BỘ GIÁO DỤC VÀ ĐÀO TẠO BỘ QUỐC PHÒNG HỌC VIỆN QUÂN Y NGÔ VIẾT THI NGHIÊN CỨU CHẪN ĐOÁN VÀ ĐIỀU TRỊ PHẪU THUẬT UNG THƯ BIỂU MÔ TẾ BÀO GAN Ở NGƯỜI CAO TUỔI Chuyên ngành NGOẠI TIÊU HÓA Mã số 62 72 01 25[.]
MINISTRY OF EDUCATION AND TRAINING BỘ GIÁO DỤC VÀ ĐÀO TẠO MINISTRY OF DEFENCE BỘ QUỐC PHÒNG MILITARY MEDICAL UNIVERSITY HỌC VIỆN QUÂN Y NGÔ VIẾT THI NGO VIET THI NGHIÊN CỨU CHẪN ĐOÁN VÀ ĐIỀU TRỊ PHẪU THUẬT UNG THƯ BIỂU MÔ BÀO GAN Ở NGƯỜI CAO TUỔI RESEARCH ONTẾ DIAGNOSIS AND SURGICAL THERARPY OF HEPATOCELLULAR CARCINOMA INHÓA ELDERLY PATIENTS Chuyên ngành: NGOẠI TIÊU Mã số: 62 72 01 25 Major: Surgery TÓM TẮT LUẬN ÁNNumber TIẾN SỸcode: 9720104 SUMMARY OF MEDICAL DOCTORAL THESIS HÀ NỘI - 2022 HA NOI - 2023 STUDY COMPLETED AT VIET NAM MILITARY MEDICAL UNIVERSITY Supervisor: Assoc., Prof Nguyen Van Xuyen Assoc., Prof Le Thanh Son Reviewer 1: Assoc., Prof Pham Đuc Huan Reviewer 2: Assoc., Prof Vu Huy Nung Reviewer 3: Assoc., Prof Trinh Tuan Dung This thesis has been defended at Institute-level Thesis Evaluation Council at 14.00 ………………… Thesis can be found at: National Library Library of Viet Nam Military Medical University INTRODUCTION Aging is associated with increasing susceptibility to development of multiple chronic diseases due to progressive degeneration of the organs and tissues The world's older population has grown at an unprecedented rate in the past 30 years The global population aged 60 years or over numbered 378 million in 1980 This number rose to 759 million older persons and is projected to reach billion by 2050 Vietnam is not exceptional In Viet Nam, the aging index has increased quickly in the past three decades: the aging index was 7.2% in 1989, 8.3% in 1999 and 9.5% in 2009 According recent reports, hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fourth leading cause of cancer-related deaths worldwide The highest incidence and mortality of HCC are observed in Southest Asia including Vietnam and SubSaharan Africa; but rarely encountered in Americas, Europe, and North America It is the most frequent cancer among males with higher incidence of deaths Despite advancement in medicine, better knowlege of etilogy and pathogenesis as well as more effective prevention of HCC, it is a malignant cancer characterized by rapid progression, poor prognosis and high rate of mortality While hepatectomy still remains a mainstay of HCC treatment, other approaches include: hepatic artery ligation, ethanol injection, hepatic endoarterial chemoembolization, radiofrequency ablation, radiation therapy However, hepatic resection remains the most effective treatment What are clinical and laboratory symptoms of HCC and which approach is effective for management HCC among the elderly? From the issue, the author conducted “Research on diagnosis and surgical therarpy of hepatocellular carcinoma in elderly patients” aiming: To present clinical and subclinical features of HCC among the elderly undergoing hepatectomy using Takasaki's technique To evaluate surgical outcome and related factores of hepactectomy using Takasaki's technique for managment of HCC among elderly patients New contribution of the thesis: This research has made some valuable contributions toward the specialties of hepatology and medical science as a whole The research has provided fundamental knowledge of HCC among the elderly both clinically and subclinically Moreover, surgical outcome of hepatectomy with Takasaki's procedure for treating HCC and some related factors to survival, recurrence of HCC have been addressed in the current study Organization of the thesis The thesis is comprised of 118 pages, of which there are 02 pages for Introduction, 40 pages for Overview - Chapter 1, 24 pages for Subjects and Methods – Chapter 2, 24 pages for Results - Chapter 3, 27 pages for Discussion; 02 pages for Conclusion; 01 page for Recommendations; 01 page for Lists of published research related to research findings The thesis also includes 25 tables, 20 figures and 10 charts There is a total of 149 references numbering 20 ones in Vietnamese and 129 in Enlgish CHAPTER OVERVIEW 1.1 Overview of the elderly 1.1.1 Definition Ageing is a course of biological nature, which is beyond human control It has a variety of meanings depending on characteristics of each society Therefore, its definitions vary among countries and regions In developed countries, older people are commonly defined as those aged 65 years or more UN defines older persons as those aged 60 year or over This boundary