. Patients were admitted and administered a standard induction therapy with infliximab (5 mg/kg; 3 infusions at 0, 2, and 6 weeks). Additionally, they received a lacto-ovo-semivegetarian diet. The primary end point was remission, defined as the disappearance of active CD symptoms at week 6. Secondary end points were Crohn Disease Activity Index (CDAI) score, C-reactive protein (CRP) concentration, and mucosal healing. RESULTS Two adults with a new diagnosis were withdrawn from the treatment protocol because of intestinal obstruction. The remission rates by the intention-to-treat and per-protocol analyses were 96% (44/46) and 100% (44/44), respectively. Mean CDAI score (314) on admission decreased to 63 at week 6 (p < 0.0001). Mean CRP level on admission (5.3 mg/dL) decreased to 0.2 (p < 0.0001). Mucosal healing was achieved in 46% (19/41) of cases. CONCLUSION IPF therapy can induce remission in most patients with CD who are naive to biologics regardless of age or whether they have a new diagnosis or relapse.

Background and Aim The accuracy for predicting virological outcomes of peginterferon-α and ribavirin therapy in patients with chronic hepatitis C is limited to approximately 80%, even with IL28B genotyping. Our in vitro study revealed that the numbers of (TA) dinucleotide repeats [(TA)n] of rs72258881, which is located in the promoter region of IL28B gene, might regulate IL28B transcription. We aimed to evaluate the usefulness of these host factors for predicting virological outcomes of this therapy in response-guided clinical settings. Methods A nationwide, multi-center prospective study in Japan determined IL28B (rs8099917) genotype, (TA)n of rs72258881, and amino acid substitutions of hepatitis C virus and used these for multivariate analysis together with other parameters at pretreatment. Results After enrolling 215 patients with genotype 1 and high viral load from 23 hospitals between October 2009 and February 2011, intent-to-treat analysis identified 202 patients in whom the final virological outcomes could be determined. Non-virological response by non-TT genotype was predicted with 79.7% accuracy. When combined with the (TA)n, the incidences of virological response tended to be higher in the longer (TA)n group, regardless of rs8099917 genotype. Multivariate logistic regression analysis revealed that rs8099917 non-TT genotype (P

Primary sclerosing cholangitis (PSC) is commonly associated with ulcerative colitis (UC). PSC progresses independently of UC ultimately resulting in liver failure. There is no established medical treatment to improve the natural course of PSC. Normalization of serum alkaline phosphatase (ALP) in early stage might delay the progress of PSC. A 20-year-old female, had a sudden attack of right hypochondralgia with high fever and abnormal liver function tests without elevation of bilirubin: ALP 478 IU/L, aspartate aminotransferase 360 IU/L, alanine aminotransferase 174 IU/L. Abnormal liver function tests returned to normal after the attacks. Morphological examinations initially indicated then confirmed a diagnosis of PSC. One month after displaying PSC symptoms administration of ursodeoxycholic acid was initiated. Similar attacks of cholangitis were repeated several times over the following two years. Even in the absence of these attacks, she always suffered postprandial hypochondralgia. There was no acute cholangitis in the year prior to the last hospitalization due to abdominal pain and bloody diarrhea. Findings were consistent with UC in the form of entire colitis. Sulfasalazine, metronidazole and semi-vegetarian diet (SVD) were initiated. Metronidazole is routinely used in inflammatory bowel disease (IBD) in our practice with the expectation of elimination of any potentially pathogenic bacteria. SVD was designed for IBD hoping to increase beneficial bacteria. A remission of UC was ascertained during hospitalization. Elevated ALP, in the absence of clinical cholangitis, was decreased to normal after the therapy for UC.

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.

