Sabino Riestra

Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohns disease in high-risk patients. METHODS A multicenter, prospective, observational study was conducted from June 2009 until June 2010. We consecutively included high-risk Crohns disease patients who had undergone an ileal/ileocolonic resection. High-risk patients were defined as two or more criteria: smokers, penetrating pattern, one or more previous surgical resections or prior extensive resection. Subcutaneous adalimumab was administered 2 wk (± 5 d) after surgery at a dose of 40 mg eow, with an initial induction dose of 160/80 mg at weeks 0 and 2. Demographic data, previous and concomitant treatments (antibiotics, 5-aminosalicylates, corticosteroids, immunomodulators or biologic therapies), smoking status at the time of diagnosis and after the index operation and number of previous resections (type and reason for surgery) were all recorded. Biological status was assessed with C-reactive protein, erythrocyte sedimentation rate and fecal calprotectin. One year (± 3 mo) after surgery, an ileocolonoscopy and/or magnetic resonance enterography was performed. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. Morphological recurrence was based on magnetic resonance (MR) score ≥ MR1. RESULTS Twenty-nine patients (55.2% males, 48.3% smokers at diagnosis and 13.8% after the index operation), mean age 42.3 years and mean duration of the disease 13.8 years were included in the study. A mean of 1.76 (range: 1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection. 51.7% had previously received infliximab. Immunomodulators were given concomitantly to 17.2% of patients. Four of the 29 (13.7%) developed clinical recurrence, 6/29 (20.7%) endoscopic recurrence and 7/19 (36.8%) morphological recurrence after 1-year. All patients with clinical recurrence showed endoscopic and morphological recurrence. A high degree of concordance was found between clinical-endoscopic recurrence (κ = 0.76, P < 0.001) and clinical-morphological recurrence (κ = 0.63, P = 0.003). Correlation between endoscopic and radiological findings was good (comparing the 5-point Rutgeerts score with the 4-point MR score, a score of i4 was classified as MR3, i3 as MR2, and i2-i1 as MR1) (P < 0.001, r(s) = 0.825). During follow-up, five (17.2%) patients needed adalimumab dose intensification (40 mg/wk); Mean time to intensification after the introduction of adalimumab treatment was 8 mo (range: 5 to 11 mo). In three cases (10.3%), a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk. One patient suffered an adverse event. CONCLUSION Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

Tamoxifen Does Not Improve Survival of Patients With Advanced Hepatocellular Carcinoma

To discover whether tamoxifen is able to extend the survival of patients with advanced hepatocellular carcinoma, we included 80 patients with cirrhosis and advanced hepatocellular carcinoma in a multicenter, double-blind, placebo-controlled trial in order to analyze the influence of treatment with tamoxifen on survival. The patients were randomized to receive tamoxifen, 40 mg/day (group 1), or placebo (group 2). Both groups were similar in age, sex, etiology of cirrhosis, biochemical, hematologic and hormonal parameters, morphology of the tumor (nodular vs multinodular or massive), Child-Pughs score, and Okudas stage. The 1-year survival rate was similar in both groups (30% in group 1 vs 37.8% in group 2; p = 0.31). Tamoxifen treatment was well tolerated by the patients. We conclude that tamoxifen does not extend the survival of patients with cirrhosis and advanced hepatocellular carcinoma.

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 1170 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 1170 (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 1b (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.

Sustained improvement of health-related quality of life in Crohn's disease patients treated with infliximab and azathioprine for 4 years

Background: Infliximab induces remission and improves the health‐related quality of life (HRQOL) of patients with refractory or fistulous Crohns disease (CD). However, little information is available as to whether its effect on HRQOL is sustained over time. The objective was to measure the HRQOL of CD patients in long‐term clinical remission. Methods: Prospective, observational study was undertaken in patients with CD in infliximab‐induced clinical remission (Harvey index <3) for at least 6 months, and receiving long‐term infliximab and azathioprine maintenance therapy. Patients were followed for 4 years or until clinical relapse (Harvey index >3). HRQOL was assessed annually using the validated Spanish version of the disease‐specific 36‐item Inflammatory Bowel Disease Questionnaire (IBDQ‐36) and the EuroQol‐5D. Results: Forty‐nine patients with CD in stable clinical remission were included at baseline. At 12 months, n = 42 patients remained in remission, at 24 months n = 32 patients, at 36 months n = 13, and in the last visit at 48 months 6 patients remained in clinical remission. The overall score on the IBDQ‐36 remained unchanged in patients with stable, inactive CD (median overall score of 6.1 at baseline and 6.5 at 4 years). Scores on all 5 dimensions of the IBDQ‐36 remained unchanged over the study period in stable patients. Patients in remission scored highly on the preference value ratings of the EuroQol‐5D (scores of 1.0) and remained unchanged in patients who remained in remission. Conclusions: Sustained clinical remission of CD achieved with maintenance treatment maintains HRQOL over long‐term follow‐up.

