Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.

Higher constitutive IL15R alpha expression and lower IL-15 response threshold in coeliac disease patients.

The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15R alpha mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15R alpha mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0.0334, on GCD P = 0.0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15R alpha expression was only triggered in non-CD controls (P = 0.0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFN gamma (P = 0.0313, P = 0.0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine.

Factors that impact health-related quality of life in adults with celiac disease: a multicenter study.

AIM: To evaluate the factors involved in the impairment of health-related quality of life (HRQOL) in patients with celiac disease. METHODS: A multicenter, cross-sectional prospective study was performed in patients with celiac disease who completed two HRQOL questionnaires: the gastrointestinal quality of life index (GIQLI) and the EuroQol-5D (EQ). RESULTS: Three hundred and forty patients (163 controlled with a gluten-free diet, and 177 newly diagnosed with a normal diet) were included. The GIQLI score was significantly better in patients on a gluten-free diet (GFD) than in non-treated patients on their usual diet, both in terms of the overall score (3.3 vs 2.7, respectively; P < 0.001), as well as on the individual questionnaire dimensions. Both the preference value of the EQ as the visual analogue scale were significantly better in treated than in non-treated patients (0.93 vs 0.72 P < 0.001 and 80 vs 70 P < 0.001, respectively). Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status. CONCLUSION: In untreated celiac disease, the most important factors that influence patient perception of health are the presence of symptoms and a normal diet. HRQOL improves to levels similar to those described in the general population in celiac disease patients well controlled with a GFD.

[Relapsing acute pancreatitis associated with gluten enteropathy. Clinical, laboratory, and evolutive characteristics in thirty-four patients]. / Pancreatitis aguda recidivante con enteropatía por gluten asociada, Características clínico-analíticas y evolutivas en 34 pacientes.

OBJECTIVES: To describe the frequency and the clinical and laboratory characteristics of relapsing acute pancreatitis (AP) associated with gluten enteropathy (GE). PATIENTS AND METHODS: We prospectively examined all acute pancreatitis cases admitted to our Department in 2006. We recorded a total of 185 patients. With recurring forms, 40 (22%) in all, we used a clinical-lab protocol including serologic and genetic markers, and duodenal biopsy to rule out GE. RESULTS: A total of 34 patients (18%) met clinical-biological criteria for GE (group1), and were compared to the remaining non-GE AP cases (n=161) (group2). Mean age in the GE group was 54 +/- 25 years, slightly younger than group 2 (61 +/- 14) (NS). There was a mild predominance of women (50%) in group 1 versus group 2 (38.5%) (NS). Seven patients in group 1 (20%) had severe AP, as compared to 27 (17%) in group 2 (NS). The presence of cholelithiasis in group 1 involved 6 cases (18%), which was significantly lower than in group 2--72 cases (45%) (p < 0.05). Four patients with GE developed pseudocysts (12%) versus 13 (8%) in group 2 (NS). Tissue transglutaminase (tTG) was elevated only in 3 patients (9%). Nine patients (34%) were DQ2 (+) and 4 (12%) DQ8 (+); the rest (54%) were all negative for both markers. From an endoscopic perspective there was diffuse duodenitis in 32 patients (95%). Duodenal biopsies revealed villous atrophy (Marsh 3) in 2 patients (6%); submucosal inflammatory infiltration (Marsh 2) in 10 (29.4%); increased intraepithelial lymphocytes (Marsh 1) in 8 cases (23.5%), and normal mucosa (Marsh 0) in 14 patients (41.2%). Response to GFD after 1 year was excellent in 30 patients (88%). CONCLUSIONS: Relapsing AP with GE represents a relatively common association that is indistinguishable from other APs from a clinical-evolutive standpoint, except for a lower presence of cholelithiasis (p < 0.05). A specific diagnostic protocol is much needed in the identification of these patients since GFD is the only effective therapy to prevent new AP events from developing.

[Increased prevalence of celiac disease in first and second-grade relatives. A report of a family with 19 studied members]. / Prevalencia aumentada de enfermedad celiaca en familiares de primer y segundo grado: descripción de una familia con 19 miembros estudiados.