In Japan, Helicobacter pylori eradication has been approved since 2013 for treatment of H pylori-induced chronic gastritis, in an attempt to reduce the prevalence of gastric cancer, a leading cancer in Japan. H pylori infection affects more than 50% of the world's population. H pylori eradication therapy is generally safe. To our knowledge, no case of newly diagnosed ulcerative colitis occurring immediately after H pylori eradication therapy has previously been reported.A 63-year-old man received a diagnosis of chronic gastritis and H pylori infection. In early March 2014, primary H pylori eradication therapy was initiated; lansoprazole, amoxicillin, and clarithromycin were administered for 1 week. Beginning on the fourth day, he had watery diarrhea twice a day. From the 11th day, bloody stools and watery diarrhea increased to 6 times a day. Colonoscopy, performed on the 40th day after termination of drug therapy, revealed diffuse inflammation in the distal aspect of the colon, with histologic findings consistent with ulcerative colitis. He was admitted to the hospital and was provided with a semivegetarian diet and metronidazole. He noticed a gradual decrease in the amount of blood in his feces then a disappearance of the blood. A fecal occult blood test on the 11th hospital day recorded 337 ng/mL. Fecal occult blood test is not indicated during macroscopic bloody stool but is indicated after disappearance of bloody stool. Therefore, he achieved clinical remission by the 11th hospital day. He was in remission on discharge.New onset of ulcerative colitis should be added to a list of adverse events of H pylori eradication therapy.

Appendiceal orifice inflammation (AOI) is observed as skip lesion in distal ulcerative colitis (UC). The endoscopic frequency of AOI is reported to be 7.9% to 76% of distal colitis. UC is a relapsing and remitting disease and a morphological change of the large bowel occurs over time. Patient and physician can easily understand the shape of the whole large bowel not through endoscopic photograph but by roentgenogram of the bowel. Therefore, the authors undertake barium enema study when a diagnosis of UC is made. We have experienced a patient with proctitis in which an appendiceal submucosal tumor (SMT) was suspected on the roentgenogram but it was turned out to be a protruding lesion of AOI. A 16-year-old boy visited us with complaining of blood in his stool for the past 10 days. Sigmoidoscopy revealed mild diffuse inflammation. Crypt abscess was found in biopsy specimen. A diagnosis of UC, proctitis type, was made. A double contrast barium enema study revealed a defect shadow with a smooth surface, length 37 mm, height 12 mm, over the appendix. An appendiceal SMT was suspected. Abdominal ultrasonography and computed tomography were non-contributory. Colonoscopy revealed a spiral inflamed mucosa at the site of an appendiceal orifice. There was an inflammation in the cecum surrounding the orifice. Biopsy specimen of the appendiceal orifice showed inflammatory cells infiltration, goblet cell depletion, and cryptitis. The suspected SMT lesion was concluded to be AOI.

A 67-year-old man with a portal-systemic shunt confirmed by three-dimensional computed tomography (3D-CT) was successfully treated by percutaneous vascular embolization. The patient had aggravated loss of memory, disorientation, and hyperammonemia. A gastrorenal shunt 16 mm in diameter was found by 3D-CT reconstructed by helical computed tomography (CT). Embolization was performed only in the shunt percutaneously through the inferior vena cava. One year after the embolization, no recurrence of portal-systemic encephalopathy and no portal hypertension have appeared, and the clinical course has been good.

A 72-year-old male visited our hospital for further evaluation of esophageal varices. Telangiectasias were present in the stomach. He had recurrent epistaxis, which was also confirmed in his family's medical history. We diagnosed this case as Osler-Weber-Rendu disease. He had concomitant with hepatic nodular change. Abdominal angiography showed arterio-portal (A-P) shunts, superior mesenteric artery (SMA)-superior mesenteric vein (SMV) shunt, extension of SMV, and dilated and meandering portal vein. Esophageal varices were treated by endoscopic variceral ligation (EVL) and argon plasma coagulation (APC) therapy for prophylaxis of bleeding.