is kept fixed for calculations This definition is prescribed in the Vietnam Law on the Elderly 1.1.2 Demographic characteristics of the elderly in the world and in Vietnam Population ageing is a global phenomenon, occurring in virtually every country in the world Global population is experiencing growth in the size and proportion of older persons Countries across the globe are aging; however, the rate of population aging in developing countries is rising at a pace among the highest in the world On average, the world's older population is projected to increase by 29 million people annually, over 80% of which are in developing countries The proportion of older people in developing countries was 65% in 2010 and continutes to grow by 80% by 2050 1.1.3 The elderly’s health condition The older persons are often susceptible to development of multiple chronic diseases due to progressive degeneration of the tissues and organs Recent findings of health condition among the elderly revealed poor health in 18.1- 57.7% according to selfassessment; four fifths of the elderly develop chronic disease and each older persons has on average 2.1 chronic illnesses 1.2 Diagnosis of Hepatocellular Carcinoma Symptoms of HCC often don't appear until the later stages of the cancer This used to be main cause of delayed diagnosis of liver cancer which was little treated radically Currently, with the advert of medical improvement providing better understanding of risk factors, screening programmes as well as the aid of more accurate diagnostic models, HCC is diagnosed more accurately at an early stage 1.1.4 Prognostic role of biomarkers for HCC 1.1.4.1 Alpha – Feto Protein (AFP) Alpha-fetoprotein (AFP) is a glycoprotein produced primarily by the fetal liver In adults, increased AFP levels may suggest the presence of HCC; nevertheless, there are other causes of increased levels such as chronic hepatitis, testicular cancer, bile duct cancer According to 2010 AASLD, for HCC tumors with a diameter under cm, the sensitivity, specificity and positive predictive value of AFP are as follows: Table 1.1: Diagnostic value of AFP for HCC AFP levels (ng/ Sensitivity Specificity Positive predictive mL) value 20 49% - 71% 49% - 86% 1.28 – 4.03 200 04% - 31% 76% -100% 1.13-54.25 Currently, Associations for the Study of the Liver by Japan, American, European and the Asia Pacific recommend AFP threshold of 200 ng/mL as a reliable cut-off for the diagnosis of HCC These guidelines attach much importance to role of AFP in poor prognosis but no significance in diagnostic HCC Previous studies have shown that AFP is found in adults in lower levels than in the youth, especially AFP threshold < 400 ng/mL, which can be of little value in diagnosis of HCC 1.1.4.2 Performance of different tumor markers for management of HCC - Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3): AFP-L3 is used to distinguish patients with HCC from those with nonmalignant chronic hepatitis B Its thredhold value is 5% - Prothrombin induced by vitamin K absence-II (PIVKA II) or known as Des-gamma-carboxyprothrombin (DCP): Serum PIVKA-II is an abnormal prothrombin protein An elevated serum level of PIVKA-II is reported to be associated with HCC Its thredhold value is 40 mAU/ml - Recently, novel serum biomarkers including Golgi protein 73 (GP73), glypican-3 (GPC-3), Osteopontin, circulating cell free DNA, and microRNA have proved no remarkeable role of HCC diagnosis as well as economic efficiency - Combined determination of serum AFP, AFP-L3 and PIVKA-II could improve the sensitivity in HCC screening and detection without reducing the specificity, therefore, this combination is recommended their application in clinical practice 1.1.2 Diagnostic role of imaging tests Ultrasound is an important investigative tool in screening and discovering cancer As a subclinical tool, it is non-invasive, common, low cost and easy-to-perform for every patients Ultrasound shows a sensitivity of 33-96% and a specificity of more than 90% for detection of HCC Ultrasound imaging of HCC shows that most lesions are hyperechoic lesion, some are mixed echogenicity due to central necrosis or fibrosis Modern medical imaging techniques include Computed tomography (CT) or Magnetic Resonance imaging (MRI) On dynamic MR imaging typical HCC exhibits contrast hyperenhancement (wash-in) in the arterial phase and contrast hypoenhancement (washout) in the portal venous or late phase and equilibrium phases, similar to the features