Hepatitis C
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Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver;<ref name=Sherris2004>Template:Cite book</ref> it is a type of viral hepatitis.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> During the initial infection period, people often have mild or no symptoms.<ref name="CDC2016">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Early symptoms can include fever, dark urine, abdominal pain, and yellow tinged skin.<ref name=CDC2016 /> The virus persists in the liver, becoming chronic, in about 70% of those initially infected.<ref name=whofactsheet/> Early on, chronic infection typically has no symptoms.<ref name=CDC2016 /> Over many years however, it often leads to liver disease and occasionally cirrhosis.<ref name=CDC2016 /> In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach.<ref name=Sherris2004 />
HCV is spread primarily by blood-to-blood contact associated with injection drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, and transfusions.<ref name=CDC2016 /><ref name=Mah2010>Template:Cite journal</ref> In regions where blood screening has been implemented, the risk of contracting HCV from a transfusion has dropped substantially to less than one per two million.<ref name=CDC2016 /> HCV may also be spread from an infected mother to her baby during birth.<ref name=CDC2016 /> It is not spread through breast milk, food, water, or casual contact such as hugging, kissing, and sharing food or drinks with an infected person.<ref name=whofactsheet>{{#invoke:citation/CS1|citation |CitationClass=web }} Updated as required.</ref> It is one of five known hepatitis viruses: A, B, C, D, and E.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Diagnosis is by blood testing to look for either antibodies to the virus or viral RNA.<ref name=CDC2016 /> In the United States, screening for HCV infection is recommended in all adults age 18 to 79 years old.<ref name=USPSTF /> There is no vaccine against hepatitis C.<ref name=CDC2016 /><ref name=Web2015>Template:Cite journal</ref> Prevention includes harm reduction efforts among people who inject drugs, testing donated blood, and treatment of people with chronic infection.<ref name=whofactsheet/><ref name="TA">Template:Cite journal</ref> Chronic infection can be cured more than 95% of the time with antiviral medications such as sofosbuvir or simeprevir.<ref name=CDC2016 /><ref name=whofactsheet/> Peginterferon and ribavirin were earlier generation treatments that proved successful in <50% of cases and caused greater side effects.<ref name=whofactsheet/>Template:Rp<ref name=Kim2016/> While access to the newer treatments was expensive, by 2022 prices had dropped dramatically in many countries (primarily low-income and lower-middle-income countries) due to the introduction of generic versions of medicines.<ref name=whofactsheet/> Those who develop cirrhosis or liver cancer may require a liver transplant.<ref name=NEJM2011 /> Hepatitis C is one of the leading reasons for liver transplantation. However, the virus usually recurs after transplantation.<ref name=NEJM2011>Template:Cite journal</ref>
An estimated 58 million people worldwide were infected with hepatitis C in 2019. Approximately 290,000 deaths from the virus, mainly from liver cancer and cirrhosis attributed to hepatitis C, also occurred in 2019.<ref name=":1">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The existence of hepatitis C – originally identifiable only as a type of non-A non-B hepatitis – was suggested in the 1970s and proven in 1989.<ref name="pmid19781804">Template:Cite journal</ref> Hepatitis C infects only humans and chimpanzees.<ref>Template:Cite book</ref>
Signs and symptomsEdit
Acute infectionEdit
Acute symptoms develop in some 20% of those infected.<ref name=whofactsheet /><ref name=CDC2016/> When this occurs, it is generally 4–12 weeks following infection (but it may take from 2 weeks to 6 months for acute symptoms to appear).<ref name=CDC2016/><ref name=whofactsheet />
Symptoms are generally mild and vague, and may include fatigue, nausea and vomiting, fever, muscle or joint pains, abdominal pain, decreased appetite and weight loss, jaundice (occurs in ~25% of those infected), dark urine, and clay-coloured stools.<ref name=CDC2016/><ref name="Book2011p4">Template:Cite book</ref><ref name="AFP2010">Template:Cite journal</ref> Acute liver failure due to acute hepatitis C is exceedingly rare.<ref name="Rao2022">Template:Cite journal</ref> Symptoms and laboratory findings suggestive of liver disease should prompt further tests and can thus help establish a diagnosis of hepatitis C infection early on.<ref name=AFP2010/>
Following the acute phase, the infection may resolve spontaneously in 10–50% of affected people; this occurs more frequently in young people and females.<ref name="Book2011p4" />
Chronic infectionEdit
About 70% of those exposed to the virus develop a chronic infection.<ref name=whofactsheet/> This is defined as the presence of detectable viral replication for at least six months. Though most experience minimal or no symptoms during the initial few decades of a chronic infection,<ref name=Book2011 /> chronic Template:Nowrap can be associated with fatigue<ref name=ID2010 /> and mild cognitive problems.<ref>Template:Cite journal</ref> After several years, chronic infection may cause cirrhosis or liver cancer.<ref name=NEJM2011 /> The liver enzymes measured from blood samples are normal in 7–53%.<ref name=Nicot2011 /> (Elevated levels indicate the virus or other disease is damaging liver cells). Late relapses after apparent cure have been reported, but these can be difficult to distinguish from reinfection.<ref name=Nicot2011 />
