Dataset Information

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

ABSTRACT:

Background

First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection.

Methods

Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016-2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU.

Results

Compared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p < 0.001), morel likely to reside in most disadvantaged (p = 0.002) and in regional/remote areas (p < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%; p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients; p = 0.51) and 'good' adherence (90.0% vs. 86.9%, respectively; p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87-0.99) and treatment initiation in 2018-2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23-21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50-0.99).

Conclusions

Our data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.

SUBMITTER: Clark PJ

PROVIDER: S-EPMC9275019 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

Clark Paul J PJ Valery Patricia C PC Ward James J Strasser Simone I SI Weltman Martin M Thompson Alexander A Levy Miriam T MT Leggett Barbara B Zekry Amany A Rong Julian J Angus Peter P George Jacob J Bollipo Steven S McGarity Bruce B Sievert William W Macquillan Gerry G Tse Edmund E Nicoll Amanda A Wade Amanda A Chu Geoff G Harding Damian D Cheng Wendy W Farrell Geoff G Roberts Stuart K SK

BMC gastroenterology 20220711 1

<h4>Background</h4>First Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection.<h4>Methods</h4>Adults who initiated DAA therapy at one of 26 hospitals across Australia, 2016-2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes in ...[more]

PMID: 35820850

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Project description:Background & aimsHCV subtypes which are unusual in Europe are more prevalent in the African region, but little is known of their response to direct-acting antivirals (DAAs). These include non-1a/1b/ non-subtypeable genotype 1 (G1) or non-4a/4d (G4). In this report we aimed to describe the genotype distribution and treatment outcome in a south London cohort of African patients.MethodsWe identified all patients born in Africa who attended our clinic from 2010-2018. Information on HCV genotype, treatment regimen and outcome were obtained. Non-subtypeable samples were analysed using Glasgow NimbleGen next-generation sequencing (NGS). Phylogenetic analysis was carried out by generating an uncorrected nucleotide p-distance tree from the complete coding regions of our sequences.ResultsOf 91 African patients, 47 (52%) were infected with an unusual subtype. Fourteen novel, as yet undesignated subtypes (G1*), were identified by NGS. Three individuals were infected with the same subtype, now designated as subtype 1p. Baseline sequences were available for 22 patients; 18/22 (82%) had baseline NS5A resistance-associated substitutions (RASs). Sustained virological response (SVR) was achieved in 56/63 (89%) overall, yet only in 21/28 (75%) of those with unusual G1 subtypes, with failure in 3/16 G1*, 1/2 G1p and 3/3 in G1l. Six treatment failures occurred with sofosbuvir/ledipasvir compared to 1 failure on a PI-based regimen. The SVR rate for all other genotypes and subtypes was 35/35 (100%).ConclusionsMost individuals in an unselected cohort of African patients were infected with an unusual genotype, including novel subtype 1p. The SVR rate of those with unusual G1 subtypes was 75%, raising concern about expansion of DAAs across Africa. Depending on the regimen used, higher failure rates in African cohorts could jeopardise HCV elimination.Lay summaryDirect-acting antiviral medications are able to cure hepatitis C in the majority of patients. The most common genotype of hepatitis C in Europe and the United States is genotype 1a or 1b and most clinical trials focused on these genotypes. We report that in a group of African patients, most of them had unusual (non-1a/1b) genotype 1 subtypes, and that the cure rate in these unusual genotypes was lower than in genotypes 1a and 1b.

