Epidemiology and natural history of HCV infection Hajarizadeh, Behzad; Grebely, Jason; Dore, Gregory J
Nature reviews. Gastroenterology & hepatology,
09/2013, Letnik:
10, Številka:
9
Journal Article
Recenzirano
Worldwide, an estimated 130-170 million people have HCV infection. HCV prevalence is highest in Egypt at >10% of the general population and China has the most people with HCV (29.8 million). ...Differences in past HCV incidence and current HCV prevalence, together with the generally protracted nature of HCV disease progression, has led to considerable diversity in the burden of advanced liver disease in different countries. Countries with a high incidence of HCV or peak incidence in the recent past will have further escalations in HCV-related cirrhosis and hepatocellular carcinoma (HCC) over the next two decades. Acute HCV infection is difficult to detect because of the generally asymptomatic nature of the disease and the marginalization of at-risk populations. Around 25% of patients with acute HCV infection undergo spontaneous clearance, with increased rates among those with favourable IL28B genotypes, acute symptoms and in women. The remaining 75% of patients progress to chronic HCV infection and are subsequently at risk of progression to hepatic fibrosis, cirrhosis and HCC. Chronic hepatitis C generally progresses slowly in the initial two decades, but can be accelerated during this time as a result of advancing age and co-factors such as heavy alcohol intake and HIV co-infection.
Globally, 12 million people are estimated to have injected drugs in the past year, 50% of whom have chronic HCV infection, with people who have previously injected drugs presenting an additional ...large reservoir of infection. The availability of simple and tolerable interferon-free direct-acting antiviral agents (DAAs) for HCV infection, which have a cure rate of >95% represents one of the most exciting advances in clinical medicine in the past few decades. Adherence and response to DAA therapy among people who inject drugs (PWID) receiving opioid substitution therapy (OST) in clinical trials are comparable to populations without a history of injecting drugs. Further data are required among current PWID not receiving OST. Given the potential prevention benefits of treatment, DAAs have enhanced cost-effectiveness among PWID. As HCV therapy is expanded to populations of PWID with high-risk behaviours for re-exposure, acknowledgement that HCV reinfection will occur is crucial, and appropriate strategies must be in place to maximize prevention of reinfection and offer retreatment for reinfection. This Review will also discuss essential components for broadening access to HCV care for PWID as we strive for the global elimination of HCV infection.
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•Recent studies have reported contradicting findings on HCC risk following DAA therapy.•The present study summarizes the evidence on HCC occurrence and recurrence following DAA or ...IFN-based therapy between 2000 and 2017.•No evidence for differential HCC occurrence or recurrence risk following SVR from DAA and IFN-based therapy.•No evidence to support withholding DAA therapy in patients with HCV-related cirrhosis or after curative HCC management.
The risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy remains unclear. The aims of this study were to compare the rate of HCC occurrence in patients with HCV-related cirrhosis, following DAA vs. interferon (IFN)-based cure, and to compare the rate of HCC recurrence in patients who received curative HCC treatment, following DAA vs. IFN-based cure.
A search was conducted for reports published between January 2000 and February 2017. Studies were included if they assessed HCC outcomes by type and response to HCV therapy. Random-effects meta-analyses were undertaken to determine a combined estimate of HCC incidence rate per 100/person-years (py) among patients with a sustained virological response (SVR).
A total of 41 studies (n=13,875 patients), including 26 on HCC occurrence (IFN=17, DAA=9; prospective=19, retrospective=5, retrospective-prospective=2), and 17 on HCC recurrence (IFN=7, DAA=10; prospective=11, retrospective=5 and retrospective-prospective=1) were included. In studies assessing HCC occurrence, average follow-up was shorter (1.0 vs. 5.5years), and average age older (60 vs. 52years) in DAA studies. In studies assessing HCC recurrence, average follow-up was shorter (1.3 vs. 5.0years), but average age similar (64 vs. 66years) in DAA studies. HCC occurrence was 1.14/100 py (95% CI 0.86–1.52) and 2.96/100 py (95% CI 1.76–4.96) in IFN and DAA studies respectively. HCC recurrence was 9.21/100 py (95% CI 7.18–11.81) and 12.16/100 py (95% CI 5.00–29.58) in IFN and DAA studies respectively. In meta-regression adjusting for study follow-up and age, DAA therapy was not associated with higher HCC occurrence (RR 0.68; 95% CI 0.18–2.55; p=0.55) or recurrence (RR 0.62, 95% CI 0.11–3.45, p=0.56).
