МОΗГОЛ УЛС ДАХЬ УΗДСЭH ХУУЛNЙH XЯHAЛT БA YЛC TθP

Академич ж.Амарсанаа(J. Amarsanaa) 한국공법학회 2005 公法硏究 Vol.33 No.4

Comparative Study of Persistent Immunity to HBV after Vaccination and Naturally Acquired Immunity Post HBV Infection in Mongolia

( O. Baatarkhuu ),( O. Otgonbayar ),( J. Amarsanaa ),( D. Munkh-orshikh ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: As of 2015 over 260 million people live with chronic hepatitis B in the world. Every year about 1 million people died due to liver cirrhosis, liver cancer caused by Hepatitis B virus. HBV and HCV are high prevalent in Mongolia,, around one fourth Mongolian has HCV or HBV . According to the study, 39.4% of people who had HBV infection got HBV vaccination which leads to viral problem in Mongolian health care system. Since 1991 all newborns have been vaccinated with HBV vaccine. And people who born before that year did not take the HBV vaccination. To determine the generation of persistent immunity from HBV vaccination or after HBV infection. Methods: 492 patients have enrolled who were investigated with quantitative HBsAb using Sysmex HISCL-800 at Happy Veritas Clinic and Diagnostic Center and MNUMS. The vaccination scheme consists of three doses. Vaccination is successful if the antibody titer is higher than 10 mlU/L. Also we have conducted questionnaires about HBV vaccination and risk factor for taking hepatitis infections from patients. Results: In this study 492 patients have participated 313(63%) female and 179 (37%) male, out of which 471(96%) people born before 1991 and remaining 21(4%), people born after 1991. 12 people (57%) who born after 1991 or vaccinated within 24 hours after birth were quantification HBsAb low titer (< 10mlU/L), remaining (43%) were qHBsAb titer ( >10mlU/L), while 297 people (64%) who born before 1991 were qHBsAb titer (<10mlU/L),and remaining 36% of patients had persistent HBV vaccine. The 99 people who born before 1991 have enrolled in HBV vaccination voluntarily while 372 people did not take HBV vaccine at all. Conclusions: Persistent immunity against HBV is generated not only in person who have taken HBV vaccination but also in person who have had slight HBV infection. It was considered that people aged between 50 and 60 years could not get persistent immunity against HBV. We assumed that persistent immunity against HBV depends on age, not other factor and sex.

Liver Fibrosis by Fibroscan in Chronic Hepatitis B Patients during Tenofovir Disoproxil Fumarate in Mongolia

( O. Baatarkhuu ),( S. Ariunaa ),( D. Munkh-orshikh ),( J. Amarsanaa ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Liver fibrosis and its sequel cirrhosis represent a major health care burden, and assessment of fibrosis by biopsy is gradually being replaced by noninvasive methods.In clinical practice, the determination of fibrosis stage is important, since patients with advanced fibrosis have faster progression to cirrhosis and antiviral therapy is indicated in these patients. To assess the performances of liver fibrosis during antiviral treatment by liver stiffness measurement (LSM)using Fibroscan in chronic hepatitis B (CHB) patients. Methods: We followed and evaluated treatment outcome of 56 patients with CHB, initiating their TDF regimen at Happy Veritas Clinic and Diagnostic Center. Each patient underwent transientelastography measurements, HBV quantification and serum liver marker assays before treatment with TDF, orally once daily. Results: The mean age of the patients 45±11. Before treatment LSM results indicated fibrosis stage F0 in 18(32.1%) patients, F1 in 6(10.7%), F2 in 19(33.9%), F3 in 18(16.1%), and F4 in 4(7.1%) patients. After SVR 12, SVR 24 months the mean stiffness score of F1 increased from 7.8 to 8.3kPa. F2 increased from 9.4 to 10.3 kPa, F3 decreased from 13.3 to 12.3kPa, F4 increased from 23.8 to 28.4 kPa. In table 1 shows the changes of liver stiffness by Fibroscan after treatment. There was a significant negative correlation between platelet count and liver stiffness score. Conclusions: In chronic hepatitis B patients who is receiving TDF regimen, annual LSM revealed that significant advanced fibrosis improvement slows but continues during treatment.

