Adverse Events of HCV Treatment Using Ledipasvir/ Sofosbuvir Combination

( Baasankhuu Enkhtuvshin ),( Dashchirev Munkh-orshikh ),( Oidov Baatarkhuu ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 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. 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. 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 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.

Peculirity of Cell Immunity and Immunogenetics of Patients with Hepatitis C and Ways for Elimination of Virus and Immunocorrection

( Oidov Baatarkhuu ),( Baasankhuu Enkhtuvshin ),( G. Sarangoo ),( S. Tsogtsaikhan ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Hepatitis C is one of actual health problem of the country. So we have rised the aim to establish peculirity of cell immunity and immunogenetics of patients with hepatitis C and to search ways for elimination of virus and immunocorrection. Methods: There were enrolled total 85 patients (47 males and 38 females) and 64 of them were with chronic and 21 patients with acute hepatitis C. Count of CD3+,CD4+,CD8+ cells (cell/mm3) and CD4/CD8 ratio in 64 patients with chronic hepatitis C were determined by flowcytometry using “BD-FACS count” machine. Lymphocyte blasttransformation reaction with T cell mytogen-phetohemoagglutinin (PHA) were performed in 25 patients with chronic hepatitis C and 15 healthy individuals (rational design sertificate No 1798 from Intellectual Property Autority of Mongolia). For purpose of elimination of virus and immunocorrection aIFN 2b and ribavirin therapy were used in 52 patients with hepatitis C and calculated portion of patients with sustainable viral response (SVR). Results: Count of lymphocytes (BТL2-BТL1) went under blasttransformation by stimulation of PHA was lower (p<0.05) in patients with chronic HC compared to control individuals. There were no side factors excluding PHA (placebo: BТL1=26.11; BТL2=26.00; BТ L2-BTL1=-0.11). It was found lower blastransformation activity (BТL2-BТL1) in patients with CD4+ cell count less than 800 cell/мм3 compared to patients with CD4+ cell count more than 800 cell/мм3 (p<0.05). Number of blasttransformed T cells had direct correlation with count of CD4+T cells (r=0.424) but had indirect correlation with count of CD8+T cells (r= - 0.77). There were more clear manifestation of clilnical signs and elevated serum ALAT level in patients with decreased CD4/CD8 ratio compared to patients with normal ratio. Decrease of CD4/CD8 ratio were caused by increased count of CD8 T cells (CD8 count: 1030±117.3 in patients with clear clinical manifestation and 573.4±98.3 in patients with inclear clinical manifestation, t=3.45, p<0.01). 71.4% of 21 patients (15 males, 6 females, aged 19-44, mean age 27.2±3.4) with acute HC developed SVR after 6 month single IFN therapy. 12 month combined IFN and ribavirin therapy were used in 31 patient patients (15 males, 16 females, mean age 45.4±4.5) with chronic HC. 45.1% of them developed SVR, 42% - PR and 12.9% had not demonstrate no response-NR. Conclusions: There were found disregulation of cell immune response in chronic HCV patients which demonstrated with decreased CD4 count and CD4/CD8 ratio, increased CD8 count and decreaed blasttransformation activity of T cells. Increased CD8+Т cell count was correlated with clear clinical manifestation, low blasttransformation activity of peripheral T cells and elevated level of serum ALAT. Interferon therapy is effective in patients with HC infection for elimi nation of virus and immunocorrection. Sustainable virus response was observed in 71.4% of patients with acute HC and in 45.1% of patients with chronic hepatitis C.

