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wileyonlinelibrary.com/journal/jvh J. Viral Hepat.. 2020;27:1270–1283.1 | BACKGROUND
The global hepatitis C virus (HCV) epidemic stimulated the World Health Organization (WHO) to develop viral hepatitis elimination targets in 2016.1 An estimated 71 million people worldwide were infected by HCV in 2015.2 Thus, the WHO set the target of a 90% reduction in new infections and a 65% reduction in viral hepatitis-re-lated mortality by 2030 as compared to 2015. These are ambitious but feasible goals, since we have ample tools at hand to curtail the current HCV epidemic. The diagnosis of active HCV can be readily made, by means of sample analysis in a central facility or through point-of-care testing. Direct-acting antivirals (DAAs) cure the
infection in ≥95% of cases.3 Pangenotypic DAAs can be used in all patients with only a few barriers such as potential drug-drug inter-actions or presence of (decompensated) cirrhosis.4,5 Most countries have assessed their specific HCV population and the availability of tools in their countries and subsequently developed national hepati-tis plans in line with the WHO elimination targets.6
HCV elimination according to the WHO goals can be achieved in various ways, which ideally should be incorporated in a multi-faceted approach. We can focus on prevention, by developing a vaccine or by increasing awareness and educating groups at risk of transmission of the virus. Secondly, we can develop or augment existing screening strategies, in order to diagnose more patients. Received: 22 May 2020
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Revised: 9 July 2020|
Accepted: 16 August 2020DOI: 10.1111/jvh.13399
N O N - C O M M I S S I O N E D R E V I E W
Loss to follow-up in the hepatitis C care cascade: A substantial
problem but opportunity for micro-elimination
Marleen van Dijk
1| Joost P.H. Drenth
1| on behalf of the HepNed study group
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd
1Department of Gastroenterology and
Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands
2Department of Infectious Diseases,
University Medical Centre Utrecht, Utrecht, the Netherlands
3Department of Gastroenterology and
Hepatology, Erasmus Medical Centre, Rottedam, the Netherlands
4Division of Infectious Diseases, Amsterdam
Infection & Immunity Institute Amsterdam University Medical Centre, Amsterdam, the Netherlands
5Department of Gastroenterology and
Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands Correspondence
Marleen van Dijk, Department of Gastroenterology & Hepatology, Radboud University Medical Centre, Internal Postal Code 458, PO Box 9101, Nijmegen, 6500 HB, The Netherlands.
Email: marleen.vandijk@radboudumc.nl Funding information
Gilead Sciences
Abstract
Since the advent of direct-acting antivirals, elimination of hepatitis C viral (HCV) in-fections seems within reach. However, studies on the HCV cascade of care show suboptimal progression through each step for all patient groups. Loss to follow-up (LTFU) is a major issue and is a barrier to HCV elimination. This review summarizes the scale of the LTFU problem and proposes a micro-elimination approach. Retrieving LTFU patients and re-engaging them with care again has shown to be feasible in the Netherlands. Micro-elimination through retrieval can contribute to reaching the World Health Organization's viral hepatitis elimination targets by 2030.
K E Y W O R D S
Lastly, we can treat as many infected patients as possible. Since the development of highly effective and tolerable DAAs, HCV elimina-tion projects have primarily focused on prevenelimina-tion and screening, since treatment was not seen as a problem anymore. However, en-suring treatment for all diagnosed patients remains a problem to this day.
Loss to follow-up (LTFU) prevents patients from receiving the care they need to be cured of their infection. The extent of this problem remains unclear, especially in the DAA era. In order to grasp the scope of the LTFU problem, one needs to understand the HCV care cascade and how patients move through its phases. This review aims to assess published literature on LTFU in the HCV cascade of care during the DAA era and will provide an overview of issues and possible solutions.
2 | CONCEPT OF LOSS TO FOLLOW-UP
Different definitions for LTFU are used in the literature, since patients become lost to follow-up for various reasons. For example, they may have moved house, emigrated, died or been imprisoned. Many times, the reason for LTFU cannot be ascertained as contact with the patient cannot be established. Retrospective observational studies often do not provide a specific definition or use nonattendance to any appoint-ment as a definition.Suppl file 1-11 Some of these studies mention death separately and do not include this as a reason for LTFU.Suppl file 12-17 Other studies that reviewed ever-diagnosed patients defined LTFU as patients who never or not recently had an appointment with an HCV specialist.Suppl file 18,19 Interventional studies aiming to improve the cascade of care also do not give a definition or define LTFU as nonat-tendance anywhere in the care cascade,Suppl file 20-49 often separating death from the LTFU group.Suppl file 50-58 There are some studies that include multiple LTFU definitions and report data on all of them, such as nonattendance, nonresponse to invitation, moved, incarcerated, no insurance and comorbidities.Suppl file 59-62
There may be a lesson to be learned on defining LTFU from stud-ies in other fields of medicine. Previously mentioned HCV studstud-ies did not take time into account when defining LTFU. Prospective
studies defined LTFU as nonattendance at the end of their study period, which varied greatly among studies. Retrospective studies defined LTFU as nonattendance since their last visit up to study initiation. HIV studies have investigated LTFU extensively and showed that the way you define LTFU greatly influences your LTFU outcomes.7 In addition, these studies have demonstrated differ-ent ways to determine the ideal timeframe to classify someone as LTFU, that is x days after last clinic visit.8,9 When different studies use different definitions, it is virtually impossible to compare care cascades and combine results. However, since this is the case for the HCV studies assessed in this review, we chose a pragmatic ap-proach that suits the illustrative purpose of this review. We define LTFU as nonattendance to any appointment in the care cascade at any time since their last visit. Patients who had died were not included in the definition of LTFU.