Fatty changes to the liver occur in about half of those infected and are usually present before cirrhosis develops.<ref name="El-Zayadi2008" /><ref>Template:Cite journal</ref> Usually (80% of the time) this change affects less than a third of the liver.<ref name="El-Zayadi2008">Template:Cite journal</ref> Worldwide hepatitis C is the cause of 27% of cirrhosis cases and 25% of hepatocellular carcinoma.<ref name=World2007>Template:Cite journal</ref> About 10–30% of those infected develop cirrhosis over 30 years.<ref name=NEJM2011 /><ref name=AFP2010 /> Cirrhosis is more common in those also infected with hepatitis B, schistosoma, or HIV, in alcoholics, and in those of male sex.<ref name=AFP2010 /> In those with hepatitis C, excess alcohol increases the risk of developing cirrhosis 5-fold.<ref>Template:Cite journal</ref> Those who develop cirrhosis have a 20-fold greater risk of hepatocellular carcinoma. This transformation occurs at a rate of 1–3% per year.<ref name=NEJM2011 /><ref name=AFP2010 /> Being infected with hepatitis B in addition to hepatitis C increases this risk further.<ref>Template:Cite journal</ref>
Liver cirrhosis may lead to portal hypertension, ascites (accumulation of fluid in the abdomen), easy bruising or bleeding, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy.<ref name=Tah2009 /> Ascites occurs at some stage in more than half of those who have a chronic infection.<ref name=Zaltron2012>Template:Cite journal</ref>
Extrahepatic complicationsEdit
The most common problem due to Template:Nowrap but not involving the liver is mixed cryoglobulinemia (usually the type II form) – an inflammation of small and medium-sized blood vessels.<ref name=Cryo2013>Template:Cite journal</ref><ref>Template:Cite journal</ref> Template:Nowrap is also associated with autoimmune disorders such as Sjögren's syndrome, lichen planus, a low platelet count, porphyria cutanea tarda, necrolytic acral erythema, insulin resistance, diabetes mellitus, diabetic nephropathy, autoimmune thyroiditis, and B-cell lymphoproliferative disorders.<ref name=Extrahepatic>Template:Cite journal</ref><ref name=Ko2012>Template:Cite journal</ref> 20–30% of people infected have rheumatoid factor – a type of antibody.<ref name=Dammacco2000>Template:Cite journal</ref> Possible associations include Hyde's prurigo nodularis<ref>Template:Cite journal</ref> and membranoproliferative glomerulonephritis.<ref name=ID2010 /> Cardiomyopathy with associated abnormal heart rhythms has also been reported.<ref name=Matsumori2006>Template:Cite book</ref> A variety of central and peripheral nervous system disorders has been reported.<ref>Template:Cite journal</ref><ref name=Monaco2012>Template:Cite journal</ref> Chronic infection seems to be associated with an increased risk of pancreatic cancer.<ref name=Web2015 /><ref name=Xu2013>Template:Cite journal</ref> People may experience other issues in the mouth such as dryness, salivary duct stones, and crusted lesions around the mouth.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite book</ref>
Occult infectionEdit
Persons who have been infected with hepatitis C may appear to clear the virus but remain infected.<ref name=Sugden2012>Template:Cite journal</ref> The virus is not detectable with conventional testing but can be found with ultra-sensitive tests.<ref name="Carreño2006">Template:Cite journal</ref> The original method of detection was by demonstrating the viral genome within liver biopsies. Still, newer methods include an antibody test for the virus' core protein and the detection of the viral genome after first concentrating the viral particles by ultracentrifugation.<ref name="CarreñoGarcía2011">Template:Cite journal</ref> A form of infection with persistently moderately elevated serum liver enzymes but without antibodies to hepatitis C has also been reported.<ref name=Pham2010>Template:Cite journal</ref> This form is known as cryptogenic occult infection.
Several clinical pictures have been associated with this type of infection.<ref name="Carreño2012">Template:Cite journal</ref> It may be found in people with anti-hepatitis-C antibodies but with normal serum levels of liver enzymes; in antibody-negative people with ongoing elevated liver enzymes of unknown cause; in healthy populations without evidence of liver disease; and in groups at risk for HCV infection including those on hemodialysis or family members of people with occult HCV. The clinical relevance of this form of infection is under investigation.<ref name="Carreño2008">Template:Cite journal</ref> The consequences of occult infection appear to be less severe than with chronic infection but can vary from minimal to hepatocellular carcinoma.<ref name="CarreñoGarcía2011" />
The rate of occult infection in those apparently cured is controversial but appears to be low.<ref name=Nicot2011>Template:Cite book</ref> 40% of those with hepatitis but with both negative hepatitis C serology and the absence of detectable viral genome in the serum have hepatitis C virus in the liver on biopsy.<ref name=Scott2007>Template:Cite journal</ref> How commonly this occurs in children is unknown.<ref name=Robinson2008>Template:Cite journal</ref>
VirologyEdit
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The hepatitis C virus (HCV) is a small, enveloped, single-stranded, positive-sense RNA virus.<ref name=NEJM2011 /> It is a member of the genus Hepacivirus in the family Flaviviridae.<ref name=ID2010>Template:Cite book</ref> There are seven major genotypes of HCV, which are known as genotypes one to seven.<ref name=Nakano2011>Template:Cite journal</ref> The genotypes are divided into several subtypes with the number of subtypes depending on the genotype. In the United States, about 70% of cases are caused by genotype 1, 20% by genotype 2, and about 1% by each of the other genotypes.<ref name=AFP2010 /> Genotype 1 is also the most common in South America and Europe.<ref name=NEJM2011 />