Study on HBV Vaccination Coverage among Healthcare Workers in Mongolia

( Nyamsuren Naranzul ),( Dashchirev Munkh-orshikh ),( Baasankhuu Enkhtuvshin ),( Oidov Baatarkhuu ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: To define HBV vaccination coverage among Mongolian healthcare workers. Introduction: Mongolia has a large burden of viral hepatitis, especially chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, which are associated with cancer and cirrhosis. The occupational risk for transmission of HBV, HCV and HIV among healthcare workers (HCWs) is well recognized. Methods: This is a cross-sectional hospital based survey which will be conducted among healthcare workers to evaluate HBV vaccination coverage and KAP towards to the HBV infection and vaccination. In total, 1200 health care workers were attended to the survey. Results: More than half of survey respondents were had full 3 doses of HBV vaccination. About 4.5% of them had infected with HBV. About 64.0% of them were health workers who are currently working at risk position and most of them had contact with blood, blood products and other body fluids, as well as the risk of needle-stick injuries. 40.0% of respondents who had full doses of HBV vaccination and 56.9% of them had immune due to natural infection. Whereas, 16.7% of respondents who did not received full doses of HBV vaccination were had immune due to natural infection. In general, 1 of 2 respondents had immune due to natural infection. Conclusions: The HBV vaccination coverage among health workers are relatively sufficient. However, already infected percentages of among health workers are high in Mongolia.

Functional Abnormalities of the Liver in Diabetic Patients with and without Viral Hepatitis C in Mongolia

( Altantuya Idkhuu ),( Dashchirev Munkh-orshikh ),( Baasankhuu Enkhtuvshin ),( Uranbaigali Enkhbayar ),( Oidov Baatarkhuu ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: We aimed to compare liver function of diabetes mellitus patients with and without viral hepatitis C using the non-alcoholic fatty liver disease fibrosis score, aspartate transaminase to platelet ratio index, Fibrosis-4 Index, Mac-2-binding protein biomarker and ultrasonic liver stiffness measurements. Introduction: Diabetic patients with viral hepatitis have a high risk of liver cirrhosis. M2BPGi biomarker helps to determine the stage of liver fibrosis in those with fatty liver disease and viral hepatitis in Mongolia. Methods: The study was conducted based on convenience sampling of 123 patients from the General hospital outpatient clinic. Slightly more than half of the study participants were male (53%, n=64). Thirty-three of the diabetics with hepatitis (mean age 52.31±9.8 years) and 90 diabetics without hepatitis (mean age 53.26±8.58) agreed to participate. Anthropometric measurements, non-alcoholic fatty liver disease fibrosis score, aspartate transaminase to platelet ratio index, Fibrosis-4 Index, Mac-2-binding protein biomarker, and ultrasonic transient elastography measurements were compared using independent t-tests for continuous variables and Wilcoxon rank sum tests for ordinal variables. Results: The median values of the Fibrosis-4 Index for those with hepatitis C and without were 1.3 vs 0.9(P<.05), Mac-2-binding proteinbiomarker2.0 vs 1.3 (P<.0001), ultrasonic liver stiffness measurements 10.3 vs 6.9 (P<.0001),aspartate transaminase to platelet ratio 0.6 vs 0.3 (P<.001), and Non-alcoholic fatty liver disease fibrosis scores were -0.2 vs -0.9( P<.004), respectively. Conclusions: Diabetic patients with hepatitis had statistically significantly higher Mac-2-binding protein biomarker, NAFLD Fibrosis Scores than patients without hepatitis. However, other fibrosis test results were similar in diabetic patients with hepatitis and without hepatitis C.

HCV Management in Mongolia

( Tsogzolmaa O. ),( Dashichirev Munkh-orshikh ),( Baasankhuu Enkhtuvshin ),( Oidov Baatarkhuu ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: To determine situation and implementation of HCV policy management Introduction: Mongolia has a large burden of viral hepatitis, especially chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, which are associated with cancer and cirrhosis. Therefore, there is need of to assess policy implementation, milestones of diagnostic and treatment development of HCV in our country. Methods: Descriptive study, analyzed policy and strategic documents and statistics issued by government organizations, reviewed treatment result published studies. Results: Since 2014, 19 policy documents were approved and updated national viral hepatitis guideline three times. In 2017 Mongolia established The Whole Liver Program (HPCE)2017-2020. It aims to eliminate HCV in Mongolia by 2020 and to significantly reduce viral hepatitisinduced liver cirrhosis and HCC related mortalities.Within the framework of the program, free general population hepatitis screening,two free-ofcharge HCV viral load testing and no-out-of-pocket-cost HCV treatment campaigns have been initiated nationwide. 959,320 people were screened viral hepatitis, 94,280 people were tested viral load, 19,896 people were treated. Conclusions: The HPCE Program in Mongolia is serving as a model for other countries in their fight against viral hepatitis.