3 | THE HCV CARE CASCADE
In order to grasp the magnitude of the LTFU problem in chronic HCV patients, we must first understand the HCV care cascade. Reviewing published literature on this subject shows that defi-nitions of the care cascade vary with each paper. However, ef-forts to come up with an unambiguous description of the HCV care cascade have been made. In 2018, the WHO established a monitoring framework that includes 10 core indicators address-ing prevention, diagnosis, treatment and mortality.10 The WHO states that four of the 10 core indicators should be used for cas-cade of care reporting: the number of patients infected, diag-nosed, treated and cured.11 Recently, a study group comprised of clinical, epidemiological and public health experts from Australia, Europe and North America have proposed a clarified and slightly extended care continuum.12 Their Consensus HCV Cascade of Care (CHCoC) is based on the WHO indicators, a review of pub-lished literature on HCV care continuums and on methodologi-cal issues in HIV cascade of care monitoring. It can be divided into four key steps (the four WHO indicators) and three supple-mentary steps: (a) estimated HCV prevalence; (b) diagnosed with
F I G U R E 1 Hepatitis C care cascade. Step 1: HCV prevalence; step 2: diagnosed with chronic HCV; step 3: linked to care; step 4: liver
disease assessed; step 5: started on treatment; step 6: achieved SVR; step 7: accessed chronic post-SVR care. Figure freely adapted with permission from Safreed-Harmon et al.12 HCV, hepatitis C virus; LTFU, lost to follow-up; SVR, sustained virological response
chronic HCV; (c) linked to HCV care; (d) liver disease assessed; (e) started on treatment in (year); (f) achieved sustained virologi-cal response (SVR) in (year); and (g) accessed chronic post-SVR care. The authors provided pragmatic definitions for the four key steps, which stakeholders can use to report on elimination progress. Understandably, by increasing the number of steps in the care cascade, the chances of being lost from care also in-crease. LTFU is seen as a major problem, because it remains un-sure whether the patient is cured or not. Liver disease in these patients may progress, and they may even contribute to HCV transmission if they still exhibit certain risk behaviour. When reviewing the literature published on HCV care cascades in the DAA era and their LTFU rates, we used the CHCoC to report our findings (see Figure 1). And overview and characteristics of the included studies in this review can be found in Table 1.
4 | LTFU DURING DIAGNOSTIC
ASSESSMENT (CHCOC STEP 2)
The first step in diagnosing chronic HCV is the determination of presence of HCV antibodies. However, the key step in confirming the diagnosis of chronic HCV is determining HCV RNA (or HCV core antigen when RNA assays are not available or not affordable).13 In many countries, HCV RNA is not tested automatically after receiving a positive antibody test result. This two-step diagnosis provides the first opportunity for patients to become LTFU. Two retrospective, observational studies have shown that approximately 72% of their anti-HCV-positive populations were tested for HCV RNA.Suppl file 1,2 This percentage is generally higher in interventional studies aiming to improve the cascade of care, often done in community-based set-tings: 67%-100% (median 90%).Suppl file 20-23,50-52,59 However, some studies have shown that only 7%Suppl file 18 or 18%Suppl file 24 of anti-HCV-positive people receive confirmatory testing. Reasons for this vary and are often unreported, but might be due to LTFU. One study confirmed that 32% of anti-HCV-positive people were LTFU before receiving an RNA test.Suppl file 50 Reflex testing, where the laboratory automatically tests for HCV RNA or HCV core antigen when the an-tibody test proves to be positive, improves this step in the cascade of care.Suppl file 27
5 | LTFU BEFORE LINK AGE TO HCV CARE
(CHCOC STEP 3)
When someone has tested positive for HCV RNA, referral to an HCV specialist for further evaluation should follow. However, attendance to this follow-up visit is only reported in 27%-91% (median 68%) of cases.Suppl file 1,18-22,25-28,52,59,60 People who inject(ed) drugs (PWID), a well-known hard to reach population, attend in 36%-65% of cases (median 50%).Suppl file 29-32 In HIV/HCV-coinfected patients, attend-ance seems to be higher with 25%-95% (median 90%).Suppl file 8,11,47,49 Generally speaking, attendance is higher for those under decentralized
care. Reasons for absence are difficult to assess; however, some stud-ies confirm LTFU in 26%-100% (median 84%) of absentees.Suppl file 22,27,32,52,59,60
6 | LTFU DURING LIVER DISEASE
ASSESSMENT (CHCOC STEP 4)
Several diagnostic procedures are available to grade and stage liver disease. Where liver biopsy was standard of care in the past, nowadays noninvasive methods are largely preferred. Liver fi-brosis may be quantified by using serological panels, such as the widely used FIB-4 (using the patient's age, platelet count, AST and ALT levels) or APRI score (using AST levels, the AST upper limit of normal and platelet count), or by using transient elastography. Almost all studies in the DAA era employ noninvasive ways to assess liver disease severity. When looking at people who have attended their first visit after being diagnosed or referred, fibro-sis was assessed with the APRI scoreSuppl file 2,24,33 in 52%-99% (median 87%) and with FibroScanSuppl file 9,12,22,25,27,30,34,35,40,41,5 0,53 in 59%-100% (median 79%). Studies which used other non-invasive measures or did not report which measures were used, reported assessment in 48%-95% (median 88%) of attendees.Suppl file 20,21,25,26,36 LTFU may contribute to this suboptimal assessment rate and should be addressed.
