Diagnóstico de la infección por Helicobacter pylori y tratamiento de la infección en pacientes con úlcera duodenal

La tesis se ha planteado en dos partes, en la primera se incluyen dos estudios terapéuticos sobre la cicatrización de la úlcera duodenal asociada a la infección por H. pylori. 1. IMPACT OF COLLOIDAL BISMUTH SUBCITRATE (SBC) IN THE ERADICATION RATES OF Helicobacter pylori INFECTION-ASSOCIATED DUODENAL ULCER USING A SHORT TREATMENT REGIMEN WITH OMEPRAZOLE AND CLARITHROMYCIN: A RANDOMIZED STUDY. Am J Gastroenterol 1995; 90:718-21. 2. RANDOMIZED CLINICAL TRIAL COMPARING TWO ONE-WEEK TRIPLE-THERAPY REGIMENS FOR THE ERADICATION OF Helicobacter pylori INFECTION AND DUODENAL ULCER HEALING. Am J Gastroenterol 1998; 93:35-38 En la segunda parte de la tesis se presenta el tercer estudio en el que se ha valorado objetivos sobre la eficacia de los métodos diagnósticos en la infección y en el control de la erradicación de la infección por H. pylori. 3. ACCURACY OF AN ENZYME IMMUNOASSAY FOR THE DETECTION OF Helicobacter pylori IN STOOL SPECIMENS IN THE DIAGNOSIS OF INFECTION AND POSTTREATMENT CHECK-UP. Am J Gastroenterol 2000; 95:2200-5 Conclusiones: 1. La cicatrización de la úlcera duodenal asociada a infección por H. pylori obtenida con pautas de tratamiento erradicador de 7 días es similar a la obtenida con omeprazol durante 4 semanas y superior a la obtenida cuando se administra el antisecretor durante 15 días. 2. La pauta de tratamiento con omeprazol 40 mg/d x 8 días, SBC 120 mg cuatro veces al día y claritromicina 500mg cada 12 horas durante 7 días, o omeprazol 40 mg / 12h, claritromicina 500 mg / 12 horas con amoxicilina 1 gr / 12h o SBC 120 mg / 6h, son muy eficaces en la erradicación de H. pylori y en la cicatrización de la úlcera duodenal. Su cumplimiento es muy bueno y los efectos secundarios mínimos. 3. El SBC aumenta la acción del omeprazol y de la claritromicina en la erradicación de H. pylori. 4. La dosis de omeprazol, cuando se utilizan estas combinaciones terapéuticas, no parece que juegue un papel importante en la erradicación de H. pylori. 5. Los pacientes que erradican la infección de la mucosa gástrica presentan una mejoría del índice de gastritis. 6. El test HpSA, utilizando el punto de corte de 0,130, puede ser útil en el diagnóstico primario de la infección por H. pylori, con una sensibilidad similar a la obtenida por la histología, el test de la ureasa rápida y el TAU, aunque con menor especificidad. 7. El test HpSA no es útil en el control de la erradicación de la infección a las 24 horas después de finalizar el tratamiento. 8. El test HpSA es ineficaz en el control de la erradicación a las 6 semanas de finalizar el tratamiento por su menor precisión en comparación con el test del aliento con urea-C13.The thesis has been planed in two parts. 1. Included two therapeutics studies about duodenal ulcer healing associated with Hp infection. 2. The assessment of efficacy of the diagnosis methods in the diagnosis of infection and posttreatment check-up. IMPACT OF COLLOIDAL BISMUTH SUBCITRATE (CBS) IN THE ERADICATION RATES OF Helicobacter pylori (Hp) INFECTION-ASSOCIATED DUODENAL ULCER (DU) USING A SHORT TREATMENT REGIMEN WITH OMEPRAZOLE AND CLARITHROMYCIN: A RANDOMIZED STUDY. Am J Gastroenterol 1995; 90:718-21. Objectives: To evaluate the efficacy of a short treatment regimen in Hp eradication UD healing and to asses the impact of colloidal bismuth subcitrate (CBS) in Hp eradication and ulcer healing. Conclusions: The addition of CBS to the double therapy with omeprazole and clarithromycin improves the eradication rate of Hp .This short therapy is a safe, well tolerated combination that achieves a 80,6% eradication rate of Hp and DU healing rates as good as hose achieved by omeprazole 20mg/d when given for 4 wk. RANDOMIZED CLINICAL TRIAL COMPARING TWO ONE-WEEK TRIPLE THERAPY REGIMENS FOR THE ERADICATION OF HELICOBACTER PYLORI INFECTION AND DUODENAL ULCER HEALING. Am J Gastroenterol 1998; 93:35-38 Objectives: To evaluate if higher doses of omeprazole improve the efficacy of two one-week triple therapy regimens in Hp eradication and DU healing. Conclusions: High rates of both Hp eradication and DU healing were obtained with both short-treatment regimens, which were safe and well-tolerated. CBS seems to be a good alternative to amoxicillin in the triple therapy combining they with omeprazole and clarithromycin. The omeprazole dose does not seem to play a major role in Hp eradication in these therapeutic combinations. ACCURACY OF AN ENZYME IMMUNOASSAY FOR THE DETECTION OF Helicobacter pylori IN STOOL SPECIMENS IN THE DIAGNOSIS OF INFECTION AND POSTTREATMENT CHECK-UP. Am J Gastroenterol 2000; 95:2200-5 Objectives: To assess the reliability of a newly developed EIA assay for Hp specific antigen detection in stools (HpSA) compared to histology (H), rapid urease test (RUT) and 13C-urea breath test (UBT) to diagnose Hp infection and to evaluate its usefulness to determine Hp status after treatment. Methods: One hundred and eighty eight patients were included. Hp infection was confirmed in all patients by HpSA test in stools, RUT, UBT and H. Patients were defined as positive for Hp if RUT and UBT or H were positive. One hundred and forty two symptomatic patients received eradication treatment and were reassessed 6 weeks after therapy; in 70 of these patient stool samples were also collected at 24 hours and 6 months after finishing eradication treatment. In the post-treatment follow-up UBT was used as gold standard. Conclusions: 1.-The HpSA stools test using a cut-off value of 0.130 may be useful for the primary diagnosis of H. pylori infection, with sensitivity similar to that obtained with other standard tests, but with less specificity. 2.- HpSA test is not useful for early monitoring of treatment efficacy; and 3.- At 6 weeks and at 6 months post-treatment, HpSA test lacks accuracy as compared to UBT to evaluate the outcome of the eradication treatment

Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis.

Background: There is little information about the effect of infliximab on the clinical course of liver disease in Crohn's disease patients with concomitant hepatitis B virus (HBV) infection. Theoretically, immunosuppression induced by infliximab will facilitate viral replication which could be followed by a flare or exacerbation of disease when therapy is discontinued. There are no specific recommendations on surveillance and treatment of HBV before infliximab infusion. Two cases of severe hepatic failure related to infliximab infusions have been described in patients with rheumatic diseases. Patients and methods: Hepatitis markers (C and B) and liver function tests were prospectively determined to 80 Crohn's disease patients requiring infliximab infusion in three hospitals in Spain. Results: Three Crohn¿s disease patients with chronic HBV infection were identified. Two of the three patients with chronic HBV infection suffered severe reactivation of chronic hepatitis B after withdrawal of infliximab therapy and one died. A third patient, who was treated with lamivudine at the time of infliximab therapy, had no clinical or biochemical worsening of liver disease during or after therapy. From the remaining 80 patients, six received the hepatitis B vaccine. Three patients had antibodies to both hepatitis B surface antigen (anti-HBs) and hepatitis B core protein (anti-HBc) with normal aminotransferase levels, and one patient had positive anti-hepatitis C virus (HCV) antibodies, negative HCV RNA, and normal aminotransferase levels. Except for the patients with chronic HBV infection, no significant changes in hepatic function were detected. Conclusions: Patients with Crohn's disease who are candidates for infliximab therapy should be tested for hepatitis B serological markers before treatment and considered for prophylaxis of reactivation using antiviral therapy if positive

