Valle Cadahía

TNF-α− 308A promoter polymorphism is associated with enhanced TNF-α production and inflammatory activity in Crohn's patients with fistulizing disease

OBJECTIVE:Tumor necrosis factor-α (TNF-α) plays a key role in the inflammatory response and pathogenesis of Crohns disease (CD). TNF-α− 308A polymorphism within the TNF-α gene promoter has been associated with enhanced TNF-α production in vitro. The aim of this study was to investigate the effect of TNF-α promoter polymorphism at −308 on the susceptibility and phenotypic expression of fistulizing CD.METHODS:The distribution of −308 TNF-α genotypes was analyzed in 50 patients with fistulizing CD and 100 healthy matched controls. TNF-α, interleukin-1β, and interleukin-6 serum levels were measured by ELISA. Serum amyloid-A, C-reactive protein, α1-antitrypsin, α1-acid glycoprotein, and haptoglobin were measured by nephelometry.RESULTS:No significant differences were found in the allele frequencies of the polymorphism between patients and controls. However, compared with −308GG patients, those carrying −308AG had a significant increase of serum levels of TNF-α (58 ± 79 vs 8 ± 19 pg/ml, p < 0.001), interleukin-1β (36 ± 45 vs 16 ± 20 pg/ml, p = 0.048), and acute phase proteins (APPs). −308A carriers had also a higher frequency of arthritis (66% vs 26%, p = 0.039). The logistic regression model showed that the patients carrying −308A polymorphism had a relative risk for developing arthritis of 5.45 (95% CI = 1.1–25.6). No other clinical or analytical findings were predictive for the risk of development of arthritis.CONCLUSIONS:TNF-α− 308A polymorphism is associated with enhanced TNF-α production, more intense inflammatory activity, and an increased risk for arthritis susceptibility in CD patients with fistulizing disease.

Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk groups.

BACKGROUND & AIMS The incidence of hepatocellular carcinoma (HCC) and associated risk factors in patients with alcoholic cirrhosis are not well defined. Surveillance for HCC among patients with cirrhosis who do not have hepatitis B is cost effective only if the expected risk of HCC exceeds 1.5% per year. We performed a prospective study to determine the incidence of HCC among patients with alcoholic cirrhosis and to identify risk factors. METHODS We analyzed data from a surveillance program of 450 patients, aged 40 to 75 years, with alcoholic cirrhosis of Child-Pugh class A or B; patients were enrolled at the liver unit of a tertiary center from September 1992 through March 2010. Data were collected on 20 demographic, clinical, and laboratory variables at the start of the study. Patients were examined every 3 to 6 months for 5 years to identify risk factors for HCC; incidence was determined from a median follow-up time of 42 months. RESULTS Over the follow-up period, 62 patients developed HCC (43 in the first 5 y of follow-up evaluation), with an annual incidence of 2.6%. By using multivariate analysis, age 55 years and older (hazard ratio, 2.39; 95% confidence interval, 1.27-4.51) and platelet counts less than 125 × 10(3)/mm(3) (hazard ratio, 3.29; 95% confidence interval, 1.39-7.85) were associated independently with the development of HCC. These variables were used to define 3 risk groups. The annual incidence of HCC in the group without either of these factors was 0.3% (n = 93), the annual incidence with 1 factor was 2.6% (n = 228), and the annual incidence with both factors was 4.8% (n = 129) (P < .0001). CONCLUSIONS The annual incidence of HCC among patients with alcoholic cirrhosis of Child-Pugh class A or B is around 2.5%. Age and platelet count can be used to classify the patients in 3 different risk groups for HCC development within the next 5 years.

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 patients 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.

Retreatment and maintenance therapy with infliximab in fistulizing Crohn's disease.