7 | LTFU BEFORE INITIATING TREATMENT
(CHCOC STEP 5)
Even in the era of highly effective DAAs, treatment initiation rates are low. LTFU proves to be a large contributor to this problem. Retrospective studies have shown that only 12%-77% (median 29%) of patients diagnosed or engaged in care during the DAA era initiated treatment after being diagnosed with chronic HCV.Suppl file 1-5,13,34 Interventional studies aimed to improve the care cas-cade show that this rate can increase to 16%-100% (median 73%).Suppl file 18-28,33,35-39,50-53,59-62 Studies in the HIV field show similar results, with 36%-91% (median 90%) initiating treatment in retrospective studiesSuppl file 9-11 and 25%-100% (median 80%) in interventional studies.Suppl file 47-49 However, the treatment rate remains suboptimal in PWID with only 20%-90% (median 53%) initiating treatment.Suppl file 29-32,40,41 Generally, treatment initia-tion rates are higher in decentralized settings, both in PWID and non-PWID populations. Reasons for poor treatment initiation rates vary. Unfortunately, many countries still experience restric-tions in who can and cannot be treated with DAAs.14,15 This prob-lem may especially apply to studies from the first stages of the DAA era.16 Other reasons for poor treatment initiation rates may be comorbidities or perceived lack of compliance. However, LTFU contributes to a large extent to these poor rates. Studies showed that LTFU is the reason for nontreatment in 0%-67% (median 33%) of cases.Suppl file 3,5,13,19,25-27,32,40,41,53,61,62
T A B LE 1 C ha ra ct er is tic s o f s tu di es i nc lu de d i n r ev ie w o n t he H C V c ar e c as ca de i n m ixe d p op ul at io ns , p eo pl e w ho i nj ec t(e d) d ru gs an d H IV /H C V-co in fe cte d p at ie nt s. Re fer en ce s a C ou ntr y Su mma ry Pe rc en ta ge o f l os s t o f ol lo w -u p i n e ac h C H C oC s te p, i nc lu di ng o ur d ef in iti on In te nt io n t o tr ea t s us ta in ed vi rolo gi cal re sp ons e b C H C oC s te p 2 : H C V RN A n ot a ss es se d in a nt i-H C V p os iti ve pat ie nt s C H C oC s te p 3: a bs en ce at f ol lo w -u p ap po int m ent a fte r dia gn os is / r ef er ra l C H C oC s te p 4: l iv er d is ea se no t a ss es se d in d ia gn os ed / at te nd ee s C H C oC s te p 5: t re at m en t no t i ni tia te d i n at te nd ee s C H C oC s te p 6 : LT FU d ur in g o r af te r t re at m ent M ix ed p op ulat io n Zuc ker , 2 01 8 1 US A Re tr os pe ct iv e a na ly si s o f a nt i-H C V po si tiv e p at ien ts in ac adem ic ho sp ita l di ag no se d i n D A A e ra , u si ng a n el ec tro ni c m ed ic al re co rd a lg or ith m 28 % 73 % c 70 % 39 % A ss ou m ou , 2020 2 US A Re tr os pe ct iv e a na ly si s o f m ult ic en tr e FQ H C c oh or t 27 % 48 % (AP RI ) 88% 31% A l-K ha zr aji , 2020 3 US A Re tr os pe ct iv e a na ly si s o f H C V po si tiv e p at ien ts in ac adem ic ho sp ita l di ag no se d i n D A A e ra w ho a re el ig ibl e f or tr ea tmen t ( RN A -p os iti ve an d n o c om or bi di tie s w ith s ho rt l ife exp ec ta nc y) 80 % ( 67 % o f t he se w er e c on fir m ed LT FU) 5. 3% M oo re , 20 18 4 US A Re tr os pe ct iv e a na ly si s o f micr obi ol og y da ta ba se (m an da te d r ep or tin g o f po si tiv e H C V t es ts ) 48% 65% N gu yen , 2 01 7 5 US A Ret ros pe ct iv e a na ly si s o f R N A -p os iti ve pa tie nt s s ee n i n a ca de m ic c lin ic i n t he DA A e ra 23 % ( 24 % o f t he se w er e c on fir m ed LT FU) 89 % M ar sh al l, 2 01 8 6 US A G T1 p at ie nt s w ho in iti ate d t re at m ent at ou tp at ie nt c lin ic c ar e o f a n a ca de m ic ce nt re 7% (d ur ing ) 15% (a ft er ) 74 % H ar id y, 2 01 8 12 A us tr al ia O bs er va tio na l, p ro sp ec tiv e s tu dy o f a ll tr ea te d p at ie nt s i n ( as so ci at io n w ith ) te rt ia ry c en tr es ( in cl ud in g p ris on s a nd co m m un ity h ea lth c en tr es v ia r em ot e co nsu lta tio n) 32 % ( Fi br os ca n) (c om m unit y-ba se d v s ho sp ita l 4 3% v s 30 %) 14 .7 % 80% Sø lu nd , 2 01 8 13 D en m ar k A na ly si s o f t he D an is h D at ab as e f or H ep at iti s B a nd C , i nc lu di ng H C V pa tien ts e lig ibl e f or tr ea tmen t 51 % ( of th es e, 3 0% w er e L TF U) 1. 5% (d ur in g) 3. 2% (a ft er ) 88% D ar vi sh ia n, 2020 14 C ana da M ul tic en tr e c oh or t s tu dy o f G T1 a nd 3 pa tie nt s, t re at ed b y s pe ci al is ts o r G Ps 8% (Co nti nue s)
Re fer en ce s a C ou ntr y Su mma ry Pe rc en ta ge o f l os s t o f ol lo w -u p i n e ac h C H C oC s te p, i nc lu di ng o ur d ef in iti on In te nt io n t o tr ea t s us ta in ed vi rolo gi cal re sp ons e b C H C oC s te p 2 : H C V RN A n ot a ss es se d in a nt i-H C V p os iti ve pat ie nt s C H C oC s te p 3: a bs en ce at f ol lo w -u p ap po int m ent a fte r dia gn os is / r ef er ra l C H C oC s te p 4: l iv er d is ea se no t a ss es se d in d ia gn os ed / at te nd ee s C H C oC s te p 5: t re at m en t no t i ni tia te d i n at te nd ee s C H C oC s te p 6 : LT FU d ur in g o r af te r t re at m ent Sc ag lio ne , 2020 16 It al y Re tr os pe ct iv e a na ly si s o f a ll t re at ed H C V p at ie nt s i n a t ea ch in g h os pi ta l 10 % 87 % A da ms on , 2020 18 US A Re tr os pe ct iv e c oh or t s tu dy c ompa rin g tr ea