Elsevier

The Lancet

Volume 394, Issue 10207, 19–25 October 2019, Pages 1451-1466
The Lancet

Seminar
Hepatitis C

https://doi.org/10.1016/S0140-6736(19)32320-7Get rights and content

Summary

Hepatitis C is a global health problem, and an estimated 71·1 million individuals are chronically infected with hepatitis C virus (HCV). The global incidence of HCV was 23·7 cases per 100 000 population (95% uncertainty interval 21·3–28·7) in 2015, with an estimated 1·75 million new HCV infections diagnosed in 2015. Globally, the most common infections are with HCV genotypes 1 (44% of cases), 3 (25% of cases), and 4 (15% of cases). HCV transmission is most commonly associated with direct percutaneous exposure to blood, via blood transfusions, health-care-related injections, and injecting drug use. Key high-risk populations include people who inject drugs, men who have sex with men, and prisoners. Approximately 10–20% of individuals who are chronically infected with HCV develop complications, such as cirrhosis, liver failure, and hepatocellular carcinoma over a period of 20–30 years. Direct-acting antiviral therapy is now curative, but it is estimated that only 20% of individuals with hepatitis C know their diagnosis, and only 15% of those with known hepatitis C have been treated. Increased diagnosis and linkage to care through universal access to affordable point-of-care diagnostics and pangenotypic direct-acting antiviral therapy is essential to achieve the WHO 2030 elimination targets.

Introduction

Persistent infection with hepatitis C virus (HCV) is a leading cause of chronic liver disease, resulting in 475 000 deaths in 2015.1 The estimated global HCV prevalence in 2015 was 1·0% (95% uncertainty interval [UI] 0·8–1·1), aggregating to 71·1 million viraemic individuals (95% UI 62·5–79·4) infected with HCV.1, 2

In 2016, WHO adopted a global hepatitis strategy to eliminate viral hepatitis as a public health threat by 2030, with ambitious targets: a 90% reduction in incident cases of hepatitis B and C and a 65% reduction in mortality.3 To reach these targets, 80% of treatment-eligible individuals with chronic hepatitis B virus (HBV) and HCV need access to care.

Unfortunately, only around 14 million (20%) people who were estimated to be infected with HCV in 2016 were diagnosed, 1·76 million (13%) people were treated, and 1·51 million (86%) of those treated were given direct-acting antivirals (DAAs).1 Between 2016 and 2017, the number of people infected with HCV who were treated increased from 1·76 million to 2·10 million, with the greatest increase occurring in middle-income countries. It is of concern that only 12 of 194 countries were on track to meet the 2030 WHO elimination targets in June, 2018. Screening, diagnosis, facilitated linkage to care, and sustainable access to affordable DAA regimens are all fundamental to achieve the WHO 2030 elimination targets.

Section snippets

Overview

Globally, 80% of all HCV infections occur in 31 countries, with six countries (China, Pakistan, Nigeria, Egypt, India, and Russia) accounting for greater than 50% of all infections.2 Prevalence data in many countries remains of low quality and requires constant reappraisal.2

An estimated 1·75 million new HCV infections (95% UI 1·57–2·12) occurred in 2015. Hepatitis C incidence is highest in the WHO European and Eastern Mediterranean regions. In 2015, an incidence of 61·8 cases per 100 000 people

Progression of liver disease with HCV infection

75–80% of individuals develop chronic infection after exposure to HCV; however, some surveys report a lower incidence. Cirrhosis and hepatic decompensation, which has an annualised risk of 2–5%, can develop as a result of chronic HCV infection. 15–20% of people with liver disease die during the first year following decompensation.45

Acute hepatitis C

Acute hepatitis C infection is typically anicteric, and less than 25% of cases are clinically apparent. Symptoms, if present, become apparent 2–26 weeks after HCV

Screening

Screening and linkage to treatment are fundamental prerequisites of the WHO elimination goals.55 Screening approaches vary by country, and although they are guided by HCV prevalence and dominant transmission routes, the approaches can be universal or targeted (eg, screening based on birth cohort or risk factors), or a combination of the two. WHO guidelines55, 56 recommend that serological testing for HCV be offered to individuals in a population with high HCV prevalence or to those who have a

Effectiveness of therapy

The primary goal of therapy is to achieve undectable HCV RNA—or an SVR—12 weeks (SVR12) or 24 weeks (SVR24) after the end of therapy, and is judged on the basis of a sensitive molecular assay with an acceptable lower limit of quantification.67 Concordance between SVR12 and SVR24 surpasses 99%.67 If a less sensitive HCV RNA test method or HCVcAg is used, SVR24 should be confirmed.51, 63 SVR is associated with improved liver-related and all-cause morbidity and mortality, and it is also associated

HCV–HIV co-infection

HCV–HIV co-infection increases the likelihood of progression to advanced liver fibrosis and cirrhosis and increases the risk of hepatocellular carcinoma. However, more than 95% of patients who are monoinfected with HCV or co-infected with HCV attain SVR following 8–12 weeks of DAA therapy.122 Potential complex drug–drug interactions between DAAs and antiretroviral therapy should be assessed before therapy is given.

HCV–HBV co-infection

HCV is often the dominant driver of chronic inflammatory activity in patients who

DAA therapy and risk of hepatocellular carcinoma

The effect of achieving SVR following DAA therapy on the risk of hepatocellular carcinoma occurrence and recurrence has been controversial.142 A systematic review and meta-analysis143 compared the risk of the occurrence and recurrence of hepatocellular carcinoma in 41 studies (n=13 875 patients); of these, 26 studies analysed de-novo occurrence of hepatocellular carcinoma (17 studies with interferon and nine studies that used DAAs), and 17 analysed the recurrence of hepatocellular carcinoma

Conclusion

HCV is a global health problem, but elimination is now possible with curative DAA therapy. Achievement of elimination will require increased diagnosis and linkage to care and universal access to affordable diagnostics and pangenotypic DAA therapy. Identifying and decriminalising key HCV-infected populations, such as PWID and MSM, and combining treatment with expansion of PWID harm reduction services, to break cycles of infection and reinfection, are essential. Upscaling blood safety programmes

Search strategy and selection criteria

We searched MEDLINE and PubMed for studies published between Jan 1, 2016, and July 31, 2019, with the search terms “HCV” or “hepatitis C virus”, and “epidemiology”, “key populations”, “natural history”, “extrahepatic manifestations”, “HIV-HCV co-infection”, “HBV-HCV co-infection”, “screening and diagnosis”, “point-of-care diagnostics”, “linkage to care”, “direct acting antivirals and hepatocellular carcinoma”, “ HCV positive donors”, “direct acting antivirals and organ transplantation” or

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