Selection of regimens for patients with hepatitis C virus genotype/serotype discrepancy.

In the present study, the usefulness of the resistance-associated variant (RAV) analysis to select direct acting antiviral (DAA) drugs for patients with hepatitis C virus (HCV) genotype/serotype discrepancy was evaluated. The core-genotype and serotype were determined in the 559 patients recruited in the study. The RAV analysis and NS5B-genotype determination were performed in the eight patients who exhibited a genotype/serotype discrepancy. One of these patients exhibited a core-genotype 1b/serotype 2, and detection by RAV analysis was possible in this patient. The other seven patients demonstrated a core-genotype 2/serotype 1, and detection using the RAV analysis was possible in four of them. The NS5B-genotype was 1b in all patients in whom detection using the RAV analysis was possible and was other than 1b in patients in whom detection using the RAV analysis was impossible. The RAV analysis could detect RNA sequences specific to genotype 1b in the NS5A region. Therefore, in patients with genotype/serotype discrepancy in whom detection using the RAV analysis is possible, the treatment regimens should be selected based on the assumption that HCV with genome that is highly homologous to genotype 1b is present in the NS5A region.

The effect of tacrolimus (FK-506) on Japanese patients with refractory Crohn's disease.

BACKGROUND: Recent evidence indicates that intravenous or oral therapy with tacrolimus (FK-506) is effective in treating patients with Crohn's disease. We evaluated the usefulness of tacrolimus therapy for Japanese patients with refractory Crohn's disease. METHODS: Fourteen adult Japanese patients with Crohn's disease that was refractory to conventional therapies, including prednisolone (n = 5), azathioprine (n = 6), and infliximab (n = 5), were enrolled. Treatment with tacrolimus was started orally or intravenously and aimed for serum trough levels of 10-15 ng/ml. After the patients achieved clinical improvement, tacrolimus maintenance therapy was administered to maintain the trough level at 5-10 ng/ml. RESULTS: All patients achieved remission or significant improvement 40 days after starting tacrolimus treatment. By 120 days after the start of therapy, 9 (64%) patients achieved remission, 2 patients (14%) achieved significant improvement, and only 3 patients (21%) relapsed. The relapsed patients were treated with infliximab therapy and achieved remission. Steroids were discontinued by the 5 patients who had taken steroids before the study began. Adverse effects of tacrolimus included a temporary increase in serum creatinine concentration (n = 1, 7%), hyperkalemia (n = 1, 7%), and tremor (n = 1, 7%). CONCLUSIONS: Tacrolimus therapy is effective and well tolerated in patients with Crohn's disease that is refractory to conventional therapies.

Clinical features of Japanese patients with colonic angiodysplasia.

BACKGROUND AND AIM: With improvements in endoscopic resolution, angiodysplasia (AGD) has become an increasingly recognized disorder. The aim of this study was to describe the clinical features of Japanese patients with colonic AGD and compare them to the clinical features of Western patients. METHODS: Retrospective analyses were performed in all patients who had undergone colonoscopical examination from March 2003 to October 2005 at the Kyoto University Hospital. Four independent literature searches were performed to document the characteristics of colonic AGD in Western countries. The characteristics of 41 Japanese patients diagnosed as having colonic AGD were compared with those of Western patients. RESULTS: The incidence of colonic AGD increased with age, and the most prevalent underlying disease in patients with colonic AGD was cardiovascular disease (56.1%). These tendencies were similar in the Japanese and Western data. Colonic AGD in Japanese patients was predominantly located in the left colon (41.7%), whereas in Western patients, it was mainly located in the right colon (54%-81.9%). The percentage of colonic AGD with a size of more than 5 mm or elevated type detected in Japanese patients was significantly higher than that in Western patients. CONCLUSION: The characteristics of Japanese patients with colonic AGD were similar to those of Western patients, except for its localization, size, and type.

Cross-primed CD8+ cytotoxic T cells induce severe Helicobacter-associated gastritis in the absence of CD4+ T cells.

