Soonthorn Chonprasertsuk

Epidemiology and treatment of hepatocellular carcinoma in Thailand.

Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor in Thailand. The high incidence rate of HCC reflects from chronic HBV infection in this endemic area. Some patients are asymptomatic at presentation whereas many of them presented at advanced stage of HCC with limited treatment options and grave outcome. The Barcelona Clinic Liver Cancer (BCLC) staging system and management allocation for HCC is widely accepted and used in many international guidelines including Thailand. Curative treatment is expected in early stage of HCC while palliative treatment, combination treatment and best supportive care are offered to advanced stage of HCC. The most effective strategy to prevent the development of HCC is prevention of HBV vertical transmission and treatment HBV or HCV infection. The purpose of this article is to update information of HCC in Thailand including epidemiology, diagnosis, clinical manifestation, and treatment.

Effect of IL-1 Polymorphisms, CYP2C19 Genotype and Antibiotic Resistance on Helicobacter pylori Eradication Comparing Between 10-day Sequential Therapy and 14-day Standard Triple Therapy with Four-Times-Daily-Dosing of Amoxicillin in Thailand: a Prospective Randomized Study.

BACKGROUND Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. MATERIALS AND METHODS This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. RESULTS A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). CONCLUSIONS Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.

CYP2C19 Genotype Could be a Predictive Factor for Aggressive Manifestations of Hepatocellular Carcinoma Related with Chronic Hepatitis B Infection in Thailand.

BACKGROUND Chronic hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC) is a major health problem in the Asia-Pacific region including Thailand. Several factors have been proposed as contributing to hepatocarcinogenesis. This study was aimed to investigate the impact of CYP2C19 genotypic polymorphism in HCC related to chronic HBV infection in Thailand. MATERIALS AND METHODS A cross-sectional study was performed between April 2014 and January 2015. Chronic HBV patients with HCC (n=50) and without HCC (n=50) were included. Clinical information and blood samples of all patients were collected. The CYP2C19 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method, and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). RESULTS The CYP2C19 genotype frequencies of RM, IM and PM in HBV patients were found to be 19/50 (38%), 25/50 (50%) and 6/50 (12%), respectively. The CYP2C19 genotype frequencies of RM, IM and PM in HBV with HCC patients were 21/50 (42%), 25/50 (50%) and 4/50 (8%), respectively. The distribution of CYP2C19 genotype was not different between patients with and without HCC. Interestingly, among HBV with HCC patients, the RM genotype of CYP2C19 tended to increase risk of aggressive manifestation (OR=2.89, 95%CI=0.76-11.25, P-value = 0.07), compared with non RM genotype carriers. CONCLUSIONS CYP2C19 genotype IM was the most common genotype in Thai patients with chronic HBV infection. In addition, genotype RM could be an associated factor for aggressive presentation in HCC related to chronic HBV infection.

T1149 Risk of Upper Gastrointestinal Bleeding in Clopidogrel and Aspirin Users Receiving Concomitant Proton Pump Inhibitors

Background and aims: Clopidogrel and aspirin (ASA) are wildly used in the prevention of cardiovascular and embolic events. However, these combined medications cause significant risk of peptic ulcers and bleeding complications. This case-control study was designed to evaluate the risk of upper gastrointestinal bleeding (UGIB) in clopidogrel and aspirin users who continue receiving standard dose of proton pump inhibitors (PPI). . Methods: Data for clinical information and endoscopic findings were collected during January 2009 and November 2009 from patients who used clopidogrel and/or ASA and continue receiving standard dose of PPI. Patients with history of prior UGIB or abdominal surgery were excluded. Clopidogrel or ASA user was defined as consumption of clopidogrel or ASA for at least 7 days period preceding the episode of bleeding. The UGIB was defined as overt bleeding (hematemesis, positive nasogastric aspirate, and melena) or fall in baseline hematocrit ≥ 5 points within 24 hours of admission. Ulcer was defined at endoscope by breaking mucosa > 3mm in diameter. Results:A total of 175 patients (82 men and 93 women, mean age of 65.3 years) were evaluated in this study including 54 patients (30.9%) with UGIB and 121 patients (69.1%) with dyspeptic symptoms. Male were significantly more common than female patients in bleeding group (61.1 % vs 38.9%: P=0.01). However, the underlying diseases of the patients including cardiovascular diseases, rheumatological diseases and diabetes mellitus were not different between these 2 groups. UGIB was significantly higher in current ASA (325mg) plus clopidogrel user than non-user (16.7% vs 5.8%; P=0.02). The multivariable model suggested that the probability of UGIB event increased with current ASA (325mg) plus clopidogrel use (OR= 2.3, 95%CI =1.2-3.9) in the patients receiving concomitant PPI. Summary: Risk of UGIB events still occur in ASA and clopidogrel users in spite of receiving concomitant PPI. Lower dose of ASA, concomitant higher dose PPI and carefully monitoring of UGIB should be considered in combined ASA and clopidogrel user patients.