Jason Grebely

EPIDEMIOLOGY AND NATURAL HISTORY OF HCV INFECTION

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.

Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals.

Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon‐free direct‐acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three‐quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale‐up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2‐, 13‐, and 15‐fold increases, respectively). Scale‐up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three‐quarters within 15 years. Less impact occurs with delayed scale‐up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US

HCV treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals.

3.2 million in Edinburgh and approximately

Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States

50 million in Melbourne and Vancouver. Conclusion: Interferon‐free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale‐up, and should be addressed. (Hepatology 2013;58:1598–1609)

The effects of female sex, viral genotype, and IL28B genotype on spontaneous clearance of acute hepatitis C virus infection.

Substantial reductions in hepatitis C virus (HCV) prevalence among people who inject drugs (PWID) cannot be achieved by harm reduction interventions such as needle exchange and opiate substitution therapy (OST) alone. Current HCV treatment is arduous and uptake is low, but new highly effective and tolerable interferon‐free direct‐acting antiviral (DAA) treatments could facilitate increased uptake. We projected the potential impact of DAA treatments on PWID HCV prevalence in three settings. A dynamic HCV transmission model was parameterized to three chronic HCV prevalence settings: Edinburgh, UK (25%); Melbourne, Australia (50%); and Vancouver, Canada (65%). Using realistic scenarios of future DAAs (90% sustained viral response, 12 weeks duration, available 2015), we projected the treatment rates required to reduce chronic HCV prevalence by half or three‐quarters within 15 years. Current HCV treatment rates may have a minimal impact on prevalence in Melbourne and Vancouver (<2% relative reductions) but could reduce prevalence by 26% in 15 years in Edinburgh. Prevalence could halve within 15 years with treatment scale‐up to 15, 40, or 76 per 1,000 PWID annually in Edinburgh, Melbourne, or Vancouver, respectively (2‐, 13‐, and 15‐fold increases, respectively). Scale‐up to 22, 54, or 98 per 1,000 PWID annually could reduce prevalence by three‐quarters within 15 years. Less impact occurs with delayed scale‐up, higher baseline prevalence, or shorter average injecting duration. Results are insensitive to risk heterogeneity or restricting treatment to PWID on OST. At existing HCV drug costs, halving chronic prevalence would require annual treatment budgets of US

Treatment of Hepatitis C Virus Infection Among People Who Are Actively Injecting Drugs: A Systematic Review and Meta-analysis

3.2 million in Edinburgh and approximately

Potential Role for Interleukin-28B Genotype in Treatment Decision-Making in Recent Hepatitis C Virus Infection

50 million in Melbourne and Vancouver. Conclusion: Interferon‐free DAAs could enable increased HCV treatment uptake among PWID, which could have a major preventative impact. However, treatment costs may limit scale‐up, and should be addressed. (Hepatology 2013;58:1598–1609)

Low uptake of treatment for hepatitis C virus infection in a large community‐based study of inner city residents

Highly effective (cure rate >90%), once-daily, oral interferon-free treatments with minimal adverse effects are now available for hepatitis C virus (HCV) infection. Worldwide, an estimated 80 to 150 million persons have chronic HCV (1, 2). If left untreated, chronic HCV can lead to cirrhosis, liver failure, and hepatocellular carcinoma (HCC) (3, 4). Rates of advanced liver disease complications, associated health care costs, and liver diseaserelated mortality are rising worldwide (3, 4). Regimens for treating HCV seem to be curative and reduce liver-related and all-cause mortality (5). Uptake of HCV treatment has been low in many settings (68) in part because of the poor tolerability of interferon-based regimens. Widespread access to interferon-free regimens has the potential to greatly affect HCV morbidity and mortality. Sofosbuvir, a pan-genotypic nucleotide analogue NS5B polymerase inhibitor indicated for treatment of chronic HCV in combination with other direct-acting antivirals (DAAs), was approved by the U.S. Food and Drug Administration (FDA) on 6 December 2013. Sofosbuvir is the first DAA indicated for use as part of an interferon-free regimen. Compared with interferon-based therapy, sofosbuvir-based interferon-free regimens show response rates greater than 90%, shortened treatment duration (8 to 12 weeks), and improved tolerability and safety (although with some combinations, lower responses are seen in persons with more advanced disease and certain HCV genotypes) (914). The wholesale acquisition cost of sofosbuvir is

Effective Treatment of Injecting Drug Users With Recently Acquired Hepatitis C Virus Infection

1000 per day (equating to

Hepatitis C virus reinfection in injection drug users

84000 for a 12-week course) and must be used with 1 or more medications at additional cost. A fixed-dose, single-tablet combination of sofosbuvir and ledipasvir (an NS5A inhibitor) is now available at a wholesale acquisition cost of