INTRODUCTION: celiac disease (CD) is an autoimmune condition that is triggered by the ingestion of gluten, a substance present in most cereals, and that affects genetically predisposed individuals. As a result, this condition is clearly familial, and mainly associated with HLA class II markers. OBJECTIVES: in this work we set out to analyze the prevalence of CD in an extensive family based on an index subject who had already died from this disease a few years ago, where CD had been complicated by the development of a small-bowel malignancy, namely an adenocarcinoma. METHODS: nineteen members were studied. They all were subjected to a diagnostic protocol including a detailed medical history, hemogram, coagulation tests, and blood biochemistry (including liver function tests, serum iron metabolism, circulating folic acid and vitamin B12 levels, thyroid function tests, tissue transglutaminase measurement, and genetic markers (DQ2 and DQ8). Suspect cases underwent gastroscopy plus multiple duodenal biopsy for confirmation. RESULTS: overall we encountered CD in 9/19 studied members, which represents 47.4% with the following distribution according to degree of kinship -four of seven siblings (57%); one of three children (33.3%); three of eight nephews and nieces (37.5%), and the only grandnephew, who was 9 years old. CONCLUSIONS: from all this it may be seen that family studies are needed every time a patient is diagnosed with celiac disease; these studies should include both first- and second-degree relatives, given the high prevalence encountered and the fact that these tests are relatively straighforward to perform.

Usefulness of duodenal biopsy during routine upper gastrointestinal endoscopy for diagnosis of celiac disease.

AIM: To describe the trend in duodenal biopsy performance during routine upper gastrointestinal endoscopy in an adult Spanish population, and to analyze its value for the diagnosis of celiac disease in clinical practice. METHODS: A 15 year-trend (1990 to 2004) in duodenal biopsy performed when undertaking upper gastrointestinal endoscopy was studied. We analysed the prevalence of celiac disease in the overall group, and in the subgroups with anaemia and/or chronic diarrhoea. RESULTS: Duodenal biopsy was performed in 1033 of 13 678 upper gastrointestinal endoscopies (7.6%); an increase in the use of such was observed over the study period (1.9% in 1990-1994, 5% in 1995-1999 and 12.8% in 2000-2004). Celiac disease was diagnosed in 22 patients (2.2%), this being more frequent in women than in men (3% and 1% respectively). Fourteen out of 514 (2.7%) patients with anaemia, 12 out of 141 (8.5%) with chronic diarrhoea and 8 out of 42 (19%) with anaemia plus chronic diarrhoea had celiac disease. A classical clinical presentation was observed in 55% of the cases, 23% of the patients had associated dermatitis herpetiformis and 64% presented anaemia; 9% were diagnosed by familial screening and 5% by cryptogenetic hypertransaminasaemia. CONCLUSION: Duodenal biopsy undertaken during routine upper gastrointestinal endoscopy in adults, has been gradually incorporated into clinical practice, and is a useful tool for the diagnosis of celiac disease in high risk groups such as those with anaemia and/or chronic diarrhoea.

Hepatitis B surface antigen detection using pooled sera. A cost-benefit analysis.

OBJECTIVES: To examine the feasibility and to perform a cost benefit analysis of a 5-sample pooling strategy using an enzyme immunoassay (EIA) for the screening of hepatitis B surface antigen (HBsAg). MATERIAL AND METHODS: To assess the sensitivity and specificity of the pooling method, each of the 40 positive sera (from weak to intensely HBsAg-positive) and 250 negative sera were tested in a pool with 4 HBsAg-negative sera. The limit of detection for HBsAg/ad and HBsAg/ay was evaluated using sera from a panel of purified subtypes. A study under real conditions was conducted using pools from 340 pregnant women. RESULTS: The sensitivity and specificity of this technique were 100%. The correlation coefficient among the sample/cutoff ratios of 40 samples studied in single and in pooled conditions was 0.792 (p < 0.005). The pooling method has lower levels of detection for HBsAg/ad and HBsAg/ay at 0.20 ng/mL and 0.12 ng/mL, and the single method at 0.34 ng/mL and 0.29 ng/mL, respectively. The pooling method loses no sensitivity for values up to 100 IU/L of anti-HBs in the four sera mixed with a positive serum. The cost-benefit analysis showed that the pooling method could save from 30% up to 75% of the cost of HBsAg determination, according to whether seroprevalences were 10% or 1%, respectively. CONCLUSIONS: The pooled HBsAg EIA yielded no worse than the single EIA test, and was a cost-effective and valid strategy in areas with a high, medium or low prevalence.

