Prevalence of hepatitis C virus exposure and infection among Indigenous and tribal populations: a global systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to estimate prevalence of hepatitis C virus (HCV) exposure and infection among Indigenous and tribal populations globally. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We systematically searched bibliographic databases and grey literature (1/01/2000-16/06/2022). Prevalence estimates were synthesised overall, by World Health Organization region and HCV-risk group. For studies with comparator populations, prevalence ratios were estimated and pooled. RESULTS: Ninety-two studies were included. Globally, among general Indigenous and tribal populations, the median prevalence of HCV antibody (HCV Ab) was 1.3% (interquartile range [IQR]: 0.3-3.8%, I2 = 98.5%) and HCV RNA was 0.4% (IQR: 0-1.3%, I2 = 96.1%). The Western Pacific Region had the highest prevalence (HCV Ab: median: 3.0% [IQR: 0.4-11.9%], HCV RNA: median 5.6% [IQR: 2.0-8.8%]). Prevalence was highest in people who injected drugs (HCV Ab: median: 59.5%, IQR: 51.5-67.6%, I2 = 96.6%; and HCV RNA: median: 29.4%, IQR: 21.8-35.2%, I2 = 97.2%). There was no association between HCV Ab prevalence and Indigenous/tribal status for general populations (prevalence ratio = 0.91; 95% CI: 0.56, 1.49) or key risk groups. CONCLUSIONS: Indigenous and tribal peoples from the Western Pacific Region and recognised at-risk sub-populations had higher HCV prevalence. HCV prevalence showed no association with Indigenous/tribal status. However, this review was limited by heterogeneity and poor quality of constituent studies, varying definitions of Indigenous/tribal status, regional data gaps, and limited studies on chronic infection (HCV RNA). Comprehensive quality evidence on HCV epidemiology in Indigenous and tribal peoples is needed to tailor preventive and treatment interventions so these populations are not left behind in elimination efforts.

Uptake of direct-acting antiviral treatment for chronic hepatitis C in Australia.

A government-funded interferon-free direct-acting antiviral (DAA) treatment programme for chronic hepatitis C virus (HCV) infection has been available in Australia since March 2016. This study assessed the levels and patterns of DAA treatment uptake during March-December 2016 in Australia and described the key features in the development of the programme. All prescriptions in Australia are submitted to the Pharmaceutical Benefits Scheme by dispensing pharmacies. Data on dispensed DAA prescriptions for a longitudinal cohort of individuals, representing a 10% random sample of the Pharmaceutical Benefits Scheme database, were used for estimating DAA treatment uptake and subgroup analyses. The estimated number of 32 400 individuals initiated DAA treatment in 2016, equating to 14% of people with chronic HCV infection in Australia. Most commonly prescribed DAA regimens included sofosbuvir/ledipasvir (56%, n = 18 020), sofosbuvir + daclatasvir (39%, n = 12 600) and sofosbuvir + other agents (4%, n = 1220). Among individuals initiated DAA treatment, 66% (n = 21 430) were men, 43% (n = 13 870) were ≤50 years old and 36% (n = 11 670) had cirrhosis. DAA prescriptions were 62% (n = 20 080) by specialists, 19% (n = 6000) by general practitioners (GP) and 20% (n = 6320) by other physicians. Proportion of individuals prescribed DAA by GPs increased from 8% to 31% and proportion of individuals ≤50 years old increased from 28% to 61% between March and December. In conclusion, rapid treatment scale-up was observed in the first 10 months of unrestricted DAA programme in Australia. The proportion of prescriptions by GPs increased over time, important for broadened access. A trend towards younger age treatment suggested the broadening of DAA-treated population, potentially including individuals at higher risk of HCV transmission.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

More than a virus: a qualitative study of the social implications of hepatitis B infection in China.

