Tóm tắt Luận án Research of hepatitis c virus genotypes in hepatocellular carcinoma patients

Nội dung tài liệu: Tóm tắt Luận án Research of hepatitis c virus genotypes in hepatocellular carcinoma patients

1. MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES ------------------------------------------------- NGUYEN THI THANH THUY RESEARCH OF HEPATITIS C VIRUS GENOTYPES IN HEPATOCELLULAR CARCINOMA PATIENTS Speciality: Gastroenterology Code: 62.72.01.43 SUMMARY THESIS’ DOCTOR OF MEDICINE HANOI – 2018
2. THE THESIS WAS DONE IN: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Supervisor: 1. Prof. PhD. Mai Hong Bang 2. Ass. Prof. PhD. Cao Minh Nga Reviewer: 1. 2. 3. This thesis will be presented at Institute Council at: 108 Institute of Clinical Medical and Pharmaceutical Sciences Day Month Year The thesis can be found at: 1. National Library of Vietnam 2. Library of 108 Institute of Clinical Medical and Pharmaceutical Sciences 3. Central Institute for Medical Science Infomation and Tecnology
3. 1 1. Introduction Hepato cellular carcinoma (HCC) is a popular cancer ranking the sixth in the world, in which ranking fifth in male and eighth in female with many changes over time. This is the third reason causing cancer-death in Asia-Pacific region. Beside hepatitis B, hepatitis C is an important causal factor related to hepato cellular carcinoma (HCC). Hepatitis C virus (HCV) causes hepato cellular carcinoma (HCC) by promoting the inflammation and fibrosis process on liver, eventually causing cirrhosis and hepato cellular carcinoma (HCC). Although there are lots of debates about the mechanism causing HCC of HCV, recent researches had mentioned the role of HCV genotype. In Vietnam, there have been researches on HCV genotypes in patients with acute or chronic hepatitis C, but not having adequate researches about HCV genotypes in HCC patients on foundation of hepatitis C virus. From the above-mentioned reasons, we conduct this research aiming to: 1.1. Describing clinical and characteristics laboratory features and identifying HCV genotype on patients of HCC. 1.2. Evaluating relationship between HCV genotypes and some clinical characteristics laboratory features,on patients of HCC. 2. Necessity Six (06) HCV genotypes have been identified currently. In Vietnam, researches on chronic hepatitis C patients are most commonly found in genetype 6, followed by genotype 1 then genotype 2. Some authors referred to the high risk of causing hepato cellular carcinoma on patients that infect HCV with genotype 1 (1b); but other researches referred to the high risk on patients that infect HCV with genotype 3. Therefore, researching the role of HCV genotypes on patients of hepato cellular carcinoma is essential work, contributing to clarify disease’s mechanism. 3. New contributions of thesis Thesis identified genotype and subtype of hepatitis C virus on 68 patients with HCC and 63 patients with HCV chronic hepatitis. Thesis concurrently showed the risk of hepato cellular carcinoma in patients with HCV genotype 1b were 4.92 times higher than patients of HCV non-1b (p = 0.008; OR = 4.92; 95% CI: 1.52 – 15.96).
4. 2 Research had also identified linear relationship between genotype 1b and HCV load in patients with hepato cellular carcinoma (HCC) 4. Thesis outline: Thesis was presented in 128 pages including introduction 2 pages, overview 38 pages, object and method of research 20 pages, research results 32 pages, discussion 33 pages, conclusion 2 pages and petition 1 pages. Thesis includes 44 tables, 14 graphs, and 146 reference documents in which 29 Vietnamese documents and 117 English documents.
