背景：口服直接作用抗病毒藥物可以有效治癒C型肝炎。但是，要讓所有C型肝炎患者都治癒，過程會遇到相當多障礙，這個遞減過程學者稱為「治療階流」。可惜，過去的研究大多是一個醫院或醫療體系樣本分析，比較少全國性樣本分析。而且，更少研究探討治療政策改變（台灣2017年健保開始給付口服直接作用抗病毒藥物，2018年放寬處方藥物醫師資格，2019年取消多項治療條件限制）之影響。
目的：一、瞭解台灣全國C型肝炎抗體檢驗數與陽性率。二、探討C型肝炎抗體陽性者的治療階流，並檢視不同年治療政策改變之影響。
方法：本研究使用2017年至2020年全民健保申報與檢驗結果資料，估計上述治療階流完成率。進一步分析性別，年齡別，醫療機構地區別與層級別差異。
結果：台灣2017年至2020年接受C型肝炎抗體篩檢之民眾共2,966,901人，其中陽性個案192,106人(6.5%)。2017年至2020年陽性率逐年遞減，分別是11.3%(63,846/564,457), 7.3%(48,862/672,306), 6.1%(46,830/773,933)與3.4%(32,568/956,205)。2017年抗體陽性63,846人，四年內有接受病毒RNA檢驗有36,701人(57.5%)，其中20,001人(54.5%)病毒RNA陽性(累積完成率31.3%)，RNA陽性者有14,913人(74.6%)接受抗病毒藥物治療(累積完成率23.4%)，有14,163人(95.0%)完整領藥(累積完成率流22.2%)，有14,135人(99.8%)再接受病毒RNA檢驗 (累積完成率22.1%)，有13,832人(97.9%)由陽性轉陰性(累積完成率21.7%)。由於2018與2019年政策改變，2017年抗體陽性63,846人會在後續幾年接受病毒RNA檢驗：2017年17,076人(26.7%)接受檢驗，2018年8870人(13.9%)接受檢驗(累積完成率41.6%)，2019年有7629人(11.9%)接受檢驗(累積完成率53.5%)，2020年有3126人(4.9%)接受檢驗(累積完成率58.4%)。經過四年，還是有43%陽性患者未接受病毒RNA檢驗。進一步檢視2017年病毒RNA檢驗陽性7155人，會在後續幾年接受藥物治療：2017年只1005人(14.0%)接受治療，2018年有1689人(23.6%)接受治療(累積完成率37.6%)，2019年有1214人(17.0%)接受治療(累積完成率54.6%)，2020年有371人(5.2%)接受治療(累積完成率59.8%)。經過四年，還是有40%病毒RNA陽性個案未接受藥物治療。治療階流人口學特徵與醫療院所特徵分析：高齡者在病毒RNA檢驗率較低，而青年則是治療率與治癒率偏低；北區醫療院所病毒RNA檢驗率最低，台北醫療院所治療率相較其他地區亦為最低；地區醫院或基層診所病毒RNA檢驗率最低，醫學中心或區域醫院其治療率最低。
結論：本研究發現C型肝炎篩檢人數逐年增加，但是陽性率逐年減少，主要原因是後來幾年篩檢對象大多是低風險個案。關於兩大治療階流：C型肝炎抗體陽性個案約六成接受病毒RNA檢驗，病毒RNA陽性個案約六成接受治療。2018年放寬藥物處方醫師資格與藥物，對於接受治療有顯著影響，2019年取消治療條件限制對於接受治療只有部分影響。

SUMMARY
This study used Taiwan National Health Insurance claims data and laboratory results data to examine the cascade of treatment of people with hepatitis C virus (HCV) from 2017 to 2020. A total of 2,966,901 Anti-HCV tests been performed from 2017 to 2020 and 192,106 people had reactive results. The reactive rate decreased yearly, which was 11.3%(63,846/564,457) in 2017, 7.3%(48,862/672,306) in 2018, 6.1%(46,830/773,933) in 2019, and 3.4%(32,568/956,205) in 2020, respectively. Among 63,846 people with Anti-HCV reactive in 2017, 36,701(57.5%) underwent confirmatory RNA testing, 20,001(54.5%) were viremic (RNA detectable), 14,913(74.6%) were referred to specialty care and initiated treatment with direct-acting antivirals (DAAs), 14,163(95.0%) completed the treatment course, 14,135(99.8%) received re-confirmatory RNA testing, 13,832 (97.9%) achieved sustained virologic response (SVR) until 2020. The cumulative cascade of treatment was 57.5%, 31.3%, 23.4%, 22.2%, 22.1%, and 21.7%, respectively. We further examined number of people with anti-HCV reactive (n=63,846) in 2017 who underwent confirmatory RNA testing in the following years, which was 17,076(26.7%) in 2017, 8870(13.9%) in 2018, 7629(11.9%) in 2019, and 3126(4.9%) in 2020, with accumulative rate of 26.7%, 41.6%, 53.5%, and 58.4%, respectively. Of 7155 people with RNA positive in 2017, 1005(14.0%) received DAAs treatment in 2017, 1689(23.6%) in 2018, 1214(17.0%) in 2019, 371(5.2%) in 2020, with cumulative rate of 14.0%, 37.6%, 54.6%, and 59.8%, respectively. Elderly people had lower percentage in performing HCV RNA testing; while younger people had lowest treatment uptake. Clinical settings in northern divisions had the lowest proportional progression to RNA testing; while Taipei divisions had the lowest proportional treatment uptake. In conclusion, despite the increase in number of people received anti-HCV tests, the reactive rates decreased. The possible reason was that people received the screening in the later years were people with lower risk of HCV infection. Almost three-fifths of people with anti-HCV reactive received confirmatory HCV RNA testing and three-fifths of people with RNA positive initiated treatment. Allowance of more specialists that can prescribe more DAAs drugs in 2018 had larger impact on the increase in treatment rates. The treatment restrictions based on fibrosis stage were removed in 2019 had only mild impact on the increase in treatment rates.

Asselah T, Marcellin P, Schinazi RF. Treatment of hepatitis C virus infection with direct-acting antiviral agents:100% cure?. Liver Int, 38 Suppl 1: 7-13, 2018.
Baid-Agrawal S, Pascual M, Moradpour D, Somasundaram R, Muche M. Hepatitis C
virus infection and kidney transplantation in 2014: what's new?. Am J Transplant, 14(10) : 2206–2220, 2014.
Bartlett SR, Yu A, Chapinal N, Rossi C, Butt Z, Wong S, Darvishian M, Gilbert M, Wong J, Binka M, Alvarez M, Tyndall M, Krajden M, Janjua NZ. The population level Treatment cascade for hepatitis C in British Columbia, Canada as of 2018: Impact of direct acting antivirals. Liver Int, 39(12): 2261-2272, 2019.
Chen CH, Yang PM, Huang GT, Lee HS, Sung JL, Sheu JC. Estimation of seroprevalence of hepatitis B virus and hepatitis C virus in Taiwan from a large-scale survey of free hepatitis screening participants. J Formos Med Assoc, 106(2):148-155, 2007.
Chen YY, Chen CL, Chen JW, Hsu NT, Wei ST, Hou SM, Lu SN, Chen PJ. Secular Trends and Geographic Maps of Hepatitis C Virus Infection among 4 Million Blood Donors in Taiwan from 1999 to 2017. Hepatol Commun, 4(8):1193-1205, 2020.
Coyle C, Moorman AC, Bartholomew T, Klein G, Kwakwa H, Mehta SH, Holtzman D. The hepatitis C virus care continuum: Linkage to hepatitis C virus care and treatment among patients at an urban health network, Philadelphia, PA. Hepatology, 70(2): 476-486, 2019.
Fourati S, Feld J, Chevaliez S, Luhmann N. Approaches for simplified HCV diagnosis algorithms. J Int AIDS Soc, 21 Suppl 2: e25058, 2018
Gisslén M, Svedhem V, Lindborg L, Flamholc L, Norrgren H, Wendahl S, Axelsson M, Sönnerborg A. Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets. HIV Med, 18(4): 305-307, 2017.
Heim MH. 25 years of interferon-based treatment of chronic hepatitis C: an epoch coming to an end. Nat Rev Immunol, 13(7): 535-542, 2013.