The half-life of the virus particles in the serum is around 3 hours and may be as short as 45 minutes.<ref name=Lerat2004 /><ref>Template:Cite book</ref> In an infected person, about 1012 virus particles are produced each day.<ref name=Lerat2004>Template:Cite journal</ref> In addition to replicating in the liver the virus can multiply in lymphocytes.<ref name=Zignego2012>Template:Cite journal</ref>
TransmissionEdit
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Percutaneous contact with contaminated blood is responsible for most infections; however, the method of transmission is strongly dependent on both geographic region and economic status.<ref>Template:Cite journal</ref> Indeed, the primary route of transmission in the developed world is injection drug use, while in the developing world the main methods are blood transfusions and unsafe medical procedures.<ref name=Mah2010 /> The cause of transmission remains unknown in 20% of cases;<ref name=Pon2011>Template:Cite journal</ref> however, many of these are believed to be accounted for by injection drug use.<ref name=Book2011p4 />
Body modificationEdit
Tattooing is associated with two- to threefold increased risk of Template:Nowrap.<ref name=Tato2010>Template:Cite journal</ref> This could be due to improperly sterilized equipment or contamination of the dyes used.<ref name=Tato2010 /> Tattoos or piercings performed either before the mid-1980s, "underground", or nonprofessionally are of particular concern, since sterile techniques in such settings may be lacking. The risk also appears to be greater for larger tattoos.<ref name=Tato2010 /> It is estimated that nearly half of prison inmates share unsterilized tattooing equipment.<ref name=Tato2010 /> It is rare for tattoos in a licensed facility to be directly associated with HCV infection.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Drug useEdit
Injection drug use (IDU) is a major risk factor for Template:Nowrap in many parts of the world.<ref name=China2008>Template:Cite journal</ref> Of 77 countries reviewed, 25 (including the United States) were found to have a prevalence of Template:Nowrap of 60–80% among people who use injection drugs.<ref name=Lancet2011>Template:Cite journal</ref><ref name=China2008 /> Twelve countries had rates greater than 80%.<ref name=Lancet2011 /> It is believed that ten million people who use intravenous drug are infected with Template:Nowrap; China (1.6 million), the United States (1.5 million), and Russia (1.3 million) have the highest absolute totals.<ref name=Lancet2011 /> [[Infectious diseases within American prisons#Hepatitis C|Occurrence of Template:Nowrap among prison inmates in the United States]] is 10 to 20 times that of the occurrence observed in the general population; this has been attributed to high-risk behavior in prisons such as IDU and tattooing with non-sterile equipment.<ref name=Jail2010>Template:Cite journal</ref><ref>Template:Cite journal</ref> Shared intranasal drug use may also be a risk factor.<ref name="Moyer2013"/>
FomitesEdit
A fomite (Template:IPAc-en) or fomes (Template:IPAc-en) is any inanimate object that, when contaminated with or exposed to infectious agents (such as pathogenic bacteria, viruses or fungi), can transfer disease to a new host.<ref name=Cramer2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Personal-care items such as razors, toothbrushes, and manicuring or pedicuring equipment can be contaminated with blood. Sharing such items can potentially lead to exposure to HCV.<ref name="pmid16907842">Template:Cite journal</ref><ref name=CDC12 /> Appropriate caution should be taken regarding any medical condition that results in bleeding, such as cuts and sores.<ref name=CDC12 /> HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils,<ref name=CDC12>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> nor is it transmitted through food or water.<ref>Template:Cite journal</ref>
Healthcare exposureEdit
Blood transfusion, transfusion of blood products, or organ transplants without HCV screening carry significant risks of infection.<ref name=AFP2010 /> The United States instituted universal screening in 1992,<ref name=Rosen2011 /> and Canada instituted universal screening in 1990.<ref>Template:Cite book</ref> This decreased the risk from one in 200 units<ref name=Rosen2011>Template:Cite book</ref> to between one in 10,000 to one in 10,000,000 per unit of blood.<ref name=Book2011p4 /><ref name=Pon2011 /> This low risk remains as there is a period of about 11–70 days between the potential blood donor's acquiring Template:Nowrap and the blood's testing positive depending on the method.<ref name=Pon2011 /> Some countries do not screen for Template:Nowrap due to the cost.<ref name=World2007 />
Those who have experienced a needle stick injury from someone who was HCV positive have about a 1.8% chance of subsequently contracting the disease themselves.<ref name=AFP2010 /> The risk is greater if the needle is hollow and the puncture wound is deep.<ref name=World2007 /> There is a risk from mucosal exposure to blood, but this risk is low, and there is no risk if blood exposure occurs on intact skin.<ref name=World2007 />
Hospital equipment has also been documented as a method of transmission of Template:Nowrap, including the reuse of needles and syringes, multiple-use medication vials, infusion bags, and improperly sterilized surgical equipment, among others.<ref name=World2007 /> Limitations in the implementation and enforcement of stringent standard precautions in public and private medical and dental facilities are known to have been the primary cause of the spread of HCV in Egypt, the country which had the highest rate of infection in the world in 2012. In 2023, Egypt became the first country to achieve WHO validation on the path to elimination of hepatitis C.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
For further information, see HONOReform (Hepatitis Outbreaks National Organization for Reform).