5. 3 CHAPTER 1 OVERVIEW 1.1. Epidemiology of hepato cellular carcinoma (HCC): Hepato cellular carcinoma is a popular cancer ranking sixth in the world. In Vietnam, author Vuong Anh Duong (2010) certified liver cancer ranking the third among other cancer diseases in male. According to statistic of author Nguyen Dinh Song Huy (2015) from 2010 to 2014, patients with HCC increased year by year mostly in male patients. The main reason was hepatitis B virus and hepatitis C virus. 1.2. Biological characteristics of hepatitis C virus 1.2.1. Characteristics of form and structure: Hepatitis C virus (HCV) is a virus in the Flaviviridae family with structure of RNA single sequence. 1.2.2. Genotype characteristics During replication period, HCV must use RNA poly merase enzyme, which is not capable of correcting in RNA synthetic process that diversifies HCV gene set, so it is classified HCV in different types. Genotype identification and classification are based on nucleotide order. If discrepant order of nucleotide > 20% we have different genotypes. If discrepant order of nucleotide ≤ 20% we have different subgroup of same genotype. It is identified currently six (06) HCV genotypes causing disease. Genotype 1 and 3 are globally distributed, in which genotype 1 is the most common (46%), followed by genotype 3 (22%), genotype 2 (13%), and genotype 4 (13%). Most of techniques previously focused on 5’UTR region (5’ untranslated region or also called 5’NC: 5’ non-coding) in identifying quality and quantity of HCV, because of its high conservation among different genotypes of HCV. However it only based on 5’NC region, it is not sufficient to distinguish familiar subtypes in the same HCV type. So, genotype identification nowadays are based on coding regions such as core region, NS5B region, NS4 or E1 region.
6. 4 Beside epidemiological sense, clinical practice identifies HCV genotype for predicting treatment response, treatment duration. Although existing conflict and debate, both domestic and international researches have recognized role of genotypes 1 and 3 affecting hepato cellular carcinoma. |In Vietnam, genotype 6 is most common, followed by genotype 1 and 2, genotype 3 has not been reported in general population, except some special addicted drug users that users HCV infected drugs. The role of genotype initially in hepato cellular carcinoma has been researched but sporadically and unsystematically. It is a reason we carry out this topic. 1.2.3. Process of hepatitis C replication: It occurs in cell’s cytoplasm due to synthetic process via RNA. 1.3. Natural progression of hepatitis C virus infection 1.3.1. Acute hepatitis C: Most have no symptoms. 1.3.2. Chronic hepatitis C: 75-85% of HCV infection will progress chronic hepatitis, which is a risk leading to cirrhosis and hepato cellular carcinoma. 1.4. Mechanism of causing hepato cellular carcinoma due to HCV infection Chronic HCV infection causes hepato cellular carcinoma mainly by direct way. Oppositely, patients of chronic hepatitis C often develop into hepato cellular carcinoma (HCC) on cirrhosis. In addition, indirect way via cirrhosis HCV causes hepato cellular carcinoma via HCV protein such as core, NS3, NS4B and NS5A.
7. 5 CHAPTER 2 OBJECT AND METHOD OF RESEARCH 2.1. Object of research Researching group: 68 patients were diagnosed HCC by surgery, they treated at Hepatoma Department of Cho Ray Hospital from October 2012 to December 2015. Controlling group: 63 patients were diagnosed chronic hepatitis C and had no abnormal tumor in liver. They treated at Hepatitis Department of Cho Ray Hospital from October 2012 to December 2015. 2.1.1. Criteria of reasrching group (HCC groupe) 2.1.1.1. Selecting criteria: Patients were diagnosed primarily HCC to base on surgery evidences with Anti HCV (+) and HBsAg (-), and identified HCV genotype at Medicine Faculty of University of Medicine and Pharmacy, Ho Chi Minh City. 2.1.1.2. Exclusive criteria: Patients did not meet selecting criteria. Those had cancer in other organs, dilating cholangioma, metastatic tumors, and secondary liver cancer diagnosis. Patients that is alcoholics, addicted to cigarettes, and accompanied with acute and chronic diseases. 2.1.2. Criteria of controlling group ( HCV groupe) 2.1.2.1. Selecting criteria: Patients were excluded abnormal tumors in liver by ultrasound with Anti HCV (+) and HBsAg (-) tested to identify HCV genotype at Medicine Faculty of University of Medicine and Pharmacy, Ho Chi Minh City. 2.1.1.2. Exclusive criteria - Did not meet selecting criteria. - To have abnormal tumors in liver. - Patients had infection, glomerular diseases, alcoholics, and other chronic diseases. 2.2. Method of research. 2.2.1.Research design: This is cross-sectional research with controlling comparison.