tm en t b y H C V s pe ci al is ts i n a pr im ar y c ar e p ra ct ic e t o t re at m en t b y H C V sp ec ial is ts in h osp ital s 93 % ( of c om bi ne d co ho rt ) 25 % v s 5 2% 58 % v s 53% 25 % v s 2 2% D ev er, 2 01 7 19 US A H C V p at ie nt s f ro m t he V et er an A ff ai rs H C V r eg is tr y w ith i nc re as ed r is k o f ad va nc ed f ib ro si s t ha t n ev er a tt en de d an a pp oi nt m en t o r w er e L TF U w er e ret rie ve d 45% 26 % ( 54 % o f t he se w er e c on fir m ed LT FU) Tro os ki n, 20 15 20 US A PO C t es tin g ( an ti-H C V a nd R N A ) i n co m m unit y-ba se d s et tin gs , p os iti ve pa tie nt s c ou ns el le d a nd r ef er re d b y pat ie nt n av ig at or 13 % 9% 5% ( liv er ult ra so un d, H epa Sc or e d o r Fi bro Su re e 43% C oy le, 2 01 9 21 US A Im pl emen ta tio n o f r ou tin e H C V te st in g an d l in ka ge t o c ar e i n f iv e F Q H C s, in cl udin g m edic al a ss is ta nt -in iti at ed te st in g, a ut om at ed h ea lth r ec or d pr om pt s, r ef le x t es tin g a nd c ar e co or di na to rs 4% 16 % 20 % ( liv er fib ro si s pa nel , liv er b io ps y, liv er u ltr as ou nd or F ib ros ca n) 78 % 53% B aj is , 20 19 22 A us tr al ia Liv er he al th p ro m ot io n c ampa ig n a nd no nin va si ve fib ro si s a ss ess m en t fo llo w ed b y R N A s cr ee ni ng a nd lin ka ge t o c ar e a m on g h om el es s i n a co m m unit y c en tre 1% 38 % ( 10 0% o f t he se w er e c on fir m ed LT FU) 0% (F ib ros ca n) 21% 65% W ak ed , 2020 23 Eg ypt Re po rt ed p ro gr es s o f t he E gy pt H C V el imina tio n p ro gr am m e 33% 8% 82 % K ha lid , 2020 24 Pa ki st an D ec en tr al is ed s cr een in g a nd tr ea tmen t in cl ud in g P O C t es tin g f or p eo pl e ≥ 1 ris k f ac to r i n p rim ar y h ea lth c lin ic a nd tr ea tm en t f re e o f c ha rg e 82 % 1% (AP RI ) 84 % H si eh , 2 01 9 25 US A K no wn c hr on ic H C V p at ien ts who vi si te d t he E D w er e o ff er ed l in ka ge t o ca re 66% 5% ( Fi br oS ur e o r Fi bros ca n) 58 % ( 27 % o f t he se w er e c on fir m ed LT FU) 94 % T A B LE 1 (Co nti nue d) (Co nti nue s)
Re fer en ce s a C ou ntr y Su mma ry Pe rc en ta ge o f l os s t o f ol lo w -u p i n e ac h C H C oC s te p, i nc lu di ng o ur d ef in iti on In te nt io n t o tr ea t s us ta in ed vi rolo gi cal re sp ons e b C H C oC s te p 2 : H C V RN A n ot a ss es se d in a nt i-H C V p os iti ve pat ie nt s C H C oC s te p 3: a bs en ce at f ol lo w -u p ap po int m ent a fte r dia gn os is / r ef er ra l C H C oC s te p 4: l iv er d is ea se no t a ss es se d in d ia gn os ed / at te nd ee s C H C oC s te p 5: t re at m en t no t i ni tia te d i n at te nd ee s C H C oC s te p 6 : LT FU d ur in g o r af te r t re at m ent Zuc ker m an , 20 18 26 US A D ec en tr al is ed tr ea tmen t b y p ha rm ac is t-le d m ult idi sc ip lina ry te am 27 % 12 % ( ul tr as ou nd , liv er b io ps y, FI B -4 o r Fi bro Su re ) 17 % ( 4% o f t he se w er e c on fir m ed LT FU) 5% (d ur ing ) 4% (a ft er ) 88% Ev an s, 2 01 8 27 U nit ed K in gd om O pt -o ut H BV a nd H C V s cr ee ni ng a nd lin ka ge t o c ar e f or p eo pl e ≥ 16 y ea rs a t th e E D , i nc lu di ng r ef le x t es tin g 22 % ( 10 0% o f t he se w er e c on fir m ed LT FU) 40 % (F ib ros ca n) 50 % ( 44 % o f t he se w er e c on fir m ed LT FU) 80% B enit ez , 2020 28 US A O ne -t im e t es tin g a cc or di ng t o C D C gu id el in es a nd t re at m en t i n F Q H C s an d s at el lit e c en tr es s er vi ng a pr ed omina nt ly h om el ess p op ula tio n, in cl udin g r ef le x t es tin g 15% 84 % 3. 4% (d ur ing ) 13 % (a ft er ) 83% C ap ileno , 2 01 7 33 Pa ki st an D ec en tr al is ed s cr een in g a nd tr ea tmen t in cl ud in g P O C t es tin g f or p eo pl e ≥ 1 ris k f ac to r i n p rim ar y h ea lth c lin ic a nd tr ea tm en t f re e o f c ha rg e 13 % (AP RI ) 81% 4. 7% (d ur ing ) 3% (a ft er ) 83% C oo pe r, 2 01 7 34 C ana da Re tr os pe ct iv e a na ly si s o f p at ie nt s tr ea te d a t ou tpa tie nt c lin ic c ompa re d to p at ie nt s m ai nl y t re at ed t hr ou gh te le m edic in e 61 % v s 8 4% ( liv er bi ops y) 38 % v s 4 1% (F ib ros ca n) 72 % v s 8 3% Shi ha , 20 18 35 Eg ypt Fr ee s cr ee ni ng a nd t re at m en t i n r ur al vill ag e 0% 0% (F ib ros ca n) 4% 98 % Fo rd , 2 01 7 36 US A D ec en tr al is ed s cr ee ni ng a nd l in ka ge to c ar e i n F Q H C s a nd a dd ic tio n c ar e se rv ic es , t re at m en t b ot h o n- a nd of f-si te 52 % 45% 91% B ar th olo m ew , 20 19 37 US A D ec en tr al is ed t re at m en t i n p rim ar y c ar e by p hy si ci an a ss is ta nt s a nd p rim ar y ca re p hy si cia ns 30% 3. 8% (d ur ing ) 10 % (a ft er ) 77% W ad e, 2 01 8 38 A us tr al ia Re m ot e c on su lta tio n b y s pe ci al is ts f or G Ps , t re at m en t b y G Ps o r a ft er r ef er ra l to s pe cia lis t 29 % T A B LE 1 (Co nti nue d) (Co nti nue s)