A population-based study on the incidence of inflammatory bowel disease in Oviedo (Northern Spain)

OBJECTIVE to assess the incidence of inflammatory bowel disease in Oviedo (Northern Spain), and to describe the clinical features of new patients. PATIENTS AND METHODS a prospective population-based study was made at the Health Area IV, Principality of Asturias (Oviedo, 312,324 inhabitants). All new diagnosed patients with inflammatory bowel disease were registered over a 2-year period. RESULTS a total of 85 patients were included, 47 of these with ulcerative colitis (UC), 37 with Crohńs disease (CD), and 1 with undetermined colitis. The overall adjusted incidence rate of UC and CD per 105 inhabitants between 15-64 years was 9.1 (95% CI: 5-13.1) and 7.5 (95% CI: 3.8-11.2), respectively. The global male/female ratio was 0.9, without significant differences between both diseases. CD patients were younger than those with UC (33 +/- 15 years vs 45 +/- 20 years; p < 0.05). Mostly, CD patients were diagnosed at an age younger than 35 years (65%), while UC patients were diagnosed at an age between 25 and 64 years (81%). Disease extension in UC was proctitis in 11%, left-side colitis in 53% and extensive colitis in 36%. With respect to CD, the ileo-colonic form predominated (49%), followed by the ileal (40%) and colonic (11%) forms; an inflammatory, stenotic and fistulous pattern was seen in 54, 22 and 24% of patients, respectively. CONCLUSIONS in our area, the incidence of CD is similar to that in other Northern European countries, while UC has a lower incidence. CD mainly affects young people, while UC predominates in middle-aged patients. At diagnosis, UC is predominantly localized, the ileo-colonic form and an inflammatory pattern being most frequent in CD patients.

MICA-A5.1 allele is associated with atypical forms of celiac disease in HLA-DQ2-negative patients

Abstract. We selected 38 consecutive celiac disease (CD) patients (from a group of 316 consecutive CD patients) and 91 healthy blood donors, all of whom were HLA-DQ2 (DQA1*0501/DQB1*0201) negative, and investigated the presence of the classically associated alleles HLA-DQ8 and HLA-DRB4. We also studied the distribution of MICA transmembrane alleles in the two clinical forms of the disease. For this reason, these 38 DQ2-negative patients were subdivided into two groups: 18 typical CD patients and 20 atypical CD patients. No differences were found in the distribution of the DRB4 allele between DQ2-negative patients and controls. The HLA-DQ8 heterodimer (DQA1*03xx/DQB1*0302) was increased in CD patients (29%) compared with controls (10%), but no statistical differences were found. No differences were observed in the frequency of these alleles between either group of CD DQ2-negative patients. MICA-A5.1 was increased in atypical CD patients when compared with the typical forms of disease (Pc=0.03) and with healthy controls (Pc=0.002). No other MICA allele was found to be significantly increased in the groups under study. The presence of MICA-A5.1 in atypical CD DQ2-negative patients may indicate a possible role of this allele in the development of CD.

Adenosine deaminase isoenzymes and neopterin in liver cirrhosis.

The aim of this study was to define the pattern of neopterin and ADA isoenzymes in liver cirrhosis. A total of 117 patients with liver cirrhosis were included. Serum levels of ADA were assayed in the presence and absence of a specific inhibitor for ADA1. Serum neopterin was measured using a competitive enzyme-linked immunosorbent assay. The grade of liver insufficiency was assessed according to the Child-Pugh classification and the monoethylglycinexylidide test. Serum ADA, ADA1, ADA2 and neopterin were higher in cirrhotic patients than in control subjects. A stepwise increase in serum ADA level was observed with increasing severity of liver cirrhosis. The probability of ADA2 being greater than the mean was approximately 2.5 times higher (2.48, CI 95%: 1.36-4.52) in patients with liver cirrhosis due to hepatitis C virus (HCV) infection than in those patients with cirrhosis of a different etiology. No correlation was found between ADA2 and neopterin. Our data show that liver insufficiency and HCV infection increase the serum levels of ADA and its major isoenzyme ADA2. Furthermore, ADA isoenzyme determination adds no value to total ADA value. The absence of a correlation between ADA2 and neopterin suggests that different physiologic processes are involved in their increase.