Epidemiology and Prognosis of Hepatocellular Carcinoma in Mongolia

( Dashchirev Munkh-orshikh ),( S. Ariunaa ),( J. Chinburen ),( M. Shagdarsuren ),( J. Amarsanaa ),( Oidov Baatarkhuu ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Hepatocellular carcinoma (HCC) is the most common cancer in Mongolia, with an occurrence of 115 cases per 100,000 people. We aimed to investigate the clinical features, therapeutic modalities, overall survival, and prognostic factors for Mongolian patients with HCC. Methods: 195 patients with HCC were consecutively enrolled in our study. Diagnosis of HCC was made according to the EASL guidelines. Results: The mean age (108 males and 87 females) was 61.7 years. A large proportion of patients (n=165, 84.6%) had underlying liver cirrhosis. The most common etiology for HCC was HBV infection (n=67, 34.4%), followed by HCV infection (n=89, 45.6%). The mean tumor diameter was 6.0 ± 2.6 cm. Only 29 (14.9%) patients had a single lesion, while 39 (20.0%) had >3 lesions. Extra hepatic metastasis to the lung (n=23), bone (n=10), and lymph node (n=3) was detected in 36 (18.5%) patients. The mean serum AFP level was 196.0 ng/ml. Most patients had advanced HCC; 88 (45.1%) in stage III and 57 (29.2%) in stage IV. Surgical resection was performed in 27 (13.8%) patients, RFA in 23 (11.8%), and TACE in 107 (54.9%). In 38 (19.5%) patients with distant metastasis or poor liver function, the best supportive care was provided. When all the patients were categorized as ‘treated’ (n=156) and ‘not treated’ (n=39), the 3 year survival was significantly lower in the ‘not treated’ group than in the ‘treated’ group (11% vs 0%, P<0.001). Tumor diameter (<3 cm vs ≥3 cm), extra hepatic metastasis, TNM stage (I/II vs. III/IV), and treatment (or supportive care) were selected as independent predictors for survival. Conclusions: The number of patients diagnosed with an advanced stage of HCC in Mongolia is relatively high, and the survival rate of these patients is lower compared to other countries due to limited treatment modalities.

HCC Screening Program in Mongolia Single Center Data

( O. Baatarkhuu ),( B. Batdelger ),( D. Munkh-orshikh ),( J. Amarsanaa ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: : Incidence of liver cancer in 4th rate of common cancers and 3rd rate of deaths due to cancer incidence in the world. In the Mongolia, cases of liver cancer are 44.1% of all cancer cases and mortalities are 43.3%, which is the first leading cause of mortality among cancer. In Mongolia, 81.2% of the liver cancer was diagnosed at an advanced stages (stage 3 or 4) and the 5-year survival rate (after diagnosed) of 19.5% are associated with lack of high risk population screening. The most common causes of liver cancer are hepatitis B, C and co infections. Screening and diagnosis in early stage of liver cancer in high risk population group Methods: In our study we used single center patient data. These patients are controlled in screening in early stage of liver cancer in Happy Veritas Clinic and Diagnostic Center. In this center, patients are included for HCC screening, when they have liver fibrosis stage higher than F2 (over 7.2kPa) that indicates higher likehood of developing HCC. Fibrosis stage was measured using a Fibroscan (Fibroscan 502 Touch, Echosens, Paris, France). The total number of patients included for screening was 10682 patients such as abdominal ultrasound and to identify serum AFP every 3 months. 181 patients were included in this study, who had complete set of data and are regularly controlled for screening in early stage of liver cancer. Medical history, results of blood test, liver function tests, AFP, liver fibrosis stage and abdominal ultrasound examination results were collected for each patient. Results: 181 patients with an average age of 54±11 (range 23- 89 years old) were included the study. In the result, causes of liver fibrosis were HCV 59.1%(107), hbv 24.9%(45), HBV/HDV 13.3%(24), HCV/HBV 2%(3), HCV/HBV/HDV 0.6%(1) and without hepatitis viruses 0.6%(1). According to the study F2 stage was 64.6%(117), F3 stage 27.1%(49) and F4 stage 8.3%(15). We studied the changes in laboratory tests and depending on the patients fibrosis stage. Increasing fibrosis stage of liver cirrhosis has decreased platelets aalbumin and total protein level (P<0,001). However, we observed ALT level, which increased in F3 stage and decreased fibrosis stage F4. Liver cancer nodule is detected in 4 patients from 181 patients during the follow-up. Those 4 patients had fibrosis stage F4 in Fibroscan analysis and average level of AFP was 86. Conclusions: We conclude that patients in F4 stage in Fibroscan analysis have higher risk of developing liver cancer. Therefore, health care providers need regularly screening and testing in early stage of liver cancer in high risk population.

