Hepatitis C
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Hepatitis C is an
infectious disease An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
caused by the
hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...
(HCV) that primarily affects the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
; it is a type of
viral hepatitis Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. The most common causes of viral hepatitis are the five unrelated hepatotropic vi ...
. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs. The virus persists in the liver in about 75% to 85% of those initially infected. Early on, chronic infection typically has no symptoms. Over many years however, it often leads to
liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the si ...
and occasionally
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
. 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 The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
. HCV is spread primarily by blood-to-blood contact associated with
injection drug use Drug injection is a method of introducing a drug into the bloodstream via a hollow hypodermic needle, which is pierced through the skin into the body (usually intravenously, but also at an intramuscular or subcutaneous location). Intravenous t ...
, poorly sterilized medical equipment,
needlestick injuries A needlestick injury is the penetration of the skin by a hypodermic needle or other sharp object that has been in contact with blood, tissue or other body fluids before the exposure. Even though the acute physiological effects of a needlestick i ...
in healthcare, and
transfusions Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
. Using blood screening, the risk from a transfusion is less than one per two million. It may also be spread from an infected mother to her baby during birth. It is not spread by superficial contact. It is one of five known hepatitis viruses: A, B, C, D, and E. Diagnosis is by blood testing to look for either antibodies to the virus or viral
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
. In the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
, screening for HCV infection is recommended in all adults age 18 to 79 years old. There is no
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
against hepatitis C. Prevention includes
harm reduction Harm reduction, or harm minimization, refers to a range of public health policies designed to lessen the negative social and/or physical consequences associated with various human behaviors, both legal and illegal. Harm reduction is used to d ...
efforts among people who inject drugs, testing donated blood, and treatment of people with chronic infection. Chronic infection can be cured more than 95% of the time with
antiviral medications Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...
such as sofosbuvir or
simeprevir Simeprevir, sold under the trade names Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with inclu ...
. Peginterferon and
ribavirin Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, pe ...
were earlier generation treatments that had a cure rate of less than 50% and greater side effects. Getting access to the newer treatments, however, can be expensive. Those who develop cirrhosis or liver cancer may require a
liver transplant Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, al ...
. Hepatitis C is the leading reason for liver transplantation, though the virus usually recurs after transplantation. 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. The existence of hepatitis C – originally identifiable only as a type of non- A non- B
hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...
– was suggested in the 1970s and proven in 1989. Hepatitis C infects only humans and
chimpanzees The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close relative th ...
.


Signs and symptoms


Acute infection

Acute Acute may refer to: Science and technology * Acute angle ** Acute triangle ** Acute, a leaf shape in the glossary of leaf morphology * Acute (medicine), a disease that it is of short duration and of recent onset. ** Acute toxicity, the adverse eff ...
symptoms develop in some 20–30% of those infected. 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). Symptoms are generally mild and vague, and may include fatigue,
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
and vomiting, fever,
muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
or joint pains, abdominal pain,
decreased appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others ...
and weight loss, jaundice (occurs in ~25% of those infected), dark urine, and clay-coloured stools. Acute liver failure due to acute hepatitis C is exceedingly rare. 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. Following the acute phase, the infection may resolve spontaneously in 10–50% of affected people; this occurs more frequently in young people, and females.


