Rates of latent and active tuberculosis in BGC vaccinated, immunosuppressed Crohn's disease patients form Bulgaria before and during anti-tumor necrosis factor therapy.

OBJECTIVE: Although the use of anti-tumor necrosis factor-alpha (anti-TNF-α) agents is highly effective in achieving and maintaining remission in patients with moderate-to-severe IBD, they place the patient at increased risk of developing opportunistic infections, including new cases of tuberculosis infection (TBI) and/or reactivation of latent tuberculosis infection (LTBI). Our study aims to determine the incidence of TBI [active tuberculosis (ATBI) and LTBI] among patients with Crohn's disease (CD) receiving anti-TNF-α therapy. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive CD patients undergoing anti-TNF-α (infliximab, adalimumab) treatment for a minimum of 6 months, in the period between June 2010 and December 2019, followed-up at a reference IBD center. All patients were HIV negative, and BCG vaccinated. In all patients, ATBI was excluded and all were tested for LTBI prior to initiating a biological treatment. RESULTS: Before starting the biological treatment, we established LTBI in 11/109 (10.1%): 8/11 (72.7%) patients were TST positive, 2/11 (18.2%) were IGRA positive and TST negative, 1/11 (9.1%) were both IGRA and TST positive. In patients undergoing biological therapy with previous negative screening test for tuberculosis, a total of 16/74 (21.6%) patients were newly diagnosed with LTBI. The median induration (not erythema) diameter of TST is 8 (IQR 5-17) mm. Active pulmonary tuberculosis infection, developed in 3/74 (4.1%) patients. One patient developed ATBI on the background of chemoprophylaxis with INH for LTBI. CONCLUSIONS: Specialists should thoroughly analyse all patient clinical data, chest X-ray results, epidemiological and BCG status, as well as perform a LTBI screening before initiating immunosuppressive and/or biological treatment. IBD patients have a higher risk of developing TBI in the first 12 months.

CHEK2 I157T and colorectal cancer in Bulgaria.

PURPOSE: Germline variants of the CHEK2 gene have been shown to act as low-penetrance cancer susceptibility alleles for a wide range of human malignancies. CHEK2 I157T has particularly been linked to colorectal cancer (CRC) risk. We aimed at establishing the population frequency and contribution of this variant to colorectal carcinogenesis in Bulgaria. METHODS: We have genotyped 802 population controls and 343 CRC patients from Bulgaria for the CHEK2 I157T variant. RESULTS: Heterozygous were 9 of 343 patients (2.62%, odds ratio/OR=1.0, 95% confidence interval/CI = 0.42 - 2.33, p=0.99% and 21 of 802 controls (2.62%). Higher frequencies were found among patients with multiple polyposis (2/40, 5%, p=0.28) and the rarer mucinous histology (1/11, 9.09%, p= 0.26). CONCLUSION: We conclude that CHEK2 I157T is not relevant for CRC risk in Bulgaria, but studies on a larger scale might help evaluate its possible significance in respect to disease characteristics.

Risk and protective factors for development of colorectal polyps and cancer (Bulgarian experience).

BACKGROUND/AIMS: Colorectal cancer takes third place among all malignancies in the Varna region. The present study aims to determine the typical and distinguishing risk and protective factors for colorectal polyps and cancer formation. METHODOLOGY: 166 patients with large bowel polyps and 107 patients with colorectal cancer were questioned, examined endoscopically and histologically. Logistic regression analysis was used to find a possible correlation between alimentary habits, way of life, and risk for colorectal polyps and cancer formation. The latter have been used to define a strategy for their prevention. RESULTS: Our results showed that fried, preserved, and grilled meat, consumption of animal fats, sugar, and being overweight are positively associated with colorectal polyps. In contrast, consumption of fruit, vegetables, rye- and brown bread, green tea, vegetable food, yoghourt, vegetarian food, fish, lamb, hare, garlic, boiled food, and mineral water, have strong protective effect against large bowel polyps. We have confirmed the role of the well-known risk factors for colorectal cancer, and discovered an association between H. pylori infection, age, villous component in the adenomatous polyps, and family history for any neoplasia and large bowel carcinoma. CONCLUSIONS: We suggest the following protective factors for CRC: vegetarian food, plant oil, rural life, aspirin intake, legumes, fish, fruit and vegetable consumption. We observe a similarity between the risk factors for colorectal polyps and cancer formation. They act simultaneously and depend on genetic predisposition. A combination of endoscopic treatment and correction of the alimentary factors could be used as a means of cancer prevention.