Celiac disease (CD), ulcerative colitis (UC), and primary sclerosing cholangitis (PSC) in one patient: a family study.

We discuss the case of a 17-year-old male who at the age of 7 was diagnosed with celiac disease (CD) together with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). The patient was treated with gluten-free diet and immunosuppressive drugs (azathioprine), and currently remains asymptomatic. The patient's younger, 12-year-old sister was diagnosed with CD when she was 1.5 years old, and at 7 years she developed type-I diabetes mellitus, which was difficult to control. A family study was made, and both parents were found to be affected with silent CD. All were DQ2 (+). In relation to the case and family study, we provide a series of comments related to CD and its complications.

Antibody to hepatitis C virus in acute, self-limited, type B hepatitis.

Sera from 104 patients with self-limited, acute type B hepatitis were tested for the presence of anti-HCV antibodies. The results show that especially drug users with acute type B (and occasionally coinfected with type D) hepatitis commonly are infected with HCV. Furthermore, HCV infection may have preceded infection with the other agents and may be responsible for high ALT levels.

Prevalence of antibodies against hepatitis C virus in primary biliary cirrhosis and autoimmune chronic hepatitis.

We have determined the prevalence of antibodies against hepatitis C virus (anti-HCV) in 45 patients with primary biliary cirrhosis (PBC) and 6 with autoimmune chronic active hepatitis (AI-CAH). Anti-HCV was positive in two cases of PBC, both with a history of previous blood transfusion, and in one patient with AI-CAH, only during an active phase of the disease.

Prevalence of antibody to hepatitis C virus in acute non-A, non-B hepatitis in patients from different epidemiological categories.

The prevalence of antibodies to hepatitis C virus (HCV) was determined in 65 patients with acute non-A, non-B hepatitis (NANBH). The results suggest that HCV is the most common causative agent in posttransfusion NANBH and in drug-related hepatitis. Detection of HCV antibodies does not appear to be a particularly useful diagnostic criterion due to the kinetics of the immune response in the course of the disease.

Prevalence of antibody to hepatitis C virus in chronic HBsAg carriers.

The presence of the anti-HCV antibody was investigated in sera from 102 chronic HBsAg carriers. The subjects varied as to the characteristics of the clinical states. It was found that HCV coinfection was more common in HBsAg positive intravenous drug addicts than in other parenteral risk groups. It also appears that HCV may be the causative agent of chronic liver disease in HBsAg carriers with undetectable HBV (and possibly HDV) replication.

Involved factors in the intrafamilial spread of hepatitis C virus.

To investigate the risk of non-parenteral HCV infection, sera from 302 relatives of 120 anti-HCV positive subjects were tested for the presence of anti-HCV antibodies. For the sake of comparison, sera from 17,000 blood donors were also assayed. The prevalence of HCV positivity was 4.3% in household contacts, compared to 0.78% in the donor population, indicating a significantly higher risk of infection for family members. Close personal contact may not be as critical a factor for infection as is duration of the disease.

Prevalence of hepatitis C virus infection in the general population of northern Spain.