Chronic infection

About 80% of those exposed to the virus develop a chronic infection. This is defined as the presence of detectable viral replication for at least six months. Most experience minimal or no symptoms during the initial few decades of the infection. Chronic can be associated with fatigue and mild cognitive problems. Chronic infection after several years may cause
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
or liver cancer. The liver enzymes measured from blood samples are normal in 7–53%. (Elevated levels indicate liver cells are being damaged by the virus or other disease). Late relapses after apparent cure have been reported, but these can be difficult to distinguish from reinfection. Fatty changes to the liver occur in about half of those infected and are usually present before cirrhosis develops. Usually (80% of the time) this change affects less than a third of the liver. Worldwide hepatitis C is the cause of 27% of cirrhosis cases and 25% of hepatocellular carcinoma. About 10–30% of those infected develop cirrhosis over 30 years. Cirrhosis is more common in those also infected with
hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
, schistosoma, or HIV, in
alcoholic Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomina ...
s and in those of male sex. In those with hepatitis C, excess alcohol increases the risk of developing cirrhosis 5-fold. Those who develop cirrhosis have a 20-fold greater risk of hepatocellular carcinoma. This transformation occurs at a rate of 1–3% per year. Being infected with hepatitis B in addition to hepatitis C increases this risk further. Liver cirrhosis may lead to portal hypertension,
ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...
(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 Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stage ...
. Ascites occurs at some stage in more than half of those who have a chronic infection.


Extrahepatic complications

The most common problem due to but not involving the liver is mixed
cryoglobulinemia Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. ...
(usually the type II form) – an inflammation of small and medium-sized blood vessels. is also associated with autoimmune disorders such as Sjögren's syndrome,
lichen planus Lichen planus (LP) is a chronic inflammatory and immune-mediated disease that affects the skin, nails, hair, and mucous membranes. It is not an actual lichen, and is only named that because it looks like one. It is characterized by polygonal, fla ...
, a low platelet count,
porphyria cutanea tarda Porphyria cutanea tarda is the most common subtype of porphyria. The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fift ...
, necrolytic acral erythema, insulin resistance,
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
,
diabetic nephropathy Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease ...
, autoimmune
thyroiditis Thyroiditis is the inflammation of the thyroid gland. The thyroid gland is located on the front of the neck below the laryngeal prominence, and makes hormones that control metabolism. Signs and symptoms There are many different signs and sympto ...
, and B-cell
lymphoproliferative disorder Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which lymphocytes are produced in excessive quantities. These disorders primarily present in patients who have a compromised ...
s. 20–30% of people infected have rheumatoid factor – a type of antibody. Possible associations include Hyde's prurigo nodularis and
membranoproliferative glomerulonephritis Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane ( GBM) thickening, activating complement and damaging the glomeruli. MPGN accounts for appr ...
. Cardiomyopathy with associated abnormal heart rhythms has also been reported. A variety of
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
disorders has been reported. Chronic infection seems to be associated with an increased risk of pancreatic cancer. People may experience other issues in the mouth such as dryness, salivary duct stones, and crusted lesions around the mouth.


Occult infection

Persons who have been infected with hepatitis C may appear to clear the virus but remain infected. The virus is not detectable with conventional testing but can be found with ultra-sensitive tests. The original method of detection was by demonstrating the viral
genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
within liver biopsies, but 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. A form of infection with persistently moderately elevated serum liver enzymes but without antibodies to hepatitis C has also been reported. This form is known as cryptogenic occult infection. Several clinical pictures have been associated with this type of infection. 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. The consequences of occult infection appear to be less severe than with chronic infection but can vary from minimal to hepatocellular carcinoma. The rate of occult infection in those apparently cured is controversial but appears to be low. 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. How commonly this occurs in children is unknown.


Virology

The
hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...
(HCV) is a small, enveloped, single-stranded, positive-sense RNA virus. It is a member of the genus ''
Hepacivirus ''Hepacivirus'' is a genus of positive-strand RNA viruses in the family ''Flaviviridae''. The hepatitis C virus (HCV), in species '' Hepacivirus C'', infects humans and is associated with hepatitis and hepatocellular carcinoma. There are fourt ...
'' in the family ''
Flaviviridae ''Flaviviridae'' is a family of enveloped positive-strand RNA viruses which mainly infect mammals and birds. They are primarily spread through arthropod vectors (mainly ticks and mosquitoes). The family gets its name from the yellow fever viru ...
''. There are seven major genotypes of HCV, which are known as genotypes one to seven. 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. Genotype 1 is also the most common in South America and Europe. The half life of the virus particles in the serum is around 3 hours and may be as short as 45 minutes. In an infected person, about 1012 virus particles are produced each day. In addition to replicating in the liver the virus can multiply in lymphocytes.