BACKGROUND: China has the largest absolute number of people living with hepatitis B with up to 300,000 people estimated to die each year from hepatitis B related diseases. Despite advances in immunisation, clinical management, and health policy, there is still a lack of accessible and affordable health care for people with hepatitis B. Through in-depth interviews, this study identifies the personal, social and economic impact of living with hepatitis B and considers the role of stigma and discrimination as barriers to effective clinical management of the disease. METHODS: Semi-structured qualitative interviews were held with 41 people living with hepatitis B in five Chinese cities. Participants were recruited through clinical and non-government organisations providing services to people with hepatitis B, with most (n = 32) being under the age of 35 years. RESULTS: People living with hepatitis B experience the disease as a transformative intergenerational chronic infection with multiple personal and social impacts. These include education and employment choices, economic opportunities, and the development of intimate relationships. While regulations reducing access to employment and education for people with hepatitis B have been repealed, stigma and discrimination continue to marginalise people with hepatitis B. CONCLUSIONS: Effective public policy to reduce morbidity and mortality associated with hepatitis B needs to address the lived impact of hepatitis B on families, employment and educational choices, finances, and social marginalisation.

Ongoing incident hepatitis C virus infection among people with a history of injecting drug use in an Australian prison setting, 2005-2014: The HITS-p study.

Hepatitis C virus (HCV) transmission is high in prisons. This study investigated trends in HCV incidence and associated factors among a cohort of prisoners with a history of injecting drug use in New South Wales, Australia. Data were available from the Hepatitis C Incidence and Transmission Study-prisons (HITS-p) from 2005 to 2014. Temporal trends in HCV incidence were evaluated. Factors associated with time to HCV seroconversion among people with ongoing injecting was assessed using Cox proportional hazards. Among 320 antibody-negative participants with a history of injecting drug use (mean age 26; 72% male), 62% (n=197) reported injecting drug use during follow-up. Overall, 93 infections were observed. HCV incidence was 11.4/100 person-years in the overall population and 6.3/100 person-years among the continually imprisoned population. A stable trend in HCV incidence was observed. Among the overall population with ongoing injecting during follow-up, ≥weekly injecting drug use frequency was independently associated with time to HCV seroconversion. Among continuously imprisoned injectors with ongoing injecting during follow-up, needle/syringe sharing was independently associated with time to HCV seroconversion. This study demonstrates that prison is a high-risk environment for acquisition of HCV infection. Needle and syringe sharing was associated with HCV infection among continually imprisoned participants, irrespective of frequency of injecting or the type of drug injected. These findings highlight the need for the evaluation of improved HCV prevention strategies in prison, including needle/syringe programmes and HCV treatment.

Higher incidence of HCV in females compared to males who inject drugs: A systematic review and meta-analysis.

Women who inject drugs have been shown to have higher incidence of HIV and risk behaviours than men, but there are conflicting reports about hepatitis C virus (HCV) incidence. We systematically reviewed the literature to examine the female-to-male (F:M) HCV incidence in female and male persons who inject drugs (PWID), and also to explore the heterogeneity (i.e. methodological diversity) in these differences. We searched PubMed and EMBASE for studies published between 1989 and March 2015 for research that reported incidence of HCV infection by sex or HCV incidence F:M rate ratio. A total of 28 studies, which enrolled 9325 PWID, were included. The overall pooled HCV incidence rate (per 100 person-years observation) was 20.36 (95% CI: 13.86, 29.90) and 15.20 (95% CI: 10.52, 21.97) in females and males, respectively. F:M ratio was 1.36:1 (95% CI: 1.13, 1.64) with substantial heterogeneity (I-squared=71.6%). The F:M ratio varied by geographic location from 4.0 (95% CI: 1.80, 8.89) in China to 1.17 (95% CI: 0.95, 1.43) in the U.S. In studies which recruited participants from community settings, the F:M ratio was 1.24 (95% CI: 1.03, 1.48), which was lower than that reported in the clinical settings (1.72, 95% CI: 0.86, 3.45). The number of studies included provided sufficient statistical power to detect sex differences in this analysis. Our findings raise questions and concerns regarding sex differences with respect to the risk of HCV. Both behavioural and biological studies are needed to investigate causes and potential mechanisms as well as sex-specific prevention approaches to HCV infection.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Factors associated with hepatitis C virus RNA levels in early chronic infection: the InC3 study.

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC(3) study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection.