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.

Ledipasvir and Sofosbuvir Fixed-Dose Combination without Ribavirin for 12 Weeks in Treatment-Naive Mongolian Patients with Hepatitis C: A Multi-Center Study

( O. Baatarkhuu ),( B. Davaakhuu ),( N. Naranzul ),( Ch. Gantuul ),( Ch. Bolormaa ),( P. Delgermaa ),( S. Ariunaa ),( G. Sarangua ),( G. Khishigjargal ),( D. Javzmaa ),( D. Ouyntuya ),( S. Nyamaa ),( 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: In Mongolia, previous studies shown HCV prevalence is over 10% and 97-98% of people with HCV infection have infected with genotype 1b. In addition, Mongolia is on first place of HCC mortality rate per 100.000 population and this is eighth times higher than globally average rate. HCV prevalence among primary hepatic carcinoma patients is 35%-45%. Therefore activities on reducing chronic infection prevalence of hepatitis viruses and preventing complications of hepatitis viral infections have been conducted in the country. One of them is availability of Harvoni treatment for HCV patients since December 2015. To evaluate data on the antiviral efficacy and safety of direct acting antiviral (DAA) treatment with respect to sustained virological response (SVR) 12 weeks after completion of treatment. Methods: We retrospectively analyzed patient monitoring records and patient registration forms for HCV patients who received Harvoni treatment at NCCD, MNUMS, provinces and districts hospitals. Quantitative methods were applied in that retrospective study. Six hundred and forty-seven patients diagnosed as HCV and treated by Harvoni(ledipasvir/sofosbuvir) were attended the study. Results: There were totally 647 patients received Harvoni for HCV infection by September 2016. People who received treatment for less than 3 months there 31% and for longer than 3 months were 8%. Among them 91.9% have chronic hepatitis and first stage of liver cirrhosis and 8% have liver cirrhosis and carcinoma. After 1 month of treatment, HCV RNA tests result was negative for 98.8% of all Harvoni patients and for the rest 1.1% resulted in decrease of HCV RNA.After 3 month of trerapy, blood test result showed 100% recovery on transaminase level. 453/465, 10/465 and 2/465 of them were respectively genotype 1b, 2 and 1a. APRI score were pre-treatment 1.3±0.58 and post treatment 0.443±0.148. FIB4 score were pre-treatment 3.8±1.2 and post treatment 1.65±0.59. Occurrences of side effects were mild. 1.2%, 5.8% and 4.6% of them were respectively with CTP C, CTP B and CTP A scores. 88.2% of the participants were chronic hepatitis C and 1.7% of them were pre-treated by interferon. Conclusions: After treatment by Harvoni tablets, excellent SVR12 results were shown among the study participants’ and the favorable side-effect profile were observed for the Mongolian context.

Results of Lutasan Treatment in Mongolia

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

Aims: Chronic liver diseases are very common among the Mongolians. Study suggests that alcohol induced pathologies composed of cirrhosis 39%, fatty liver disease 27%, and 11% chronic hepatitis respectively. “Lutasan” (reduced glutathione) injection is known as hepatoprotector, antioxidant, immune modulator and detoxifying functions. As chronic disease progresses, glutathione insufficiency leads to poor cognitive outcomes and tremor in upper limbs. Therefore, we aimed to study treatment efficacy of “Lutasan” injection for chronic liver diseases and the complications. Methods: Total of ten subjects were recruited randomly from GI Department of Third General Hospital. Liver functions were evaluated by serum total bilirubin, total protein, albumin, AST, ALT, GGT, and alkaline phosphatase measures and hepatic neurocognitive deterioration was evaluated by Reitan neurophysiological test. Results: 10% of the patients were alcohol induced, and 60% had combination of viral and alcoholic reasons, and remaining 20% had biliary tract disorders. Compare to the first day’s results, on the 10th day of hospitalization, serum indicators were much improved within the treatment period (^*-P<0.05) including AST 3.02 times, ALT 2.21 times, ALP 2.56 times and GGT 1.78 times were decreased respectively (Table 1). Also neuro-cognitive improvements were significantly observed, by 1.74 times on Reitan neurophysiological test when comparing before and after treatment scores, 58.6±4.61 and 33.7±1.34, respectively. Conclusions: These findings suggest that Lutasan, a glutathione supplement has effects of minimizing hepatic cytolysis, cholestasis in the biliary tract, reducing destruction of hepatocytes, and aiding regeneration of liver cells. Moreover, it reduces symptoms of hepatic neurocognitive disorders significantly.

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.

