Status Paper – Availability and Accessibility of Hepatitis C Diagnosis in Malaysia

Status paper on availability & accessibility of diagnosis and follow up with MoH to remediate to the issues highlighted in the paper.

Availability and accessibility of Hepatitis C diagnosis in Malaysia

The Malaysian Government, particularly the Ministry of Health, has shown a strong commitment to hepatitis C (HCV), in particular, with the availability of effective, all oral direct-acting antiviral (DAA) hepatitis C treatment earlier this year. It is estimated that 380,000 Malaysians are living with Hepatitis C, yet a minority or only less than 10 % have been detected. Therefore, a key factor still outstanding is to find the missing thousands of individuals in Malaysia who are currently infected with hepatitis C but not diagnosed. Early detection of those infected is crucial as successful HCV therapy improves liver disease, reduces the risk of death and liver cancer.

The Foundation for Innovative New Diagnostics (FIND) and the Drugs for Neglected Diseases initiative (DNDi) had recently announced their collaboration with the Ministry of Health (MOH), Malaysia to scale up of hepatitis C (HCV) diagnosis and treatment. The initial diagnostic step that will be taken is decentralized HCV screening at MOH health clinics using pre-qualified rapid diagnostic tests:  HCV positive cases will subsequently undergo HCV confirmation to enable them to be linked to HCV treatment as part of a DNDi clinical trial or in government hospitals (https://www.dndi.org/2018/media-centre/press-releases/find-dndi-malaysianmoh-efforts-hepatitisc-screening-treatment/).

The objective of this report is to

  1. assess availability and accessibility of HCV diagnostic tools in Malaysia
  2. identify strategies to improve access to HCV testing and improve linkage to care and therefore, support, strengthen and complement Ministry of Health’s existing efforts to scale up of HCV diagnosis and treatment

Key observations

Figure 1 shows the HCV Care Cascade, not only focusing on the major gap in those diagnosed and aware, but also the possible gaps all along after HCV diagnosis.

HCV screenings

The initial step for HCV diagnosis in all hospitals and health centres where mandatory or opportunistic HCV screening done is testing for the presence of Hepatitis C antibodies using laboratory-based assay. Rapid diagnostic test (RDT) for HCV is currently mainly performed by non-governmental organisations such as Positive Malaysian Treatment Access & Advocacy Group and Hepatitis Free Malaysia/Hepatitis Free Pahang.

HCV Confirmation

As the presence of Hepatitis C antibodies implies either current or past or infection, a confirmation step is crucial as only those with HCV viraemia will be considered for HCV treatment. Confirmation of HCV viraemia can be done using either HCV RNA test or HCV Core Ag as recommended by all major international guidelines on HCV management.

In public hospital setting, HCV confirmatory tests can only be done in very few MOH hospitals in Malaysia (Hospital Kuala Lumpur, Hospital Sungai Buloh, Hospital Selayang, Hospital Sultanah Bahiyah, Hospital Umum Sarawak and Hospital Melaka), University Malaya Medical Centre (UMMC) and University Kebangsaan Malaysia Medical Centre (UKMMC). Currently, HCV confirmatory tests are not yet accessible to primary care physicians.

Until recently, HCV RNA testing is limited to HCV RNA quantitative test, which costs at least three times higher compared to the HCV RNA  qualitative test. WHO and EASL guidelines recommended using either quantitative or quantitative HCV RNA tests as both tests are equally sensitive assays with a lower limit of detection of ≤15 IU/ml.

In the public hospital setting, HCV RNA qualitative testing was only available in UMMC until recently, where its now available at Hospital Kuala Lumpur and Hospital Umum Sarawak. The test is also available in the Institute for Medical Research (IMR).

In hospitals where HIV RNA tests is done, testing for HCV RNA can also be made available on the same platform in Hospital Pulau Pinang and Hospital Raja Perempuan Zainab II, Kota Bharu.

Although HCV core antigen assays is slightly less sensitive than HCV RNA, a WHO commissioned systematic review which included 44 studies, has provided a high level of evidence that HCV core antigen is good alternative to HCV RNA detection and is strongly recommended both by WHO and EASL guidelines for HCV confirmation. Awareness of HCV core antigen as a confirmatory test for HCV is still lacking, although there is increasing access to this test in 7 MOH hospitals (Hospital Kuala Lumpur, Hospital Ampang, Hospital Selayang, Hospital Sultanah Bahiyah,  Hospital Raja Perempuan Zainab, Hospital Sultanah Aminah and Hospital Queen Elizabeth)

Liver disease assessment

The main reason to assess the stage of liver disease is not to miss cirrhosis. Fibroscan is a reliable non-invasive test, but its only available in UMMC and 3 MOH hospitals (Hospital Selayang, Hospital Sultanah Bahiyah, Hospital Raja Perempuan Zainab). Serum biomarkers of fibrosis such as APRI and FIB-4 can be used and have been shown to have a good negative predictive value to rule out cirrhosis.