Mother-to-child transmissionEdit
Mother-to-child transmission of Template:Nowrap occurs in fewer than 10% of pregnancies.<ref name=Preg10>Template:Cite journal</ref> There are no measures that alter this risk.<ref name=Preg10 /> It is not clear when transmission occurs during pregnancy, but it may occur both during gestation and at delivery.<ref name=Pon2011 /> A long labor is associated with a greater risk of transmission.<ref name=World2007 /> There is no evidence that breastfeeding spreads HCV; however, to be cautious, an infected mother is advised to avoid breastfeeding if her nipples are cracked and bleeding,<ref>Template:Cite book</ref> or if her viral loads are high.<ref name=Pon2011 />
Sexual intercourseEdit
Sexual transmission of hepatitis C is uncommon.<ref name=Kim2016/> Studies examining the risk of HCV transmission between heterosexual partners, when one is infected and the other is not, have found very low risks.<ref name=Kim2016/> Sexual practices that involve higher levels of trauma to the anogenital mucosa, such as anal penetrative sex, or that occur when there is a concurrent sexually transmitted infection, including HIV or genital ulceration, present greater risks.<ref name=Kim2016/><ref name=Sex2010>Template:Cite journal</ref> The United States Department of Veterans Affairs recommends condom use to prevent Template:Nowrap transmission in those with multiple partners, but not those in relationships that involve only a single partner.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
DiagnosisEdit
There are several diagnostic tests for Template:Nowrap, including HCV antibody enzyme immunoassay (ELISA), recombinant immunoblot assay, and quantitative HCV RNA polymerase chain reaction (PCR).<ref name=AFP2010 /> HCV RNA can be detected by PCR typically one to two weeks after infection. In contrast, antibodies can take substantially longer to form and thus be detected.<ref name=Tah2009 />
Diagnosing patients is generally a challenge as patients with acute illness often present with mild, non-specific flu-like symptoms,<ref>Template:Cite journal</ref> while the transition from acute to chronic is sub-clinical.<ref>Template:Cite journal</ref> Chronic Template:Nowrap is defined as infection with the Template:Nowrap virus persisting for more than six months based on the presence of its RNA.<ref name=Book2011>Template:Cite book</ref> Chronic infections are typically asymptomatic during the first few decades,<ref name=Book2011 /> and thus are most commonly discovered following the investigation of elevated liver enzyme levels or during a routine screening of high-risk individuals. Testing is not able to distinguish between acute and chronic infections.<ref name=World2007 /> Diagnosis in infants is difficult as maternal antibodies may persist for up to 18 months.<ref name=Robinson2008 />
SerologyEdit
Template:Nowrap testing typically begins with blood testing to detect the presence of antibodies to the HCV, using an enzyme immunoassay.<ref name=AFP2010 /> If this test is positive, a confirmatory test is then performed to verify the immunoassay and to determine the viral load.<ref name=AFP2010 /> A recombinant immunoblot assay is used to verify the immunoassay and the viral load is determined by an HCV RNA polymerase chain reaction.<ref name=AFP2010 /> If there is no RNA and the immunoblot is positive, it means that the person tested had a previous infection but cleared it either with treatment or spontaneously; if the immunoblot is negative, it means that the immunoassay was wrong.<ref name=AFP2010 /> It takes about 6–8 weeks following infection before the immunoassay will test positive.<ref name=ID2010 /> Several tests are available as point-of-care testing (POCT), which can provide results within 30 minutes.<ref>Template:Cite journal</ref>
Liver enzymes are variable during the initial part of the infection<ref name=Book2011 /> and on average begin to rise seven weeks after infection.<ref name=ID2010 /> The elevation of liver enzymes does not closely follow disease severity.<ref name=ID2010 />
BiopsyEdit
Liver biopsies are used to determine the degree of liver damage present; however, there are risks from the procedure.<ref name=NEJM2011 /> The typical changes seen are lymphocytes within the parenchyma, lymphoid follicles in portal triad, and changes to the bile ducts.<ref name=NEJM2011 /> There are many blood tests available that try to determine the degree of hepatic fibrosis and alleviate the need for biopsy.<ref name=NEJM2011 />
ScreeningEdit
It is believed that only 5–50% of those infected in the United States and Canada are aware of their status.<ref name=Tato2010 /> Routine screening for those between the ages of 18 and 79 was recommended by the United States Preventive Services Task Force in 2020.<ref name=USPSTF>Template:Cite journal</ref> Previously, testing was recommended for those at high risk, including injection drug users, those who have received blood transfusions before 1992,<ref name="Moyer2013"/> those who have been incarcerated, those on long-term hemodialysis,<ref name=Moyer2013>Template:Cite journal</ref> and those with tattoos.<ref name=Tato2010 /> Screening is also recommended for those with elevated liver enzymes, as this is frequently the only sign of chronic hepatitis.<ref>Template:Cite journal</ref> Template:As of, the U.S. Centers for Disease Control and Prevention (CDC) recommends a single screening test for those born between 1945 and 1965.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In Canada, a one-time screening is recommended for those born between 1945 and 1975.<ref>Template:Cite journal</ref>
PreventionEdit
Template:See also As of 2022, no approved vaccine protects against contracting Template:Nowrap.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A combination of harm reduction strategies, such as the provision of new needles and syringes and treatment of substance use, decreases the risk of Template:Nowrap in people using injection drugs by about 75%.<ref>Template:Cite journal</ref> The screening of blood donors is important at a national level, as is adhering to universal precautions within healthcare facilities.<ref name=ID2010 /> In countries where there is an insufficient supply of sterile syringes, medications should be given orally rather than via injection (when possible).<ref name=World2007 /> Recent research also suggests that treating people with active infection, thereby reducing the potential for transmission, may be an effective preventive measure.<ref name="TA" />