Dear Editor, There are a lot of papers on plant-based diets by researchers, nutritionists, or specialists in the fields, but there is a paucity of comprehensive review for physicians. Therefore, we enjoyed greatly the article, “Nutritional update for physicians: plant-based diets.” Tuso et al1 recommend a plant-based diet to all patients, especially those with hypertension, diabetes, cardiovascular disease, or obesity. We want to comment on our experience of a plant-based diet in treating Crohn’s disease (CD). Symptoms of CD subside easily with total parenteral nutrition or total enteral nutrition. But CD is well known to flare up after the resumption of meals. Therefore, meals per se are thought to cause gut inflammation. Takagi et al2 named their therapy “half elemental diet.” Generally, the more the amount of the elemental diet, the less the relapse rate is. Consequently, about half of the daily energy is provided by an elemental diet, which is a standard regimen in quiescent CD in Japan.2 Relapse rates with an “elemental diet” occur at the rate of 27% at one year,2 whereas the control group rate is 60% to 70% in the studies by Takagi et al2 and Sandborn et al.3 When more than 30 kcal/kg ideal body weight/day of elemental diet is given, the remission rate at 1 year is about 95%.4 However, increasing the amount of elemental diet decreases the quality of life. We regard CD as a lifestyle-related disease mainly mediated by Westernized diets, which tend to cause dysbiosis in gut microflora.5 Namely, the greatest environmental factor in CD is diet-associated gut microflora.6 A design for increasing beneficial bacteria led us to a semivegetarian diet (SVD): lactoovo-vegetarian with fish once a week and meat once every two weeks.5 SVD and infliximab induction therapy were initiated simultaneously. Patients were admitted until completion of standard induction therapy of infliximab. Patients were advised to continue the SVD after discharge. Relapse rates at 1 year and 2 years were 0% and 8% in patients on SVD and 33% and 75% in patients on an omnivorous diet. These results were obtained in the absence of scheduled infliximab maintenance therapy or immunosuppressive agents,5 and they are far better than the scheduled infliximab maintenance therapy.7 SVD is provided during hospitalization and is recommended not only in CD but also in other intestinal diseases including ulcerative colitis8–10 and cytomegalovirus enteritis.11 As Tuso et al1 pointed out, current diseases are a reflection of our lifestyle, particularly a Westernized diet, in wealthy nations.12 Diet reviews recommend plant-based diets to treat and prevent a variety of common diseases. Inflammatory bowel disease (IBD) is not an exception. However, evidence level of our study is not enough to make gastroenterologists appreciate the efficacy of a plant-based diet in IBD. Clinical studies providing high levels of evidence showing the efficacy of a plant-based diet in IBD is eagerly awaited.

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.

We have previously reported 2 subtypes of hepatitis B virus (HBV) genotype B, one of which has the recombination with genotype C over the precore region plus core gene (Ba) and the other of which does not (Bj). A restriction fragment-length polymorphism method with 2 endonucleases was newly developed for distinguishing between subtypes Ba and Bj and was applied to 313 carriers of HBV genotype B in Japan. Subtype Ba was detected in 38 (12%) and subtype Bj in 275 (88%) of the carriers of HBV genotype B. Hepatitis B e antigen in serum was found more frequently in patients with chronic infection with subtype Ba than in those with chronic infection with subtype Bj (8 [32%] of 25 vs. 25 [9%] of 273; P

We report two cases of hypertriglyceridemic necrotizing pancreatitis treated by plasma exchange (PE). The outcome of each case was quite different according to the timing of PE. A 36 year old man presented with abdominal pain, and a diagnosis of severe acute pancreatitis was made. His serum triglyceride (TG) level was 6,460 mg/dl. He did not undergo PE at first, however, his condition never improved and PE was performed 20 days after the onset of his illness. Finally, he died of multiple organ failure and sepsis. In contrast, a 52 year old man with acute necrotizing pancreatitis was referred to our department. He received PE quickly after hospital admission. His serum TG level, which was 3,540 mg/dl at hospital admission, dramatically returned to normal limits, and he was discharged from the hospital 62 days after admission. The prognosis of severe necrotizing pancreatitis due to hypertriglyceridemia is extremely poor. PE should be applied for the treatment of hypertriglyceridemic necrotizing pancreatitis immediately after its onset.