HCV Genotyping

There is no role for HCV genotyping in the 2018 WHO guidelines as only pangenotypic regimens are recommended. However, as Genotype 3 is the in predominant HCV genotype in Malaysia, accounting for 63% of all HCV in Malaysia, HCV genotyping is still required for cirrhotic patients as the duration of treatment and the need for ribavirin differ according to genotype and treatment experience for certain pangenotypic regimen (eg Daclatasvir/Sofosbuvir)

In the public hospital setting, HCV genotyping is only available in UMMC and Hospital Kuala Lumpur. The test is also available in Institute for Medical Research (IMR).

Assessment of cure and monitoring

HCV RNA test is only required once if used for HCV confirmation and 12 weeks post treatment to assess cure/SVR. For those with cirrhosis, surveillance for HCC is required for life with US +/- AFP measurement, and these are only done at tertiary centres.

If available, HCV RNA quantitative test should be used to assess cure/SVR to save costs.

Strategies to improve access to HCV testing and improve linkage to care

Lack of access to HCV Diagnostic is undoubtedly a major barrier in the HCV care continuum. As recently highlighted, this is fuelled by quasi-monopolies on HCV diagnostics, and the lack of competition has kept prices of reagents at a high price

  • Increase public awareness to identify those at risk of HCV

Engagement with family medicine specialists to facilitate identification of those at high risk for HCV had started since 2014 which have been shown to result in an increase detection and notification of new HCV cases in 2016. These should be strengthened further with the use of rapid diagnostic tests (RDT) for HCV screening of those at high risk of HCV.

In addition, the quest to “Find the Missing Thousands” living with hepatitis C who have not been detected should involve many stakeholders, including NGOs and those living with hepatitis C, to make  testing more accessible and remove barriers for testing amongst them. There is a need to increase public awareness programmes to identify those at risk of HCV and the use of rapid diagnostic tests for HCV screening is recommended in these settings

  • Decentralizing HCV confirmation tests and liver disease assessment

For those tested HCV positive with the initial HCV screening/RDT, reflex HCV confirmatory tests is recommended at the same sitting so these patients are not lost to follow-up.

Nearly 60% of HCV in Malaysia were transmitted amongst people who use drug (PWUD). Mandatory HCV screenings have been conducted in patients with opioid use disorder who are being followed at primary care facilities and medication-assisted treatment (MAT) clinics, with approximately 64% of the 3000 registered patient at government MAT setting annually with slightly higher number of cumulative registered patients at private MAT clinics who are HCV-infected. HCV testing in these settings is limited to anti-HCV test, therefore a large proportion of patients who were tested positive for HCV antibody have not undergone confirmatory HCV testing and liver disease assessment, so these tests should be prioritized at primary care facilities and (MAT) clinics

  • Providing simple HCV diagnostic and treatment algorithm

The recently updated WHO guidelines provides a simple algorithm for HCV diagnosis, treatment and monitoring, which can definitely increase the understanding on the steps needed to achieve HCV cure and monitoring thereafter.

  • Increase access to DAAs and increase treatment sites

Access to generic DAA is only available at 22 MOH hospitals. To reach the goal of HCV elimination by 2030, the government needs to expand HCV diagnosis and treatment services. To achieve this will require moving beyond hospital settings and necessitate the greater involvement of a broad range of health professionals, especially primary-care providers.

  • Efficient procurement and supply management of diagnostics (and DAAs)

Centralised or bulk procurement system or negotiation of cost of HCV diagnostics and DAAs at a national level can translate to more efficiency and lower cost of procurement of reagent and drugs for the government.

The use of using open diagnostic platforms for HCV platforms has been suggested as the way forward to introduce competition and can potentially be very efficient and decrease prices of reagents in the near future. In addition, a nationwide access to generic DAA therapy is urgently needed so that the burden of HCV diagnosis and care management is shared by both the public (including university hospitals) and private sectors.

References

  1. McDonald SA, Azzeri A, Shabaruddin FH, Dahlui M, Tan SS, Kamarulzaman A, Mohamed R. Projections of the Healthcare Costs and Disease Burden due to Hepatitis C Infection under Different Treatment Policies in Malaysia, 2018–2040. Appl Health Econ Health Policy. 2018 Aug 25. doi: 10.1007/s40258-018-0425-3
  2. Ho SH, Ng KP, Kaur H, Goh KL. Genotype 3 is the predominant hepatitis C genotype in a multi-ethnic Asian population in Malaysia. Hepatobiliary Pancreat Dis Int. 2015;14(3):281–6. 5
  3. Freiman JMTran TMSchumacher SG, et al. Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis. Ann Intern Med.2016 Sep 6;165(5):345-55. doi: 10.7326/M16-0065
  4. World Health Organization. Global health sector strategy on viral hepatitis 2016–2021. 2016.
  5. Fatiha S, et al. Estimated 3-year acquisition cost of direct acting antiviral (DAA) for the treatment of Hepatitis C in Malaysia in 2018 to 2020. APASL 2018 Delhi
  6. Near-Monopolies On HCV Diagnostics Curb Competition, Keep Prices High, Research Finds

http://www.ip-watch.org/2018/10/24/near-monopolies-hcv-diagnostics-curb-competition-keep-prices-high-research-finds/Accessed 25 October 2018.