observed with dynamic CT According to the practice guidelines of the Associations for the Study of Liver Diseases in the world, liver tumor with typical characteristics of HCC in dynamic contrast enhancement CT or MRI could be diagnosed as HCC with no biopsy is required Older people are prone to be at a high risk of developing medical disease, especially kidney failure Much attention should be paid to these old subjects because MRI and CT posed a risk for people with severe kidney failure Diagnostic value of CT is comparable to that of MRI in both the elderly and the young 1.1.3 Role of liver biopsy Liver biopsy currently remains the gold standard in the diagnosis of hepatic lesions Depending on the skills and experience of the operator, ultrasound-guided liver biopsy allows a sensitivity of 70-90% A research demonstrated that biopsy allows cancer cell detection in 60% of cases with tumor less than 2cm 1.2 Surgical therapy of HCC 1.2.2 Hepatic resection using Takasaki’s procedure Anatomic liver resection (Takasaki K Glissonean pedicle transection method) Takasaki described the surgical technique based on structure of Glisson pedicle at the hepatic hilus According to Takasaki, the liver was divided into sectors for the liver as a whole and an additional caudate area, including the right segment in Takasaki’s classification corresponds to the posterior segment Ton That Tung’s segmental anatomy; middle segment (corresponding to the anterior segment in Ton That Tung’s); left segment (equivalent to middle and lateral segment in Ton That Tung’s At liver pedicle, hepatic artery, portal vein, and biliary duct are isolated in their extrahepatic course but enter the hepatic hilum wrapped in the Glisson’s capsule, which is referred to as the hilar plate Anatomical variation only occur under the hilar plane whereas above this hilar system, all posterior, middle and left sectional branches of the Glissonean pedicle are separated constantly Glisson pedicle division - primary branches, secondary branches, peripheral branches and cone units: According to Takasaki, three Glisson branches of the left - middle right lobes can be dissected at the hepatic hilus These are called primary branches Glisson’s capsule continues to encircle these components in the liver parenchyma firmly without separation Within the liver, the main branches split into secondary branches in the subsegments The secondary branches, further split into terminal branches in more peripheral branches The terminal branches of Glisson’s pedicle represent the smallest anatomically resectable part in conial shape, therefore Takasaki called it the “cone unit” In resection limits, one or more cone units of corresponding subsegment can be resected Hilar dissection allows an exposure to three Glisson’s pedicles equivalent to left liver, anterior and posterior segment Ligation of Glisson’s pedicles provides ind-depth understanding of accurate border of liver segments due to ischemic color changes of other unexpected segment surfaces Fig 1.1 Hilar dissection in control of three Glissonean pedicles Advantages of hepatectomy using Takasaki’s procedure Technical benefit: Control bleeding into liver; Identify accurately borders of segment division; minimize bleeding upon parenchymal resection Preservation of liver function: Avoid maximum ischemia of remnant liver volume; Contribute to preserve future remnant volume accurately, mininimize hepatic failure Oncological benefit: Anatomical hepatectomy involves the complete removal of a liver segment or sub-segment that which includes tumor-bearing portal vein, Fig 1.2 Anterior segment resection Fig 1.3 Cone – unit of subsegment 1.2.3 Foreign studies on hepatectomy for HCC management Doan Huu Nam conducted a study on a total of 4062 HCC patients over eight-year period (1995-2003) at Ho Chi Minh City Oncology Hospital His findings showed that viral hepatitis occurred in 88%, B and C co-infection in 3.8% Most patients visited hospital at a late stage Only 8.4% were eligible for liver resection According to the UICC classification, there were 79% of patients in stage IIIA and IIIB Common complications and mortality rate Intraoperative hemorrhage requiring blood tranfusion is the major post-operative complications found in 24.5% in Van Tan’s study and 27.2% in Doan Huu Nam’s Research by Van Tan revealed a surgical site infection rate of 8.6%, ascites of 5.3% and liver failure of 4.6%, which is frequently encountered post-hepatectomy Trieu Trieu