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.

There is limited information in the use of antitumor necrosis factor α, 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.

Background and aims: Recent studies suggest that Fas-mediated apoptosis is involved in the pathogenesis of inflammatory bowel disease (IBD). This study was conducted to clarify whether soluble forms of Fas (sFas) and Fas ligand (sFasL) are concerned with inflammation in IBD. Methods and patients: Concentration of serum sFas and sFasL was measured by enzyme-linked immunosorbent assay in 10 patients with ulcerative colitis (UC), 10 with Crohn's disease (CD) in both active and remission stages, and 20 controls. Expression of Fas and sFas in colonic mucosa was examined by western blot. Distribution of Fas and FasL in colonic mucosa was examined by immunohistochemistry in 20 UC, 20 CD, and 10 non-IBD colitis patients and in 10 controls. Apoptotic cells were examined by TUNEL. Results: Concentration of systemic sFas was significantly lower in active UC than controls. The number of FasL-containing cells was significantly higher in active UC than in remission UC, non-IBD colitis, and controls. Apoptotic cells were increased in active UC. Conclusions: Our results demonstrate that systemic and local Fas-mediated apoptosis is promoted in UC, which might be involved in the pathogenesis in UC.

This study examined auditory and visual interaction in the aesthetic evaluation of the environment. Road traffic noise, sounds from leaves, and motion pictures coherent to auditory stimuli were used. There were four conditions: only auditory stimuli were presented in condition A, only visual stimuli in condition V, both auditory and visual stimuli in condition A+V, and after both auditory and visual stimuli were presented together, auditory stimuli were presented alone and judged in condition (V)A. A semantic differential technique indicated that scenery that included green plants contributed to the improvement of the environment even if only shown as an image. A scene with many cars gave a negative impression. However, even if the sound from the cars was audible, visual masking by green plants seemed effective in reducing the negative impression of road traffic noise.

A 66-year-old woman with an altered mental status caused by hypoglycemia was referred to Akita City Hospital. Abdominal ultrasonography (US) and endoscopic US revealed an isoechoic mass measuring 25 mm in the head of the pancreas. Endoscopic retrograde cholangiopancreatography (ERCP) revealed that the main pancreatic duct and its branches were displaced around the mass in the head of the pancreas. On arteriography, a poorly vascularized tumor was observed. Dynamic contrast-enhanced computed tomography (CT) showed a low-attenuation mass in the head of the pancreas. A pylorus-preserving pancreaticoduodenectomy was performed. Microscopically, the diagnosis was malignant insulinoma.

GB virus C/hepatitis G virus (GBV-C/HGV) is reported to be transmitted by blood products. This study reports infection with GBV-C/HGV from Area-O of town T, an area of high prevalence of antibody to hepatitis C virus (anti-HCV). Four hundred and thirty-five inhabitants of Area-O in town T were examined. Three hundred and forty-three inhabitants of Area-H in town T (where differences of age or sex are not markedly different to Area-O) were studied as controls. We investigated the virus markers and conducted a survey of life history in both areas. The seroprevalence of anti-HCV and GBV-C/HGV markers in Area-O was 17·7% and 11·7%, significantly higher than in Area-H (1·5% and 4·4%). The prevalence of GBV-C/HGV markers was significantly higher in the anti-HCV-positive group than in the sero-negative group. Anti-HCV- or GBV-C/HGV positive subjects tended to have a history of intravenous medications at hospital C in town T, suggesting iatrogenic infection through insufficient sterilization of needles and/or syringes.

