The complete chloroplast genome sequences of eight Orostachys species: Comparative analysis and assessment of phylogenetic relationships.

We analyzed the complete chloroplast genomes of eight Orostachys species and compared the sequences to those of published chloroplast genomes of the congeneric and closely related genera, Meterostachys and Hylotelephium. The total chloroplast genome length of thirteen species, including the eight species analyzed in this study and the five species analyzed in previous studies, ranged from 149,860 (M. sikokianus) to 151,707 bp (H. verticillatum). The overall GC contents of the genomes were almost identical (37.6 to 37.8%). The thirteen chloroplast genomes each contained 113 unique genes comprising 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. Among the annotated genes, sixteen genes contained one or two introns. Although the genome structures of all Orostachys and Hylotelephium species were identical, Meterostachys differed in structure due to a relatively large gene block (trnS-GCU-trnS-GGA) inversion. The nucleotide diversity among the subsect. Orostachys chloroplast genomes was extremely low in all regions, and among the subsect. Appendiculatae, genus Orostachys, and all thirteen chloroplast genomes showed high values of Pi (>0.03) in one, five, or three regions. The phylogenetic analysis showed that Orostachys formed polyphyly, and subsect. Orostachys and Appendiculatae were clustered with Hylotelephium and Meterostachys, respectively, supporting the conclusion that each subsection should be considered as an independent genus. Furthermore, the data supported the taxonomic position of O. margaritifolia and O. iwarenge f. magnus, which were treated as synonyms for O. iwarenge in a previous study, as independent taxa. Our results suggested that O. ramosa and O. japonica f. polycephala were individual variations of O. malacophylla and O. japonica, respectively. The exact taxonomic position of O. latielliptica and the phylogenetic relationship among the three species, O. chongsunensis, O. malacophylla and O. ramosa, should be a topic of future study.

A cost-effectiveness study of universal screening for hepatitis C virus infection in South Korea: A societal perspective.

BACKGROUND/AIMS: This study aimed to evaluate the cost-effectiveness of hepatitis C virus (HCV) screening compared to no screening in the Korean population from societal and healthcare system perspectives. METHODS: A published decision-tree plus Markov model was used to compare the expected costs and quality-adjusted life years (QALY) between one-time universal HCV screening and no screening in the population aged 40-65 years using the National Health Examination (NHE) program. Input parameters were obtained from analyses of the National Health Insurance claims data, Korean HCV cohort data, or from the literature review. The population aged 40-65 years was simulated in a model spanning a lifetime from both the healthcare system and societal perspectives, which included the cost of productivity loss due to HCV-related deaths. The incremental cost-effectiveness ratio (ICER) between universal screening and no screening was estimated. RESULTS: The HCV screening strategy had an ICER of $2,666/QALY and $431/QALY from the healthcare system and societal perspectives, respectively. Both ICERs were far less than the willingness-to-pay threshold of $25,000/QALY, showing that universal screening was highly cost-effective compared to no screening. In various sensitivity analyses, the most influential parameters on cost-effectiveness were the antibodies to HCV (anti-HCV) prevalence, screening costs, and treatment acceptance; however, all ICERs were consistently less than the threshold. If the anti-HCV prevalence was over 0.18%, screening could be cost-effective. CONCLUSION: One-time universal HCV screening in the Korean population aged 40-65 years using NHE program would be highly cost-effective from both healthcare system and societal perspectives.

Costs of viral hepatitis B in the Republic of Korea, 2002-2015.