Disease Burden of Chronic Hepatitis C Virus Infection in Mongolia: Potential Impact of Attaining World Health Organization (WHO) 2030 Goals

( O. Baatarkhuu ),( M. Batzaya ),( S. Brandon ),( C. Estes ),( B. Chiang ),( J. Amaarsanaa ),( H. Razavi ),( P. Nymadawa ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Mongolia has a large burden of viral hepatitis with the highest rates of liver cancer incidence and mortality In the world. An estimated 95% of liver cancer patients in Mongolia are infected with HCV and/or HBV. While HCV prevalence is likely declining, the burden of advanced liver disease will continue at a high level. Direct acting antivirals (DAAs) achieve higher sustained viral response rate (SVR) than interferon-based treatment regimens. In 2015, over 10,000 patients were treated in Mongolia with DAA regimens, an important first step on the path toward HCV elimination. Implementation of new treatments requires epidemiological data and modeling to assess the potential impact of improved treatment strategies. Use a modeling approach to describe HCV-related disease progression at the national level in Mongolia through 2030. Consider the impact of two scenarios on disease burden: Base Scenario and WHO Targets 2030 Scenario. Methods: Disease progression used age-and gender-defined cohorts to track HCV incidence, prevalence, morbidity and mortality. Data for prevalence, incidence, diagnosis, liver transplants and mortality risk factors were derived from Mongolian data sources when available, and expert consensus. A starting prevalence of 200,000 chronic cases in 2013 was used and was consistent with adult prevalence estimates collected in prevalence surveys from 2005 and 2013, after adjustment for prevalence in younger age groups. Two scenarios were considered with one based on the status quo and another designed to achieve WHO 2030 goals. Base Scenario: Treat 10,300 =F2 patients in 2016, gradually declining to 1200 treated patients by 2030. Assume 3230 new infections and 1300 newly diagnosed annually. WHO Targets 2030 Scenario: Achieve 2030 WHO Global Health Sector Strategy on viral hepatitis including a diagnosis rate of 90%, 65% decrease in liver-related mortality and a 90% decrease in new infections by 2030. Achieved in Mongolia by increasing treatment to 10,000-15,000 =F0 cases annually, diagnosing up to 10,000 cases annually, and gradually reducing new infections to 300 annually by 2025 (90% reduction) (Figure 1). The incidence and prevalence of HCV-related morbidity and mortality through 2030 were projected. Results of the WHO Targets 2030 scenario were compared to the Base scenario. Results: Base Scenario Viremic infections decline to 141,000 in 2030 as compared to 188,000 in 2016 (25% decrease), largely due to mortality (Figure 2). By 2030 incident decompensated cirrhosis cases will decrease by 17% from 630 cases in 2016 to 520 cases in 2030. The number of incident HCC cases was projected at 650 in 2030, a decrease of 18% as compared to 2016 (800 cases). By 2030, annual HCV-related liver deaths will decrease by 28% as compared to 2016, from 1280 deaths to 920 deaths (Figure 2). There will be 13900 cumulative liver deaths during 2016-2030 (Figure 3). WHO Targets 2030 Scenario Chronic infections decline 87% during 2016-2030 from 188,000 cases to 24,100 cases. As compared to the Base Scenario, cases decline by 83% in 2030. Incident HCC cases in 2030 were estimated at 170 respectively (74% decrease from Base Scenario. Incident liver deaths in 2030 were estimated at 330 (64% decrease from Base Scenario). During 2016-2030, there are a cumulative total of over 2800 fewer HCV-related deaths as compared to the Base Scenario. Conclusions: HCV disease is a substantial health burden in Mongolia, especially HCC and related deaths. Even under the Base Scenario, total viremic prevalence will decline by 2030, due to fewer new infections and mortality among an aging population. Scenario results emphasize the importance of in-creasing awareness, diagnosis and treatment of HCV, along with preventing new infections. Mongolia achieves WHO tar-gets for HCV hepatitis elimination by 2030 under the WHO Tar-gets 2030 Scenario, when including disease reduction achieved prior to 2016. The projected impact of the scenarios will facili-tate disease forecasting, resource planning, and rational strate-gies for HCV management in Mongolia.

Adverse Events of HCV Treatment Using Ledipasvir/Sofosbuvir Combination

( O. Baatarkhuu ),( O. Tsevelmaa ),( Ch. Nagir ),( D. Munkh-orshikh ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The incidence of liver cancer in Mongolia generally caused by HBV and HCV. It is 7 times higher that that world’s average in recent studies. 27% of the population has been diagnose and it is very one of four people has the virus and most prevalent cause of HCC and causing number one public health issue. Mongolia is one of the first countries that registered LED/SOF regimen from developing countries. The HCV treatment program in Mongolia has started on January of 2016. Methods: We followed and evaluated treatment outcomes of the patients with HCV infection using Harvoni (manufactured by Gilead Science). We started our prospective analysis on August until December 2016. For 3 months on 1230 patients. All patients were treated with SOF/LDV for 12 weeks and their treatment was evaluated by quantitative HCV RNA assays prior and week 4 and week 12 of treatment . Sustained Virological Response (SVR) after 12 weeks of treatment was assessed . Virus genotype analysis using cDNA microarray liver enzymes. CBC and drug related adverse events were assessed in every patient. All the tests were conducted at Happy Veritas laboratories in Ulaanbaatar, Mongolia. Results: Total of 40 adverse events were observed in 527/1230 patients (43%) . Single adverse events were observed in 358/527(68%), whereas 2 events were observed in 116/527(22%) and 3 or more events were observed 52/537(10%) on patients respectively. Age wise35 or lower aged patients were 43/153 (28%), age of 36 to 55, 295/655(45%) and age of 56 of more, 190/422(45%) were adverse events were observed. Our result by gender wise, out of 406/781(52%) on female patients, on male patients 121/449(27%) were observed adverse events. 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 have achieved 95.5% SVR 12 week for 3 months treatment with SOF/LDV this time. Despite the identical adverse events were found in other Asian and other regions in the world during treatment, unrecorded adverse events were observed such as the facial paralysis, paraproctitis, AFP and facial skin darkening in Mongolia.

