Hepatitis C virus (HCV) infection in Malaysia: findings from a nationwide cross-sectional study

Abstract

New cases of HCV are reported each year, with an estimated 58 million people worldwide,1World Health Organization Hepatitis C.https://www.who.int/news-room/fact-sheets/detail/hepatitis-cDate accessed: February 2, 2023Google Scholar and 10 million people in the Western Pacific, carrying the infection.2World Health Organization Western Pacific. Hepatitis.https://www.who.int/westernpacific/health-topics/hepatitis#tab=tab_1Date accessed: April 4, 2023Google Scholar While in Malaysia, McDonald et al. previously modelled that, 2.5% prevalence with an estimated 453,700 HCV infection.3Mcdonald S.A. Mohamed R. Dahlui M. Naning H. Kamarulzaman A. Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis.BMC Infect Dis. 2014; 14: 564Crossref PubMed Scopus (0) Google Scholar Although models might provide insightful information, it might take some time to interpret the findings. Hence, seroprevalence study was conducted to estimate the true burden of HCV infection and chronic HCV in Malaysia and to determine the proportion of diagnosis and treatment status among those who were infected with HCV. We organized a cross-sectional study at the end of 2020 across Malaysia. We used a two-stage stratified random sampling technique to select representative community dwelling individuals aged ≥15 years. The optimum size sample required was 5000 based on the single proportion sample size formula, adjusted for design effect and non-response. We obtained written consents and assent (if ≤ 18 years) and conducted face-to-face interviews to collect sociodemographic characteristics and HCV status. We collected blood samples and extracted serum to test for HCV antibodies. A positive sample (denotes HCV infection) would be tested further for HCV core antigen. Positive results on both tests denote chronic infection.4Clinical practice guidelines management of chronic hepatitis C in adults. Ministry of Health Malaysia and Malaysia Academy of Medicine Malaysia, 2019https://www.moh.gov.my/moh/resources/Penerbitan/CPG/Gastroenterology/CPG_Management_of_Chronic_Hepatitis_C_in_Adults.pdfDate accessed: April 4, 2023Google Scholar We used SPSS v26 to perform descriptive analysis and apply weights in complex sampling analysis to obtain representative prevalence's and their 95% Confidence Interval (CI) (Detailed methodology and other information in Supplementary Materials). Out of 5957 eligible individuals, test results were available for 4076 (response rate 68.4%). Their mean age was 41.2 ± 17.3 years. The weighted prevalence of HCV infection in Malaysia was 0.4% (95% CI 0.2–0.7) amounting to an estimated of 90,119 infected population age ≥15 years. More than half of them (≈51,675) chronically infected with the prevalence of 0.2% (95% CI 0.1–0.4) (Table 1). All participants tested positive in our study were previously undiagnosed, hence received referral for further management.Table 1Sociodemographic and seroprevalence of HCV infection among participants age 15 years old and above in Malaysia.VariablesParticipantaThe number of participants in the study and representativeness of Malaysia's general population after applying weight., n (%)Estimated populationaThe number of participants in the study and representativeness of Malaysia's general population after applying weight., N (%)HCV InfectionChronic HCV InfectionnEstimated population, NPrevalencebDenominator for each weighted prevalence was the total estimated population correspond subpopulation ≥15 years in Malaysia. (%)RSEnEstimated population, NPrevalencebDenominator for each weighted prevalence was the total estimated population correspond subpopulation ≥15 years in Malaysia. (%)RSEOverall4076 (100.0)24,142,146 (100.0)1990,1190.4 (0.2, 0.7)0.3311451,6750.2 (0.1, 0.4)0.346Residential area Urban2186 (53.6)18,706,908 (77.5)971,3980.4 (0.2, 0.9)0.408cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.534,9770.2 (0.1, 0.5)0.479cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Rural1890 (46.4)5,435,238 (22.5)1018,7200.3 (0.2, 0.7)0.349916,6980.3 (0.1, 0.6)0.374cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.Gender Male1919 (47.1)12,430,875 (51.5)1482,6090.7 (0.3, 1.3)0.358944,1640.4 (0.2, 0.8)0.396cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Female2157 (52.9)11,711,271 (48.5)575100.1 (0.0, 0.2)0.512cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.575110.1 (0.0, 0.2)0.512cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.Age group 15–39 years2040 (50.1)14,090,749 (58.4)528,0070.2 (0.1, 0.6)0.533cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.528,0070.2 (0.1, 0.6)0.533cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. 