Duong reported common complications including pleural effusion 13.1%, subdiaphragmatic abscess 2%, bile leak 2%, postoperative bleeding 1.16% and liver failure 0.29% In Van Tan’s study, there was 2.6% of the patients requiring reoperation due to bleeding and fluid leak The mortality rate was 15% prior to 1970 and 3.4% after the 1970 Regarding 30‐day mortality rates, Van Tan’s study revealed that only 3% of surgery‐related mortalities were capture Patients died from liver impairment Multi-organ dysfunction and postoperative hemorrhage Mortality rates in researches by Doan Huu Nam and Trieu Trieu Duong were 0.6% and 0.58%, respectively Recurrence and survival The percentage of patients who are alive one year and five years after liver resection was 25% and 2.6% (Doan Huu Nam’s study) Meanwhile, Trieu Trieu Duong’s gave promising results with the five-year survival rate of 46% CHAPTER SUBJECTS AND METHODS 2.1 Subjects of research - All elderly patients diagnosed with HCC and undergoing hepatic resection with Takasaki’s procedure - Location of study: Binh Dan Hospital - Study period: Between January, 2015 and January, 2019 2.1.1 Selection criteria - Patients aged 60 years and over - Patients were diagnosed with HCC based on the American Association for Study of Liver Disease (2010) including one of the following two criteria: + Contrast-enhanced CT and contrast-enhanced MRI found HCC nodules are typically hyperenhanced in the arterial phase and show washout in the portal venous and delayed phase + Liver biopsy shows as a diagnostic confirmation of HCC - Patients are indicated for hepatectomy according to the Guidelines of the Asia-Pacific Association for the Study of Liver Diseases 2010: No extrahepatic metastasis, no invasion into the portal vein and guarante of liver function In terms of liver function Child Pugh A Total blood bilirubin ≤ mg% Platelet count ≥ 100,000/mm3 Esophageal vein: no dilation Hepatic volume is expected to preserve ≥ 40% of standard liver volume Number and size of tumor Solitary liver tumor or multiple nodules localize on the left and right liver or on the segments and subsegments that liver mass can be resected 11 Hepatic vein resection: was perfomed after completion of liver parenchyma resection Using 5-0 Prolene thread to suture the hepatic vein Step 7: Control hemostasis, biliary leakage and abdominal closure All cases of hepatic resection followed the Takasaki’s procedure 2.2.4.4 Follow-up and postoperative care 2.2.4.5 Follow-up and post-hospital discharge follow-up appointments 2.2.5 Research criteria 2.2.5.1 General features * Age: caculated according to years at surgical time * Gender: male/female ratio 2.2.5.2 Clinical and subclinical features * Clinical features: Pain, fatigue, loss of appetite, jaundice and abdominal tumor đau, mệt mỏi, chán ăn, vàng da, u bụng * Risk factors * Laboratory tests: Albumin, Biliubin, platelet, TQ, TCK, serum AFP features of abdominal ultrasound, CT scan, MRI and liver biopsy 2.2.5.3 Surgical results of hepatectomy using Takasaki’s technique and some related factors Intraoperation - Surgical time - Amount of blood loss (ml) - The prevalence of patients with blood transfusion requirement and amount of transfused blood - Complications - Evaluation of association between tumor site, cirhossis and operation time - Evaluation of association between tumor site, cirhossis and blood loss - Specimens: - Distance from tumor to margin resection - The margins contain cancer cells or not - Pathological lesions: types of malignancy, level of differentiation, microscopical cirrhosis, lymph node metastasis - Classification of disease staging according to AJCC 2010 12 Postoperation - Complications: Liver failure, bleeding, biliary leakage, pleural effusion, pneumonia, residual abscess, surgical site infection… - Clavien-Dindo classification of complication - Length of hospital stay - Mortality Long-term outcomes and some related factors - The survival rate at one year, two years and three years - Recurrence rate at one year, two years and three years - Associations of survival time and recurrence with some other factors: AFP, tumor size, disease staging and blood transfusion 2.2.6 Data processing 2.3 Ethics in the research CHAPTER RESULTS OF STUDY 3.1 General characteristics 3.1.1 Age Patient’s median age was 65.8 ± 4.7 (range, 60 – 78 years) The age group of 60-70 years was the most prevalent (75%) 3.1.2 Gender Females represented 30%; and males accounted for 70% Female/male