The Republic of Korea has a high prevalence of hepatitis B virus (HBV) infection, and the policies concerning costly antiviral medication have been revised recently. However, in the past 10 years, no related research on costs has been conducted. The objective of this study was to estimate the economic burden of viral hepatitis B and determine the trend of changes in its costs between 2002 and 2015. Claims data from the National Health Insurance Service were used. To identify viral hepatitis B cases, the ICD-10th code B16, B17.0, B18.0 and B18.1 were used based on a primary diagnosis. This study was conducted from a societal perspective regarding both direct and indirect costs. Annual costs were adjusted for inflation by calculations based on the 2015 costs. The number of patients with viral hepatitis B increased from 213 758 in 2002 to 342 672 in 2015. The total socio-economic costs increased from 127.1 million USD in 2002 to 459.1 million USD in 2015, mainly due to the increase in pharmaceutical costs, which accounted for the largest proportion of total costs since 2009-220.5 million USD in 2015, which was ~15 times higher than that in 2002. The healthcare costs for viral hepatitis B accounted for 0.13% of the national health expenditure in 2002, increasing to 0.31% in 2015. The economic burden of viral hepatitis B has increased in the Republic of Korea. It is therefore essential to reduce the healthcare costs of HBV infection by establishing an effective management policy.

Cost-effectiveness and health-related outcomes of screening for hepatitis C in Korean population.

BACKGROUND/AIM: In the era of direct-acting antivirals (DAA), active screening for hidden hepatitis C virus (HCV) infection is important for HCV elimination. This study estimated the cost-effectiveness and health-related outcomes of HCV screening and DAA treatment of a targeted population in Korea, where anti-HCV prevalence was 0.6% in 2015. METHODS: A Markov model simulating the natural history of HCV infection was used to examine the cost-effectiveness of two strategies: no screening vs screening and DAA treatment. Screening was performed by integration of the anti-HCV test into the National Health Examination Program. From a healthcare system's perspective, the cost-utility and the impact on HCV-related health events of one-time anti-HCV screening and DAA treatment in Korean population aged 40-65 years was analysed with a lifetime horizon. RESULTS: The HCV screening and DAA treatment strategy increased quality-adjusted life years (QALY) by 0.0015 at a cost of $11.27 resulting in an incremental cost-effectiveness ratio (ICER) of $7435 per QALY gained compared with no screening. The probability of the screening strategy to be cost-effective was 98.8% at a willingness-to-pay of $27 205. Deterministic sensitivity analyses revealed the ICERs were from $4602 to $12 588 and sensitive to screening costs, discount rates and treatment acceptability. Moreover, it can prevent 32 HCV-related deaths, 19 hepatocellular carcinomas and 15 decompensated cirrhosis per 100 000 screened persons. CONCLUSIONS: A one-time HCV screening and DAA treatment of a Korean population aged 40-65 years would be highly cost-effective, and significantly reduce the HCV-related morbidity and mortality compared with no screening.

Cost-effectiveness of sofosbuvir plus ribavirin therapy for hepatitis C virus genotype 2 infection in South Korea.

BACKGROUND AND AIM: For genotype 2 chronic hepatitis C (CHC), the efficacy and safety of sofosbuvir plus ribavirin therapy (SOF + RBV) was better than pegylated interferon plus ribavirin therapy (PR) at a greater drug cost. This study investigated the cost-effectiveness of SOF + RBV compared with PR for treatment-naïve genotype 2 CHC in South Korea. METHODS: Using a decision analytic Markov model, a cost-effectiveness analysis comparing SOF + RBV with PR or no treatment for treatment-naïve genotype 2 CHC was performed with probabilistic and deterministic sensitivity analyses from the payer's perspective in 2017. Three cohorts of patients aged 40-49, 50-59, and 60-69 years were simulated to progress through the fibrosis stages F0-F4 to end-stage liver disease, hepatocellular carcinoma, or death. Published and calculated data on the clinical efficacy of the regimen, health-related quality of life, costs, and transition probabilities were used. RESULTS: While the incremental cost-effectiveness ratio for PR was dominant over no treatment, the incremental cost-effectiveness ratios for SOF + RBV were $20 058 for the patients in their 40s, $19 662 for those in their 50s, and $22 278 for those in their 60s compared with PR. Probabilistic sensitivity analysis indicated an 89.0% probability for the SOF + RBV to be cost-effective at a willingness to pay of $29 754.4 (per-capita gross domestic product in 2017) for the patients in their 40s and 94.1% and 89.1% for the patients in their 50s and 60s, respectively. CONCLUSIONS: The SOF + RBV is a cost-effective option for genotype 2 treatment-naïve CHC patients, especially for the patients with liver cirrhosis in Korea.