HBV : Prevalence and Genotype Distribution of Hepatitis B, C and D Viruses among Patients with Chronic Liver Diseases of Mongolia

( Oidov Baatarkhuu ),( N Tuvshinjargal ),( T Alimaa ),( B Tsatsralt Od ),( J Amarsanaa ),( H Okamoto ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background/aims: Mongolia is known for its high endemicity for HBV, HCV, and HDV infections among apparently healthy populations. However there are little or no data on the prevalence and genotype distribution of HBV, HCV and HDV among patients with chronic liver diseases in Mongolia. Materials and methods: Serum samples obtained in 2009 from 207 patients (51.0±1.9 years) including those chronic hepatitis (n=90), liver cirrhosis (n=41), and HCC (n=76) were tested for serological and molecular markers of HBV, HCV, and HDV infections. Results: Of the 207 patients, 144 (69.6%), 106 (51.2%), and 117 (56.5%) tested positive for HBsAg and HBV DNA , HCV RNA, and HDV RNA, respectively. Collectively, 172 patients (83.1%) were viremic for one or more of these viruses, including dual viremia of HBV/HDV (26.6%) or HBV/HCV (7.7%) and triple HBV/HCV/HDV viremia (30.0%). Of note, triple ongoing infection was significantly more frequent among patients with HCC than among those with chronic hepatitis (63.2%) vs. 14.4%, P≤0.0001). The distribution of HBV genotypes among the 116 HBV-viremic patients was: A (0.9%), B (0.9%), C (6.0%), D (88.8%), and C plus D(3.4%). All 117 HDV isolates were classified into genotype 1. The 106 HCV RNA positive samples were typed as genotype 1b (92.5%). Conclusions: The present study revealed that ongoing dual or triple infection of HBV, HCV and HDV is highly prevalent among patients with chronic liver diseases of Mongolia.

Comparative Study of Cirrhosis Stage in Patients with HBV Infection and HBV/HDV Co-Infection in Mongolia

( O. Baatarkhuu ),( Ts. Munkhchuluun ),( B. Batsukh ),( D. Enkh-tuya ),( J. Amarsanaa ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: There are about 350 million people with HBV infection in the world.. 5% or about 15-20 million people of them are co-infected HDV. Every year an average of 7500 people are detected HDV new infection and 1,000 people die due to HDV infection in the United States. The Middle East, Pakistan, Central and Northern Asia, some areas of Africa, have high prevalence of HDV infection. North America, Northern Europe, Southern Africa and East Asia have low prevalence of HDV infection. There is 70-90%higher risk of liver cirrhosis in patients with HBV/HDV co-infection than patients with HBV infection. Comparative study of cirrhosis stage in patients with HBV infection and HBV/HDV co-infection Methods: Our study continued from January 2015 to March 2017 and we measured liver fibrosis stage in patients with HBV infection and HBV/HDV co-infection using a Fibroscan (Fibroscan 502 Touch, Echosens, Paris, France) who are controlled in Happy Veritas Clinic and Diagnostic Center. When we measured liver fibrosis stage in 5504 patients with HBV infection, 20% or 1115 of the patients is determined HDV co-infection . In our study in random sampling cases are selected 354 patients with HBV monoinfection and 177 of all patients have HBV/HDV co-infection. We selected parameters from patients medical histories in our study, such as serologic markers of HBV quantification of HBV and HDV in serum samples, blood test, liver function tests, and liver fibrosis stage. Summary statistics were perfomed using sPSS 22.0 siftware. Results: 354 patients 47.7 %(169) was men. Range with an average age of 44±17 (range 18-75 years old) were included the study. According to the comparative study in laboratory tests, ALT level was HBV - 44 (36; 51.5) and HBV/HDV co-infection 61 (39.8; 97.5), AST level was HBV - 39.1(30; 83) and HBV/ HDV co-infection - 50 (33.1; 77.8), Platelet count was HBV- 193±66 and HBV/HDV - 181±62.8. When we compared liver fibrosis stage were HBV- F0 67(37.9%), HBV/HDV-F0 57(32.2%), HBV-F1 22(12.4%), HBV/HDV-F1 17(9.6%), HBV-F2 39(22%), HBV/HDV- F2 39(22%), HBV-F3 29(16.4%), HBV/HDV-F3 41(23.2%), HBV- F4 20(11.3%) and HBV/HDV -F4 23(13%). In table 1 shows the difference of liver fibrosis by age group. Conclusions: 65.5% of all patients with HBV/HDV co-infection are from 30 to 50 years old. Liver fibrosis of patients with HBV/ HDV co-infection is a higher 11.88kPa than patients with HBV mono-infection. Our study shows that, the hepatitis is more severe in patients with HBV/HDV co-infection and the platelet count is less than HBV infection only.

