To estimate stage-specific transition probabilities in individuals coinfected with HIV and hepatitis C virus (HCV), to examine the effect of covariates on these rates, and to investigate the effect ...of HIV on HCV-related cirrhosis in the era of highly active antiretroviral therapy (HAART).
Systematic review of natural history studies among HCV-infected individuals.
Markov maximum likelihood estimation method was used to estimate stage-specific transition probabilities. A meta-analysis was performed to obtain pooled transition probabilities, and a meta-regression to investigate the impact of covariates on these rates. Risk of cirrhosis between individuals monoinfected with HCV and coinfected with HIV/HCV were compared by HAART status.
The estimated mean (95% confidence intervals) annual transition probabilities of 3567 individuals coinfected with HIV/HCV (n = 17 studies) were as follows: fibrosis stage (F) F0 --> F1 0.122 (0.098-0.153); F1 --> F2 0.115 (0.095-0.140); F2 --> F3 0.124 (0.097-0.159); and F3 --> F4 0.115 (0.098-0.135) units/year. The prevalence of cirrhosis after 20 and 30 years of HCV infection was 21% (16-28%) and 49% (40-59%), respectively. Longer duration of HCV infection was significantly associated with slower rate of fibrosis progression. The overall rate ratio of cirrhosis between individuals coinfected with HIV/HCV and monoinfected with HCV (n = 27 studies) was 2.1 (1.5-3.0), 2.5 (1.8-3.4) in the non-HAART group, and 1.7 (1.1-2.8) in the HAART group.
The rate of fibrosis progression among individuals coinfected with HIV/HCV appears constant. Our results confirm that chronic hepatitis C outcomes are worse among coinfected individuals. Over the period studied, HAART did not appear to fully correct the adverse effect of HIV infection on HCV prognosis.
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•Prior to the introduction of DAA therapy, the disease burden of HCV was rising in New South Wales.•DAA scale-up has had a major population-level impact on HCV morbidity and ...mortality.•The World Health Organization has set a 65% HCV mortality reduction target by 2030.•To achieve this target, enhanced efforts are required to continue DAA scale-up.•In the DAA era, the impact of heavy alcohol use on liver disease should be monitored.
Population-level evidence for the impact of direct-acting antiviral (DAA) therapy on hepatitis C virus (HCV)-related disease burden is lacking. We aimed to evaluate trends in HCV-related decompensated cirrhosis and hepatocellular carcinoma (HCC) hospitalisation, and liver-related and all-cause mortality in the pre-DAA (2001–2014) and DAA therapy (2015–2017) eras in New South Wales, Australia.
HCV notifications (1993–2016) were linked to hospital admissions (2001–2017) and mortality (1995–2017). Segmented Poisson regressions and Poisson regression were used to assess the impact of DAA era and factors associated with liver-related mortality, respectively.
Among 99,910 people with an HCV notification, 3.8% had a decompensated cirrhosis diagnosis and 1.8% had an HCC diagnosis, while 3.3% and 10.5% died of liver-related and all-cause mortality, respectively. In the pre-DAA era, the number of decompensated cirrhosis and HCC diagnoses, and liver-related and all-cause mortality consistently increased (incidence rate ratios 1.04 95% CI 1.04–1.05, 1.08 95% CI 1.07–1.08, 1.07 95% CI 1.06–1.07, and 1.05 95% CI 1.04–1.05, respectively) over each 6-monthly band. In the DAA era, decompensated cirrhosis diagnosis and liver-related mortality numbers declined (incidence rate ratios 0.97 95% CI 0.95–0.99 and 0.96 95% CI 0.94–0.98, respectively), and HCC diagnosis and all-cause mortality numbers plateaued (incidence rate ratio 1.00 95% CI 0.97–1.03 and 1.01 95% CI 1.00–1.02, respectively) over each 6-monthly band. In the DAA era, alcohol-use disorder (AUD) was common in patients diagnosed with decompensated cirrhosis and HCC (65% and 46% had a history of AUD, respectively). AUD was independently associated with liver-related mortality (incidence rate ratio 3.35; 95% CI 3.14–3.58).
In the DAA era, there has been a sharp decline in liver disease morbidity and mortality in New South Wales, Australia. AUD remains a major contributor to HCV-related liver disease burden, highlighting the need to address comorbidities.
Rising hepatitis C-related morbidity and mortality is a major public health issue. However, development of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) means hepatitis C could be eliminated as a public health threat by 2030. This study shows a sharp decline in liver disease morbidity and mortality since the introduction of DAAs in New South Wales, Australia. Despite this, heavy alcohol use remains an important risk factor for liver disease among people with hepatitis C. To ensure that the benefits of new antiviral treatments are not compromised, management of major comorbidities, including heavy alcohol use must improve among people with hepatitis C.
Abstract Background Hepatitis C virus (HCV) infection is endemic among people who inject drugs (PWID) globally. Despite high prevalence, treatment uptake is low, with cumulative uptake <10% in most ...settings. This study aimed to populate the cascade of HCV testing, care and treatment among PWID using data collected in Australia prior to the introduction of broadly accessible interferon-free direct-acting antiviral (DAA) therapies in March 2016. Methods The Australian Needle and Syringe Program Survey is a cross-sectional surveillance system that recruits ∼2300 PWID annually and collects behavioural data and dried blood samples (DBS). HCV antibody and ribonucleic acid (RNA) test results from DBS collected in 2015 were combined with data on HCV diagnostic testing, care and treatment to populate the HCV cascade among Australian PWID. Results Among an estimated 93,000 PWID in Australia in 2015, the majority (89%) had a lifetime history of HCV antibody testing. More than half (57%) of PWID tested HCV antibody positive and of these, 79% had detectable HCV RNA consistent with active infection. Less than half (46%) of HCV antibody positive PWID had received confirmatory HCV RNA testing. Among the estimated 43,201 PWID with active infection or chronic infection that had been successfully treated, 31% had received specialist HCV assessment, 8% had received antiviral treatment and 3% were cured. Conclusion This study provides baseline estimates of the cascade of HCV testing, care and treatment among PWID through enhancement of a well-established surveillance mechanism. Characterisation of the HCV cascade among PWID will be crucial to evaluating and monitoring the roll out of direct-acting antiviral therapies in Australia, including assessing potential HCV treatment as prevention benefits.