Re fer en ce s a C ou ntr y Su mma ry Pe rc en ta ge o f l os s t o f ol lo w -u p i n e ac h C H C oC s te p, i nc lu di ng o ur d ef in iti on In te nt io n t o tr ea t s us ta in ed vi rolo gi cal re sp ons e b C H C oC s te p 2 : H C V RN A n ot a ss es se d in a nt i-H C V p os iti ve pat ie nt s C H C oC s te p 3: a bs en ce at f ol lo w -u p ap po int m ent a fte r dia gn os is / r ef er ra l C H C oC s te p 4: l iv er d is ea se no t a ss es se d in d ia gn os ed / at te nd ee s C H C oC s te p 5: t re at m en t no t i ni tia te d i n at te nd ee s C H C oC s te p 6 : LT FU d ur in g o r af te r t re at m ent M en di za ba l, 20 19 39 A rg en tina Te le -m en to rin g o f p rim ar y c ar e ph ys ic ia ns a nd s pe ci al is ts b y a m ult idi sc ip lina ry te am o f s pe ci al is ts a t an a ca de m ic c en tr e ( EC H O ), c om pa re d to tr ea tmen t i n t er tia ry c en tr e 13 % ( in e nt ire co ho rt ) 68 % v s 72 % N or to n, 2 01 7 42 US A Pa tie nt s t re at ed b y s pe ci al is t a nd H C V ca re c oo rd in at or i n a F Q H C 0% (d ur ing ) 2. 2% (a ft er ) 96 % K at ta ku zh y, 20 17 43 US A N on ra ndo m iz ed tr ia l c ompa rin g de ce nt ra lis ed t re at m en t b y n ur se pr ac tit io ne rs , G Ps o r s pe ci al is ts i n co m m unit y h ea lth c en tre s 2% v s 2 .5 % v s 3. 5% (d ur ing ) 4% v s 5 % v s 4. 8% (a ft er ) 89 % v s 8 7% v s 84 % C ar val ho -L ou ro , 2020 50 B ra zi l Fr ee P O C t es tin g f or p eo pl e > 40 y ea rs ol d vi si tin g l ab or at or ie s 32 % ( 10 0% o f t he se w er e c on fir m ed LT FU) 12 % (F ib ros ca n) 29 % 0% (d ur ing ) 92 % A ve rh of f, 2020 51 G eo rg ia Re po rt ed p ro gr es s o f t he G eo rg ia H C V el imina tio n p ro gr am m e 20 % 21% 0. 4% (d ur ing ) 25% (a ft er ) 66% H ut ton , 2 01 9 52 A us tr al ia Sc re en in g a nd l in ka ge t o c ar e o f p at ie nt s pr es en te d a t E D w ith ≥ 1 r is k f ac to r, in cl udin g P O C te st in g 10 % 67 % ( 85 % o f t he se w er e c on fir m ed LT FU) 0% 0% (d ur ing ) 0% (a ft er ) 70 % C hi on g, 20 19 53 A us tr al ia Sc re en in g a nd l in ka ge t o c ar e o f in pa tien ts in a ter tia ry ho sp ita l 23 % (F ib ros ca n) 15 % ( 50 % o f t he se w er e c on fir m ed LT FU) 6. 5% (d ur ing ) 4. 3% (a ft er ) 80% Ko re n, 20 19 55 US A Re tr os pe ct iv e a na ly si s o f a p ha rm ac is t-dr iv en m ult idi sc ip lina ry tr ea tm en t m ode l 1. 8% (d ur in g) 5. 5% (a ft er ) 86% No uc h, 2 01 8 56 C ana da D ec en tr al is ed m ult idi sc ip lina ry c ar e in co m m unit y h ea lth c en tre s 3. 6% (d ur ing ) 9% (a ft er ) 86% W hit e, 20 19 57 A us tr al ia D ec en tr al is ed t re at m en t b y p rim ar y c ar e ph ys ic ia ns o r i n se co nd ar y c ar e 4. 3% (d ur ing ) 89 % M cM ah on , 20 19 59 US A A na ly si s o f t he c as ca de o f c ar e f or A la sk an N at iv es t es te d a nt i-H C V po si tiv e vi a h ep at iti s p ro gr am me 3% 37 % ( 83 % o f t he se w er e c on fir m ed LT FU) 23 % T A B LE 1 (Co nti nue d) (Co nti nue s)
Re fer en ce s a C ou ntr y Su mma ry Pe rc en ta ge o f l os s t o f ol lo w -u p i n e ac h C H C oC s te p, i nc lu di ng o ur d ef in iti on In te nt io n t o tr ea t s us ta in ed vi rolo gi cal re sp ons e b C H C oC s te p 2 : H C V RN A n ot a ss es se d in a nt i-H C V p os iti ve pat ie nt s C H C oC s te p 3: a bs en ce at f ol lo w -u p ap po int m ent a fte r dia gn os is / r ef er ra l C H C oC s te p 4: l iv er d is ea se no t a ss es se d in d ia gn os ed / at te nd ee s C H C oC s te p 5: t re at m en t no t i ni tia te d i n at te nd ee s C H C oC s te p 6 : LT FU d ur in g o r af te r t re at m ent Sh er bu k, 2 01 9 60 US A H C V p at ie nt s t re at ed i n t er tia ry c en tr e w ith d edic at ed n ur se c oo rdina to r 24 % ( 47 % o f t he se w er e c on fir m ed LT FU) 20 % 19 % (a ft er ) 74 % Fr an ch ev ill e, 20 18 61 C ana da Pr ov in ce -w id e m od el o f c ar e w ith ce nt ra lize d r ef er ra l, t ria ge a nd i nt ak e by a n ur se c oo rd in at or , t re at m en t b y sp ec ia lis t 24 % ( 0% o f t he se w er e c on fir m ed LT FU) 88% M oh se n, 2 01 9 62 A us tr al ia Te le -m en to rin g o f p rim ar y c ar e ph ys ic ia ns a nd s pe ci al is ts b y a m ult idi sc ip lina ry te am o f s pe ci al is ts a t an a ca de m ic c en tr e ( EC H O ), c om pa re d to tr ea tmen t i n t er tia ry c en tr e 22 % ( 36 % o f t he se w er e c on fir m ed LT FU ) v s 1 9% 0% v s 1 1% (d ur ing ) 12 % v s 3 % (a ft er ) 77 % v s 8 3% Peo pl e w ho in jec t(e d) d rug s Ch ris ten sen , 20 18 7 G er m any A na ly si s o f t he G er m an h ep at iti s C re gi st ry , c ompa rin g f or m er /c ur re nt dr ug u se rs o n O ST w ith f or m er /c ur re nt dr ug u se rs n ot o n O ST a nd p eo pl e w ith no d oc umen te d d ru g u se 2. 7% v s 2 .0 % v s 0. 7% (d ur ing ) 7. 6% v s 6 .5 % v s 2. 5% (a ft er ) 85 % v s 8 6% v s 92 % Fa la de-N w ul ia , 2020 29 US A Pe er -p ro m ot ed s cr ee ni ng a nd l in ka ge t o ca re in a P W ID p op ula tio n, in cl udin g inc en tiv es fo r t es tin g 6% 64 % 80 % ( 66 % in cl udin g p at ie nt s w ho w er e a lre ad y lin ke d t o c ar e) B aj is , 2020 30 A us tr al ia Liv er he al th p ro m ot io n c ampa ig n a nd no n-i nv as iv e f ib ro si s a ss es sm en t fo llo w ed b y R N A s cr ee ni ng a nd l in ka ge to c ar e i n a dd ic tio n c ar e s er vi ce s 51 % 0% (F ib ros ca n) 47 % ( 23 % i nc lu di ng pa tien ts who w er e a lre ad y lin ke d t o c ar e) A lim oh amm ad i, 20 18 31 C ana da Ra nd om ize d c on tr ol le d t ria l a bo ut de ce nt ra lis ed t re at m en t i n c om m un ity po p-up c lin ic s f or P W ID t hr ou gh di re ct ly o bse rv ed tr ea tm en t, c ompa re d to g rou p t he ra py a nd s ta nd ar d c ar e, inc lu di ng P O C te st in g a nd inc en tiv es 50 % 39 % 6% (a ft er ) 85% T A B LE 1 (Co nti nue d) (Co nti nue s)