Hepatitis C vaccine phase 1 clinical trials are set to begin in the summer of 2023.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
TreatmentEdit
Those with chronic Template:Nowrap are advised to avoid alcohol and medications that are toxic to the liver.<ref name=AFP2010 /> They should also be vaccinated against hepatitis A and hepatitis B due to the increased risk if also infected.<ref name=AFP2010 /> Use of acetaminophen is generally considered safe at reduced doses.<ref name=Kim2016>Template:Cite journal</ref> Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended in those with advanced liver disease due to an increased risk of bleeding.<ref name=Kim2016/> Ultrasound surveillance for hepatocellular carcinoma is recommended in those with accompanying cirrhosis.<ref name=AFP2010 /> Regular, moderate coffee consumption, especially caffeinated, has been associated with a slower rate of liver scarring in those infected with HCV.<ref name=Kim2016/><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
MedicationsEdit
More than 95% of chronic cases are resolved with treatment.<ref name=whofactsheet/> Treatment with antiviral medication is recommended for all people with proven chronic hepatitis C who are not at high risk of death from other causes.<ref name=IDSA2015>Template:Cite journal</ref> People with the highest complication risk, based on the degree of liver scarring, should be treated first.<ref name=IDSA2015 /> The initial recommended treatment depends on the type of hepatitis C virus, if the person has received previous hepatitis C treatment, and whether the person has cirrhosis.<ref name=IDSA2017/> Direct-acting antivirals are the preferred treatment and have been validated by testing for virus particles in patients' blood.<ref>Template:Cite journal</ref>
No prior treatmentEdit
- HCV genotype 1a (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or ledipasvir/sofosbuvir (the latter for people who do not have HIV/AIDS, are not African-American, and have less than 6 million HCV viral copies per milliliter of blood) or 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir.<ref name="HCVGuidelinesGenotype1a">Template:Cite book</ref> Sofosbuvir with either daclatasvir or simeprevir may also be used.<ref name=IDSA2017>{{#invoke:citation/CS1|citation
|CitationClass=web }}</ref>
- HCV genotype 1a (with compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. An alternative treatment regimen of elbasvir/grazoprevir with weight-based ribavirin for 16 weeks can be used if the HCV is found to have antiviral resistance mutations against NS5A protease inhibitors.<ref name="HCVGuidelinesGenotype1acompensated">Template:Cite book</ref>
- HCV genotype 1b (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or ledipasvir/sofosbuvir (with the aforementioned limitations for the latter as above) or 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. Alternative regimens include 12 weeks of ombitasvir/paritaprevir/ritonavir with dasabuvir or 12 weeks of sofosbuvir with either daclatasvir or simeprevir.<ref name="HCVGuidelinesGenotype1b">Template:Cite book</ref>
- HCV genotype 1b (with compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of elbasvir/grazoprevir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. A 12-week course of paritaprevir/ritonavir/ombitasvir with dasabuvir may also be used.<ref name="HCVGuidelinesGenotype1bcompensated">Template:Cite book</ref>
- HCV genotype 2 (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir. Alternatively, 12 weeks of sofosbuvir/daclatasvir can be used.<ref name="HCVGuidelinesGenotype2">Template:Cite book</ref>
- HCV genotype 2 (with compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir. An alternative regimen of sofosbuvir/daclatasvir can be used for 16–24 weeks.<ref name="HCVGuidelinesGenotype2compensated">Template:Cite book</ref>
- HCV genotype 3 (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir or sofosbuvir and daclatasvir.<ref name="HCVGuidelinesGenotype3">Template:Cite book</ref>
- HCV genotype 3 (with compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir, or if certain antiviral mutations are present 12 weeks of sofosbuvir/velpatasvir/voxilaprevir (when certain antiviral mutations are present), or 24 weeks of sofosbuvir and daclatasvir.<ref name="HCVGuidelinesGenotype3compensated">Template:Cite book</ref>
- HCV genotype 4 (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir, elbasvir/grazoprevir, or ledipasvir/sofosbuvir. A 12-week ombitasvir/paritaprevir/ritonavir regimen is also acceptable in combination with weight-based ribavirin.<ref name="HCVGuidelinesGenotype4">Template:Cite book</ref>
- HCV genotype 4 (with compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir, elbasvir/grazoprevir, or ledipasvir/sofosbuvir is recommended. A 12-week course of ombitasvir/paritaprevir/ritonavir with weight-based ribavirin is an acceptable alternative.<ref name="HCVGuidelinesGenotype4compensated">Template:Cite book</ref>
- HCV genotype 5 or 6 (with or without compensated cirrhosis): 8 weeks of glecaprevir/pibrentasvir is recommended. If cirrhosis is present, then a 12-week course of sofosbuvir/velpatasvir, or ledipasvir/sofosbuvir is an alternative option.<ref name="HCVGuidelinesGenotypes5and6">Template:Cite book</ref>
More than 95% of people with chronic infection can be cured when treated with medications;<ref name=CDC2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> this could be expensive, but by 2022 prices had dropped dramatically.<ref name=whofactsheet/> The combination of sofosbuvir, velpatasvir, and voxilaprevir may be used in those who have previously been treated with sofosbuvir or other drugs that inhibit NS5A and were not cured.<ref>Template:Cite press release</ref>