Kaposi's sarcoma: An opportunistic infection by human herpesvirus-8 in ulcerative colitis

Kaposis sarcoma is a vascular tumor caused by human herpesvirus-8 infection. Iatrogenic Kaposis sarcoma often occurs in patients receiving immunosuppressive therapy. To date, a few cases of colonic Kaposis sarcoma have been reported in ulcerative colitis patients treated with immunomodulators. We describe a 65-year-old male diagnosed with left-sided ulcerative colitis who was treated with methotrexate and low-dose steroids for greater than 6 years. He presented with several papular, violet lesions on both legs. Colonoscopy revealed the presence of multiple reddish, elevated lesions in the sigmoid colon and rectum. Histological evaluation of skin and colonic biopsies showed findings suggestive of Kaposis sarcoma; immunohistochemistry for human herpesvirus-8 was positive in the colonic lesions. To avoid the need for further immunosuppressive treatment, the patient underwent a colectomy. Following immunomodulator discontinuation, the patient experienced spontaneous regression of his skin lesions. With the present case, we wish to stress the important interaction of immunosuppressive therapy (mainly corticosteroids) used in ulcerative colitis patients in relation to the development of colonic Kaposis sarcoma. Human herpesvirus-8 infection should be recognized as a possible opportunistic infection in patients with inflammatory bowel disease.

T-cell profiling and the immunodiagnosis of latent tuberculosis infection in patients with inflammatory bowel disease.

Background:Factors associated with performance of interferon-&ggr; release assays (IGRA) and the tuberculin skin test (TST) in screening for latent tuberculosis infection in patients with inflammatory bowel diseases (IBD) are still poorly understood. The influence of peripheral T-cell subset counts on the results also remain unclear. Methods:Prospective single-center study in 205 patients with IBD. Latent tuberculosis infection screening included a chest radiograph, TST (retest if negative), and 2 IGRAs: QuantiFERON-TB Gold In-Tube (QFT-GIT) and TSPOT-TB (TSPOT). T-cell subpopulations were determined by flow cytometry. Results:Twenty-one (10.2%) patients had an abnormal chest radiograph, 55 (26.8%) had a positive TST, 16 (7.8%) had a positive QFT-GIT, and 25 (12.6%) had a positive TSPOT. TST positivity was lower in patients on ≥2 immunosuppressants compared with the controls (5-aminosalicylic acid treatment) (10.4% versus 38.2%, respectively) (P = 0.0057). No other drugs influenced TST or IGRA positivity. In patients on corticosteroid treatment, anti-TNF treatment, or ≥2 immunosuppressants, IGRAs detected 10 cases of latent tuberculosis infection not identified by TST. TSPOT and QFT-GIT increased yield by 56% and 22%, respectively. No significant differences in T-cell subpopulations were found between patients with positive or negative TST or TSPOT results. However, patients with positive QFT-GIT findings had more CD8+ T cells (mean, 883 ± 576 versus 484 ± 385 cells per microliter in patients with negative results) (P = 0.022). Conclusions:IGRAs can improve TST-based screening in patients with IBD on immunosuppressive therapy. A low CD8+ count can affect QFT-GIT results. We suggest combining TSPOT and TST screening in patients with IBD on immunosuppressants.

Nodular Regenerative Hyperplasia of the Liver in a Patient With Celiac Disease

We present the case of dual adult celiac disease and liver disease with portal hypertension (esophageal varices); a percutaneous liver biopsy was compatible with nonspecific reactive hepatitis. Clinically, celiac disease was characterised by poor response to a gluten-free diet, with the development of a biochemical cholestasis and marked malnutrition. Our patient died of cerebral hemorrhage, at the age of 50 years, without associated risk factors. The necropsy demonstrated the existence of a nodular regenerative hyperplasia of the liver, splenic atrophy, gelatinous transformation of the bone marrow, and lymphocytic colitis. We discuss the different types of liver disorders associated with celiac disease and the possible relation between nodular regenerative hyperplasia and celiac disease, based on immunologic mechanisms.