Improving Linkage to Care of Hepatitis C: Clinical Validation of GeneXpert® HCV Viral Load Point-of-Care Assay in Indonesia.

Hepatitis C virus (HCV) infection large-scale diagnosis and treatment are hampered by lack of a simple, rapid, and reliable point-of-care (POC) test, which poses a challenge for the elimination of hepatitis C as a public health problem. This study aimed to evaluate Cepheid Xpert® HCV Viral Load performance in comparison with the Roche Cobas® TaqMan® HCV Test using serum samples of HCV-infected patients in Indonesia. Viral load quantification was performed on 243 anti-HCV positive patients' samples using both Xpert HCV VL and Roche HCV tests, followed by HCV genotyping by reverse hybridization. Strength of the relationship between the assays was measured by Pearson correlation coefficient, while level of agreement was analyzed by Deming regression and Bland-Altman plot analysis using log10-transformed viral load values. Quantifiable viral load was detected in 180/243 (74.1%), with Xpert HCV VL sensitivity of 100% (95% CI 0.98, 1.00) and specificity of 98.4% (95% CI 0.91, 0.99) based on the Roche HCV test, while HCV genotypes were determined in 172/180 (95.6%) samples. There was a good correlation between both assays (r = 0.97, P < 0.001), overall and per genotype, with good concordance by Deming regression and a mean difference of -0.25 log10 IU/mL (95% CI -0.33, -0.18) by Bland-Altman plot analysis. Xpert HCV VL test was demonstrated as a POC platform with good performance for HCV diagnosis and treatment decision that would be beneficial for decentralized services in resource-limited areas. HCV testing sites, alongside additional GeneXpert modular systems distributed toward the fight against COVID-19, could ensure some continuity, once this pandemic is controlled.

High Prevalence of Hepatitis B Virus Infection in Young Adults in Ternate, Eastern Indonesia.

The incidence of hepatitis B virus (HBV) infection has been declining thanks to the universal hepatitis B infant immunization program. Nevertheless, young adults born before the program implementation might have acquired HBV in early childhood or remain susceptible to infection. This study aimed to evaluate hepatitis B epidemiology in asymptomatic young adult population in Ternate, eastern Indonesia. Serum samples of 376 subjects (aged 17-25, mean 19.82 ± 1.69 years; male/female 138/238) were screened for HBV parameters serologically (HBV surface antigen [HBsAg]; its antibody [anti-HBs]; anti-core antigen [anti-HBc]), and molecularly (HBV DNA). HBsAg, anti-HBc, anti-HBs, and HBV DNA prevalence were 15.7%, 36.2%, 24.2%, and 27.9%, respectively, with male predominance. Of all subjects, 13.0% were HBsAg negative with detectable HBV DNA (occult hepatitis B [OHB]), and 56.4% showed negativity for all seromarkers. This population showed high hepatitis B prevalence with substantial occurrence of OHB. However, a high percentage of the population were still susceptible and at risk of HBV infection. This study emphasizes the necessity to improve prevention strategies to screen and manage HBV carriers, including the adoption of catch-up or booster vaccination targeted to young adult populations. Investigations on the roles of host-virus interactions associated with OHB and its implications are warranted.

Genogeography and Immune Epitope Characteristics of Hepatitis B Virus Genotype C Reveals Two Distinct Types: Asian and Papua-Pacific.

Distribution of hepatitis B virus (HBV) genotypes/subgenotypes is geographically and ethnologically specific. In the Indonesian archipelago, HBV genotype C (HBV/C) is prevalent with high genome variability, reflected by the presence of 13 of currently existing 16 subgenotypes. We investigated the association between HBV/C molecular characteristics with host ethnicity and geographical distribution by examining various subgenotypes of HBV/C isolates from the Asia and Pacific region, with further analysis on the immune epitope characteristics of the core and surface proteins. Phylogenetic tree was constructed based on complete HBV/C genome sequences from Asia and Pacific region, and genetic distance between isolates was also examined. HBV/C surface and core immune epitopes were analyzed and grouped by comparing the amino acid residue characteristics and geographical origins. Based on phylogenetic tree and geographical origins of isolates, two major groups of HBV/C isolates--East-Southeast Asia and Papua-Pacific--were identified. Analysis of core and surface immune epitopes supported these findings with several amino acid substitutions distinguishing the East-Southeast Asia isolates from the Papua-Pacific isolates. A west-to-east gradient of HBsAg subtype distribution was observed with adrq+ prominent in the East and Southeast Asia and adrq- in the Pacific, with several adrq-indeterminate subtypes observed in Papua and Papua New Guinea (PNG). This study indicates that HBV/C isolates can be classified into two types, the Asian and the Papua-Pacific, based on the virus genome diversity, immune epitope characteristics, and geographical distribution, with Papua and PNG as the molecular evolutionary admixture region in the switching from adrq+ to adrq-.

HBsAg, HBeAg and HBV DNA level changes and precore/basal core promoter mutations in the natural history of chronic hepatitis B in Indonesian patients.

INTRODUCTION: Chronic hepatitis B (CHB) is a state of complex interactions between the hepatitis B virus (HBV) and host. We studied the changes in hepatitis B surface antigen (HBsAg), hepatitis B 'e' antigen (HBeAg) and HBV DNA levels, considering the implications of HBV genotype, basal core promoter (BCP) A1762T/G1764A and precore G1896A mutations in CHB. METHODS: One hundred fifty-two treatment-naïve CHB patients were classified into immune-tolerant (IT), immune-clearance (IC), low/non-replicative (LR) and 'e'-negative hepatitis B (ENH) phases, based on HBeAg status, HBV DNA and ALT levels. HBV DNA was detected and quantified by polymerase chain reaction, then analyzed by sequencing. HBsAg and HBeAg levels were measured serologically. RESULTS: HBsAg and HBV DNA levels varied between CHB phases, with HBsAg highest in IT and lowest in LR, and HBV DNA high in IT and IC, and lowest in LR. Both markers increased in ENH. Correlation between HBsAg and HBV DNA was significant in IT and IC, modest in ENH, but missing in LR. HBeAg and HBV DNA levels were dissociated in HBeAg-positive patients. Genotypes B and C were similarly distributed, with precore mutations higher in HBeAg-negative patients and BCP mutations comparable in all phases. Temporal association between HBeAg seroconversion and an increase of BCP/precore mutations was observed. CONCLUSION: HBsAg and HBV DNA levels were high and correlated in early CHB phases and dissociated after HBeAg seroconversion, indicating different controls affecting HBV replication and HBsAg production. Selection of BCP/precore mutants may affect disease course and explain the HBeAg-HBV DNA dissociation, a precaution for clinical application of quantitative HBeAg.