Before 2011, treatments consisted of a combination of pegylated interferon alpha and ribavirin for a period of 24 or 48 weeks, depending on HCV genotype.<ref name=AFP2010 /> This treatment produces cure rates of 70–80% for genotype 2 and 3, respectively, and 45–70% for genotypes 1 and 4.<ref name=NEJM2013>Template:Cite journal</ref> Adverse effects with these treatments were common, with 50–60% of those being treated experiencing flu-like symptoms and nearly a third experiencing depression or other emotional issues.<ref name=AFP2010 /> Treatment during the first six months of infection (the acute stage) is more effective than when Template:Nowrap has entered the chronic stage.<ref name=Tah2009 /> In those with chronic hepatitis B, treatment for hepatitis C results in reactivation of hepatitis B about 25% of the time.<ref name="Mücke2018">Template:Cite journal</ref>
SurgeryEdit
Cirrhosis due to hepatitis C is a common reason for liver transplantation,<ref name=Tah2009>Template:Cite journal</ref> though the virus usually (80–90% of cases) recurs afterwards.<ref name=NEJM2011 /><ref>Template:Cite book</ref> Infection of the graft leads to 10–30% of people developing cirrhosis within five years.<ref name=Ciria2013>Template:Cite journal</ref> Treatment with pegylated interferon and ribavirin post-transplant decreases the risk of recurrence to 70%.<ref name=Coilly2013>Template:Cite journal</ref> A 2013 review found no clear evidence as to whether antiviral medication is useful if the graft became reinfected.<ref>Template:Cite journal</ref>
Alternative medicineEdit
Several alternative therapies are claimed by their proponents to be helpful for Template:Nowrap, including milk thistle, ginseng, and colloidal silver.<ref name=NCCAM>Hepatitis C and CAM: What the Science Says Template:Webarchive. National Center for Complementary and Alternative Medicine (NCCAM). March 2011. (Retrieved 7 March 2011)</ref> However, no alternative therapy has been shown to improve outcomes for Template:Nowrap patients, and no evidence exists that alternative therapies have any effect on the virus.<ref name=NCCAM /><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
PrognosisEdit
The response to treatment is measured by sustained viral response (SVR), defined as the absence of detectable RNA of the hepatitis C virus in blood serum for at least 24 weeks after discontinuing treatment,<ref>Template:Cite book</ref> and rapid virological response (RVR), defined as undetectable levels achieved within four weeks of treatment. Successful treatment decreases the future risk of hepatocellular carcinoma by 75%.<ref>Template:Cite journal</ref>
Before 2012, sustained response occurred in about 40–50% of those with HCV genotype 1 who received 48 weeks of treatment.<ref name=NEJM2011 /> A sustained response was seen in 70–80% of people with HCV genotypes 2 and 3 following 24 weeks of treatment.<ref name=NEJM2011 /> A sustained response occurs for about 65% of those with genotype 4 after 48 weeks of treatment. For those with HCV genotype 6, a 48-week treatment protocol of pegylated interferon and ribavirin results in a higher rate of sustained responses than for genotype 1 (86% vs. 52%). Further studies are needed to determine results for shorter 24-week treatments and those given at lower dosages.<ref>Template:Cite journal</ref>
Spontaneous resolutionEdit
Around 30% (15–45%) of those with acute HCV infections will spontaneously clear the virus within six months before the infection is considered chronic.<ref name=whofactsheet /> Spontaneous resolution following acute infection appears more common in females and younger patients and may be influenced by certain genetic factors.<ref name=Book2011p4/> Chronic HCV infection may also resolve spontaneously months or years after the acute phase has passed, though this is unusual.<ref name="Book2011p4" />
EpidemiologyEdit
The World Health Organization estimated in a 2021 report that 58 million people globally were living with chronic hepatitis C as of 2019.<ref name=":1" /> About 1.5 million people are infected per year, and about 290,000 people die yearly from hepatitis C–related diseases, mainly from liver cancer and cirrhosis.<ref name=whofactsheet/>
Hepatitis C infection rates increased substantially in the 20th century due to a combination of intravenous drug abuse and the reuse of poorly sterilized medical equipment.<ref name="World2007" /> However, advancements in treatment have led to notable declines in chronic infections and deaths from the virus. As a result, the number of chronic patients receiving treatment worldwide has grown from about 950,000 in 2015 to 9.4 million in 2019. During the same period, hepatitis C deaths declined from about 400,000 to 290,000.<ref name=whofactsheet /><ref name=":1" />
Previously, a 2013 study found high infection rates (>3.5% population infected) in Central and East Asia, North Africa and the Middle East, intermediate infection rates (1.5–3.5%) in South and Southeast Asia, sub-Saharan Africa, Andean, Central and Southern Latin America, Caribbean, Oceania, Australasia and Central, Eastern and Western Europe; and low infection rates (<1.5%) in Asia-Pacific, Tropical Latin America and North America.<ref name="Mohd2013">Template:Cite journal</ref>
Among those chronically infected, the risk of cirrhosis after 20 years varies between studies but has been estimated at ~10–15% for men and ~1–5% for women. The reason for this difference is not known. Once cirrhosis is established, the rate of developing hepatocellular carcinoma is ~1–4% per year.<ref name=Yu2009>Template:Cite journal</ref> Rates of new infections have decreased in the Western world since the 1990s due to improved screening of blood before transfusion.<ref name=Tah2009 />
In Egypt, following Egypt's 2030 Vision, the country managed to bring down the infection rates of hepatitis C from 22% in 2011 to just 2% in 2021.<ref name="egypttoday.com">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It was believed that the high prevalence in Egypt was linked to a discontinued mass-treatment campaign for schistosomiasis, using improperly sterilized glass syringes.<ref name="World2007" />
In the United States, about 2% of people have chronic Template:Nowrap.<ref name=AFP2010 /> In 2014, an estimated 30,500 new acute hepatitis C cases occurred (0.7 per 100,000 population), an increase from 2010 to 2012.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> The number of deaths from hepatitis C rose to 15,800 in 2008<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> having overtaken HIV/AIDS as a cause of death in the US in 2007.<ref>Template:Cite news</ref> In 2014, it was the single greatest cause of infectious death in the United States.<ref name="CDC2016a">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> This mortality rate is expected to increase, as those infected by transfusion before HCV testing become apparent.<ref name=Cola2004>Template:Cite book</ref> In Europe, the percentage of people with chronic infections has been estimated to be between 0.13 and 3.26%.<ref>Template:Cite journal</ref>