OBJECTIVES Infliximab has clearly demonstrated its efficacy in the short-term treatment of fistulizing Crohns disease. We present here the results of retreatment and long-term maintenance therapy. PATIENTS AND METHODS Eighty one consecutive patients with active fistulizing Crohns disease, in whom previous treatments had failed, were treated with infliximab. All patients received as the initial treatment of 5 mg/kg i.v. infusions (weeks 0, 2, and 6). Those patients who failed to respond after the initial cycle (group 1, n = 25), or those who relapsed after having responded (group 2, n = 13), received retreatment with three similar doses (weeks 0,2, and 6). Those who responded to retreatment were included in a long-term maintenance programme (n = 44), with repeated doses (5 mg/kg i.v. infusions) every eight weeks for 1-2 years. RESULTS In the initial treatment 56% of the patients responded partially; this response being complete in 44%. In the retreatment, 28% of group 1 (non-responders) presented a complete response, compared to 77% in group 2 (relapsers) (p < 0.0001). In the maintenance treatment, the global response was 88% (39/44). The mean number of doses per patient was 4.4 +/- 2 (range 1-9) with a duration of 36 +/- 12 weeks (range 8-72). Adverse effects were not significantly increased in either treatment. CONCLUSIONS Both retreatment and long-term maintenance therapy with infliximab, are highly effective and well tolerated in fistulizing Crohns disease patients.

Adherence to a Semiannual Surveillance Program for Hepatocellular Carcinoma in Patients With Liver Cirrhosis

Background: Patient adherence to screening for hepatocellular carcinoma (HCC) is not well known. Our aims were to analyze the adherence to a surveillance program in a prospective cohort of cirrhotic patients and to examine its association with HCC stage at diagnosis. Materials and Methods: A total of 770 patients with cirrhosis were examined semiannually by ultrasound and alpha-fetoprotein at a tertiary center. We collected data on 17 variables at baseline. Suboptimal adherence was defined as failure to complete 2 consecutive screening rounds. Results: Over a median follow-up period of 42.0 months (interquartile range: 60.0), 125 patients (16.2%) had suboptimal adherence. Active or previous intravenous drug use [hazard ratio (HR), 5.33; 95% confidence interval (CI), 3.07-9.23], active alcohol consumption (HR, 3.03; 95% CI, 2.03-4.51), absence of liver decompensation before the inclusion in the program (HR, 1.65; 95% CI, 1.07-2.55) and aspartate transaminase/alanine transaminase ratio ≥1.6 (HR, 1.82; 95% CI, 1.23-2.70) were independent predictors of suboptimal adherence. Compared with those with optimal adherence, patients with suboptimal adherence had a more advanced HCC stage at diagnosis (P=0.015), they were less frequently treated with curative intention (P=0.078) and survived less (median: 14.2 mo; IQR: 36.0 vs. 22.7 mo; IQR: 47.4; P=0.160), although these differences were not significant. Conclusions: The adherence to the process of HCC surveillance can be considered as adequate among cirrhotic patients. Active alcohol consumption and a history of intravenous drug use are the strongest predictors of suboptimal adherence. These patients have a more advanced HCC stage at diagnosis and tend to be less frequently treated with curative intention.

Lower GI bleeding secondary to a stromal rectal tumor (rectal GIST).

We present the case of a 64-year-old woman without any known allergies to drugs, who had smoked 20 cigarettes a day for more than thirty years, and with no other relevant history, who presented to our Department of Gastroenterology complaining of rectal bleeding and secondary ferropenic anemia with a hemodynamic repercussion. A colonoscopy was made to reveal the presence of a polypoid, submucous, ulcerated lesion in its vertex (8 cm from the anal margin) (Fig. 1). An endoanal ultrasound scan showed a heterogeneous mass located in the posterior wall of the rectum, approximately 7 cm in size, with no infiltration of perirectal fat (Fig. 2). A biopsy was made with a tru-cut needle, and the pathological study showed a proliferation of fusiform cells, with no mitoses or atypias, and strongly positive for the CD-117 marker; staining by other markers (CD-34, desmine, actine, and S-100) was negative, except for one slight ki-67-related positivity, less than 10%. An abdominal CAT scan revealed no metastases at all levels. With a preoperative diagnosis of rectal stromal tumor, the mass was removed by local excision with preservation of the rectum. The patient is currently in the eighteenth month of follow-up, and has no signs or symptoms of relapse, neither locally nor distally.