Role of Fibroscan and APRI Score in Detection of Liver Fibrosis in Patients with Hepatitis B

( O. Baatarkhuu ),( M. Oyun-erdene ),( D. Munkh-orshikh ),( Ts. Gerelchimeg ),( J. Amarsanaa ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The assessment of liver fibrosis is essential for predicting the prognosis and outcome of all forms of chronic liver disease. A liver biopsy is the gold standard for the assessment of liver fibrosis, but it has its limitations which include life-threatening complications. Alternative methods of non-invasive laboratory and radiological testing for the assessment of liver fibrosis in hepatitis have evolved during the past decade and these methods may be able to overcome the limitations of liver biopsy. This study was conducted in order to asses liver fibrosis using Fibroscan and to compare these results to the AST. Platelet ratio index (APRI scores) on HBV patients. Methods: A cross-sectional study was conducted on HBV patients who underwent Fibroscan examinations between March 15, 2015 and February 30, 2017 in Happy Veritas Clinic and Diagnostic Center. Demographic data was collected including sex, age, and nationality, serum alanine aminotransferase levels (ALT 6-24 U/l), serum aspartate aminotransferase levels (13- 33U/L) and platelet counts (180-320-10⁹) wre also determined. The stages of fibrosis (F0 0-7.2; F1 7.2-8.2; F2 8.2-11; F3 11- 18.3 and F4 >18.3) were in kPa. The result of APRI was compared with the Fibroscan fibrosis scores. Results: The results of 228 patients were analyzed including 126(55%) males with a mean age of 42 years (SD:9.9, range :22-67). The males were significantly younger than the females (47 years (SD:10.5 ( range 18-72) (P<0,001). The mean stiffness score was 11:29(SD:8.7)kPa and most patients exhibited no fibrosis (37%) and mid-moderate level (38 %) of fibrosis. Thirty patients(13%) had advanced fibrosis. The mean platelet and serum ALT levels were 1.11 (SD:1.42; range 0.12-3.7). There was a significant positive correlation between the Fibroscan results and the APRI scores (P<0,001). Similarly, there was a significant positive correlation between age and fibrosis score and a significant negative correlation between platelet count and stiffness score. Conclusions: This study has shown that the combination of Fibroscan and APRI methods providers a valuable approach for assessing liver fibrosis in patients with hepatitis. This can eliminate the need for liver biopsy in patients without clear indication.

Cause of Cirrhosis in Mongolia Evaluated by Non-Invasive Methods Including Fibroscan, FIB4 and APRI