8. 6 2.2.2. Sample size: Selecting sample that are convenient for both groups, researching group of 68 HCC patients with and controlling group of 63 HCV patients 2.2.3. Research facilities: Machine system Cobas 6000 Analyzer Series of Hitachi. Kit automatic detaching and extracting DNA/RNA of Roche. Set kit of quantitative and HCV genotype identification “Accupid HCV Genotyping Kit” of Khoa Thuong Company; and some other machines, equipment and facilities. 2.2.4 Research content and criteria 2.2.4.1. Clinical research: To record symptoms HCC. 2.2.4.2. Subclinical research 2.2.4.2.1. Tests of peripheral blood cells 2.2.4.2.2. Tests of blood chemistry 2.2.4.2.3. Immunoassay 2.2.4.2.4. Tests of HCV quantitative and identifying HCV genotype - Time taking blood: when hospitalizing. - Tests were carried out at Microbiology Faculty of |University of Medicine and Pharmacy, Ho Chi Minh City. Process consists of five (5) steps: sample receiving – processing, RNA extraction, reverse transcription of RNA to cDNA, DNA replication by real time PCR. Both primer and probe were designed basing on sequence of core genes in HCV by Khoa Thuong Company. After identifying HCV genotype by realtime PCR,we continued identify HCV subtypes by sequencing. 2.2.4.3. Evaluating tumors condition in ultrasound, computed tomography or magnetic resonance imaging 2.2.4.4. Liver biopsy: Sending tumors’ samples for histiology 2.2.4.5. Evaluating liver function according to Child-Pugh 2.2.4.6. Evaluating relationship between HCV genotype and some subclinical, clinical characteristics 2.3. Data collecting and processing: - Collecting date: Collecting tests and clinical information according to the medical reports - Processing data according to the method of medical statistics, using SPSS 13 software. 2.4. Ethical issue in research: To ensure medical ethics in research.
9. 7 CHAPTER 3 RESEARCH RESULTS 3.1. General characteristics of researching group Table 3.1. Age characteristics of researching group HCC group HCV group Age (n=68) (n=63) p n Rate % n Rate % ≤ 40 0 0,0 8 12.7 41 – 60 26 38.2 40 63.5 < 0,001 > 60 42 61.8 15 23.8 Total 68 100.0 63 100.0 Average age 64.81 ± 8.82 52.13 ± 9.3 < 0,001 Maximum age 85 71 Minimum age 47 32 HCC group mainly over 60 age, majority of male. Table 3.2. Genders’ characteristics of researching group HCC group HCV group Gender (n=68) (n=63 p n Rate % n Rate % Female 13 19.1 35 55.6 < 0.001 Male 55 80.9 28 44.4 Total 68 100.00 63 100.00 Comment: Male patients accounts 80.9%; the ratio of male/female = 4.24. There is gender discrepancy between researching and controlling group. 3.2. Clinical symptoms and laboratory tests of HCC and HCV groups
10. 8 3.2.1. Clinical symptoms Table 3.3. Some symptoms of mechanical energy HCC group HCV group Symptoms of (n=68) (n=63) mechanical energy p n Rate n Rate % % No 19 27.9 55 87.3 < Fatigue Yes 49 72.1 8 12.7 0.001 Pain in right No 20 29.4 57 90.5 < hypochondrium Yes 48 70.6 6 9.5 0.001 No 35 51.5 60 95.2 < Weight loss Yes 33 48.5 3 4.8 0.001 Digestive No 36 52.9 48 7.2 0.006 disorder Yes 32 47.1 15 23.8 No 47 69.1 53 84.1 Anorexia 0.04 Yes 21 30.9 10 15.9 Fatigue, weight loss and pain in right hypochondrium are common symptoms in the HCC group. Table 3.4. Some signs HCC group HCV group (n=68) (n=63) Entity symptoms p n Rate n Rate % % Liver under No 30 44.1 57 90.5 < right Yes 38 55.9 6 9.5 0.001 hypochondrium No 60 88.2 52 82.5 Jaundice 0.36 Yes 8 11.8 11 17.5 Collateral No 56 82.4 63 100 < circulation Yes 12 17.6 0 0 0.001 No 59 86.8 63 100 Leg oedema 0.003 Yes 9 13.2 0 0