Re fer en ce s a C ou ntr y Su mma ry Pe rc en ta ge o f l os s t o f ol lo w -u p i n e ac h C H C oC s te p, i nc lu di ng o ur d ef in iti on In te nt io n t o tr ea t s us ta in ed vi rolo gi cal re sp ons e b C H C oC s te p 2 : H C V RN A n ot a ss es se d in a nt i-H C V p os iti ve pat ie nt s C H C oC s te p 3: a bs en ce at f ol lo w -u p ap po int m ent a fte r dia gn os is / r ef er ra l C H C oC s te p 4: l iv er d is ea se no t a ss es se d in d ia gn os ed / at te nd ee s C H C oC s te p 5: t re at m en t no t i ni tia te d i n at te nd ee s C H C oC s te p 6 : LT FU d ur in g o r af te r t re at m ent Ha rr iso n, 2 01 9 32 U nit ed K in gd om M ult ic en tr e s tu dy o n in cr ea si ng sc re en in g a nd l in ka ge t o c ar e i n add ic tio n c ar e s er vi ce s 35 % ( 26 % o f t he se w er e c on fir m ed LT FU) 66 % ( 6% o f t he se w er e c on fir m ed LT FU) 82 % W ad e, 2020 40 A us tr al ia , N ew Zeala nd Ra nd om ize d c on tr ol le d t ria l o n tr ea tm en t o f P W ID i n p rim ar y c ar e fa ci lit ie s t ha t p ro vi de O ST , c om pa re d t o tre at m en t i n h os pit al 21 % v s 3 8% (F ib ros ca n) 10 % ( 40 % o f t he se w er e c on fir m ed LT FU ) v s 3 8% (4 5% o f t he se w er e c on fir m ed LT FU) 4. 7% v s 5 .6 % (d ur ing ) 28 % v s 6 % (a ft er ) O’ Su lli va n, 2020 41 U nit ed K in gd om D ec en tr al is ed s cr een in g a nd tr ea tmen t in a n ur se -le d p ro gr am m e i n a dd ic tio n ca re s er vic es , in cl udin g r ef le x t es tin g 0% 13 % (F ib ros ca n) 52 % ( 0% o f t he se w er e c on fir m ed LT FU) 4. 3% (a ft er ) 90 % M or ris , 2 01 7 44 A us tr al ia D ec en tr al is ed c ar e i nc lu di ng c ar e co or di na to rs fo r p at ie nt s in a ddic tio n m edic in e 2% (d ur ing ) 20 % (a ft er ) 80% Read , 2 01 7 54 A us tr al ia D ec en tr al is ed t re at m en t i n p rim ar y c ar e fa ci lit y t ar ge te d t o P W ID 2. 8% (d ur ing ) 12 .5 % (a fte r) 82 % Ko us te ni s, 2020 58 G re ec e Re tr os pe ct iv e a na ly si s o f s in gl e c en tr e PW ID c oh or t t re at ed i n t er tia ry c en tr e 2. 3% (d ur ing ) 10. 3% (a ft er ) 80% H IV /HC V-coi nf ec te d p op ulat io n Fa la de-N w ul ia , 20 19 8 US A Re tr os pe ct iv e a na ly si s o f a ll H IV /H C V-co in fe ct ed p at ie nt s i n a n a ca de m ic hos pit al 5% 18 % 8.8 % (a ft er ) 87 % Sa ris, 2 01 7 9 N et he rla nds Re tr os pe ct iv e a na ly si s o f a ll H IV /H C V-co in fe ct ed p at ie nt s f ro m t w o h os pi ta ls (o ne a ca de m ic ), p la nne d f or D A A tr eat m ent 19 % (F ib ros ca n) 9% ( no ne L TF U ) 80% K ro nf li, 20 18 10 C ana da Re tr os pe ct iv e a na ly si s o f m ult ic en tr e H IV /H C V-co in fe ct ed c oh or t ( ho sp ita ls , co m m unit y-ba se d cl ini cs a nd s tre et ou tre ac h p ro gr am m es ) 64 % ( 28 % o f t he se w er e c on fir m ed LT FU) A de ku nl e, 2020 11 US A Re tr os pe ct iv e a na ly si s o f H IV /H C V-co in fe ct ed h os pi ta l c oh or t 10 % 10 % ( 8% o f t he se w er e c on fir m ed LT FU) 0% 96 % T A B LE 1 (Co nti nue d) (Co nti nue s)
Re fer en ce s a C ou ntr y Su mma ry Pe rc en ta ge o f l os s t o f ol lo w -u p i n e ac h C H C oC s te p, i nc lu di ng o ur d ef in iti on In te nt io n t o tr ea t s us ta in ed vi rolo gi cal re sp ons e b C H C oC s te p 2 : H C V RN A n ot a ss es se d in a nt i-H C V p os iti ve pat ie nt s C H C oC s te p 3: a bs en ce at f ol lo w -u p ap po int m ent a fte r dia gn os is / r ef er ra l C H C oC s te p 4: l iv er d is ea se no t a ss es se d in d ia gn os ed / at te nd ee s C H C oC s te p 5: t re at m en t no t i ni tia te d i n at te nd ee s C H C oC s te p 6 : LT FU d ur in g o r af te r t re at m ent C acha y, 2 01 9 15 U SA , S pa in , It al y Re tr os pe ct iv e a na ly si s o f a ll H IV /H C V-co in fe ct ed p at ie nt s t re at ed i n f iv e ho sp ita ls i n t hr ee c ou nt rie s 1% 93 % St ar bi rd , 2020 47 US A Ra nd om ize d c on tr ol le d t ria l w he re H IV / H C V-co in fe ct ed p at ien ts who w er e no t in H C V c ar e w ou ld r ec ei ve u su al c ar e or n ur se c as e m an ag em en t f oc us in g o n lin ka ge t o c ar e 75 % v s 5 3% 0% v s 7 5% ( 11 % of t he se w er e co nf irm ed L TF U) W ard , 20 19 48 US A Ra nd om ize d c on tr ol le d t ria l o f s cr ee ni ng an d l in ka ge t o c ar e o f H IV /H C V-co in fe ct ed pa tie nt s, c ompa rin g u sua l ca re (n ur se-le d m ult idi sc ip lina ry te am in cl udin g i nc en tiv es fo r s tu dy -s pe ci fic vi si ts ) w ith u su al c ar e i nc lu di ng p ee r su pp or t a nd u su al c ar e i nc lu di ng inc en tiv es . T re at men t w as fr ee o f cha rg e 24 % ( 33 % v s 1 7% vs 24 % ) 2. 7% ( du rin g; 4. 2% v s 2 .2 % vs 2 .4 % ) 0% (a ft er ) 91 % ( 92 % v s 91 % v s 9 0% ) Ri zk , 2 01 9 49 US A Re tr os pe ct iv e a na ly si s o f a s in gl e c en tr e H IV /H C V-co in fe ct ed c oh or t t re at ed b y a d edic at ed m ult idi sc ip lina ry te am 9% 17 % C D C , C en te rs f or D is ea se C on tr ol a nd P re ve nt io n; C H C oc , C on se ns us H C V C as ca de o f C ar e; D A A , d ire ct a ct in g a nt iv ira l; ED , emer genc y dep ar tmen t; F Q H C , f eder al ly q ua lif ie d h ea lth c en tr e; G P, g en er al p rac tit io ner ; G T, g eno ty pe ; H C V, h ep at iti s C v iru s; LT FU , l os s t o f ol lo w -u p; O ST , o pi oi d s ub st itu tio n t he ra py ; P O C , p oi nt o f c ar e; P W ID , p eo pl e w ho i nj ec t d ru gs ; U SA , U ni te d S ta te s o f A m er ic a. aIn S up pl emen ta ry fi le 1 . bD ef in ed a s S V R a m on g t ho se w ho i ni tia te d t he ra py . cFr om t hi s s te p o n, p at ie nt s w ith ou t a v ira l l oa d a ss es sm en t w er e i nc lu de d. dH ep aS co re u se s t he p at ie nt ’s a ge , s ex a nd b ili ru bi n, γ-gl ut am yl tr an sf er ase , α 2-m ac ro gl ob ul in a nd h ya lu ro ni c a ci d l ev el s t o d et er m in e f ib ro si s s ta ge . eFi br oS ur e u se s t he p at ie nt ’s a ge , s ex a nd A LT , b ili ru bi n, γ-gl ut am yl tr an sf er ase , α -2 m acr ogl ob ul in , ha pt ogl obin a nd a po lip op ro tei n A 1 l ev el s to d et er m in e f ib ro si s a nd n ec ro in fla m m at or y s ta ge . T A B LE 1 (Co nti nue d)