Transmission

Percutaneous {{More citations needed, date=January 2021 In surgery, a percutaneous procedurei.e. Granger et al., 2012 is any medical procedure or method where access to inner organs or other tissue is done via needle-puncture of the skin, rather than by using ...
contact with contaminated blood is responsible for most infections; however, the method of transmission is strongly dependent on both geographic region and economic status. Indeed, the primary route of transmission in the
developed world A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...
is
injection drug use Drug injection is a method of introducing a drug into the bloodstream via a hollow hypodermic needle, which is pierced through the skin into the body (usually intravenously, but also at an intramuscular or subcutaneous location). Intravenous t ...
, while in the developing world the main methods are
blood transfusions Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mod ...
and unsafe medical procedures. The cause of transmission remains unknown in 20% of cases; however, many of these are believed to be accounted for by injection drug use.


Drug use

Injection drug use Drug injection is a method of introducing a drug into the bloodstream via a hollow hypodermic needle, which is pierced through the skin into the body (usually intravenously, but also at an intramuscular or subcutaneous location). Intravenous t ...
(IDU) is a major risk factor for in many parts of the world. Of 77 countries reviewed, 25 (including the United States) were found to have a prevalence of of between 60% and 80% among people who use injection drugs. Twelve countries had rates greater than 80%. It is believed that ten million intravenous drug users are infected with ; China (1.6 million), the United States (1.5 million), and Russia (1.3 million) have the highest absolute totals. Occurrence of 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. Shared intranasal drug use may also be a risk factor.


Healthcare exposure

Blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
, transfusion of blood products, or
organ transplants Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpo ...
without HCV screening carry significant risks of infection. The United States instituted universal screening in 1992, and Canada instituted universal screening in 1990. This decreased the risk from one in 200 units to between one in 10,000 to one in 10,000,000 per unit of blood. This low risk remains as there is a period of about 11–70 days between the potential
blood donor A blood donation occurs when a person voluntarily has blood drawn and used for transfusions and/or made into biopharmaceutical medications by a process called fractionation (separation of whole blood components). Donation may be of whole bloo ...
's acquiring and the blood's testing positive depending on the method. Some countries do not screen for due to the cost. 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. The risk is greater if the needle in question is hollow and the puncture wound is deep. There is a risk from mucosal exposures to blood, but this risk is low, and there is no risk if blood exposure occurs on intact skin. Hospital equipment has also been documented as a method of transmission of , including reuse of needles and syringes; multiple-use medication vials; infusion bags; and improperly sterilized surgical equipment, among others. 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 Egypt ( ar, مصر , ), officially the Arab Republic of Egypt, is a transcontinental country spanning the northeast corner of Africa and southwest corner of Asia via a land bridge formed by the Sinai Peninsula. It is bordered by the Mediter ...
, the country that had the highest rate of infection in the world in 2012, and currently has one of the lowest in the world in 2021. For more, see HONOReform (Hepatitis Outbreaks National Organization for Reform).


Sexual intercourse

Sexual transmission of hepatitis C is uncommon. Studies examining the risk of HCV transmission between
heterosexual Heterosexuality is romantic attraction, sexual attraction or sexual behavior between people of the opposite sex or gender. As a sexual orientation, heterosexuality is "an enduring pattern of emotional, romantic, and/or sexual attractions" ...
partners, when one is infected and the other is not, have found very low risks. Sexual practices that involve higher levels of trauma to the
anogenital The perineum in humans is the space between the anus and scrotum in the male, or between the anus and the vulva in the female. The perineum is the region of the body between the pubic symphysis (pubic arch) and the coccyx (tail bone), includin ...
mucosa, such as anal penetrative sex, or that occur when there is a concurrent sexually transmitted infection, including
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
or
genital ulcer A genital ulcer is an open sore located on the genital area, which includes the vulva, penis, perianal region, or anus. Genital ulcers are most commonly caused by infectious agents (fungal infections, secondary bacterial infections, or sexually t ...
ation, present greater risks. The
United States Department of Veterans Affairs The United States Department of Veterans Affairs (VA) is a Cabinet-level executive branch department of the federal government charged with providing life-long healthcare services to eligible military veterans at the 170 VA medical centers a ...
recommends condom use to prevent transmission in those with multiple partners, but not those in relationships that involve only a single partner.


