The global prevalence of HCV-infected individuals, i.e., those in whom HCV antibody positivity has been detected, has been estimated at 1.6 percent number which corresponds to approximately 115 million individuals. This number, however, does not include only individuals who are currently infected with HCV: some have cleared the virus spontaneously or as a result of treatment. Therefore, the overall number of currently positive individuals is lower and is estimated at 1 percent, or 71 million HCV-infected individuals. These estimates are based on extrapolations from 100 countries where generalizable studies have been conducted. The availability of reliable global data is unfortunately limited: only 29% of low-income countries and 60% of high-income countries report HCV prevalence. In addition, the quality of reported data is not always consistent, but varies from country to country. The prevalence of HCV infection shows considerable variation around the world. The highest rate is found in countries with a past or present history of iatrogenic infections (i.e., infections due to a physician's activity or medical therapy). The adult populations of Cameroon, Egypt, Gabon, Georgia, Mongolia, Nigeria, and Uzbekistan have an anti-HCV antibody prevalence >5%; iatrogenic infection is a key risk factor in these countries. The source of HCV infection in Egypt is well documented and attributed to intravenous treatment of schistosomiasis during the 1960s-1970s. Western countries account for only a small percentage of global HCV infections. China, Pakistan, India, Egypt, and Russia together account for half of total viral HCV2 infections. The age of HCV patients correlates with the primary source of infection in specific areas. Where injection drug use is an important ongoing risk factor (e.g., Australia, the Czech Republic, Finland, Luxembourg, Portugal, Russia, and the United Kingdom) the HCV-infected population has a peak age around 30 years. In contrast, the peak age is raised (50-60 years) in countries where iatrogenic infections are predominant. This difference is explained by the fact that active injection drug users are generally young, while most iatrogenic infections occurred before the 1990s, when HCV diagnostics became available. Then there are countries where the age profile is mixed, as there are of different risk factors present. The distribution of HCV genotype also varies by region and has implications for the clinical course and requirements for treatment and drug development.
In most cases, acute infection occurs without symptoms and without clinically manifest disease.
A minority of patients develop acute hepatitis C with jaundice, fatigue, pain or discomfort in the right upper abdomen, or arthralgia (joint pain).
Acute HCV infection leads to chronic infection in about 75-85% of people; over the next 20-30 years, a percentage of patients will progress to cirrhosis and other consequences of cirrhosis, such as liver decompensation and hepatocellular carcinoma.
Before developing symptoms of decompensation, patients may experience symptoms such as fatigue, weight loss, muscle and joint pain, or discomfort, pain, or itching in the right upper abdomen.
Progression is not necessarily a linear process and can be accelerated by many factors, including the patient's age, gender, alcohol consumption, and co-infection with other viruses, such as hepatitis B virus (HBV) and HIV, or other infectious agents such as schistosomiasis.
Finally, many patients with chronic HCV infection remain asymptomatic for years and become aware of this life-threatening disease only after they have already developed cirrhosis.
Several virological tools can be used to diagnose and monitor HCV infection. Today, the diagnosis of hepatitis C is based on the use of two blood tests: the detection of specific antibodies to the infection and the detection of viral particles by HCV-RNA testing. These tests are sensitive and specific, can be fully automated, and are relatively inexpensive. The serologic window between infection and seroconversion, that is, when HCV antibodies become detectable varies on average between 2 and 8 weeks. Testing only for antiHCV antibodies therefore may not detect early infection. Once the presence of the virus is established, further investigations can be performed to precisely define the impact on the liver, such as liver biopsy or other indirect methods. AntiHCV antibodies are detected in patients who develop chronic infection and persist for years or even decades in those who clear the virus. Rapid diagnostic tests for the detection of HCV antibodies are increasingly used for screening in low-to-moderate risk populations. Indeed, this tool is critical for diagnosis, improving the health of people with active infection, and preventing transmission. It is estimated that 45 to 85 percent of infected people are unaware of their condition because Hepatitis C usually does not produce symptoms until the late stages. HCV testing is recommended in specific populations based on HCV prevalence, proven benefits of treatment (i.e., signs of disease progression and/or impaired liver function) and treatment in reducing the risk of hepatocellular carcinoma and all-cause mortality. In most countries, hepatitis C virus (HCV) testing is recommended for the following increased risk groups:
- Current or former drug users;
- Those who received clotting factor concentrates before 1990;
- Transfusion recipients who received blood from donors who later tested positive for HCV and recipients of blood, blood components, or organ transplants before the 1990s;
- Patients currently or previously on long-term hemodialysis and with persistently abnormal levels of alanine aminotransferase (a marker of liver function);
- Individuals subject to past invasive medical procedures, such as surgery and endoscopic procedures;
- Individuals with HIV infection;
- Health and public safety workers affected by needle sticks, stab wounds or more generally by mucosal exposure to HCV-positive blood;
- Children born to HCV-positive women;
- Individuals with multiple sexual partners;
- Birth cohort screening, for example, in the United States (individuals born between 1945 and 1965).
Acute Infection
Recommendations for treatment of acute hepatitis C are still under discussion and will be influenced by ongoing and future studies. Only patients with proven HCV infection, that is, after detection of HCV RNA in serum, should receive antiviral therapy. There are no indications for prophylactic treatment of hepatitis C (e.g., in health care workers after needlestick injury). Individuals with acute HCV infection with increased levels of liver enzymes and bilirubin (those with jaundice, so-called symptomatic acute hepatitis C) are more likely to recover spontaneously, but response rates to treatment are similar.
Chronic Infection
The development of DAAs (direct-acting antiviral agents) has led to a revolution in the treatment of chronic HCV infection. In recent years, research has elucidated the HCV life cycle, leading to the development of drugs that target the three proteins involved at crucial stages of its existence. A combination of one to three of these different drugs leads to cure rates of 90-100%. Because of rapidly developing research and the approval of new drugs every few months, recommendations for HCV treatment by national and international scientific societies have been updated regularly over the past five years.All patients with chronic hepatitis C and detectable HCV RNA in serum should be considered for antiviral treatment. However, before starting treatment, other causes of liver disease should be ruled out, the stage reached, if any, and an evaluation of biochemical disease activity should then follow.
therapy.
No vaccines are available to prevent HCV infection.
To reduce the viral load and the chance of contracting related diseases, primary prevention activities are necessary. This is aimed at reducing or eliminating HCV transmission due to infected blood, blood components, and plasma-derived products; high-risk activities, such as unsafe injection drug use and unprotected sex with multiple partners; and exposure to blood in health care facilities and other venues (e.g., tattoo and piercing studios).
Secondary prevention activities can reduce the risk of chronic disease by identifying HCV-infected persons through screening and providing appropriate medical management and antiviral therapy.
A major problem in preventing HCV infection is that the disease does not immediately produce symptoms, so many individuals do not know they are infected. Identifying the large number of people who unknowingly have the chronic disease should be a major goal of current prevention programs.