  1. Ministry of Health Malaysia. Press Statement Minister of Health 20th September 2017 – Implementation of the Rights of Government for Sofosbuvir Tablet to Increase Access for Hepatitis C Treatment in Malaysia. 2017.
  2. World Health Organization. Guidelines for the screening, care and treatment of persons with chronic hepatitis C infection. 2018.
  3. AASLD/IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. September 2017 Retrieved from https://www. hcvguidelines.org/Treatment-Naive. Accessed 4 September 2018.

Appendix 1

Study Profile

Number of interviews: 15

The interview was conducted throughout Malaysia from the period of end of July 2018 to early October 2018, covering non-medical personals and doctors from the government clinics and hospitals.

Below are the summary of our interviewees profile.

Question 1
Non-Medical Personnel 2
FMS 3
Hepatologist 3
Gastro 1
Total 9

 

Question 2
Microbiologist 2
Patologist 4
Non-Medical Personnel 2
Total 8

 

Notes :

The non-medical personals answered both questions one and two thus we recorded their presence in both column on question 1 and question 2.

Appendix 2

HCV Diagnostic Survey, Malaysia – July 2018 – Summary Report

ACCESS TO DIAGNOSTIC TESTING

Question 1. Please note the availability of the following tests and their prices in the public sector.

Add rows as needed.

Test (Diagnosis) Available in public sector? Length of result Total price (per test) Price paid out-of-pocket by patient Length of result  

Venue of lab & name.

HCV Rapid Test Kit X On the spot        
HCV antibody (HCV Ab or anti-HCV) X Ranges from 1 – 3 days to

1 – 2 weeks

RM20 Nil   HKL
HCV core antigen X Ranges from 2 – 3 days to 1 week or more. RM80 Nil    
HCV RNA PCR X 1 – 8 weeks RM400 Nil   Sungei Buloh
HCV Genotype X 4 – 8 weeks       HKL / IMR
Fibroscan X   Depends on opportunities as 3 years ago was immediately     Selayang

 

Main issues captures from all the interviews are listed below :

  1. Budget allocation in government hospital.
  2.  Not maximising use of the existing Gene Expert Machine.
  3. The length of result available is too long.
  4. HCV RNA PCR, HCV Genotype can not be ordered directly from KK and has to be referred to the hospital specialist.
  5. Not aware about the existing Gene Expert Machine available.
  6. Need to refer patients to hospital for confirmation test (HCV RNA PCR).
  7. Budget constrain especially for HCV RNA PCR is very expensive test.
  8. Further (HCV RNA PCR) testings are based on criteria (selective criteria such as patients who are planned for treatment, co-infection cases) at cost constraint.

Recommendations :

  1. More budget allocation as some may not be repeated cases.
  2. Need integration with TB department.
  3. Government subsidize cost for reagent.

 

Usage of Diagnostic   

Manufacturer

Price procured for the machine.

RM

Cost per reagent /cartridge Number of test requested

per day

Number of test was used per day Number of free testing. Number of out source testing.
HCV Rapid Test Kit SD Bioline/ Others            
HCV antibody (HCV Ab or anti-HCV) Abbott     23 – 40 tests

per day

  40 test  
HCV core antigen  

 

          Available at HKL only
HCV RNA PCR

(for TB usage)*

Abbott/Cobas/

Cepheid

(Gene Xpert)

RM34K – RM80K

per unit

RM70 – RM80

per unit

 

> 50 tests/day 50 tests/day   Malaysia Liver Foundation
HCV RNA PCR

(for IMR)

Cobas   RM200 – RM300   10 – 20 tests per week    
HCV Genotype Abbott/Cobas

 

          30 tests and mostly available at HKL only
HCV Genotype

(for IMR)

Cobas   RM300 – RM400   1 – 5 tests per week (New)    
Fibroscan

 

  RM200K – RM700K   10 cartridges 25 cartridges per week All free No.

* Note:  Gene Expert IV – existing 19 units for TB usage in MoH hospitals, and propose 14 units for HIV/HCV usage, and most of them are on reagent rental contract. Prices are based on procurement through reagent rental. This would also depends on workload such as number of tests performed per year basis. Obviously analyser as an asset would offer lower prices.

 

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