Summary Hepatitis C virus (HCV) was discovered more than two decades ago, but progress towards a vaccine has been slow. HCV infection will spontaneously clear in about 25% of people. Studies of ...spontaneous HCV clearance in chimpanzees and human beings have identified host and viral factors that could be important in the control of HCV infection and the design of HCV vaccines. Although data from studies of chimpanzees suggest that protection against reinfection is possible after spontaneous clearance, HCV is a human disease. Results from studies of reinfection risk after spontaneous clearance in injecting drug users are conflicting, but some people seem to have protection against HCV persistence. To guide future vaccine development, we assess data from studies of HCV reinfection after spontaneous clearance, discuss flaws in the methods of previous human studies, and suggest essential components for future investigations of control of HCV infection.
Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID).
To evaluate elbasvir-grazoprevir in treating HCV infection in PWID.
Randomized, placebo-controlled, double-blind trial. ...(ClinicalTrials.gov: NCT02105688).
Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States.
301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT).
The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks.
The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events.
The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebo-phase DTG (1 of 100) discontinued treatment because of an adverse event.
These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID.
Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT.
Merck & Co.
Summary
Background
Direct‐acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection is highly curative and tolerable. Among patients with hepatocellular carcinoma (HCC), optimal timing of ...DAA therapy remains unclear. Data on efficacy of DAA therapy in patients with HCC would inform this decision‐making.
Aim
To evaluate response to DAA therapy among patients diagnosed with HCV infection and HCC.
Methods
Bibliographic databases and conference s were searched. Meta‐analysis was conducted to pool sustained virologic response (SVR) estimates.
Results
Fifty‐six studies with 5522 patients with HCV and HCC were included. Overall SVR was 88.3% (95% CI 86.1‐90.4). Twenty‐seven studies included patients with prior or present HCC (n = 3126) and patients without HCC (n = 49 138), in which SVR was 88.2% (95% CI 85.0‐91.4) and 92.4% (95% CI 91.1‐93.7) among patients with and without HCC, respectively (odds ratio: 0.54, 95% CI 0.43‐0.68, P < .001). In the subgroup analyses, higher SVR was seen in patients who received curative HCC management (SVR 90.4%, 95% CI 88.3‐92.4), or treated with sofosbuvir + NS5A inhibitor DAAs (SVR 96.9%, 95% CI 94.3‐99.4), or in patients with HCV genotype 1 infection (SVR 92.0%, 95% CI 88.1‐95.6).
Conclusion
Response to DAA therapy was lower in patients with HCC compared to those without HCC, regardless of cirrhosis status. Among HCC patients, there was an impact of proportion with curative HCC management on DAA therapy response.
Of ∼10.2 million people with chronic HCV infection in Europe, 6.7 million live in Eastern Europe, 2.3 million in Western Europe and 1.2 million in Central Europe.
HCV transmission continues to occur ...in parallel with an increasing HCV-related liver disease burden, the result of an ageing population infected during peak HCV epidemics decades earlier. In 2016, the World Health Organization set targets to eliminate HCV infection as a major public health threat by 2030. Across Europe, an estimated 36% of those living with chronic HCV infection have been diagnosed and ∼5% have been treated. A major barrier to enhancing HCV treatment uptake has been restrictions set by payers, including national governments and others, in response to the initially high list prices of direct-acting antiviral (DAA) therapies. The aims of this article are to discuss DAA restrictions in Europe, why DAA restrictions are still in place, what has facilitated the removal of DAA restrictions, and what challenges remain as we attempt to eliminate HCV as a major public health threat in the region by 2030.
Background and Aims
People who have recently injected drugs are a priority population in efforts to achieve hepatitis C virus (HCV) elimination. This study estimated the prevalence and number of ...people with recent injecting drug use living with HCV, and the proportion of people with recent injecting drug use among all people living with HCV infection at global, regional and country‐levels.
Methods
Data from a global systematic review of injecting drug use and HCV antibody prevalence among people with recent (previous year) injecting drug use were used to estimate the prevalence and number of people with recent injecting drug use living with HCV. These data were combined with a systematic review of global HCV prevalence to estimate the proportion of people with recent injecting drug use among all people living with HCV.
Results
There are an estimated 6.1 million 95% uncertainty interval (UI) = 3.4–9.2 people with recent injecting drug use aged 15–64 years living with HCV globally (39.2% viraemic prevalence; UI = 31.6–47.0), with the greatest numbers in East and Southeast Asia (1.5 million, UI = 1.0–2.1), eastern Europe (1.5 million, UI = 0.7–2.4) and North America (1.0 million, UI = 0.4–1.7). People with recent injecting drug use comprise an estimated 8.5% (UI = 4.6–13.1) of all HCV infections globally, with the greatest proportions in North America (30.5%, UI = 11.7–56.7), Latin America (22.0%, UI = 15.3–30.4) and eastern Europe (17.9%, UI = 8.2–30.9).
Conclusions
Although, globally, 39.2% of people with recent injecting drug use are living with hepatitis C virus (HCV) and 8.5% of all HCV infections occur globally among people with recent injecting drug use, there is wide variation among countries and regions.
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