Body modification

Tattooing A tattoo is a form of body modification made by inserting tattoo ink, dyes, and/or pigments, either indelible or temporary, into the dermis layer of the skin to form a design. Tattoo artists create these designs using several tattooing p ...
is associated with two to threefold increased risk of . This could be due to either improperly sterilized equipment or contamination of the dyes being used. Tattoos or
piercings Body piercing, which is a form of body modification, is the practice of puncturing or cutting a part of the human body, creating an opening in which jewelry may be worn, or where an implant could be inserted. The word ''piercing'' can refer to ...
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. It is estimated that nearly half of prison inmates share unsterilized tattooing equipment. It is rare for tattoos in a licensed facility to be directly associated with HCV infection.


Shared personal items

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. Appropriate caution should be taken regarding any medical condition that results in
bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
, such as cuts and sores. HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils, nor is it transmitted through food or water.


Mother-to-child transmission

Mother-to-child transmission A vertically transmitted infection is an infection caused by pathogenic bacteria or viruses that use mother-to-child transmission, that is, transmission directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. It can ...
of occurs in fewer than 10% of pregnancies. There are no measures that alter this risk. It is not clear when transmission occurs during pregnancy, but it may occur both during gestation and at delivery. A long labor is associated with a greater risk of transmission. There is no evidence that
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
spreads HCV; however, to be cautious, an infected mother is advised to avoid breastfeeding if her nipples are cracked and bleeding, or if her viral loads are high.


Diagnosis

There are a number of diagnostic tests for , including HCV
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
enzyme immunoassay An enzyme immunoassay is any of several immunoassay methods that use an enzyme bound to an antigen or antibody. These may include: * Enzyme-linked immunosorbent assay The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analyti ...
(ELISA), recombinant immunoblot assay, and quantitative HCV
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(PCR). HCV
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
can be detected by PCR typically one to two weeks after infection, while antibodies can take substantially longer to form and thus be detected. Diagnosing patients is generally a challenge as patients with acute illness generally present with mild, non-specific flu-like symptoms, while the transition from acute to chronic is sub-clinical. Chronic is defined as infection with the virus persisting for more than six months based on the presence of its RNA. Chronic infections are typically asymptomatic during the first few decades, 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. Diagnosis in infants is difficult as maternal antibodies may persist for up to 18 months.


Serology

testing typically begins with blood testing to detect the presence of antibodies to the HCV, using an enzyme immunoassay. If this test is positive, a confirmatory test is then performed to verify the immunoassay and to determine the
viral load Viral load, also known as viral burden, is a numerical expression of the quantity of virus in a given volume of fluid, including biological and environmental specimens. It is not to be confused with viral titre or viral titer, which depends on the ...
. A recombinant immunoblot assay is used to verify the immunoassay and the viral load is determined by an HCV RNA polymerase chain reaction. 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. It takes about 6–8 weeks following infection before the immunoassay will test positive. A number of tests are available as
point-of-care testing Point-of-care testing (POCT or bedside testing) is defined as medical diagnostic testing at or near the point of care—that is, at the time and place of patient care. This contrasts with the historical pattern in which testing was wholly or most ...
(POCT), which can provide results within 30 minutes. Liver enzymes are variable during the initial part of the infection and on average begin to rise at seven weeks after infection. The elevation of liver enzymes does not closely follow disease severity.