A controlled trial was conducted to compare the efficacy of interferon (IFN) between two groups of patients with type C liver. Thirty-five patients were randomly assigned to group A (17 patients) or group B (18 patients). The former received 3 megaunits (MU) of human lymphoblastoid IFN six days per week for two weeks, followed by three days per week for 50 weeks; the latter group received 6 MU six days per week for two weeks followed by three days per week for 24 weeks. The percentages of biological sustained responders (B-SR) and virological sustained responders (V-SR) were 29.4 and 23.5%, respectively, in group B, and 17.6% for both in group A. The therapeutic effects were not different between two groups. HCV genotype 2 accounted for significantly higher percentage of B-SR and V-SR (both 57.1%, respectively). These findings indicate that IFN is effective in type C cirrhosis with genotype 2.

BACKGROUND The effectiveness of interferon against hepatitis C has been found to be greatly affected by viral factors. However, few controlled interferon trials have involved seemingly intractable cases of chronic hepatitis C. METHODS In 44 patients with high hepatitis C virus RNA levels (> or = 10(5) copies/mL), we carried out a prospective, controlled study of two natural interferon-alpha regimens, seeking predictors of therapeutic efficacy. Total natural interferon-alpha doses over 6 months in two groups were 780 and 840 million units, respectively. RESULTS High therapeutic efficacy was achieved with no significant outcome difference between the regimens. The virus eradication rate was 35% and the rate of sustained biochemical response was 45% for both regimens. Multivariate logistic regression analysis identified viral genotype as the only significant predictor of success in viral eradication. CONCLUSIONS Hepatitis C virus genotype 2 showed high sensitivity to interferon-alpha and this therapy can be recommended even for patients with a high viral load of this genotype. In contrast, with genotype 1b, cure was extremely difficult in cases with 10(7) or more copies/mL with a single 6-month course of interferon-alpha.

We tested the effects of four bile acids, taurochenodeoxycholate, taurocholate, tauroursodeoxycholate and taurodeoxycholate, on kinesin-driven microtubule motility, which may have a major influence on membrane organelle transport in cholestasis. Reconstituted microtubules were incubated with kinesin purified from rabbit liver and brain. Binding and gliding of microtubules were visualized by video-enhanced differential interference contrast microscopy. Liver and brain kinesin produced similar microtubule gliding velocities. The effect of bile acids on liver and brain kinesin was also similar. Low concentrations of the four bile acids (0.25–0.5 mM) enhanced the speed of microtubule gliding by up to 152%. Higher concentrations of taurochenodeoxycholate and taurodeoxycholate inhibited attachment, but did not slow the speed of gliding. Detachment was inhibited by the addition of tauroursodeoxycholate. ATPase activity showed no changes in the presence of low concentrations of tauroursodeoxycholate and taurochenodeoxycholate. Triton X-100, a nonionic detergent, increased microtubule gliding by up to 147% at lower concentrations, while higher concentrations (up to 5%) caused a return to normal speed without detachment. Low concentrations of bile acids in hepatocytes may enhance kinesin-driven microtubule dependent organelle transport. In contrast, higher concentrations of toxic bile acids, chenodeoxycholate and deoxycholate, associated with cholestasis may inhibit kinesin-driven motility by detaching microtubules from kinesin.

BACKGROUND/AIMS—Decreased tear volume in patients with chronic hepatitis C has been reported in the literature. Lactoferrin is abundantly present in human tears, the main source of which is the acini of the lacrimal glands. In this study tear lactoferrin levels were measured to investigate the dry eye condition of patients with chronic hepatitis C. METHODS—Lactoferrin in tears/fluid was measured by a radial immunodiffusion assay in 42 patients with chronic hepatitis C. The rate of lacrimal secretion was determined by the cotton thread test. Rose bengal staining of the ocular surface was also performed. RESULTS—Only three patients out of 42 complained of dry eye sensation and, in 31 patients, six showed positive results on the rose bengal staining test of the ocular surface. The lactoferrin concentration of tear fluid in the chronic hepatitis C group (1.42 (SD 0.56) mg/ml) was significantly lower than in the control group (1.90 (0.62) mg/ml; p

A 33-year-old woman was admitted to our department for evaluation of liver dysfunction and proteinuria. A liver biopsy specimen showed ductular proliferation and moderate portal fibrosis indicating stage II primary biliary cirrhosis. A renal biopsy specimen showed mild to moderate mesangial cell proliferation without crescent formation or interstitial nephritis. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG), third component of complement (C3), and Clq on glomerular basement membranes. The findings indicated stage I membranous glomerulonephritis. Administration of ursodesoxycholic acid together with prednisolone, azathioprine, and dipyridamole decreased proteinuria and improved cholestatic liver dysfunction.