( Oidov Baatarkhuu ),( Munkhchuluun Batzaya ),( D. Enkhutya ),( S. Munkhdemberel ),( S. Ariunaa ),( B. Davaakhuu ),( B. Erkhem ),( G. Egelmaral ),( J. Amarsanaa ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Liver cirrhosis is the one of the most deadly diseases in Mongolia and in rest of the world. To determine the main cause of liver cirrhosis through using methods as AST-to-Platelet Ratio Index (APRI), Fibrosis 4 score (FIB4), and Fibroscan. Methods: We collected 2758 patients who had Fibroscan, then divided them in three groups, HBV positive, HCV positive, and virus negative. Depending on the result of the Fibro scan ,we made a cut-off point of 12kPa to separate patients with F4 stage from F0, F1, F2, and F3 patients. To compare the result of the Fibroscan with other techniques we collected other laboratory results including AST, ALT level, thrombocyte number, viral markers, and viral load. Results: Among 2758 subjects 57.7% (1591) of patients were anti-HCV positive, 35.7% (984) of patients were HBV positive and 6.6% (182) of patients were virus negative. Amongst 1590 patients who were anti-HCV positive, 62.4%(992) of patients diagnosed with F4 stage of fibrosis by Fibroscan. On the other hand, 34.7%(551) of patients with HBV positive has developed cirrhosis and 2.9% (47) of patients had cirrhosis without any evidence of virus. We randomly selected 100 patients from both HBV and HCV positive groups to determine the correlation between Fibroscan, FIB4 and APRI. The correlation between Fibroscan and other non-invasive method including APRI and FIB4 was not strong. In our further study, among 2.9% patients with cirrhosis caused by non-viral etiology, 70% were frequent alcohol consumers and only 15%t admitted that they were addicted to alcohol, and rest of the patients developed liver cirrhosis caused by other factors. Conclusions: The most common cause of liver cirrhosis is HCV, followed by HBV in Mongolia.

Efficacy and Safety of Ledipasvir/Sofosbuvir Treatment of HCV Genotype 1b in Mongolia

( O. Baatarkuu ),( B. Enkhtuvshin ),( N. Lkhaasuren ),( B. Batsukh ),( G. Sarangua ),( D. Enkhtuya ),( N. Choijamts ),( J. Amarsanaa ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The incident of liver cancer in Mongolia generally caused by HBV and HCV, and it is 7 times higher than that of world average. HCV, the most prevalent cause of HCC in Mongolia, is number one public health issue. Mongolia is one of the first countries that registered ledipasvir/sofosbuvir (LDV/SOF) regimen from developing countries. By the support of Access program run by Gilead Sciences, USA, we started HCV treatment program from January 2016. Methods: We followed and evaluated treatment outcome of patients with HCV infection using combination of 90 mg ledispavir/400 mg sofosbuvir (manufactured by Gilead Science) in 937 treatment naive and 83 treatment experienced patients. All patients were treated with LDV/SOF for 12 weeks and, their treatment was evaluated by quantitative HCV-RNA assays prior and W (week) 4 and W12 of treatment. Sustained virological response (SVR) after 12 weeks treatment was assessed. Virus genotype analysis using cDNA microarray, liver enzymes, CBC and drug related adverse events were assessed in every patient. The laboratory tests were conducted at National Center of Communicable Diseases and Happy Veritas Laboratories. Results: We conducted largest ever (415/1020) HCV genotype (GT) distribution study in Mongolian chronic HCV patients. 96.6% (n = 401) of assessed patients were GT1b; 0.7% (n = 3) were GT2; 0.2% (n = 1) were GT1a and b; 0.9% (n = 4) were GT1b and 2; 0.5% (n = 2) were GT1b and 6; 0.2% (n = 1) were GT5 and 0.2% (n = 1) were GT1b and 80 k mutants respectively. 992/1020 (97.3%) patients achieved SVR12W, 28 (2.7%) patients who did not achieve SVR12 W were all genotype 1b. Median ALT level significantly dropped during treatment from 95.5 ± 84.1 IU/L to 27.2 ± 18.6 IU/L and slightly increased by the end of treatment 42.9 ± 17.4 IU/L. Total of 39 adverse events were observed in 595/1020 patients (58.3%). Single adverse events were observed in 401/1020 (39.3%) whereas 2 and more events were observed in 194 (19%) patients respectively. Unreported adverse events such as partial facial palsy, AFP (alpha-fetoprotein) increase, melasma were observed. Conclusions: Treatment of HCV in Mongolia using all-oral dual DAA was divided in 3 phases due to shortness of drugs and logistics arrangements. We were able to include only stage-one patients in this study. We achieved 97.3% SVR12W for 3 months treatment with LDV/SOF this time. But viral relapse has to be determined repeatedly at weeks 24 and 48 post treatment. All viral relapses (n = 14) and non-responders (n = 14) were GT1 in our study. According to HCV genotype assessment, there was no difference in treatment outcomes between patients who had different genotypes. HCV RNA clearance during treatment was no different than clinical trials, but the slight increase of ALT by the end of treatment was commonly observed. It might have happened due to rebound of immune reaction after clearance of HCV or a drug induced effect.