Marianne Martinello, PhD et al.
Hepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required.
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Hepatitis C virus (HCV) is a hepatotropic positive sense single-stranded RNA virus belonging to the family Flaviviridae, which causes acute and chronic hepatitis. Chronic HCV infection with progressive liver injury can result in cirrhosis and associated complications, including decompensated liver disease and hepatocellular carcinoma. Following identification of HCV in 1989, there has been enormous progress in basic, translational, clinical, and public health research, culminating in the development of direct-acting antiviral (DAA) therapy, which is a curative oral treatment for HCV infection.
Given the global burden of disease, WHO adopted the first global hepatitis strategy in 2016, proposing to eliminate viral hepatitis as a public health threat by 2030, with targets focused on reducing incidence and mortality, and increasing diagnosis and treatment (appendix p 2).
The availability of DAA therapy has revolutionised HCV clinical care and provided impetus for elimination. However, despite major advances in therapeutics, only 21% of people with chronic HCV infection have been diagnosed and 13% have started HCV treatment.
In 2020, 57 million people were estimated to be living with chronic HCV infection (HCV RNA viraemic prevalence 0·7%), with over 70% residing in low-income and middle-income countries.
The decline in estimated chronic HCV infections over the preceding 5 years (from 64 million in 2015) occurred more as a result of revised prevalence data than elimination progress, although substantial country-specific treatment-related reductions have also contributed (eg, in Egypt).
Countries with the highest burden of HCV include China, India, Pakistan, Russia, and the USA, with 30 countries accounting for 80% of the burden of those living with HCV infection.
An estimated 1·5 million new HCV infections occur each year, with transmission related largely to injecting drug use and unsafe health-care injections. Although annual HCV incidence peaked in most countries between 1970 and 2005 and is falling in people who inject drugs in many high-income countries, sustained high or increasing incidence has been reported in the USA and some low-income and middle-income countries.
Eight HCV genotypes have been identified.
HCV genotype 1 is prevalent in North and South America, Europe, Australia, and central and east Asia. HCV genotype 3 accounts for most infections in India and Pakistan, and genotype 4 is predominant in Egypt and central and sub-Saharan Africa.
The clinical relevance of genotype and subtype determination has waned with pan-genotypic DAA therapy; however, HCV genotype could affect natural history, liver disease progression, and treatment response.