Project description:Background: As First Nations Peoples are a priority focus of Canada’s commitment to eliminating hepatitis C virus (HCV) as a public health threat, understanding individuals’ progression from diagnosis to cure can guide prioritization of elimination efforts. We sought to characterize and identify gaps in the HCV care cascade for Status First Nations peoples in Ontario. Methods: In this retrospective cohort study, a partnership between the Ontario First Nations HIV/AIDS Education Circle and academic researchers, HCV testing records (1999–2018) for Status First Nations peoples in Ontario were linked to health administrative data. We defined the cascade of care as 6 stages, as follows: tested positive for HCV antibody, tested for HCV RNA, tested positive for HCV RNA, HCV genotyped, initiated treatment and achieved sustained viral response (SVR). We mapped the care cascade from 1999 to 2018, and estimated the number and proportion of people at each stage. We stratified analyses by sex, diagnosis date and location of residence. We used Cox regression to analyze the secondary outcomes, namely the associations between undergoing HCV RNA testing and initiating treatment, and demographic and clinical predictors. Results: By Dec. 31, 2018, 4962 people tested positive for HCV antibody. Of those testing positive, 4118 (83.0%) were tested for HCV RNA, with 2480 (60.2%) testing positive. Genotyping was completed in 2374 (95.7%) of those who tested positive for HCV RNA, with 1002 (42.2%) initiating treatment. Nearly 80% (n = 801, 79.9%) of treated people achieved SVR, with 34 (4.2%) experiencing reinfection or relapse. Undergoing testing for HCV RNA was more likely among people in older age categories (within 1 yr of antibody test; adjusted hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.19–1.41, among people aged 41–60 yr; adjusted HR 1.47, 95% CI 1.18–1.81, among people aged > 60 yr), those living in rural areas (adjusted HR 1.20, 95% CI 1.10–1.30), those with an index date after Dec. 31, 2013 (era of treatment with direct-acting antiviral regimens) (adjusted HR 1.99, 95% CI 1.85–2.15) and those with a record of substance use or addictive disorders (> 1 yr after antibody test; adjusted HR 1.38, 95% CI 1.18–1.60). Treatment initiation was more likely among people in older age categories at index date (adjusted HR 1.32, 95% CI 1.15–1.50, among people aged 41–60 yr; adjusted HR 2.62, 95% CI 1.80–3.82, among people aged > 60 yr) and those with a later diagnosis year (adjusted HR 2.71, 95% CI 2.29–3.22). Interpretation: In comparison with HCV testing and diagnosis, a substantial gap in treatment initiation remains among Status First Nations populations in Ontario. Elimination efforts that prioritize linkage to care and integration with harm reduction and substance use services are needed to close gaps in HCV care among First Nations populations in Ontario.

Project description:BackgroundFirst Nations children hospitalised with acute lower respiratory infections (ALRIs) are at increased risk of future bronchiectasis (up to 15-19%) within 24-months post-hospitalisation. An identified predictive factor is persistent wet cough a month after hospitalisation and this is likely related to protracted bacterial bronchitis which can progress to bronchiectasis, if untreated. Thus, screening for, and optimally managing, persistent wet cough one-month post-hospitalisation potentially prevents bronchiectasis in First Nations' children. Our study aims to improve the post-hospitalisation medical follow-up for First Nations children hospitalised with ALRIs and thus lead to improved respiratory health. We hypothesize that implementation of a strategy, conducted in a culturally secure manner, that is informed by barriers and facilitators identified by both parents and health care providers, will improve medical follow-up and management of First Nations children hospitalized with ALRIs.MethodsOur trial is a multi-centre, pseudo-randomized stepped wedge design where the implementation of the strategy is tailored for each study site through a combined Participatory Action Research and implementation science approach informed by the Consolidated Framework of Implementation Research. Outcome measures will consist of three categories related to (i) health, (ii) economics and (iii) implementation. The primary outcome measure will be Cough-specific Quality of Life (PC-QoL). Outcomes will be measures at each study site/cluster in three different stages i.e., (i) nil-intervention control group, (ii) health information only control group and (iii) post-intervention group.DiscussionIf our hypothesis is correct, our study findings will translate to improved health outcomes (cough related quality of life) in children who have persistent wet cough a month after hospitalization for an ALRI. Trial registration ACTRN12622000224729, prospectively registered 8 February 2022, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382886&isReview=true .

Dataset Information

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

Background

Methods

Results

Conclusions

Publications

Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up.

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