The Development of DAA Treatment for HCV in Mongolia

( O. Baatarkhuu ),( Sosorbaram Ariunaa ),( N. Naranzul ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: During last several years, internationally available diagnostics, treatments and medicines of HCV have changed dramatically. Interferon-based therapy for HCV has comparatively low result of treatment effect, more side effects, long treatment duration, high cost of single dose and limited option of treatment. Since introduction of direct antiviral agents including in 2011 Boceprevir, Telaprevir, in 2013 Simeprevir, Sofosbuvir, in 2014 Harvoni (ledipasvir/sofosbuvir), Daklinza (daclatasvir), Vikera Pack (ombitasvir/paritaprevir/dasabuvir), the new era HCV treatment came up. thanks to those new drugs HCV infection became one of the curable diseases, and entire world is targeting free from HCV /WHO/. Therefore, there is need of to access milestones of diagnostic and treatment development of HCV in our country. Our study aims to determine implementation of global trend for HCV diagnostic and treatment in Mongolia. Methods: This study is qualitative one and we analyzed policy and strategic documents and statistics issued by Mongolian Government, Ministry of Health, National Center for Communicable Disease, Mongolian National University of Medical Sciences and other organizations. Results: Ministry of Health played very large role in introduction of new management of HCV into the country. It provided all the legal ground and support to service providers at all levels of care. New guideline was approved which includes all new schemes of the treatment, diagnostic methods, new drugs were registered, specialist doctors were trained and access of the new drug were widened thanks to joining the Access programme from Gilead Sciences. It can be said that the tentative result of DAA treatment is successful, compare few years ago interferon treatment effect was fewer than 20 percent to the 99 percent effective of current new treatment. Conclusions: All those achievements show that Mongolia has been able to introduce a comprehensive and efficient short-term treatment for HCV and free the population of that disease which may increase the mortality level due to liver cancer.

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.

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.

HBV : PE-028 ; Prevalence of hepatitis A, B, C and D viruses among patients with acute hepatitis in Mongolia

( O Baatarkhuu ),( Do Young Kim ),( B Bayarmagnai ),( N Khorolsuren ),( B Baigal ),( R Ouyngerel ),( D Enkhsaikhan ),( Y Dahgwahdorj ),( Sang Hoon Ahn ),( Kwang Hyub Han ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1

Background and Aims: Mongolia is an endemic area of acute and chronic viral hepatitis. To determine the prevalence of HAV, HBV, HCV and HDV infections among patients with acute hepatitis in Mongolia during outbreaks. Methods: A total of 624 patients (353 males and 271 females; age, 18.6±8.1 years; range 2-66 years) who were clinically diagnosed with acute hepatitis during outbreak from October 2011 to March 2012 in Ulaanbaatar, Mongolia have been studied. The prevalence of hepatitis virus infections was determined by testing of serum for the IgM class of antibodies against HAV, HBV, HCV, HDV, and HBsAg. Results: Acute hepatitis A (AHA) (IgM anti-HAV positive) was diagnosed in 284 patients (45.5%). Acute hepatitis B (AHB) (IgM anti-HBc positive) was diagnosed in 191 patients (30.6%) and 22 patients (3.5%) was diagnosed as co-infection of B and D. Acute hepatitis C (AHC) (IgM anti-HCV positive) was diagnosed in 33 patients (5.3%). There were 52 (8.3%) HBV carriers who had detectable HBsAg and anti-HDV but who were negative for both IgM anti-HAV and IgM anti-HBc, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. Forty-two (6.5%) patients were found to be infected by various combinations of dual viruses such as HAV/HBV (2.8%), HAV/HDV (0.6%), HBV/HCV (2.5%), and HCV/HDV (0.6%). AHA was the most prevalent in subjects aged 1-19 years, AHB and HBV+HDV superinfection were the first and second most prevalent in the age group of 20-29 years, and AHC was the most common type in 40-49 years. Conclusion: Dual hepatitis viral infection was detected in approximately 6.5% among patients with acute hepatitis in Mongolia.