8 | LTFU DURING OR AFTER TREATMENT
(CHCOC STEP 6)
As we know from registration trials, DAAs are highly effective. Real-world studies yield similar results. However, LTFU influ-ences result in real-world studies significantly more. Recently, Darvishian et al showed that LTFU exceeded viral failure in their real-world study, impeding the cascade of care. Studies show that 0%-11% (median 3.4%) of patients become LTFU during thera-pySuppl file 6,13,26,28,33,37,42,43,50-53,55-57,62 and that 0%-25% (median 4.9%) become LTFU after therapy completion, with missing SVR values.Suppl file 6,13,26,28,33,37,42,43,51-53,55,56,60,62 PWID show simi-lar results with 0.7%-5.6% (median 2.5%) becoming LTFU during treatmentSuppl file 7,40,44,54,58 and 2.5%-28% (median 7.1%) after.Suppl file 7,31,40,41,44,54,58
Many studies report intention-to-treat SVR percentages, defined as the proportion of patients who reached SVR out of the number of patients that initiated DAA therapy (see Figure 2). In studies in-cluding mixed populations, ITT SVR varies from 22% to 98% (median 83%).Suppl file 1,2,4-6,12,13,16,18,21-23,25-28,33,35-37,39, 42,43,50-53,55-57,60-62 In studies focusing on PWID populations, ITT SVR ranges from 80% to 92% (median 85%).Suppl file 7,29-32,40,41,44,54,58 Lastly, in studies focus-ing on HIV/HCV-coinfected populations, ITT SVR ranges from 80% to 96% (median 91%).Suppl file 8-11,15,47-49
9 | LTFU AFTER SVR (CHCOC STEP 7)
Guidelines suggest that people with advanced fibrosis (METAVIR score F3) or cirrhosis (F4) who reached SVR should be subjected to surveillance for hepatocellular carcinoma (HCC) every six months by means of ultrasound.13,17 Furthermore, cirrhotic patients with varices present at pre-treatment endoscopy should be surveyed for oesophageal varices.13,17 Unfortunately, data on how many cured patients actually receive such surveillance are lacking. Most studies stop reporting on the care cascade at the moment SVR is reached. A recent review showed that less than 30% of cirrhotic patients are included in surveillance programmes, independent from aetiology.18 More studies on the surveillance adherence among cured HCV pa-tients with an indication for surveillance are needed.
10 | FACTORS ASSOCIATED WITH LTFU
Younger age (~45 and younger),Suppl file 12,46,58,60 treatment in hospital,Suppl file 18 a history of homelessness,Suppl file 19,54 mental illnessSuppl file 15,45 and insurance typeSuppl file 26,60 were some of the most common factors associated with LTFU. Factors associated with retention in care were older age (~60 and older)Suppl file 14,16 and HIV coinfection.Suppl file 14,46 However, one study with HIV co-infected patients showed that detectable HIV viral load was actu-ally associated with LTFU,Suppl file 45 possibly reflecting suboptimal retention in HIV care. Studies on the HCV care cascade in people
living with HIV confirm relatively good retention in care, espe-cially after starting treatment.Suppl file 8-11,15,17,45,47-49 The last fac-tors that were often associated with LTFU are linked to injecting drug use. Past,Suppl file 14 recentSuppl file 7,14 or ongoing drug useSuppl file 15,19,45 was mentioned in several studies as being associated with LTFU. Receiving opioid substitution therapy in one centre and DAA treatment in another was also associated with LTFU.Suppl file 7,56
11 | MICRO-ELIMINATION OF LTFU
PATIENTS THROUGH RETRIEVAL
LTFU occurs in all steps of the care cascade and may severely im-pact HCV care and opportunities for cure. It is reasonable to as-sume that data from the interferon era on LTFU are worse, due to the fact that fewer patients had an indication for treatment, more patients refused treatment, fewer patients finished the ill-tolerated treatment and only a limited number of patients achieved cure, compared to the DAA era. This hypothesis was confirmed in a recent study by Aleman et al19 The authors included HCV patients from their national register diagnosed between 2001 and 2011 and alive in 2013, and found that an impressive 61% was LTFU. A study from Belgium using a similar approach showed that PWID and patients who never received HCV treatment had a higher risk of becoming LTFU (OR 2.2 for both).20 This provides us with an opportunity as the LTFU HCV population may be an excellent candidate for micro-elimination, the process of eliminating HCV in subpopulations.21 Micro-elimination is the favoured approach in many countries, especially in those with a relatively low national prevalence, but higher prevalence in specific subpopulations. Lazarus et al have recently described which subpopulations should be considered for micro-elimination, such as aboriginal and indig-enous communities, HIV/HCV-coinfected people, migrants from high-prevalence countries, people who inject drugs, people with inherited blood disorders and prisoners.22 We propose that LTFU patients should be added to this list. As indicated, LTFU is a sub-stantial problem across the entire care cascade. Because this HCV population has already been identified, it is obvious that retrieval of these patients can be considered ‘low-hanging fruit’.