Biopsy

Liver biopsies are used to determine the degree of liver damage present; however, there are risks from the procedure. The typical changes seen are
lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s within the parenchyma,
lymphoid follicles A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include ...
in
portal triad In histology (microscopic anatomy), the lobules of liver, or hepatic lobules, are small divisions of the liver defined at the microscopic scale. The hepatic lobule is a building block of the liver tissue, consisting of a portal triad, hepatocyte ...
, and changes to the bile ducts. There are a number of blood tests available that try to determine the degree of hepatic fibrosis and alleviate the need for biopsy.


Screening

It is believed that only 5–50% of those infected in the United States and Canada are aware of their status. Routine screening for those between the ages of 18 and 79 was recommended by the
United States Preventive Services Task Force The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...
in 2020. Previously, testing was recommended for those at high risk, including injection drug users, those who have received blood transfusions before 1992, those who have been incarcerated, those on long-term
hemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
, and those with tattoos. Screening is also recommended for those with elevated liver enzymes, as this is frequently the only sign of chronic hepatitis. , the U.S.
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
(CDC) recommends a single screening test for those born between 1945 and 1965. In Canada, a one-time screening is recommended for those born between 1945 and 1975.


Prevention

, no approved
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
protects against contracting . A combination of
harm reduction Harm reduction, or harm minimization, refers to a range of public health policies designed to lessen the negative social and/or physical consequences associated with various human behaviors, both legal and illegal. Harm reduction is used to d ...
strategies, such as the provision of new needles and syringes and treatment of substance use, decreases the risk of in people using injection drugs by about 75%. The screening of blood donors is important at a national level, as is adhering to
universal precautions Universal precautions refers to the practice, in medicine, of avoiding contact with patients' bodily fluids, by means of the wearing of nonporous articles such as medical gloves, goggles, and face shields. The infection control techniques were ...
within healthcare facilities. In countries where there is an insufficient supply of sterile
syringes A syringe is a simple reciprocating pump consisting of a plunger (though in modern syringes, it is actually a piston) that fits tightly within a cylindrical tube called a barrel. The plunger can be linearly pulled and pushed along the inside o ...
, medications should be given orally rather than via injection (when possible). Recent research also suggests that treating people with active infection, thereby reducing the potential for transmission, may be an effective preventive measure.


Treatment

Those with chronic are advised to avoid alcohol and medications that are toxic to the liver. They should also be
vaccinated A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.< ...
against
hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
and
hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
due to the increased risk if also infected. Use of acetaminophen is generally considered safe at reduced doses. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended in those with advanced liver disease due to an increased risk of bleeding.
Ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...
surveillance for hepatocellular carcinoma is recommended in those with accompanying cirrhosis.
Coffee Coffee is a drink prepared from roasted coffee beans. Darkly colored, bitter, and slightly acidic, coffee has a stimulant, stimulating effect on humans, primarily due to its caffeine content. It is the most popular hot drink in the world. S ...
consumption has been associated with a slower rate of liver
scarring A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a na ...
in those infected with HCV.


Medications

Approximately 90% of chronic cases clear with treatment. Treatment with
antiviral medication Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do ...
is recommended for all people with proven chronic hepatitis C who are not at high risk of death from other causes. People with the highest complication risk, which is based on the degree of liver scarring, should be treated first. 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.
Direct-acting antivirals Direct-acting antivirals (DAA) are drugs used to treat hepatitis C infections. They are a combination of antiviral drugs that target stages of the hepatitis C virus reproductive cycle. They are more effective than older treatments such as ribavirin ...
are the preferred treatment and have been validated by testing for virus particles in patients' blood.