Population-based prevalence, incidence, and disease burden of autoimmune hepatitis in South Korea.

BACKGROUND AND AIM: Little is known about population-based epidemiology and disease burden of autoimmune hepatitis (AIH). The aim of this study was to investigate the prevalence, incidence, comorbidity and direct medical cost of AIH in South Korea. METHODS: The data was from the nationwide, population-based National Health Insurance Service claims database and the Rare Intractable Disease registration program. Age and gender-specific prevalence rates were calculated, and data on comorbidity, diagnostic tests, prescribed drugs, and medical costs were retrieved for patients registered under the disease code K75.4 (AIH) from 2009 to 2013. RESULTS: A total of 4,085 patients with AIH were identified between 2009 and 2013 with a female-to-male ratio of 6.4. The age-adjusted prevalence rate was 4.82/100,000 persons and gender adjusted prevalence rates were 8.35 in females and 1.30 in males. The age-adjusted calculated incidence rate was 1.07/100,000 persons (gender-adjusted 1.83 in females and 0.31 in males). Ascites, variceal bleeding, and hepatocellular carcinoma were found in 1.4%, 1.3%, and 2.2% of the patients, respectively. Forty-six patients (1.1%) underwent liver transplantation during the study period. Case-fatality was 2.18%. Corticosteroid and azathioprine were prescribed in 44.1% and 38.0% of prevalent patients with AIH in 2013, respectively. The nationwide total direct medical cost was less than 4.0 million USD, and the average cost for each patient was 1,174 USD in 2013. CONCLUSION: This is the first report on the nationwide epidemiology of AIH in Korea, and it showed a lower prevalence than that of Western countries with considerable disease burden.

Healthcare Costs for Chronic Hepatitis C in South Korea from 2009 to 2013: An Analysis of the National Health Insurance Claims' Data.

BACKGROUND/AIMS: The introduction of direct-acting antivirals (DAA) in 2013 revolutionized hepatitis C virus (HCV) treatment, offering a cure rate >90%. However, this therapy is expensive, and estimations of the number of chronic HCV-infected (CHC) patients and their treatment costs pre-2013 are therefore essential for creating policies and expanding drug access. Herein, we aimed to investigate the number of HCV-related liver disease patients, their healthcare utilization, their annual direct medical costs, and the interferon-based antiviral treatment rates and costs from 2009 to 2013 in South Korea. METHODS: The National Health Insurance database was reviewed, and patients diagnosed with CHC from 2009 to 2013 were extracted. Data regarding detailed healthcare utilization, prescribed drugs, and direct medical costs were obtained. For annual direct healthcare cost calculations, a prevalence-based approach was used. RESULTS: Overall, 181,768 CHC patients were identified. In 2013, the annual per-patient costs for chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and the first year post-liver transplant were 895, 1,873, 6,945, and 67,359 United States dollars, respectively. Interferon-based antiviral therapeutics were prescribed to 25,223 patients (13.9%). CONCLUSIONS: Healthcare costs have increased remarkably with increasing liver disease severity. Thus, efforts to stop disease progression are needed. Moreover, the low rate of interferon-based therapy indicates an unmet need for DAA.

The Usefulness of Argon Plasma Coagulation Compared with Endoscopic Submucosal Dissection to Treat Gastric Adenoma.