In the United Kingdom, about 118,000 people were chronically infected in 2019.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> About half of people using a needle exchange in London in 2017–18 tested positive for hepatitis C of which half were unaware that they had it.<ref>Template:Cite journal</ref> As part of a bid to eradicate hepatitis C by 2025, NHS England conducted a large procurement exercise in 2019. Merck Sharp & Dohme, Gilead Sciences, and Abbvie were awarded contracts, which, together, are worth up to £1 billion over five years.<ref>Template:Cite news</ref>
The total number of people with this infection is higher in some countries in Africa and Asia.<ref>Template:Cite book</ref> Countries with particularly high rates of infection include Pakistan (4.8%) and China (3.2%).<ref name=WHO2011>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Since 2014, extremely effective treatments have been available to eradicate the disease within 8–12 weeks in most people.<ref name=":0">Template:Cite journal</ref> In 2015, about 950,000 people were treated while 1.7 million new infections occurred, meaning that overall the number of people with HCV increased.<ref name=":0" /> These numbers differ by country and improved in 2016, with some countries achieving higher cure rates than new infection rates (mostly high-income countries).<ref name=":0" /> By 2018, twelve countries are on track to achieve HCV elimination.<ref name=":0" /> While antiviral agents will curb new infections, it is less clear whether they impact overall deaths and morbidity.<ref name=":0" /> Furthermore, for them to be effective, people need to be aware of their infection – it is estimated that worldwide only 20% of infected people are aware of their infection (in the US, fewer than half were aware).<ref name=":0" />
HistoryEdit
In the mid-1970s, Harvey J. Alter, Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the National Institutes of Health, and his research team demonstrated how most post-transfusion hepatitis cases were not due to hepatitis A or B viruses. Despite this discovery, international research efforts to identify the virus, initially called non-A, non-B hepatitis (NANBH), failed for the next decade. In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation, collaborating with Daniel W. Bradley at the Centers for Disease Control and Prevention, used a novel molecular cloning approach to identify the unknown organism and develop a diagnostic test.<ref name = Boyer>Template:Cite book</ref> In 1988, Alter confirmed the virus by verifying its presence in a panel of NANBH specimens, and Chiron announced its discovery at a Washington, D.C. press conference in May 1988.
At the time, Chiron was in talks with the Japanese health ministry to sell a biotech version of the hepatitis B vaccine. Simultaneously, Emperor Hirohito had developed cancer and required numerous blood transfusions. The Japanese health ministry placed a screening order for Chiron's experimental NANBH test. Chiron's Japanese marketing subsidiary, Diagnostic Systems KK, introduced the term "Hepatitis C" in November 1988 in Tokyo news reports publicizing the testing of the emperor's blood.<ref>Template:Cite news</ref> Chiron sold a screening order to the Japanese health ministry in November 1988, earning the company US$60 million a year. However, because Chiron had not published any of its research and did not make a culture model available to other researchers to verify Chiron's discovery, hepatitis C earned the nickname "The Emperor's New Virus."
In April 1989, the "discovery" of HCV was published in two articles in the journal Science.<ref name="choo">Template:Cite journal</ref><ref name="kuo">Template:Cite journal</ref> Chiron filed for several patents on the virus and its diagnosis.<ref name="houghton">Template:Cite patent</ref> A competing patent application by the CDC was dropped in 1990 after Chiron paid $1.9 million to the CDC and $337,500 to Bradley. In 1994, Bradley sued Chiron, seeking to invalidate the patent, have himself included as a co-inventor, and receive damages and royalty income. The court ruled against him, which was sustained on appeal in 1998.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Because of the unique molecular "isolation" of the hepatitis C virus, although Houghton and Kuo's team at Chiron had discovered strong biochemical markers for the virus and the test proved effective at reducing cases of post-transfusion hepatitis, the existence of a hepatitis C virus was essentially inferred.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> In 1992, the San Francisco Chronicle reported that the virus had never been observed under an electron microscope.<ref>Template:Cite news</ref> In 1997, the American FDA approved the first hepatitis C drug on the basis of a surrogate marker called "Sustained Virological Response." In response, the pharmaceutical industry established a nationwide network of "Astro-Turf" patient advocacy groups to raise awareness (and fear) of the disease.<ref>Template:Cite news</ref>
Hepatitis C was finally "discovered" in 2005 when a Japanese team was able to propagate a molecular clone in a cell culture called Huh7.<ref>Template:Cite journal</ref> This discovery enabled proper characterization of the viral particle and rapid research into the development of protease inhibitors replacing early interferon treatments. The first of these, sofosbuvir, was approved on December 6, 2013. These drugs are marketed as "cures;" however, because they were approved on the basis of surrogate markers and not clinical endpoints such as prolonging life or improving liver health, many experts question their value.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
After blood screening began, a notable hepatitis C prevalence was discovered in Egypt, which claimed six million individuals were infected by unsterile needles in a late 1970s mass chemotherapy campaign to eliminate schistosomiasis (snail fever).<ref>Template:Cite news</ref>