No prior treatment

* HCV genotype 1a (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or
ledipasvir/sofosbuvir Ledipasvir/sofosbuvir, sold under the trade name Harvoni among others, is a medication used to treat hepatitis C. It is a fixed-dose combination of ledipasvir and sofosbuvir. Cure rates are 94% to 99% in people infected with hepatitis C virus ...
(the latter for people who do not have
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
, are not
African-American African Americans (also referred to as Black Americans and Afro-Americans) are an Race and ethnicity in the United States, ethnic group consisting of Americans with partial or total ancestry from sub-Saharan Africa. The term "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. Sofosbuvir with either
daclatasvir Daclatasvir, sold under the brand name Daklinza, is an antiviral medication used in combination with other medications to treat hepatitis C (HCV). The other medications used in combination include sofosbuvir, ribavirin, and interferon, vary depe ...
or
simeprevir Simeprevir, sold under the trade names Olysio among others, is a medication used in combination with other medications for the treatment of hepatitis C. It is specifically used for hepatitis C genotype 1 and 4. Medications it is used with inclu ...
may also be used. * HCV genotype 1a (with compensated cirrhosis): 12 weeks of elbasvir/grazoprevir, glecaprevir/pibrentasvir, 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. * 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 Ombitasvir/paritaprevir/ritonavir, sold under the brand name Technivie among others, is a medication used to treat hepatitis C. It is a fixed-dose combination of ombitasvir, paritaprevir, and ritonavir. Specifically it is used together with da ...
with
dasabuvir Dasabuvir, sold under the brand name Exviera, is an antiviral medication for the treatment of hepatitis C. It is often used together with the combination medication ombitasvir/paritaprevir/ritonavir specifically for hepatitis C virus (HCV) type ...
or 12 weeks of sofosbuvir with either daclatasvir or simeprevir. * HCV genotype 1b (with compensated cirrhosis): 12 weeks of elbasvir/grazoprevir, glecaprevir/pibrentasvir, ledipasvir/sofosbuvir, or sofosbuvir/velpatasvir. A 12-week course of paritaprevir/ritonavir/ombitasvir with dasabuvir may also be used. * 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. * HCV genotype 2 (with compensated cirrhosis): 12 weeks of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir. An alternative regimen of sofosbuvir/daclatasvir can be used for 16–24 weeks. * HCV genotype 3 (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir or sofosbuvir and daclatasvir. * HCV genotype 3 (with compensated cirrhosis): 12 weeks of glecaprevir/pibrentasvir, 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. * HCV genotype 4 (no cirrhosis): 8 weeks of glecaprevir/pibrentasvir or 12 weeks of sofosbuvir/velpatasvir, elbasvir/grazoprevir, or ledipasvir/sofosbuvir. A 12-week regimen of ombitasvir/paritaprevir/ritonavir is also acceptable in combination with weight-based
ribavirin Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, pe ...
. * HCV genotype 4 (with compensated cirrhosis): A 12-week regimen of sofosbuvir/velpatasvir, glecaprevir/pibrentasavir, elbasvir/grazoprevir, or ledipasvir/sofosbuvir is recommended. A 12-week course of ombitasvir/paritaprevir/ritonavir with weight-based ribavirin is an acceptable alternative. * HCV genotype 5 or 6 (with or without compensated cirrhosis): If no cirrhosis is present, then 8 weeks of glecaprevir/pibrentasvir is recommended. If cirrhosis is present, then a 12-week course of glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, or ledipasvir/sofosbuvir is warranted. More than 90% of people with chronic infection can be cured when treated with medications. However, accessing these treatments can be expensive. 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. Prior to 2011, treatments consisted of a combination of
pegylated interferon Pegylated interferon (PEG-IFN) is a class of medication that includes three different drugs as of 2012: * Pegylated interferon-alpha-2a * Pegylated interferon-alpha-2b * Pegylated interferon-beta-1a In these formulations, Polyethylene glycol (PEG ...
alpha and ribavirin for a period of 24 or 48 weeks, depending on HCV genotype. This treatment produces cure rates of between 70 and 80% for genotype 2 and 3, respectively, and 45 to 70% for genotypes 1 and 4. Adverse effects with these treatments were common, with 50 to 60% of those being treated experiencing
flu-like symptoms Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss ...
and nearly a third experiencing depression or other emotional issues. Treatment during the first six months of infection (the acute stage) is more effective than when has entered the chronic stage. In those with chronic hepatitis B, treatment for hepatitis C results in reactivation of hepatitis B about 25% of the time.