Hu TH, Su WW, Yang CC, Yang CC, Kuo WH, Chen YY, Yeh YH, Chen SS, Tsao YY, Chen KM, Yan SL, Lai JH, Yao CD, Lim CH, Jen HH, Yeh YP, Chen SL, Chen HH, Chen SC; Changhua Hepatitis C Elimination Task Force. Elimination of Hepatitis C Virus in a Dialysis Population: A Collaborative Care Model in Taiwan. Am J Kidney Dis, S0272-6386(21) 00575-8, 2021.
Janjua NZ, Kuo M, Yu A, Alvarez M, Wong S, Cook D, Wong J, Grebely J, Butt ZA, Samji H, Ramji A, Tyndall M, Krajden M. The population level cascade of care for hepatitis C in British Columbia, Canada: the BC Hepatitis Testers Cohort (BC-HTC). EBioMedicine, 12: 189-195, 2016.
Konerman MA, Lok ASF. Hepatitis C Treatment and Barriers to Eradication. Clin Transl Gastroenterol, 7(9):e193, 2016.
Kåberg M, Weiland O. Hepatitis C elimination - Macro-elimination. Liver Int, 40 Suppl 1:61-66, 2020.
Lee PC, Kao FY, Liang FW, Lee YC, Li ST, Lu TH. Existing Data Sources in Clinical Epidemiology: The Taiwan National Health Insurance Laboratory Databases. Clin Epidemiol,13:175-181, 2021.
Levi J, Raymond A, Pozniak A, Vernazza P, Kohler P, Hill A. Can the UNAIDS 90-90-90 target be achieved? A systematic analysis of national HIV treatment cascades. BMJ Glob Health, 1(2): e000010, 2016.
Maier MM, Ross DB, Chartier M, Belperio PS, Backus LI. Cascade of care for hepatitis C virus infection within the US veterans health administration. Am J Public Health, 106(2): 353-358, 2016.
Maurice P, & WHO Global Tuberculosis Programme. A simulation model of case finding and treatment in tuberculosis control programmes. https://apps.who.int/iris/handle/10665/69827; Published 1967.Accessed 16 February, 2021.
Miller LS, Millman AJ, Lom J, Osinubi A, Ahmed F, Dupont S, Rein D, Vellozzi C, Harris AM. Defining the hepatitis C cure cascade in an Urban health system using the electronic health record. J Viral Hepat, 27(1): 13-19, 2020.
Millman AJ, Nelson NP, Vellozzi C. Hepatitis C: review of the epidemiology, clinical care, and continued challenges in the Direct Acting Antiviral Era. Curr Epidemiol Rep, 4(2):174-185, 2017.
Mold JW, Stein HF. The cascade effect in the clinical care of patients. N Engl J Med, 314(8): 512-514, 1986.
Moore MS, Bocour A, Laraque F, Winters A. A surveillance-based hepatitis C care
cascade, New York City,2017. Public Health Rep, 133(4): 497-501, 2018.
Moretti M, Pieretti B, Masucci A, Sisti D, Rocchi M, Delprete E. Role of Signal-to-Cutoff Ratios in Hepatitis C Virus Antibody Detection. Clin Vaccine Immunol, 19(8): 1329-1331, 2012.
O'Neil CR, Buss E, Plitt S, Osman M, Coffin CS, Charlton CL, Shafran S.
Achievement of hepatitis C cascade of care milestones: a population-level analysis in Alberta, Canada. Can J Public Health, 110(6): 714-721, 2019.
Perlman DC, Jordan AE, Nash D. Conceptualizing care continua: Lessons from HIV, hepatitis C virus, tuberculosis and implications for the development of improved care and prevention continua. Front Public Health, 4: 296, 2017.
Pawlotsky JM, Ramers CB, Dillon JF, Feld JJ, Lazarus JV. Simplification of care for chronic hepatitis C virus infection. Semin Liver Dis, 40 : 392-402, 2020.
Reader SW, Kim HS, El-Serag HB, Thrift AP. Persistent Challenges in the Hepatitis C Virus Care Continuum for Patients in a Central Texas Public Health System. Open Forum Infect Dis, 7(8): ofaa322, 2020.
Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC recommendations for hepatitis C screening among adults - United States, 2020. MMWR Recomm Rep, 69(2):
1-17, 2020.
Seo YS, Jung ES, Kim JH, Jung YK, Kim JH, An H, Yim HJ, Yeon JE, Byun KS, Kim CD, Ryu HS, Um SH. Significance of anti-HCV signal-to-cutoff ratio in predicting hepatitis C viremia. Korean J Intern Med, 24(4): 302-308, 2009.