On October 5, 2020, Houghton and Alter, together with Charles M. Rice, were awarded the Nobel Prize in Physiology or Medicine for their work.<ref>Template:Cite news</ref><ref>Template:Cite journal</ref>
Society and cultureEdit
Template:See also World Hepatitis Day, held on July 28, is coordinated by the World Hepatitis Alliance.<ref>Template:Cite journal</ref> The economic costs of hepatitis C are significant both to the individual and to society. In the United States, the average lifetime cost of the disease was estimated at US$33,407 in 2003<ref name=Cost2006>Template:Cite journal</ref> with the cost of a liver transplant Template:As of costing approximately US$200,000.<ref name=Cost2011 /> In Canada, the cost of a course of antiviral treatment is as high as 30,000 CAD in 2003,<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> while the United States costs are between 9,200 and US$17,600 in 1998.<ref name=Cost2006 /> In many areas of the world, people cannot afford treatment with antivirals as they either lack insurance coverage or their insurance will not pay for antivirals.<ref>Template:Cite book</ref> In the English National Health Service treatment rates for hepatitis C were higher among less deprived groups in 2010–2012.<ref name=UK2015>Template:Cite news</ref>
Hepatitis C–infected Spanish anaesthetist Juan Maeso was jailed for the maximum possible period of 20 years for infecting 275 patients between 1988 and 1997, as he used the same needles to give both himself and the patients opioids.<ref>Template:Cite news</ref><ref>Template:Cite news</ref>
Special populationsEdit
Children and pregnancyEdit
{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} Compared with adults, infection in children is much less understood. Worldwide the prevalence of Template:Nowrap virus infection in pregnant women and children has been estimated to be 1–8% and 0.05–5% respectively.<ref name=Arshad2011>Template:Cite journal</ref> The vertical transmission rate has been estimated to be 3–5% and there is a high rate of spontaneous clearance (25–50%) in the children. Higher rates have been reported for both vertical transmission (18%, 6–36%, and 41%)<ref name=Hunt1997>Template:Cite journal</ref><ref name=Thomas1998>Template:Cite journal</ref> and prevalence in children (15%).<ref name=Fischler2007>Template:Cite journal</ref>
In developed countries, transmission around the time of birth is now the leading cause of HCV infection. In the absence of the Hepatitis C virus in the mother's blood, transmission is rare.<ref name=Thomas1998 /> Factors associated with an increased rate of infection include membrane rupture of longer than 6 hours before delivery and procedures exposing the infant to maternal blood.<ref name=Indolfi2009>Template:Cite journal</ref> Cesarean sections are not recommended. Breastfeeding is considered safe if the nipples are not damaged. Infection around the time of birth in one child does not increase the risk in a subsequent pregnancy. All genotypes appear to have the same risk of transmission.
HCV infection is frequently found in children who have previously been presumed to have non-A, non-B hepatitis, and cryptogenic liver disease.<ref name="González-Peralta1997">Template:Cite journal</ref> The presentation in childhood may be asymptomatic or with elevated liver function tests.<ref name=Suskind2004>Template:Cite journal</ref> While the infection is commonly asymptomatic, both cirrhosis with liver failure and hepatocellular carcinoma may occur in childhood.
ImmunosuppressedEdit
Template:See also The rate of Template:Nowrap in immunosuppressed people is higher. This is particularly true in those with human immunodeficiency virus infection, recipients of organ transplants, and those with hypogammaglobulinemia.<ref name=Einav2002>Template:Cite journal</ref> Infection in these people is associated with an unusually rapid progression to cirrhosis. People with stable HIV who never received medication for HCV may be treated with a combination of peginterferon plus ribavirin with caution to the possible side effects.<ref>Template:Cite journal</ref>
ResearchEdit
Template:As of, there are about one hundred medications in development for Template:Nowrap.<ref name=Cost2011>Template:Cite journal</ref> These include vaccines to treat hepatitis, immunomodulators, and cyclophilin inhibitors, among others.<ref>Template:Cite journal</ref> These potential new treatments have come about due to a better understanding of the Template:Nowrap virus.<ref>Template:Cite journal</ref> There are several vaccines under development and some have shown encouraging results.<ref name=Vac2016>Template:Cite journal</ref>
The combination of sofosbuvir and velpatasvir in one trial (reported in 2015) resulted in cure rates of 99%.<ref>Template:Cite journal</ref> More studies are needed to investigate the role of the preventive antiviral medication against HCV recurrence after transplantation.<ref>Template:Cite journal</ref>
Animal modelsEdit
One barrier to finding treatments for Template:Nowrap is the lack of a suitable animal model. Despite moderate success, research highlights the need for pre-clinical testing in mammalian systems such as mouse, particularly to develop vaccines in poorer communities. Chimpanzees remain the only living system to study, yet their use has ethical concerns and regulatory restrictions. While scientists have used human cell culture systems such as hepatocytes, questions have been raised about their accuracy in reflecting the body's response to infection.<ref name=Sand2013>Template:Cite journal</ref>
One aspect of hepatitis research is to reproduce infections in mammalian models. A strategy is to introduce liver tissues from humans into mice, a technique known as xenotransplantation. This is done by generating chimeric mice and exposing the mice to HCV infection. This engineering process is known to create humanized mice and provide opportunities to study hepatitis C within the 3D architectural design of the liver and evaluate antiviral compounds.<ref name=Sand2013 /> Alternatively, generating inbred mice with susceptibility to HCV would simplify the process of studying mouse models.
See alsoEdit
- PSI-6130, an experimental drug treatment
ReferencesEdit
External linksEdit
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