Eosinophil granulocytes are activated during the remission phase of ulcerative colitis

AIM: The aim of this study was to establish a method of investigating intestinal eosinophil and neutrophil granulocytes by flow cytometry, and to compare the distribution and activity of these cells in different stages of ulcerative colitis (UC). METHODS: Biopsy samples were taken from six locations of the entire colon and from the terminal ileum in 10 patients with active total UC, 10 patients with inactive total UC, eight patients with active distal UC, and 11 control subjects. Cell suspensions from biopsies and from peripheral blood were incubated with fluorophore conjugated monoclonal antibodies. The use of scatter plot-gating and specific antibodies was established in a flow cytometry assay. RESULTS: Eosinophils were more numerous and more active in patients with active UC than in controls. Interestingly, during inactive UC, the number of activated eosinophils was even larger. Eosinophil activity was high in the rectum of patients with distal colitis but was also slightly elevated in the proximal colon. Neutrophils were increased in number and activity during active but not inactive UC. In patients with distal colitis, activated neutrophils were only found in the sigmoid colon and rectum. CONCLUSION: With this method, we confirm that neutrophils participate in the inflammatory process during active UC, and that they express a resting phenotype during remission. The finding of activated eosinophils in inflamed intestine strengthens the view of these cells as proinflammatory and tissue damaging. Nevertheless, our new finding of high eosinophil activation during inactive UC suggests that eosinophils play a role in repair of injured epithelium.     

Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission

BACKGROUND AND AIM: Studies have identified abnormal characteristics of the gut microbiota in patients with active IBD, but whether the changes are causal or secondary to inflammation remains uncertain. We investigated dynamics of fecal microbiota in ulcerative colitis (UC) during remission by genomic technology. PATIENTS AND METHODS: Patients in clinical remission and on stable maintenance mesalazine therapy were recruited (N = 33). Fecal samples were collected at regular intervals over a period of 1 yr. Sixteen patients who remained in remission and eight healthy controls were included in the analysis. Variable V6 to V8 regions of the 16S rRNA gene in DNA extracts from fecal samples were amplified by polymerase chain reaction. Amplicons were separated by denaturant gradient gel electrophoresis, band profiles were compared by software, and similarity indices were calculated from densitometric curves. RESULTS: Band profiles showed unique patterns with low similarity index between individuals, suggesting host specificity in the predominant microbiota. Within the same individual, profiles were stable in controls but varied notably over time in patients. In controls, the similarity index was remarkably stable (78 +/- 8% mean +/- SD) over a period of 24 months. However, patients showed a steady decline in similarity index versus the initial profile, dropping down to 42 +/- 24% at month 3 of follow-up and to 23 +/- 19% at month 12 (P < 0.001). Biodiversity of the dominant microbiota, as estimated by number of bands, was lower in patients (17 +/- 4) than controls (23 +/- 4, P < 0.01). CONCLUSION: Molecular analysis of fecal bacteria in patients with inactive UC shows low biodiversity and temporal instability.     

Overestimation of ulcerative colitis due to melanosis coli

Melanosis coli is a benign pigment deposition in the colonic mucosa that can be seen at the time of colonoscopy especially in patients with history of laxative use. In conditions in which the endoscopic findings influence therapeutic decisions, melanosis coli can lead to overestimation of disease aggressiveness and unnecessary therapy. We describe a case in which the finding of melanosis coli affected the treatment of a patient with mild ulcerative colitis exacerbation.     

Long-term use of mesalamine enemas to induce remission in ulcerative colitis

The courses of 90 patients with left-sided ulcerative colitis that was unresponsive or intolerant to conventional therapy were retrospectively reviewed. They had been treated with 5-aminosalicylic acid enemas (mesalamine) on a long-term basis. After an initial 12-week course of treatment, 87% of the patients had improved by at least one grade of inflammation (improvement), and 54% of these were asymptomatic with normal colonic mucosa (remission). Overall, there was an 80% remission rate by 34 weeks. Remission rate was not affected by extent of sigmoid or left-sided colon disease before treatment or prior medication use for ulcerative colitis. Treatment with mesalamine enemas allowed patients to decrease or discontinue glucocorticoid treatment. Patients treated for relapse episodes responded as well as they did to the first course of treatment, whether the relapse occurred after discontinuation of mesalamine or during a tapering of the dose. In conclusion, extending mesalamine treatment to at least 34 weeks was beneficial in inducing a complete remission in 80% of patients unresponsive to conventional therapy.     