Sirin MC, Aridogan BC, Cetin ES, Sirin FB. Evaluation of biochemical,
hematological, RIBA and PCR assays in predicting viremia in anti-HCV positive patients. J Infect Dev Ctries, 13(8) : 736-743, 2019.
Simmons R, Ireland G, Irving W, Hickman M, Sabin C, Ijaz S, Ramsay M, Lattimore S, Mandal S. Establishing the cascade of care for hepatitis C in England-benchmarking to monitor impact of direct acting antivirals. J Viral Hepat , 25(5): 482-490, 2018.
Spearman CW, Dusheiko GM, Hellard M, Sonderup M. Hepatitis C. Lancet, 394
(10207):1451-1466, 2019.
Safreed-Harmon K, Blach S, Aleman S, Bollerup S, Cooke G, Dalgard O, Dillon JF, Dore GJ, Duberg AS, Grebely J, Boe Kielland K, Midgard H, Porter K, Razavi H, Tyndall M, Weis N, Lazarus JV. The Consensus Hepatitis C Cascade of Care: Standardized Reporting to Monitor Progress Toward Elimination. Clin Infect Dis, 69(12):2218-2227, 2019.
Tsertsvadze T, Gamkrelidze A, Chkhartishvili N, Abutidze A, Sharvadze L, Kerashvili V, Butsashvili M, Metreveli D, Gvinjilia L, Shadaker S, Nasrullah M, Adamia E, Zeuzem S, Afdhal N, Arora S, Thornton K, Skaggs B, Kuchuloria T, Lagvilava M, … Averhoff F. Three years of progress towards achieving hepatitis C elimination in the country of Georgia, April 2015‐March 2018. Clin Infect Dis, 71(5): 1263-1268, 2020.
Viner K, Kuncio D, Newbern EC, Johnson CC. The continuum of hepatitis C testing and care. Hepatology, 61(3): 783-789, 2015.
World Health Organization. Global health sector strategy on viral hepatitis,2016-2021: towards ending viral hepatitis. https://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/, 2016.
Yehia BR, Schranz AJ, Umscheid CA, Lo Re 3rd V. The treatment cascade for chronic hepatitis C virus infection in the United States: a systematic review and meta-analysis. PLoS One, 9(7): e101554, 2014.
Yu ML, Yeh ML, Tsai PC, Huang CI, Huang JF, Huang CF, Hsieh MH, Liang PC, Lin YH, Hsieh MY, Lin WY, Hou NJ, Lin ZY, Chen SC, Dai CY, Chuang WL, Chang WY. Huge gap between clinical efficacy and community effectiveness in the treatment of chronic hepatitis C: a nationwide survey in Taiwan. Medicine (Baltimore), 94(13): e690, 2015.
Zeuzem S. Treatment Options in Hepatitis C- The Current State of the Art. Dtsch Arztebl Int, 114(1-2): 11-21, 2017.
Zucker J, Aaron JG, Feller DJ, Slowikowski J, Evans H, Scherer ML, Yin MT, Gordon P. Development and validation of an electronic medical record-based algorithm to identify patient milestones in the hepatitis C virus Treatment cascade. Open Forum Infect Dis, 5(7): ofy153, 2018.
Zuckerman A, Douglas A, Nwosu S, Choi L, Chastain C. Increasing success and evolving barriers in the hepatitis C cascade of care during the direct acting antiviral era. PLoS ONE,13(6): e0199174, 2018.
吳慧敏、楊雯雯、劉嘉玲、鄭國本、陳時中、陳建仁、蒲若芳。台灣2025年C肝消除的策略與進度。台灣衛誌，40(1)，1-4，2021。
劉建榮、林振文。臨床病毒學。合記：台北市。2011。
衛生福利部。國家消除C肝政策綱領2018-2025。國家消除C肝政策綱領編輯團隊：台北市。2019。
衛生福利部統計處。衛生福利統計專區-性別統計專區-性別統計指標-衛生類-門診-西醫門診件數、住院件數。https://dep.mohw.gov.tw/DOS/lp-1720-113-6-20.html。2020。
蘇湘雲。精準篩檢，全方位減少C型肝炎威脅—消除 C 型肝炎超前部署。衛福季刊，26期，26-29，2020。