ratio: 7/3 (2.33) 3.2 Clinical features 3.2.1 Risk factors 38.4% had HCV infection and 36.7% had HBV infection the prevalence of HIV and the pravalence of coinfection with HBV and HCV was 3.3%, alcohol-associated cirhosis was found in 3.3% and other causes explained for 18.4% 3.2.2 Physical symptoms 65% of patients have abdominal pain, fatigue - decreased appetite 40%, accidentally detected tumor 38%, palpable tumor 5% 3.2.3 Comorbidities Table 2.2: Comorbidities Comorbidities Cardiovascula r Hypertension Old myocardial Number of patients (n) 32 Percentag e (%) 52.4 13.1 13 infarction / angina Heart failure Asthma Respiratory COPD 14.7 Diabetes 13.1 Metabolic Osteoporosis, 10 16.3 Osteoarthritis Hypertension explained for the highest rate (52.4%), followed by COPD, diabetes and cardiovascular diseases 3.2.4 Surgical risks ASA I: 30%, ASA II: 70% 3.3 Blood testing 3.3.1 Preoperative liver function Child A: 95%, Child B: 5% 3.3.2 Platelet counts: 60 patients with platelet counts greater than 100,000/mm3 3.3.3 Preoperative AFP level Average concentrations of AFP in serum in the HCC was 237.5 ng/mL High levels of AFP greater than 400 ng/mL was observed in only 11.7% 3.4 Imaging tests 3.4.1 Abdominal ultrasound Ultrasound appearances of hepatic tumor were mainly welldemarcated (95%) and rich blood vessels (98.3%) 3.4.2 CT scan Most tumors showed heterogeneous density (80%) 82% of tumors had typical appearances 3.4.3 MRI Whereas 11 patients had no typical features of HCC were found on CT scan, patients with typical features of HCC were detected on MRI 3.4.4 An ultrasound-guided liver biopsy Because the HCC confirmation was not performed by imaging tests, patients were indicated for ultrasound-guided liver biopsy All patients had pathologically confirmed HCC 3.5 Pathological features 3.5.1 Number of nodules 14 Most patients had solitary HCC (93.3%), and a small proportion of cases had multinodular HCC (6.7%) 3.5.2 Nodular size Mean nodules size was 5.7 ± 1.8 cm (range, 3.8-11 cm) 56.7% had nodules < cm and 43.3% ≥ 3.5.3 Level of differentiation Most HCC tumors were well-differentiated (43.4%); poor differentiation was present in 41,7% and a small proportion of patients had moderate differentiation (15%) 3.5.4 Tumor encapsulation of HCC Most patients (86.7%) had completely encapsulated HCC as compared to 13.3% of non- encapsulation 3.6 Surgical results and related factors 3.6.1 Intraoperative findings 3.6.1.1 Tumor site Table 2.3: Tumor site Tumor site Number of patients 5 Percentage (%) 1.7 11.7 8.3 8.3 10 11.6 Subsegment II Subsegment II IV Subsegment V Subsegment VI Subsegment VII Subsegment VIII Left lateral subsegment 12 20.1 (II-III) Posterior subsegment 6.7 Right liver Left liver 10 16.6 The incidence of liver resection on the right and the left liver was 21.6% 15.6% had tumor located in one subsegment and 26.8% in two subsegments 3.6.1.2 Types of hepatectomy Table 2.4 Types of hepatectomy Types Liver resection Number Percentag 15 of surger y Minor resectio n Major resectio n segments segments segments Posterior segment Anterior segment Left lateral segment Resection of left liver Resection of right liver Total of patients e (%) 17 28.3 8.3 13 21.7 17 28.4 13.3 60 100 Major liver resection constituted 41.7%, and minor resection in 58.3% 3.6.1.2 Operation time: 128.6 ± 47.3 mins (60-300 mins) 3.6.1.3 Intraoperative blood loss and transfusion Average blood loss 427.25 ± 158.4 mL (100 - 1500 ml) Most patients required no blood transfusion (88.3%) 11.7% received red blood cell transfusion due to blood loss of over 50 mL 3.6.1.4 Relationship between resection margin and tumor mass 56 patients (93.4%) achieved an R0 resection There were cancer cells at the resection margin in cases (6.6%) 3.6.1.5 Staging system for HCC according to AJCC’s classification Most patients were in stage I (76.7%), followed by stage III (18.3%) and only 5% of patients were in stage III 3.6.2 Postoperative complications Average length of hospital stay 8.9 ± days, shortest days and longest 18 days Complication Table 2.5: Post operative complications Number of patients Complications Surgeryrelated Liver failure Biliary leak Percentag e (%) 1.7 3.3 16 complications Ascites Fluid collection Abscess Pleural effusion Surgical site infection 2 1.7 3.3 3.3 1.7 Underlying Hospital pneumonia disease-related 3.3 complications Ascites, residual abscess were prevalent complications (5%) Hospital pneumonia, pleural effusion and biliary leak shared the same rate (3.3%) 1.7% of patients with liver dysfunction responded to medical therapy Clavien - Dindo classification: Grade I: 1.7% Grade II: 10%: patients underwent successful internal therapy Grade III: 3.3%: patients with residual abscess was aspirated under ultrasound guidance 3.6.3 Long-term results Average follow-up: 22.3 ± 8.4 months with the longest 36 months Survival time according to Kaplan-Meier estimate was 24.4 ± 1.25 months Survival probability at one year, two years and three years was 88.3%, 66.1% and 50.9% 3.6.3.1 Factors related to survival time Serum AFP concentrations Kaplan-Meier survival curve of patients with AFP ≤ 400 ng/ml was 27.5 ± 1.4 (24.8 - 30.3) months; that of patients with AFP ≥ 400 ng/ml was 10.8 ± 1.7 (7.5 – 14.3) months This difference was statistically significant with p = 0.0000001 Tumur size Kaplan-Meier survival curve of patients with tumor < 5cm was 29.4 ± 1.7 (26.1 – 32.7) months and that of patients with tumor ≥ cm was 19.8 ± 2.0 (16 – 23.7) months This difference was statistically significant with p=0.001 Level of differentiation Mean survival time of differentiated tumour groups 17 Well-differentiation: 26.8 ± 10,4 months Moderate differentiation: 20.3 ± 10.2 months Poor differentiation: 18.7 ± 8.1 months This difference was not statistically significant Staging of HCC Kaplan-Meier survival curve of patients at stages of HCC differed statistically significantly (p < 0.05) Stage I provided the best prognosis with 32.3 months 3.6.3.2 Rate of recurrence The 1-year, 2-year and 3-year survival rates were 20%, 55% and 65% with a median time of 22.9 ± 1.6 (according to Kaplan-Meier estimate) (minimum time of months and maximum of 36 months) Risk of recurrence according to AFP concentrations Patients with AFP < 400 ng/mL had the time of recurrence of 24.6 ± 1.6 (21.4 – 27.7) months and those with AFP ≥ 400 ng/ml had recurrence time of 8.8 ± 1.3 (6.1 – 11.5) months This difference was statistically significant with p = 0.000002 Risk of recurrence according to tumor size Based on Kaplan Meier method, the mean time for relapse of patients with tumor > cm: 15.9 ± 1.8 (12.3 – 19.6) months and that of patients with tumor ≤ cm: 27.6 ± 2.0 (23.7 – 31.4) months This difference was statistically significant with p = 0.000012 Risk of recurrence according the amount of blood transfusion intra-and-postoperation Average time of recurrence according to Kaplan Meier method in the group of blood transfusion: 8.5 ± 1.1 (6.4 - 10.6) months and in the group of non-transfusion: 24.6 ± 1.6 (19.8 - 26) months This difference is statistically significant with p = 0.00000003 Level of differentiation Level of differentiation Total Moderat Well e Poor 24 recurrenc Yes 13 No 14 16 36 e Total 27 24 60 Chi square test showed that liver tumor differentiation and recurrence rate were not significantly different, p = 0.5 18 CHAPTER DISCUSSION 4.1 Patient characteristics 4.1.1 Age The age group of 60 - 70 years was the most prevalent (45/60 patients accounting for 75%, of which group of 60-64 years of age explained for the highest rate (43.3%) 4.1.2 Gender Male to femal ratio was 2.33 (70% males; 30% females) Many studies also showed that male outnumbered females 4.2 Clinical features 4.2.1 Risk factors Hepatitis infection is the most common risk factors The prevalence of HCV infections was higher than that of HBV (38.4% vs 36.7%) This data are similarly found in other studies ASA group consists of group I and III 4.2.4 HCC Comorbodities Hypertension was prevalent (52.4%), followed by COPD, diabetes, and coronary artery disease, osteoarthritis (13-16%) This finding is consistent with other reports These comorbidities were optimized to minimize the complication 4.3 Subclinical features 4.3.1 AFP concentration in the blood The majority of patients had AFP < 400 ng/ml, only 11.7% had AFP ≥ 400 ng/ml Serum AFP level is one of the criteria for dignostic HCC of Ministry of Public Health of Vietnam AFP threshold greater than 200 ng/mL is considered to be high risk of HCC 4.3.2 Diagnostic imaging modalities The ultrasound imaging showed most tumors were welldemarcated (95%) CT scan shows before injection tumor heterogeneity rate of 80% 82% had typical tumors MRI provides a 72.7 percent typical imaging of HCC These findings are lower than other studies due to a small number of sample sizes 4.3.3 Pathological features Tumor encapsulation is a favorable prognostic factor for HCC management Encapsulated HCC has higher differentiation and