Incidence of colectomy during long-term follow-up after cyclosporine-induced remission of severe ulcerative colitis.

BACKGROUND & AIMS: Cyclosporine (CSA) has been shown to be effective in steroid-refractory ulcerative colitis (UC) and as an alternative to glucocorticosteroids in patients with severe attacks of UC. Our aim was to investigate the long-term efficacy of CSA. METHODS: We conducted a retrospective cohort study of all patients admitted to our institution with an attack of UC treated with intravenous CSA between November 1992 and October 2004. Patients who responded to intravenous CSA were switched to Neoral for 3 months. Kaplan-Meier curves were used for survival analysis with quantitative variables compared using a 2-tailed Student t test with qualitative variables and differences compared with a chi(2) analysis. RESULTS: A total of 118 (83%) of the 142 patients had an initial response to CSA and avoided colectomy during hospitalization. Of the 118 patients, 41 (35%) [corrected] required a future colectomy. The rate of colectomy in those already on azathioprine compared with those starting azathioprine concurrently with CSA was 59% vs 31%, respectively (P < .05). Also, 88% of patients already on azathioprine and requiring colectomy underwent surgery within the first year of receiving CSA. Life-table analysis shows that although only 33% of patients require colectomy at 1 year, 88% will require colectomy at 7 years. CONCLUSIONS: CSA is an effective short- to medium-term treatment for patients with severe UC but at 7 years, 88% of patients will require a colectomy. Azathioprine-naive patients have better outcomes.     

类固醇激素依赖型溃疡性结肠炎缓解期IL-23表达的研究

目的 探讨IL-23在缓解期类固醇激素依赖型溃疡性结肠炎患者结肠组织中表达的病理意义.方法 采用Western blot分析及免疫组化SABC法检测15例缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达情况,予统计学软件统计分析,并以30例缓解期的一般溃疡性结肠炎患者（15例SASP维持治疗,15例强的松维持治疗）炎症修复区结肠组织及10例正常结肠黏膜组织为对照组.结果 与正常对照组比较,SASP维持治疗及强的松维持治疗缓解期一般溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达均轻度升高（P〉0.05）,而缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达显著高于一般溃疡性结肠炎组（P〈0.01）.结论 IL-23的过度表达可能在溃疡性结肠炎类固醇激素依赖发病机制中起关键作用.     

类固醇激素依赖型溃疡性结肠炎缓解期IL-23表达的研究

目的 探讨IL-23在缓解期类固醇激素依赖型溃疡性结肠炎患者结肠组织中表达的病理意义.方法 采用Western blot分析及免疫组化SABC法检测15例缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达情况,予统计学软件统计分析,并以30例缓解期的一般溃疡性结肠炎患者(15例SASP维持治疗,15例强的松维持治疗)炎症修复区结肠组织及10例正常结肠黏膜组织为对照组.结果 与正常对照组比较,SASP维持治疗及强的松维持治疗缓解期一般溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达均轻度升高(P>0.05),而缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达显著高于一般溃疡性结肠炎组(P<0.01).结论 IL-23的过度表达可能在溃疡性结肠炎类固醇激素依赖发病机制中起关键作用.     