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.

The laparoscopic appearance of the liver surface in patients with primary sclerosing cholangitis (PSC) has not been fully delineated. We examined 5 patients with PSC and reviewed 35 previously reported cases. Intense white markings in a mesh-like pattern were characteristic of PSC. The findings varied depending on the histologic stage and affected site. Red patches which have also been seen in primary biliary cirrhosis (PBC), green patches indicating cholestasis, and dilatation of the terminal bile ducts were also observed. The red patches were wider than those in PBC. The white markings were less well defined in the red patches than in other areas. The severity of the fibrosis and histologic damage was judged to be mild at the red sites. The green patches were caused by localized cholestasis. This indicated that PSC unevenly affects the liver. Severe obstruction may be present between the interlobular bile ducts and the septal bile ducts in anicteric stages. (Dig Endosc 1999; 10: 37–41)

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.

In ballooned hepatocytes associated with alcoholic liver disease, secretory proteins are abundant, possibly due to an impairment of the microtubule-dependent vesicular transport system. We studied the effects of ethanol and acetaldehyde on microtubules and hepatic kinesin function. Tubulin and microtubule-associated protein 2 was purified by phosphocellulose and hydroxyapatite column chromatography from microtubule proteins of bovine brain. Hepatic kinesin was purified from rabbit liver. The assembly of microtubules was quantified by spectro-photometer. The kinesin motility assay is done with or without various concentrations of ethanol or acetaldehyde using video-enhanced differential interference contrast microscopy. Ethanol had no effect on the assembly or disassembly of the microtubules or on hepatic kinesin function, even at high concentrations of up to 100 mM. In contrast, acetaldehyde reduced hepatic kinesin function at concentrations greater than or equal to 100 μ M and induced microtubular disassembly at concentrations greater than or equal to 200 μ M. In alcoholic liver injury, chronic reduction of hepatic kinesin function may cause retention of secretory proteins and hepatocyte swelling. Moreover, reduction of the microtubule concentrations due to acetaldehyde may further impair the vesicular transport system and reduce the cells ability to maintain morphology, in turn accelerating hepatocyte ballooning.

We studied the levels of serum hepatitis C virus (HCV)-RNA, the HCV genotype before interferon therapy, and the kinetics of serum HCV-RNA at the initial stages of therapy to determine their utility in predicting the therapeutic efficacy of interferon in 44 patients with chronic hepatitis C infection. We also looked at the efficacy of repeated interferon treatment in relation to the kinetics of serum HCV-RNA. The level of serum HCV-RNA determined by a branched DNA probe assay before interferon treatment and that by a reverse transcription nested polymerase chain reaction assay during the initial stages of interferon administration were useful for predicting the efficacy of treatment. Furthermore, detection of serum HCV-RNA by the reverse transcription nested polymerase chain reaction assay after the completion of interferon therapy indicated relapse at its earliest stage. In patients who experience relapse, repeated treatment with an appropriate dose of interferon before an increase in viral levels may increase the proportion of complete responses.

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.