40–59 years1310 (32.1)6,650,625 (27.5)1039,9950.6 (0.3, 1.4)0.411cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.720,0790.3 (0.1, 0.8)0.496cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. 60 years and above726 (17.8)3,400,772 (14.1)422,1170.7 (0.2, 2.5)0.694cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.235890.1 (0.0, 0.5)0.763cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.Ethnicity Malay2492 (61.1)11,545,690 (47.8)1346,6600.4 (0.2, 0.8)0.334922,8460.2 (0.1, 0.5)0.435cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Chinese387 (9.5)5,449,457 (22.6)114,6310.3 (0.0, 2.0)1.030cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.–––– Indian200 (4.9)1,526,953 (6.3)165970.4 (0.1, 3.3)1.035cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.165970.4 (0.1, 3.3)1.035cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Bumiputera Sabah704 (17.3))2,693,310 (11.2)422,2320.8 (0.2, 2.8)0.614cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.422,2320.8 (0.2, 2.8)0.614cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Others293 (7.2)2,926,737 (12.1)––––––––Marital status Single1164 (28.6)7,639,678 (31.6)576,6070.4 (0.1, 1.0)0.522cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.276900.1 (0.0, 0.6)0.872cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Married/Living with partner2560 (62.8)14,529,839 (60.2)1151,9730.4 (0.1, 1.0)0.496cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.1037,3420.3 (0.1, 0.6)0.422cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Widowed (er)/Divorcee351 (8.6)1,969,974 (8.2)310,5400.5 (0.2, 1.7)0.593cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.266430.3 (0.1, 1.4)0.736cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.Highest education level No formal education235 (5.8)1,319,923 (5.5)125190.2 (0.0, 1.5)1.042cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.125190.2 (0.0, 1.5)1.042cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Primary education882 (21.8)4,761,056 (20.0)418,0370.4 (0.1, 1.4)0.671cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals.365360.1 (0.0, 0.5)0.634cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Secondary education1925 (47.6)10,596,604 (44.5)1354,9320.5 (0.3, 1.0)0.3271042,6200.4 (0.2, 0.9)0.392cThe relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Tertiary education1005 (24.8)7,158,253 (30.0)0–––0–––a The number of participants in the study and representativeness of Malaysia's general population after applying weight.b Denominator for each weighted prevalence was the total estimated population correspond subpopulation ≥15 years in Malaysia.c The relative standard error (RSE) value more than 0.35 indicating a lack of precision. The point estimates should be interpreted strictly with its 95% confidence intervals. Open table in a new tab Our HCV infection finding corroborates with population cohort studies (0.3%)5Muhamad N.A. Melati R. Ghani A. et al.Seroprevalence of hepatitis B virus and hepatitis C virus infection among Malaysian population.Sci Rep. 2020; 1021009Crossref PubMed Scopus (4) Google Scholar but lower compared to study from McDonald et al.3Mcdonald S.A. Mohamed R. Dahlui M. Naning H. Kamarulzaman A. Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis.BMC Infect Dis. 2014; 14: 564Crossref PubMed Scopus (0) Google Scholar The prevalence is comparable to those in neighbouring countries like Indonesia (0.5%), and Thailand (0.5%) but lower than Vietnam (0.9%) and Cambodia (1.1%).6The Polaris Observatory HCV CollaboratorsGlobal change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study.Lancet Gastroenterol Hepatol. 