There is no evidence for differential HCC occurrence or recurrence risk following SVR from DAA and IFN-based therapy.
The risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy remains unclear. We conducted a meta-analysis to compare occurrence and recurrence of HCC in patients receiving either DAA or interferon (IFN) therapy. There is no evidence that HCC occurrence or recurrence is different between patients receiving DAA or IFN therapy.
The aim of this study was to systematically evaluate state Medicaid policies for the treatment of hepatitis C virus (HCV) infection with sofosbuvir in the United States. Medicaid reimbursement ...criteria for sofosbuvir were evaluated in all 50 states and the District of Columbia. The authors searched state Medicaid Web sites between 23 June and 7 December 2014 and extracted data in duplicate. Any differences were resolved by consensus. Data were extracted on whether sofosbuvir was covered and the criteria for coverage based on the following categories: liver disease stage, HIV co-infection, prescriber type, and drug or alcohol use. Of the 42 states with known Medicaid reimbursement criteria for sofosbuvir, 74% limit sofosbuvir access to persons with advanced fibrosis (Meta-Analysis of Histologic Data in Viral Hepatitis METAVIR fibrosis stage F3) or cirrhosis (F4). One quarter of states require persons co-infected with HCV and HIV to be receiving antiretroviral therapy or to have suppressed HIV RNA levels. Two thirds of states have restrictions based on prescriber type, and 88% include drug or alcohol use in their sofosbuvir eligibility criteria, with 50% requiring a period of abstinence and 64% requiring urine drug screening. Heterogeneity is present in Medicaid reimbursement criteria for sofosbuvir with respect to liver disease staging, HIV co-infection, prescriber type, and drug or alcohol use across the United States. Restrictions do not seem to conform with recommendations from professional organizations, such as the Infectious Diseases Society of America and the American Association for the Study of Liver Diseases. Current restrictions seem to violate federal Medicaid law, which requires states to cover drugs consistent with their U.S. Food and Drug Administration labels.
The next decade will be a crucial period in the public health response to hepatitis C virus (HCV) infection. The rapid development of direct-acting antiviral (DAA) therapy for HCV infection has ...brought considerable optimism to the HCV sector, with the realistic hope that therapeutic intervention will soon provide near-optimal efficacy with well-tolerated short-duration, all-oral regimens. As the zenith in HCV therapeutic development approaches, there remain several key obstacles to the broad implementation of interferon-free DAA regimens. The extent of HCV screening and disease assessment, global and national public health prioritization, and drug pricing will determine the potential impact on disease burden derived from introduction of these exciting new HCV therapies. Public health partnerships and advocacy will be crucial to remove barriers to enhanced HCV treatment access.
The burden of hepatitis C virus (HCV)-related morbidity and mortality continues to rise. Progression to advanced liver disease among HCV-infected individuals generally requires decades, but we are ...entering an era where those infected with HCV in the 1970s and 1980s are at significant risk of mortality. Liver disease has overtaken drug-related harm as the major cause of mortality in HCV-infected individuals in many settings. Direct-acting antiviral therapies have provided renewed optimism, but HCV treatment uptake will need to increase markedly to reduce liver disease mortality. This review provides updated information on the natural history of HCV, disease-specific causes of mortality among people with HCV, estimates and projections of HCV-related disease burden and mortality and individual and population-level strategies to reduce mortality. The considerable variability in mortality rates within subpopulations of people with HCV will be outlined, such as in people who inject drugs and those with HIV co-infection.