OBJECTIVES: To estimate the prevalence of hepatitis C in a population of northern Spain and describe (i) the risk factors associated with infection and (ii) the distribution of genotypes. DESIGN: Randomized cross-sectional study. METHODS: A random sample of 1,170 people participated in the study. Sociodemographic data were obtained. Antibodies against hepatitis C virus (anti-HCV) and hepatitis C virus (HCV) genotypes were determined. RESULTS: Nineteen of 1,170 (1.6%) subjects were anti-HCV positive (95% CI 1.0-2.6%). In 12 cases (63%), viraemia was present, and the predominant genotype was 1 b (80%). Anti-HCV positive subjects were older than anti-HCV negative subjects (55.8 +/- 15.3 v. 44.8 +/- 20.9; P = 0.02). Two peaks of maximum frequency were found (in the fourth decade and in those over 60 years). Parenteral drug addiction predominates among those of the fourth decade, while transfusion and surgery predominate in people over 60 years. Three (16%) subjects knew they were carriers of HCV. Only three variables remained significant in the multivariate model (illegal drug use, P< 0.0001; previous hepatitis, P< 0.0001; and age, P< 0.02). CONCLUSIONS: Our study emphasizes the need to develop health policies that can cope with the foreseeable increases in the problems associated with HCV infection in the near future.

[A comparative analysis of blood donors with antibodies to the hepatitis C virus, positivity for the hepatitis B surface antigen and hypertransaminasemia in Asturias]. / Análisis comparativo de donantes de sangre con anticuerpos frente a los virus C de la hepatitis, positividad para el antígeno de superficie de la hepatitis B y con hipertransaminasemia en Asturias.

BACKGROUND: A comparative study of the differences with respect to prevalence, epidemiologic risk factors, clinical and analytical status and histologic data of blood donors with different liver diseases detected in the same geographical area and time period was carried out. METHODS: HBsAg or anti-HCV positive blood donors detected in Asturias (Spain) from October 1989-1991, and a third group of 115 consecutive donors with negative viral markers and an increase in ALT, as well as a fourth control group with no alterations were compared with a BMDP statistical program and logistic regression analysis. RESULTS: The prevalence of anti-HCV+ donors was greater than that of those with HBsAg+ in both general donors (0.87% vs 0.28%) as well as in new donors (1.77% vs 1.2%) with a constant incidence of HBsAg+ cases of around 0.16% of the donations with a decrease being observed in the anti-HCV+ (ELISA 1) cases from 0.76% to 0.25%. The mean age was significantly higher among the anti-HCV+ donors with respect to the remaining groups (41 vs 36 years). Likewise, the cases of anti-HCV+ presenting parenteral risk factors, such as intravenous drug addiction, transfusion or surgery were significantly higher, with the latter two having an independent predictive value. Signs or symptoms of liver disease were more frequently detected in the anti-HCV+ (10.8%) vs the HBsAg+ (2.3%) as were an increase in ALT (52.8% vs 12.7%) and histologic signs of chronic hepatitis (36.4% vs 6.9%). CONCLUSIONS: Anti-HCV+ blood donors more frequently present previous parenteral risk factors, signs or symptoms of chronic liver disease, hypertransaminasemia or histologic data of chronic hepatitis, thus its detection in al altruistic blood donor indicates a high probability of chronic subjacent liver disease. This is in contrast to donors with HBsAg+ which do not normally present liver disease and those with hypertransaminasemia with negative viral markers who generally have slight liver lesions.

[The prevalence of anti-HCV positivity among blood donors in Asturias. A clinical-epidemiologic study]. / Prevalencia de la positividad del anti-VHC entre donantes de sangre en Asturias. Un estudio clinicoepidemiológico.

BACKGROUND: The aim of this study was to know the prevalence, epidemiology, clinical manifestations and analytical changes present in anti-HCV positive blood donors detected in Asturias. METHODS: A prospective analysis of the incidence and prevalence of anti-HCV positivity in the blood donations carried out in Asturias from October 1989 to October 1991 was performed, as was a clinical and analytical study of the anti-HCV positive cases who attended a clinic specifically created for the same. RESULTS: The prevalence of the anti-HCV was 0.87% of the donors (372/42,789) and 0.50% of the donations (372/73,831) being higher among new donors (1.77%, 165/9,322). Of the 288 cases studied (77.4%), only 51 (17.7%) had been transfused and 105 (36.5%) lacked the previous parenteral risk factor. Only 31 (10.8%) presented symptoms or signs of liver disease and the positivity of the anti-HBc was not associated to any relevant analytical change. The existence of previous major surgery or transfusion was variable with the independent predictive value versus a negative anti-HCV control group. The mean follow up was 12.4 +/- 7.3 months (6-30 months) with an increase in aminotransferases (ALT) being detected in 108 cases (52.7%). A good correlation was found between this data, an ELISA-2 score greater than 5 and RIBA-2 positivity: of the 177 cases in whom RIBA-2 was determined this was found to be positive in 109 (61.6%); 84 cases (77.1%) had an increase in ALT and 100 (91.8%) an ELISA-2 score greater than 5. CONCLUSIONS: In Asturias the prevalence of anti-HCV positivity among blood donors is almost 1% and is greater if new donors are considered, being confirmed by RIBA-2 in 61% of the cases. The subjects are usually asymptomatic and up to one third of the same lack any known risk factor, while almost half have hypertransaminasemia during follow up.

[Blood donors with positive HBsAg in Asturias: its current prevalence and significance]. / Donantes de sangre con HBsAg positivo en Asturias: prevalencia actual y su significado.

BACKGROUND: The aim of the present study was to know the current prevalence of HBsAg positivity in Asturias blood donors and to carry out a clinical study of the carriers of the hepatitis B virus (HBV) accidentally detected in a blood donation program. METHODS: A prospective study of incidence and prevalence of HBsAg positivity in blood donations performed in Asturias over two years from October 1989 and 1991 was carried out and the epidemiologic, clinical, and analytical characteristics, as well as histologic liver lesions in the HBsAg positive cases were determined. RESULTS: Among the 42,789 blood donors during this above mentioned period in Asturias 119 cases of HBsAg positivity were found, representing a prevalence of 0.16% of the donations and 0.28% of the donors, generally new donors (95.8%) with a prevalence of 1.2% in this subgroup. No risk factors or known source of contagion were found in 43.6% of the cases and in most occasions the donors were asymptomatic HBsAg carriers (96.5%) with normal transaminases (87.3%) with 4.6% of the cases being HBeAg positive and 3.5% being mutant "e minus" carriers. CONCLUSIONS: The prevalence of HBsAg was almost limited to new donors with a higher prevalence being observed with respect to other regions. Most of the cases may be considered as "apparently healthy" and in the group with positive replicative markers a similar number of positive HBeAg carriers and "e minus mutants" were present.

[Liver involvement in coeliac disease]. / Afectación hepática en la enfermedad celíaca.

Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.

Diverse clinical presentations of celiac disease in the same family.

We performed a family study to evaluate a total of 34 extended family members (8 siblings, 23 children and nephews, and 3 grandchildren) of an adult patient with celiac disease (CD), a 58- year-old male with severe neurologic involvement manifested as myoclonias. We found 3 other members affected with CD (a 44-year old sister, a 39-year old niece, and a 26-year old nephew). Two of them were completely asymptomatic and all had hypertransaminasemia. All exhibited a villous atrophy pattern of the duodenal mucosa (1 mild, 1 moderate, 1 severe). Overall family involvement was 11.8% (4/14). We wish to emphasize the need to perform extended family studies when diagnosing a case of CD, since risk is not restricted to only first-degree relatives.

[Ulcerative colitis with Coombs+ autoimmune hemolytic anemia. A report of a case with favorable response to medical treatment]. / Colitis ulcerosa con anemia hemolítica autoinmune Coombs+. Descripción de un caso con respuesta favorable al tratamiento médico.

We report the case of a patient with ulcerative colitis and autoimmune hemolytic anemia, that improved with steroid therapy, and during the follow-up showed analytical changes of iron deficiency anemia and anemia of chronic disorders. We discuss the possible etiologies of the anemia in patients with ulcerative colitis, and the treatments suggested for the associated Coombs-positive hemolytic anemia in these cases, stressing the good response to steroids in our patient.