Leukocytes from obese individuals exhibit an impaired SPM signature

Specialized proresolving mediators (SPMs) biosynthesized from docosahexaenoic acids (DHAs) including resolvins (Rvs), protectins, and maresins are potent endogenous autacoids that actively resolve inflammation, protect organs, and stimulate tissue regeneration. Our hypothesis was that failure of resolution programs may lead to unremitting inflammation in obesity, contributing to the development of metabolic comorbidities in this condition. Obese individuals with persistent low-grade systemic inflammation showed reduced leukocyte production of the DHA-derived monohydroxy fatty acid 17- hydroxy-DHA (HDHA) and unbalanced formation of SPMs (in particular D-series Rvs) accompanied by enhanced production of proinflammatory lipid mediators such as leukotriene B4. Mechanistic studies attributed this impairment to reduced 15-lipoxygenase (LOX) activity rather than altered DHA cellular uptake. Moreover, leukocytes from obese individuals exhibited decreased 5-LOX levels and reduced 5-LOX Ser271 phosphorylation and distinct intracellular 5-LOX redistribution. However, 15-LOX appears to be the most critical factor for the deficient production of SPMs by obese leukocytes because the formation of D-series Rvs was completely rescued by incubation with the intermediate precursor 17-HDHA. These data provide proof of concept that administration of intermediate precursors of SPM biosynthesis ( e.g., 17-HDHA) could be more efficient in overriding impaired formation of these proresolving lipid mediators in conditions characterized by dysfunctional LOX activity, such as obesity

Spectrum of gluten sensitive enteropathy in first degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

Background: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. Aims: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. Patients and methods: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. Results: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II¿III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p=0.002). Marsh I relatives had more severe abdominal pain (p=0.006), severe distension (p=0.047) and anaemia (p=0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). Conclusions: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet

Low dose alpha interferon therapy can be effective in chronic active hepatitis C. Results of a multicentre, randomised trial

BACKGROUND--There is some controversy concerning the efficacy of low dose alpha interferon therapy in chronic hepatitis C. AIMS--To evaluate the effectiveness of treatment with low doses of alpha interferon in chronic hepatitis C. PATIENTS--One hundred and forty one patients with anti-HCV positive chronic active hepatitis C from six hospitals were enrolled in the study. METHODS--Patients were randomised to treatment with 5 MU (group A) or 1.5 MU (group B) injections. The dose was reduced in responders from group A or increased in non-responders from group B to maintain treatment with the minimal effective dose. Patients were treated for 48 weeks and followed up for 24 additional weeks with no treatment. Normalisation of alanine aminotransferase (ALT) was used to evaluate response. RESULTS--A sustained response was seen in eight patients from group A (12%) and in 15 (21%) from group B. This difference was not statistically significant. Increasing the dose of interferon led to sustained response in only five of 58 patients (9%) from group B who did not respond to 1.5 MU injections. In contrast, 15 of 21 patients (71%) in whom ALT remained normal with 1.5 MU injections developed a sustained response. By multivariate analysis sustained response seemed associated with young age and was more frequent in patients with genotype 3 HCV infection. Sustained response was preceded by a rapid normalisation of ALT and was inversely related to the amount of alpha interferon necessary to maintain ALT at low values during treatment. CONCLUSIONS--Some patients with chronic hepatitis C are very sensitive to alpha interferon and can be successfully treated with low doses. Treatment with higher doses may be effective in a minority of patients who do not respond to low doses

Low dose alpha interferon therapy can be effective in chronic active hepatitis C. Results of a multicentre, randomised trial

BACKGROUND--There is some controversy concerning the efficacy of low dose alpha interferon therapy in chronic hepatitis C. AIMS--To evaluate the effectiveness of treatment with low doses of alpha interferon in chronic hepatitis C. PATIENTS--One hundred and forty one patients with anti-HCV positive chronic active hepatitis C from six hospitals were enrolled in the study. METHODS--Patients were randomised to treatment with 5 MU (group A) or 1.5 MU (group B) injections. The dose was reduced in responders from group A or increased in non-responders from group B to maintain treatment with the minimal effective dose. Patients were treated for 48 weeks and followed up for 24 additional weeks with no treatment. Normalisation of alanine aminotransferase (ALT) was used to evaluate response. RESULTS--A sustained response was seen in eight patients from group A (12%) and in 15 (21%) from group B. This difference was not statistically significant. Increasing the dose of interferon led to sustained response in only five of 58 patients (9%) from group B who did not respond to 1.5 MU injections. In contrast, 15 of 21 patients (71%) in whom ALT remained normal with 1.5 MU injections developed a sustained response. By multivariate analysis sustained response seemed associated with young age and was more frequent in patients with genotype 3 HCV infection. Sustained response was preceded by a rapid normalisation of ALT and was inversely related to the amount of alpha interferon necessary to maintain ALT at low values during treatment. CONCLUSIONS--Some patients with chronic hepatitis C are very sensitive to alpha interferon and can be successfully treated with low doses. Treatment with higher doses may be effective in a minority of patients who do not respond to low doses