Background and Aims
HCV cure reduces but does not eliminate the risk of HCC. HCC surveillance is recommended in populations where the incidence exceeds 1.5% per year. In cirrhosis, HCC surveillance ...should continue after HCV cure, although it is uncertain if this should be indefinite. For patients with advanced fibrosis (F3), guidelines are inconsistent in their recommendations. We evaluated the incidence of HCC after HCV cure among patients with F3 fibrosis or cirrhosis.
Approach and Results
This systematic review and meta‐analysis identified 44 studies (107,548 person‐years of follow‐up) assessing the incidence of HCC after HCV cure among patients with F3 fibrosis or cirrhosis. The incidence of HCC was 2.1 per 100 person‐years (95% CI, 1.9–2.4) among patients with cirrhosis and 0.5 per 100 person‐years (95% CI, 0.3–0.7) among patients with F3 fibrosis. In a meta‐regression analysis among patients with cirrhosis, older age (adjusted rate ratio aRR per 10‐year increase in mean/median age, 1.32; 95% CI, 1.00–1.73) and prior decompensation (aRR per 10% increase in the proportion of patients with prior decompensation, 1.06; 95% CI, 1.01–1.12) were associated with an increased incidence of HCC. Longer follow‐up after HCV cure was associated with a decreased incidence of HCC (aRR per year increase in mean/median follow‐up, 0.87; 95% CI, 0.79–0.96).
Conclusions
Among patients with cirrhosis, the incidence of HCC decreases over time after HCV cure and is lowest in patients with younger age and compensated cirrhosis. The substantially lower incidence in F3 fibrosis is below the recommended threshold for cost‐effective screening. The results should encourage the development of validated predictive models that better identify at‐risk individuals, especially among patients with F3 fibrosis.
Australia is on-track to achieve World Health Organization hepatitis C virus (HCV) elimination targets. An active HCV screening program led to 82% of HCV-infected population being diagnosed. An ...unrestricted direct-acting antiviral (DAA) program, launched in March 2016 resulted in an estimated 58,500 individuals (26% of total HCV-infected population, including 70% of those with cirrhosis) initiating treatment through 2017. Treatment uptake was high among sub-populations at greater HCV transmission risk with 22% of people injecting drugs and >60% of those with HIV/HCV coinfection initiating DAA treatment in 2016. A monitoring and evaluation program will inform strategies required to achieve HCV elimination targets.
Patients with hepatitis C virus (HCV) genotype 3 infection, especially those with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination ...of daclatasvir (DCV; pangenotypic nonstructural protein 5A inhibitor) and sofosbuvir (SOF; nucleotide nonstructural protein 5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY‐3+ study (N = 50) evaluated DCV‐SOF with ribavirin (RBV) in treatment‐naïve (n = 13) or treatment‐experienced (n = 37) genotype 3‐infected patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open‐label DCV‐SOF (60 + 400 mg daily) with weight‐based RBV for 12 or 16 weeks. The primary endpoint was sustained virological response at post‐treatment week 12 (SVR12). SVR12 (intention‐to‐treat) was 90% overall (45 of 50): 88% (21 of 24) in the 12‐week (91% observed) and 92% (24 of 26) in the 16‐week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31 of 36): 83% (15 of 18) in the 12‐week (88% observed) and 89% (16 of 18) in the 16‐week group; for treatment‐experienced patients with cirrhosis, these values were 87% (26 of 30), 88% (14 of 16; 93% observed), and 86% (12 of 14), respectively. One patient (12‐week group) did not enter post‐treatment follow‐up (death unrelated to treatment). There were 4 relapses (2 per group) and no virological breakthroughs. The most common adverse events (AEs) were insomnia, fatigue, and headache. There were no discontinuations for AEs and no treatment‐related serious AEs. Conclusion: The all‐oral regimen of DCV‐SOF‐RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3‐infected patients with advanced liver disease, irrespective of past HCV treatment experience. (Hepatology 2016;63:1430‐1441)
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