BACKGROUND/AIMS: To date, the best therapeutic modality for gastric adenoma, especially low-grade adenoma, has not been established. The aim of this study was to assess the usefulness of argon plasma coagulation (APC) in treating gastric adenoma compared with endoscopic submucosal dissection (ESD). METHODS: We included 210 patients with gastric adenoma, who underwent treatment with either APC (97 patients) or ESD (113 patients). The clinical and pathologic characteristics, mean duration of hospital stay, complications, and recurrence rates between the two groups were compared. RESULTS: The mean adenoma size was 0.9 cm and 1.1 cm in the APC group and ESD group, respectively (p<0.001). The mean duration of hospital stay was significantly shorter in the APC group than in the ESD group (1.6 days vs. 5.8 days, p<0.001). Complications did not occur in the APC group. However, one case of perforation (0.9%) and 6 cases of bleeding (5.3%) occurred in the ESD group. The recurrence rates were 15.3% (15/97 patients) in the APC group and 3.5% (4/113 patients) in the ESD group (p=0.003). The proportion of hospitalization was less in the APC group (43.3%, 42/97) than in the ESD group (100.0%, 113/113) (p<0.001). Medical expense was less in the APC group (377,172 won) than in the ESD group (1,430,610 won) (p<0.001). CONCLUSIONS: The findings of this study suggest that APC is a safe treatment method for gastric adenoma without serious complications. However, regular endoscopic follow-up is necessary to detect any residual or recurrent lesions due to the relatively high rate of local recurrence after APC.

Final Report of Unmet Needs of Interferon-Based Therapy for Chronic Hepatitis C in Korea: Basis for Moving into the Direct-Acting Antiviral Era.

BACKGROUND/AIMS: To evaluate the era of direct acting antivirals (DAAs), we must understand the treatment patterns and outcomes of interferon-based therapy for hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate, factors affecting treatment decisions, and efficacy of interferon- based therapy in a real-world setting. METHODS: This nationwide cohort study included 1,191 newly diagnosed patients with chronic HCV infection at seven tertiary hospitals in South Korea. Subjects were followed retrospectively until March 2015, which was just before the approval of DAA therapy. RESULTS: In total, 48.2% and 49.3% of the patients had HCV genotypes 1 and 2, respectively. Interferon-based therapy was initiated in 541 patients (45.4%). The major reasons for no treatment included ineligibility (18.9%), concern about adverse events (22.3%), cost (21.5%), and an age >75 years (19.5%). Interferon-based therapy was discontinued (18.5%) mainly due to adverse events (n=66). The intent-to-treat analysis found that the sustained virologic response (SVR) rate was 58.3% in genotype 1 patients and 74.7% in nongenotype 1 patients. CONCLUSIONS: Approximately one-third of newly diagnosed HCV patients in South Korea received interferon-based therapy and showed a suboptimal SVR rate. Diagnosis of patients at younger ages and with a less advanced liver status and reducing the DAA therapy cost may fulfill unmet needs.

Incidence, prevalence and complications of Budd-Chiari syndrome in South Korea: a nationwide, population-based study.

BACKGROUND & AIMS: The population-based epidemiology of Budd-Chiari syndrome (BCS), a rare disease of hepatic venous outflow obstruction, is largely unknown. This study aimed to elucidate the nationwide population-based incidence, prevalence, complications, case fatalities and direct medical cost of BCS in South Korea from 2009 to 2013. METHODS: Using two large data sources, the Health Insurance Review and Assessment Service Claims database and Rare Intractable Disease registration program database in Korea, we identified all patients with BCS who were registered under International Classification of Diseases 10 (code I82.0). The age- and sex-adjusted incidence and prevalence of BCS were calculated with analysis of complications and direct medical costs. RESULTS: A total of 424 patients with BCS were identified in 2009-2013, with a female-to-male ratio of 1.8 and a median age of 51 years old. The average age- and sex-adjusted incidence from 2011 to 2013 was 0.87 per million per year, and the average age- and sex-adjusted prevalence from 2009 to 2013 was 5.29 per million population. Among them, 10.3% accompanied liver cancer and 3.3% underwent liver transplantation. Annual case-fatality rate was 2.8%. Direct medical costs excluding uninsured services for BCS increased by year from 385 720 USD in 2009 to 765 983 USD in 2013. CONCLUSIONS: This is the first population-based study on the epidemiology of BCS in an Asian country, which presented a higher prevalence than in Western studies. It suggests early diagnosis or improved prognosis of BCS in recent years, and clinical features of BCS that differ by geography.