类固醇激素依赖型溃疡性结肠炎缓解期IL-23表达的研究

目的 探讨IL-23在缓解期类固醇激素依赖型溃疡性结肠炎患者结肠组织中表达的病理意义.方法 采用Western blot分析及免疫组化SABC法检测15例缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达情况,予统计学软件统计分析,并以30例缓解期的一般溃疡性结肠炎患者(15例SASP维持治疗,15例强的松维持治疗)炎症修复区结肠组织及10例正常结肠黏膜组织为对照组.结果 与正常对照组比较,SASP维持治疗及强的松维持治疗缓解期一般溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达均轻度升高(P>0.05),而缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达显著高于一般溃疡性结肠炎组(P<0.01).结论 IL-23的过度表达可能在溃疡性结肠炎类固醇激素依赖发病机制中起关键作用.     

Symptoms of irritable bowel syndrome in ulcerative colitis in remission

The prevalence of symptoms suggestive of a motility disturbance similar to the irritable bowel syndrome was investigated in 98 patients with ulcerative colitis in remission, and a similar number of age- and sex-matched healthy controls. Thirty-three per cent of patients compared with 7% of controls fulfilled the criteria for such a syndrome (p<0·01). Contrary to expectations these symptoms were not confined to patients with distal disease. Other symptoms such as constipation were also very common in the colitic group (31%).     

A case study: interferon-beta-induced remission of ulcerative colitis in a patient with type C chronic hepatitis

A 66-year-old man patient with chronic hepatitis (CH) C and complications from ulcerative colitis (UC) was treated with interferon-beta (IFN-beta). Endoscopically, the UC disease activity was moderate before IFN-beta treatment but was in remission eight week after treatment. However, a few months after stopping IFN treatment, endoscopy revealed that the UC disease activity had returned to moderate levels. This result shows that UC improved with IFN treatment.     

Spontaneous remission of hepatitis B virus reactivation during direct‐acting antiviral agent‐based therapy for chronic hepatitis C

The administration of direct‐acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported to cause hepatitis B virus (HBV) reactivation. However, the actual conditions of HBV reactivation and the ideal timing of medical intervention have not been fully evaluated. We report the cases of two female patients dually infected with HBV and HCV. Both patients were inactive HBV carriers. Although the serum HCV RNA levels promptly decreased after the initiation of DAA‐based therapy, the serum HBV DNA levels gradually increased during DAA‐based therapy, with the peak serum HBV DNA levels observed at 16 weeks after the initiation of DAA‐based therapy in both cases. Subsequently, we checked the serum HBV DNA levels closely every week several times. Fortunately, the serum HBV DNA levels gradually decreased without medical intervention. Neither case developed an alanine aminotransferase flare‐up. The HCV genotypes were 2a and 1b, and the DAA‐based therapies of Cases 1 and 2 were 12 weeks of sofosbuvir/ribavirin and ombitasvir/paritaprevir/ritonavir, respectively. The significance of our case reports is the demonstration of the existence of spontaneous remission of HBV reactivation that developed during DAA‐based therapy, the avoidance of intervention of nucleot(s)ide analogs by frequent monitoring of serum HBV DNA levels, and development of HBV reactivation regardless of the viral genotype or class of DAA. In conclusion, the close monitoring of serum HBV DNA levels during and after DAA‐based therapy is essential and medical intervention for HBV reactivation should be carefully considered on an individual basis.     

Poorly controlled ulcerative colitis treated by colectomy during remission induced by extracorporeal leukocyte removal therapy

Both monocyte-granulocytapheresis (M-GCAP) and leukocytapheresis (LCAP) are categorized as extracorporeal leukocyte removal therapies (ECCTs). These therapies have been recognized as efficient adjuncts for patients of steroid-resistant ulcerative colitis (UC). This study aimed to consider the adaptation and the limitation of these new therapies from the clinical standpoint based on a case of UC showing strong resistance to high-dose continuous steroid injection therapy. The patient successfully underwent a scheduled colectomy while maintaining remission after applying M-GCAP and LCAP independently. Surgical therapy was chosen because of a deep ulcer in the patient's sigmoid colon, which was assumed to constitute a future risk for perforation. This case suggests that combining ECCT with steroid therapy can maintain such poorly controlled and high-risk UC patients safely for the scheduled colectomy while improving the prognosis by reducing the dosage of steroid efficiently prior to operation.