BACKGROUND: Although previous studies have reported important roles of CD4(+) type 1-helper T cells and regulatory T cells in Helicobacter-associated gastritis, the significance of CD8(+) cytotoxic T cells remains unknown. To study the roles of CD8(+) T cells, we examined the immune response in the gastric mucosa of Helicobacter felis-infected major histocompatibility complex (MHC) class II-deficient (II(-/-)) mice, which lack CD4(+) T cells. MATERIALS AND METHODS: Stomachs from H. felis-infected wild-type and infected MHC II(-/-) mice were examined histologically and immunohistochemically. Gastric acidity and serum levels of anti-H. felis antibodies were measured. The expression of pro-inflammatory and anti-inflammatory cytokine, Fas-ligand, perforin, and Foxp3 genes in the gastric mucosa was investigated. RESULTS: H. felis-infected MHC II(-/-) mice developed severe gastritis, accompanied by marked infiltration of CD8(+) cells. At 1 and 2 months after inoculation, mucosal inflammation and atrophy were more severe in MHC II(-/-) mice, although gastritis had reached similar advanced stages at 3 months after inoculation. There was little infiltration of CD4(+) cells, and no Foxp3-positive cells were detected in the gastric mucosa of the infected MHC II(-/-) mice. The expression of the interleukin-1beta and Fas-ligand genes was up regulated, but that of Foxp3 was down regulated in the infected MHC II(-/-) mice. Serum levels of anti-H. felis antibodies were lower in the infected MHC II(-/-) mice, despite severe gastritis. CONCLUSIONS: The present study suggests that cross-primed CD8(+) cytotoxic T cells can induce severe H.-associated gastritis in the absence of CD4(+) helper T cells and that Foxp3-positive cells may have an important role in the control of gastric inflammation.

Open label trial of clarithromycin therapy in Japanese patients with Crohn's disease.

BACKGROUND AND AIM: The pathogenesis of Crohn's disease is unclear, but many studies suggest that luminal bacteria play an important role in chronic intestinal inflammation in patients with this condition. Clarithromycin is a macrolide antibiotic with immunomodulatory activity. The aim of this study was to evaluate the effect of clarithromycin therapy in Japanese patients with Crohn's disease. METHODS: Fourteen patients with active Crohn's disease (12 with ileocolonic, one with colonic, one with small bowel type) were treated with oral clarithromycin 200 mg twice daily for 4 weeks. Patients who showed a clinical response within 4 weeks continued the therapy for up to 24 weeks. Four patients also received azathioprine. Clinical activity was assessed with the Crohn's Disease Activity Index (CDAI) at entry and at 4, 12, and 24 weeks after starting clarithromycin. RESULTS: The mean CDAI score at entry was 343.5. Within 4 weeks, eight (57.1%) of the 14 patients showed clinical improvement, and five (35.7%) of the eight patients achieved remission. All of those eight patients continued clarithromycin therapy after 4 weeks, and six (42.9%) were in clinical remission at 12 weeks. Of the 14 total patients, four (28.6%) continued clarithromycin for more than 24 weeks, and have remained in remission. Patients who received azathioprine concomitantly had a better response to clarithromycin therapy. No severe side-effects were observed during the study period. CONCLUSIONS: This open label study showed encouraging results of clarithromycin therapy in Japanese patients with active Crohn's disease.

Rescue therapy with tacrolimus for a patient with severe ulcerative colitis refractory to combination leukocytapheresis and high-dose corticosteroid therapy.

A19-year-old man complaining of severe diarrhea and hematochezia was admitted to our hospital. Endoscopic findings and laboratory data revealed that he had ulcerative colitis (UC). Despite combination therapy with high-dose corticosteroids and intensive granulocytapheresis, his condition did not improve. Therefore, we initiated tacrolimus therapy. Intravenous administration of tacrolimus with a trough level of 10 to 15 ng/ml relieved his abdominal symptoms within 1 week. The patient experienced no UC relapse 1 year after treatment with oral tacrolimus. Tacrolimus is a promising therapy for patients with UC refractory to the combination of high-dose corticosteroids and leukocytapheresis.

Adminstration of PEG-Interferon to a Patient with Ulcerative Colitis and Chronic Hepatitis C Correlated with Reduced Colonic Inflammation and Reversal of Peripheral Th1/Th2 Ratios.

A 42-year-old man with chronic hepatitis C and ulcerative colitis (UC) was referred to our hospital in August 2004 because of bloody diarrhea. He was clinically and endoscopically diagnosed with flare of UC. After informed consent had been obtained, he was treated with PEG-IFN-α-2a. Four weeks after initiation of PEG-IFN therapy, his abdominal symptoms gradually subsided. Intracellular cytokine assay revealed that the ratio of T-helper (Th) 1 (IFN-?)/Th 2 (IL-4) increased after IFN therapy. Three months after starting IFN therapy, colonoscopy revealed a normal mucosal pattern. He was uneventfully treated with PEG-IFN-α-2a for one year. When last seen in November 2006, he was still in remission of UC. Our intracellular cytokine data suggested that alteration of Th1/Th2 cytokine balance by IFN is one possible mechanisms of reducing intestinal inflammation in patients with UC. In this regard, IFN therapy could be useful for some patients with UC refractory to other conventional therapies.