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

( Tsevelmaa Munkhchuluun ),( Dashchirev Munkh-orshikh ),( Baasankhuu Enkhtuvshin ),( Oidov Baatarkhuu ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: 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, and 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 mono infection and 177 of all patients have HBV/HDV co-infection. We selected parameters from patient’s 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. 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.

Prevalence of HBV and HCV in Mongolia

( Munkhchuluun Batzaya ),( Dashchirev Munkh-orshikh ),( Baasankhuu Enkhtuvshin ),( Oidov Baatarkhuu ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Mongolia is the highest prevalent of hepatitis B and C virus infections. Viral hepatitis is still decreasing when observing its movements, but the disease will remain highly prevalent until 2030. Using high-sensitivity test results of CLEIA we aimed to investigate the prevalence of hepatitis B and C virus, and compare levels of AST, ALT and M2BPGI in the Mongolian population in the age between 40-64. Methods: In order to reflect the administrative and geographical features of Mongolia, the sampling was done at three levels: urban, province center, and rural. Immunological test was measured by chemiluminescence enzyme immunoassay (CLEIA). The statistical package for the social sciences (SPSS) version 25 was used for the statistical analyses. Results: The survey covered 3196 people. 71.8 percent of the patients surveyed had a negative in hepatitis test. 10.1 percent had a positive HBsAg test. 17 percent had a positive anti-HCV test. 1.1 percent had both a positive both HBsAg and anti-HCV (<.0001). AST and ALT increased more frequently during co-infection. M2BPGI protein average level in the non-infected group was 1.00 C.O.I, in the HBsAg positive group 1.65 C.O.I, in the anti-HCV positive group 1.83 C.O.I, and in the co-infection group 1.87 C.O.I (<.0001). Conclusions: 10.1 percent of 40-64year-olds in Mongolia were infected with hepatitis B virus, and 17 percent had Hepatitis C virus and 1.1 percent had hepatitis B and C virus co-infections. Serum M2BPGi is increasing in hepatitis C virus infection and in co-infection.

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

( Oidov Baatarkhuu ),( Dashchirev Munkh-orshikh ),( Baasankhuu Enkhtuvshin ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 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.

Acute hepatitis A, B and C but not D is still prevalent in Mongolia: a time trend analysis

( Oidov Baatarkhuu ),( Hye Won Lee ),( Jacob George ),( Dashchirev Munkh-orshikh ),( Baasankhuu Enkhtuvshin ),( Sosorbaram Ariunaa ),( Mohammed Eslam ),( Sang Hoon Ahn ),( Kwang-hyub Han ),( Do Young 대한간학회 2017 Clinical and Molecular Hepatology(대한간학회지) Vol.23 No.2

Background/Aims: Mongolia has one of the highest hepatitis A, C, B and D infection incidences worldwide. We sought to investigate changes in the proportion of acute viral hepatitis types in Mongolia over the last decade. Methods: The cohort comprised 546 consecutive patients clinically diagnosed with acute viral hepatitis from January 2012 to December 2014 in Ulaanbaatar Hospital, Mongolia. A time trend analysis investigating the change in proportion of acute hepatitis A virus, hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis delta virus (HDV) infection among the cohort with respect to a previous published study was undertaken. Results: Acute hepatitis A, B and C was diagnosed in 50.9%, 26.2% and 6.0% of the cohort. Notably, 16.8% of the cohort had a dual infection. The etiologies of acute viral hepatitis were varied by age groups. The most common cause of acute viral hepatitis among 2-19 year olds was hepatitis A, HBV and superinfection with HDV among 20-40 year olds, and HCV among 40-49 year olds. Patients with more than one hepatitis virus infection were significantly older, more likely to be male and had a higher prevalence of all risk factors for disease acquisition. These patients also had more severe liver disease at presentation compared to those with mono-infection. Conclusions: Acute viral hepatitis is still prevalent in Mongolia. Thus, the need for proper infection control is increasing in this country. (Clin Mol Hepatol 2017;23:147-153)