Liver Stiffness Decrease Post Ledipasvir/Sofosbuvir Combination Treatment in Mongolian Patients with Chronic Hepatitis C

( D. Munkh-orshikh ),( D. Enkhtuya ),( N. Choijamts ),( Ch. Gantuul ),( O. Baatarkhuu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The prevalence of liver cancer in Mongolia is 7 times higher than that of world average, generally caused by HBV and HCV. The most prevalent cause of HCC in Mongolia, HCV, accompanied with liver stiffness and cirrhosis, is an emerging 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 298 treatment nai¨ve 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: Out of 298 patients underwent treatment, 138 patients were examined for pre-treatment liver stiffness using Fibroscan. When patients were examined by Fibroscan test, 25% (n = 35) of assessed patients were F0 stage; 13.57% (n = 19) were F1 stage; 10% (n = 14) were F2 stage; 20.71% (n = 29) were F3 stage; and 30.72% (n = 43) were F4 stage. Patients (n = 35) with fibrosis stage F0 were omitted from post-treatment control examinations. The one hundred three patients were selected for further post-treatment fibrosis staging. The twenty three patients were successfully contacted and complied posttreatment Fibroscan scanning. 23/23 (100%) patients achieved SVR12. W, were all genotype 1b. Median ALT level significantly dropped during treatment from 121.19 ± 98.3 IU/L to 33.2 ± 14.7 IU/L and slightly increased by the end of treatment 41.4 ± 18.8 IU/L. The ninety one percent of the patients had improved in liver stiffness while remaining patients were observed increased stiffness. Conclusions: After treatment, 30.43% (n = 7) of patients moved to the F0 stage from liver stiffness. There are many studies that assess liver fibrosis after cure of HCV, but varying numbers were observed. We assess liver stiffness after treatment of HCV in Mongolian population for the first time. Though study population was small, we had 91% of.

Epidemiology and Prevalence of Hepatitis B and C Virus Infections among Nurses in Mongolia

( D. Batbold ),( Z. Bolortuya ),( D. Munkh-orshikh ),( S. Badamjav ),( O. Chimedsuren ),( O. Baatarkhuu ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: M.Colombo, W.Lange studies showed that 30-40% of people become chronic after suffering from-Hepatitis B and C virus, about 50% chronic cases transformed into primary liver cancer. There are a few studies in our country were conducted on hepatitis among health care professionals, particular nursing personnel. The study was conducted to identify of hepatitis B and C virus among nurses and make recommendations to prevent and control of hepatitis B and C virus infections. Methods: We carried out cross-sectional study among selected nurses to determine surface antigen of hepatitis B virus and antibodies to hepatitis C virus. For identification of these antibody and antigen and validation of results ELISA tests from CTK, Biotech company (USA) and simplifying diagnostics were used. Results: There were 598 nurses from the First Central hospital, the Second Central hospital, the Third central hospital, Railway Central hospital, Hospital Ministry of Justice and Internal Affairs and National Center of Maternal and Child Health who participated in the study. From 5 hospitals 598 nurses surveyed and revealed the hepatitis B virus surface antigen positive 18.9%, hepatitis C virus antibodies in 23.1%, co-infection of hepatitis B and C were detected 1.2%. There is an urgent need to provide knowledge to medical personnel regarding standards during the procedures, concerning hepatitis infections monitoring and improve technology used during procedures. Conclusions: The study identified that 43.2% of nurses surveyed on hepatitis B and C viruses were detected . It shows a high prevalence among the nurses in Mongolia.

Epidemiology and Genotype Distribution of HCV in Mongolia

( Sosorbaram Ariunaa ),( D. Munkh-orshikh ),( Ch. Bolormaa ),( B. Gansaikhan ),( Oidov Baatarkhuu ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Mongolia is a unique country with high endemicity for three blood borne hepatitis viruses, namely HBV, HCV and HDV. The number of patients with acute hepatitis decreased considerably with an estimated annual number of cases 13,000/ year in 1991 to 1700/year in 2013 in Mongolia.Hepatitis B and C virus infection are one of the major causes of liver cirrhosis and HCC in Mongolia. However, viral hepatitis C is still one of the serious public health concerns in Mongolia. To investigate of HCV infection among apparently healthy populations in Mongolia. Methods: The study population was consisted of 1512 subjects from 13 provinces and Ulaanbaatar city which is the capital city of Mongolia, and the age ranged from 0 to 80 years. Results: According to our study results, the prevalence of anti-HCV was 15.6%, and the HCV RNA was detected in 11 %; therefore, we can say that the prevalence of this infection is very high in Mongolia.The prevalence of anti-HCV and HCV RNA had a tendency to increase with age. The prevalence of anti-HCV and HCV RNA in population aged over 61 years was significantly higher than those aged 31 to 40 year. The history of dental care, surgery, and tattooing was significantly more frequent in anti-HCV positive subjects compared with anti-HCV negative subjects. Interestingly, the most of HCV infection is caused by genotype 1. However, Genotype 2 of HCV is very rare, less than 2 percent in Mongolia. The extreme predominance of HCV genotype 1b in the Mongolian population may be explained by the greater ethnic and genetic homogeneity of current Mongolian population. Conclusions: The epidemiological situation of HCV infection in Mongolia is catastrophic. This infection was evenly distributed in all areas and has endemic characteristics for the country. The rate of positive anti-HCV and HCV-RNA was increasing age-dependently. The predominant genotype of HCV in Mongolia is 1b.

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.

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.

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.

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.

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.

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.

Current Status New Direct Acting Anti-Viral Treatment of Hepatitis C in Mongolia

( O. Baatarkhuu ),( Z. Bat-erdene ),( D. Munkh-orshikh ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 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 program 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 shortterm treatment for HCV and free the population of that disease which may increase the mortality level due to liver cancer.