12 | RETRIEVAL IN THE NETHERL ANDS:
THE CELINE PROJECT
Several regional projects have been executed in the Netherlands fo-cused on the LTFU population. We found that up to 14% of our HCV population diagnosed in the previous 15 years was LTFU before being cured and eligible for retrieval.23-25 Based on best practices from these projects, a nationwide approach was developed.26,27 The hepatitis C Elimination in the Netherlands (CELINE) project aims to retrieve LTFU chronic HCV patients and re-engage them with care. The protocol is described in detail elsewhere.27 In short, we identify diagnosed
patients based on laboratory data, which we combine with information from their medical records. Patients who were still HCV-positive when they left care are classified as eligible for retrieval if they are alive and currently residing in the Netherlands. They are subsequently invited by letter to an outpatient clinic of their choice after their current address is verified through municipality records or general practitioners. Data will be collected on patient and disease characteristics of patients who sign informed consent.
What we have learned since the start of CELINE in 2018 is that retrieval is feasible when conducted by a dedicated team. The project gives great insight into our care cascade and gives vital information for our hepatitis elimination plan. The nationwide approach ensures that retrieval is done to the same standards in each participating centre. Identification of LTFU patients and ensuring they adhere to their clinic appointments are the most time-consuming. This is why we advise that a dedicated team, rather than individual clinicians, should execute these tasks.
13 | INCLUDE RETRIEVAL IN STANDARD
CARE
Ideally, micro-elimination through retrieval should become standard of care. This concept is not (yet) mentioned in any guidelines or elimi-nation plans, but deserves attention since it can contribute to HCV
elimination. Retrieval could be done yearly, to reduce workload, and requires close collaboration between microbiologists/virologists, infectious disease specialists, hepatologists, hepatitis nurses and other parties such as addiction care medicine, prisons, public health institutes and/or general practitioners. Each centre could form a multidisciplinary team led by a dedicated retrieval coordinator, for example a hepatitis nurse. This coordinator could check the care cascade of all people who had a positive HCV test result in the previ-ous year. The team could subsequently develop a multidisciplinary approach to retrieve LTFU patients. Patient-centred care is key in retrieving LTFU patients.
14 | ENSURING RETAINMENT IN CARE
Efforts should be made to retain LTFU and non-LTFU patients in care. The cascade of care should be simplified as much as possible, as is stated in the call to action from the American Association for the Study of Liver Diseases (AASLD), the European Association for the Study of the Liver (EASL), the Asian Pacific Association for the Study of the Liver (APASL) and the Latin American Association for the Study of the Liver (ALEH), in partnership with the Clinton Health Access Initiative (CHAI).28 Pre-treatment diagnostic as-sessment should be performed in one appointment. Treatment should be offered to all RNA-positive patients. Patients should be
F I G U R E 2 Intention-to-treat sustained
virological response percentages in studies included in this review in mixed populations, people who inject(ed) drugs and HIV/HCV-coinfected patients. Each line represents one study or one study group. The corresponding number refers to the reference in Supporting File 1
1 2 4 5 6 12 13 16 18 28 33 35 36 37 39 39 42 43 43 43 50 51 52 53 55 56 57 60 61 62 62 7 7 7 31 32 41 44 54 58 8 9 11 15 48 21 22 23 25 26 27 18 100% 90% 80% 70% 60% 50% 40% 30% 10% 20% Peop le w ho in ject (ed) dru gs HIV/H CV-coinfe cted patients Mixe d pop ulatio n
treated using pangenotypic regimens, making genotyping before-hand obsolete. Monitoring during treatment should be kept to a minimum. Care should be decentralized and/or integrated within other disease programmes as much as possible. Task-sharing be-tween HCV specialists and other healthcare workers should be encouraged. Patients should be educated about the risk of re-in-fection. Lastly, some patients should be retained in post-SVR care, according to guidelines. This includes patients with a continuing risk of developing HCC, such as patients with advanced fibrosis (METAVIR score F3) or cirrhosis (F4) or patients with other risk factors such as excessive alcohol drinking, obesity and/or type 2 diabetes, but also patients with persisting abnormal liver tests that could indicate other causes of liver disease. These efforts can contribute to retainment in care and can therefore contribute to HCV elimination.
15 | CONCLUSION
LTFU is a problem in each step in the HCV care cascade, even in the current era where highly effective treatments are available and where it has been possible to simplify the cascade of care. HCV can be micro-eliminated in the LTFU population through retrieval. We present an example of nationwide retrieval in the Netherlands, which shows retrieval is feasible and can contribute to HCV elimi-nation. We propose that micro-elimination through retrieval be-comes standard of care on the road to viral hepatitis elimination. Furthermore, efforts to retain patients in care should be imple-mented in daily clinical practice.
ACKNOWLEDGEMENTS
The CELINE project is part of the LEGA-C™ programme. LEGA-C is meant to suggest ‘Local Elimination Programs leading to Global Action in HCV’, and Gilead is using the LEGA-C programme to help streamline and support multiple HCV elimination initiatives across the world, in-cluding the SCALE (SCreening, Access, and Linkage to CarE) programme. The HepNed study group consists of Joop E. Arends, University Medical Centre Utrecht, Utrecht, the Netherlands; Sylvia M. Brakenhoff, Erasmus Medical Centre, Rotterdam, the Netherlands; Cas J. Isfordink, University Medical Centre Utrecht, Utrecht, the Netherlands, and Amsterdam Infection & Immunity Institute Amsterdam University Medical Centre, Amsterdam, the Netherlands; Rob de Knegt, Erasmus Medical Centre, Rotterdam, the Netherlands; and Marc van der Valk, Amsterdam Infection & Immunity Institute Amsterdam University Medical Centre, Amsterdam, the Netherlands.
ORCID
Marleen van Dijk https://orcid.org/0000-0001-9092-0481
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SUPPORTING INFORMATION
Additional supporting information may be found online in the Supporting Information section.
How to cite this article: van Dijk M, Drenth JPH; the HepNed
study group. Loss to follow-up in the hepatitis C care cascade: A substantial problem but opportunity for micro-elimination. J.
Viral Hepat.. 2020;27:1270–1283. https://doi.org/10.1111/ jvh.13399