The efficacy of Interferon (IFN) therapy against hepatitis C is greatly affected by viral factors such as the level of viremia and the HCV genotype. The prognosis of those with high serum HCV-RNA levels in genotype 1b is poor. In the present report, we carried out a randomized controlled study of two IFN doses for patients with genotype 1b chronic hepatitis C whose serum HCV-RNA levels were at least 10 6 copies/ml as determined by multicyclic polymerase chain reaction (PCR) assay. These patients were randomly divided into two groups. Group A received 6 million units (MIU) of IFN 6 days per week for 8 weeks, followed by the same dose 3 days per week for 16 weeks (total IFN dose: 576 MIU). Group B received 6 MIU of IFN 6 days per week for 2 weeks, followed by the same dose 3 days per week for 22 weeks (total IFN dose: 480 MIU). The number of complete responders was four of 24 (16.6%) in group A and three of 20 (15.0%) in group B. There was no significant difference between the groups. On the basis of these findings, it appears that there is no advantage in lengthening the initial period of consecutive IFN administration to 8 weeks or in increasing the total dose by 100 MIU for those with genotype 1b hepatitis C and high virus levels.

A controlled trial comparing combination therapy with ofloxacin (OFLX) and interferon (IFN) versus IFN monotherapy was conducted in patients with chronic hepatitis C who failed IFN therapy. Twenty patients were assigned randomly to two groups. Equal doses of recombinant IFNα-2b were administered to each group for 24 weeks. For the IFN plus OFLX group, OFLX was administered for 12 weeks at a daily dose of 600 mg. Levels of hepatitis C virus RNA declined significantly from the first month after the start of IFN treatment compared with those before administration in both groups. Serum alanine aminotransferase levels were significantly lower in the IFN plus OFLX group at two and six months after the start of treatment than levels in the IFN group. The fraction of subjects whose levels of serum ALT normalized was also higher in the IFN plus OFLX group. Larger clinical trials should be undertaken.

Heat shock proteins are ubiquitous intracellular proteins induced by various physiological stress-related events. A 72-kDa heat shock protein (HSP72) has been reported to be an endogenous cytoprotectant in variety of cells in vitro. In order to study the cytoprotective function of HSP72 in the liver, the effect of preinduction of HSP72 in rat liver by systemic hyperthermia on thioacetamide-induced hepatic injury was investigated in this study. Expression of HSP72 in the liver was investigated by immunoblot and densitometric analysis. Rats were injected with thioacetamide (100 mg/kg, subcutaneously) with or without preinduction of HSP72 by hyperthermia. Serum AST and ALT concentrations were measured before and after thioacetamide injection in both group. Histologic alteration of the liver was evaluated also. Systemic hyperthermia (42.5 degrees C, 20 min) significantly induced HSP72 in the liver. Thioacetamide-induced hepatic injury was clearly prevented by preinduction of HSP72 by hyperthermia. Prevention of hepatocyte damage was more clear in the area around central veins where HSP72 induction was apparent. Our findings might suggest that HSP72 has an important function in the liver with respect to cytoprotection. These results might be important for understanding the mechanism of "adaptive cytoprotection" in the liver mediated by the function of heat shock proteins as "molecular chaperons" as reported in vitro.

Objective To investigate the efficacy and safety of 14 days’ orally administered tolvaptan as adjunctive treatment for hepatic oedema in Japanese liver cirrhosis patients with insufficient response to conventional diuretics, with the option to increase dose in those who did not respond initially. Methods This multicentre, single-arm, phase 3 study allocated patients with liver cirrhosis and persistent ascites to 7-day treatment with 7.5 mg/day tolvaptan followed by an additional 7 days’ treatment. Responders at day 7 (achieving ≥1 kg body-weight reduction) continued on 7.5 mg/day tolvaptan; nonresponders (Results A total of 51 patients received 7.5 mg/day tolvaptan for 7 days, which caused a significant reduction in mean body weight (55% response rate). During the second 7-day treatment period, 30 patients received 7.5 mg/day tolvaptan and 13 patients received tolvaptan 15 mg/day: response rates were 43% and 23%, respectively. Two serious adverse events were observed. Serum sodium was within normal range. Conclusions Tolvaptan therapy for 14 days (with possible dose increase as necessary), in combination with conventional diuretics, effectively reduced body weight in patients with hepatic oedema.