Prevalence and epidemiology of hepatitis D among patients with chronic hepatitis B virus infection: a report from Northern Spain

Background The incidence of hepatitis delta virus (HDV) infection has decreased during the last decades. However, an increasing trend has been reported recently. Patients and methods We carried out a case–control study to analyze changes in its prevalence in 1215 chronic hepatitis B virus (HBV) patients, diagnosed consecutively in a tertiary center, between 1983 and 2012. According to the year of diagnosis, patients were distributed into two groups: A [1983–1997 (n=786)] and B [1998–2012 (n=429)]. Results The prevalence of anti-HDV was 8.2% (9.4% in group A and 6.1% in group B) (P=0.04). Multivariate regression revealed that intravenous drug use [odds ratio (OR) 261.0; 95% confidence interval (CI), 28.7–2368.5; P<0.001], blood transfusion (OR 28.0; 95% CI, 2.7–295.9; P=0.03), anti-HIV(+) (OR 4.8; 95% CI, 1.6–14.5; P=0.004), and high alanine aminotransferase (OR 14.4; 95% CI, 3.4–60.6; P<0.001) were associated independently with the presence of anti-HDV in group A, whereas in group B, it was associated with immigration (OR 20.0; 95% CI, 4.7–84.9; P<0.001), intravenous drug use (OR 683.5; 95% CI, 52.7–8855.7; P<0.001), promiscuous sexual activity (OR 22.6; 95% CI, 2.2–228.5; P=0.008), and high alanine aminotransferase (OR 3.4; 95% CI, 1.1–10.0; P=0.02). Conclusion Although a significant decrease in the prevalence of HDV infection has been observed, it is still above 5%. Immigration and sexual transmission have emerged as new risk factors for HDV infection.

Incidence and risk factors associated with hepatocellular carcinoma surveillance failure: Hepatocellular carcinoma surveillance

Surveillance for hepatocellular carcinoma (HCC) intends to detect tumors at an early stage to improve survival. The study aims were to assess the frequency and risk factors associated with HCC surveillance failure.

Retreatment and maintenance therapy with infliximab in fistulising Crohn's disease

OBJECTIVES Infliximab has clearly demonstrated its efficacy in the short-term treatment of fistulizing Crohns disease. We present here the results of retreatment and long-term maintenance therapy. PATIENTS AND METHODS Eighty one consecutive patients with active fistulizing Crohns disease, in whom previous treatments had failed, were treated with infliximab. All patients received as the initial treatment of 5 mg/kg i.v. infusions (weeks 0, 2, and 6). Those patients who failed to respond after the initial cycle (group 1, n = 25), or those who relapsed after having responded (group 2, n = 13), received retreatment with three similar doses (weeks 0,2, and 6). Those who responded to retreatment were included in a long-term maintenance programme (n = 44), with repeated doses (5 mg/kg i.v. infusions) every eight weeks for 1-2 years. RESULTS In the initial treatment 56% of the patients responded partially; this response being complete in 44%. In the retreatment, 28% of group 1 (non-responders) presented a complete response, compared to 77% in group 2 (relapsers) (p < 0.0001). In the maintenance treatment, the global response was 88% (39/44). The mean number of doses per patient was 4.4 +/- 2 (range 1-9) with a duration of 36 +/- 12 weeks (range 8-72). Adverse effects were not significantly increased in either treatment. CONCLUSIONS Both retreatment and long-term maintenance therapy with infliximab, are highly effective and well tolerated in fistulizing Crohns disease patients.