2022; 7: 396-415Summary Full Text Full Text PDF PubMed Scopus (34) Google Scholar Our study is the first to report chronic HCV infection in this region. Our study found a lower burden of HCV and chronic HCV infections among the general population, but all of them we undiagnosed. In 2019, Malaysia released the National Strategic Plan for Hepatitis B and C 2019–2030 to combat hepatitis and one of the targets was to diagnose 90% of population living with viral hepatitis.7Disease Control Division and Gastroenterology & Hepatology Services Ministry of Health MalaysiaNational strategic plan for hepatitis B and C.https://www.moh.gov.my/moh/resources/Penerbitan/Pelan%20Strategik%20/NSP_Hep_BC_2019_2023.pdfDate: 2019Date accessed: April 4, 2023Google Scholar Therefore, the Malaysian government took many initiatives such as conducting early screening to save more lives and prevent chronic sequelae that can burden the healthcare system. This early screening also included in the program among antenatal mothers as part of the prevention of mother-to-child transmission program. In addition, strengthening knowledge and awareness about HCV is important to curb the spread of the disease in the community. Having sufficient knowledge or awareness about HCV and its risk factors will foster early HCV self-screening, especially among those who engage in high-risk behaviours. Efforts to minimize the stigma associated with HCV testing have also been shown to encourage testing for early treatment. Data received from the Ministry of Health Malaysia reported, there were 3438 new chronic infection in 2019 and the number increased to 4626 in 2022 with a notification rate of 10.55 and 14.17 per 100,000 population, respectively. Started year 2018, sofosbuvir and daclatasvir were used as the standard Direct-Acting Antivirals (DAAs) regimen to treat HCV infection in Malaysia, which is the choice of DAAs and length of treatment vary according to the stage of liver disease.4Clinical practice guidelines management of chronic hepatitis C in adults. Ministry of Health Malaysia and Malaysia Academy of Medicine Malaysia, 2019https://www.moh.gov.my/moh/resources/Penerbitan/CPG/Gastroenterology/CPG_Management_of_Chronic_Hepatitis_C_in_Adults.pdfDate accessed: April 4, 2023Google Scholar Currently, the Ministry of Health was providing HCV screening and treatment in 63 public hospitals and 618 public health clinics across country, which have treated 4819 patients in 2022. Although treatment is free at public health facilities in Malaysia, there remain several barriers that patients may overcome while seeking treatment, such as the expense of transportation costs and loss productivity in jobs and daily activities because of multiple treatment follow-up.8Chan H.K. Hassali M.A. Mohammed N.S. Azlan A. Hassan M.R.A. Barriers to scaling up hepatitis C treatment in Malaysia: a qualitative study with key stakeholders.BMC Publ Health. 2022; 22: 1-9Crossref PubMed Scopus (3) Google Scholar However, the prevalence of HCV infection is likely higher on the targeted populations e.g. prisoners or vulnerable population, which not covered in this study. Further studies and screening efforts must be concentrated towards these populations to high the yield and the rate. Failing to recognise them prevents linkage to care and effective HCV control. HCV screening is therefore crucial for increasing the diagnosis of infected people, who can then obtain better care and be cured. Conception and design of the study: ENM, MHAM, ZLC, MRAH; Data collection, data analysis and interpretation: ENM, MHAM, HKC, FY, NAA; Drafting of manuscript and critical revision: ENM, MHAM, ZLC, HKC, FY, NAA, MRAH; Approval of the final version of the article: ENM, MHAM, ZLC, HKC, FY, NAA, MRAH. The dataset used and/or analysed are included in this published article and supplementary material. Also available from the corresponding author upon reasonable request. All authors disclose that there is no competing interest. All authors had no potential conflict of interest regarding the publication of this article. The authors would like to thank the Director General of Health, Malaysia for his kind permission to present this paper. Many thanks to the research team members, data collectors and all participants for their contributions, kind cooperation and commitment in this study. Download .docx (.04 MB) Help with docx files Supplementary material