Surgery

Cirrhosis due to hepatitis C is a common reason for
liver transplant Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, al ...
ation, though the virus usually (80–90% of cases) recurs afterwards. Infection of the graft leads to 10–30% of people developing cirrhosis within five years. Treatment with pegylated interferon and ribavirin post-transplant decreases the risk of recurrence to 70%. A 2013 review found no clear evidence as to whether antiviral medication is useful if the graft became reinfected.


Alternative medicine

Several alternative therapies are claimed by their proponents to be helpful for , including
milk thistle ''Silybum marianum'' is a species of thistle. It has various common names including milk thistle, blessed milkthistle, Marian thistle, Mary thistle, Saint Mary's thistle, Mediterranean milk thistle, variegated thistle and Scotch thistle (thou ...
,
ginseng Ginseng () is the root of plants in the genus '' Panax'', such as Korean ginseng ('' P. ginseng''), South China ginseng ('' P. notoginseng''), and American ginseng ('' P. quinquefolius''), typically characterized by the presence of ginsenosides ...
, and
colloidal silver The medical uses of silver include its use in wound dressings, creams, and as an antibiotic coating on medical devices. Wound dressings containing silver sulfadiazine or silver nanomaterials may be used to treat external infections. The limited ...
.Hepatitis C and CAM: What the Science Says
.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Integrative Health (NCCIH) is a United States government agency which explores complementary and alternative medicine (CAM). It was initially created in 1991 as the Office of Alternative Medicine (OAM), ...
(NCCAM). March 2011. (Retrieved 7 March 2011)
However, no alternative therapy has been shown to improve outcomes for patients, and no evidence exists that alternative therapies have any effect on the virus.


Prognosis

The responses to treatment is measured by ''sustained viral response'' (SVR), defined as the absence of detectable
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
of the
hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...
in blood serum for at least 24 weeks after discontinuing treatment, 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%. Prior to 2012, sustained response occurred in about 40–50% of those with HCV genotype 1 who received 48 weeks of treatment. A sustained response was seen in 70–80% of people with HCV genotypes 2 and 3 following 24 weeks of treatment. 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 for those given at lower dosages.


Spontaneous resolution

Depending on a variety of patient factors, between 15 and 45% of those with acute HCV infections will spontaneously clear the virus within six months, before the infection is considered chronic. Spontaneous resolution following acute infection appears more common in females and in patients who are younger, and may be influenced by certain genetic factors. Chronic HCV infection may also resolve spontaneously months or years after the acute phase has passed, though this is unusual.


Epidemiology

The World Health Organization estimated in a 2021 report that 58 million people globally were living with chronic hepatitis C as of 2019. 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. 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. 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. 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. Among those chronically infected, the risk of
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...
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. Rates of new infections have decreased in the Western world since the 1990s due to improved screening of blood before transfusion. 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. It was believed that the high prevalence in Egypt was linked to a discontinued mass-treatment campaign for schistosomiasis, using improperly sterilized glass syringes. In the United States, about 2% of people have chronic . In 2014, an estimated 30,500 new acute hepatitis C cases occurred (0.7 per 100,000 population), an increase from 2010 to 2012. The number of deaths from hepatitis C has increased to 15,800 in 2008 having overtaken HIV/AIDS as a cause of death in the US in 2007. In 2014 it was the single greatest cause of infectious death in the United States. This mortality rate is expected to increase, as those infected by transfusion before HCV testing become apparent. In Europe the percentage of people with chronic infections has been estimated to be between 0.13 and 3.26%. In the United Kingdom about 118,000 people were chronically infected in 2019. About half of people using a needle exchange in London in 2017/8 tested positive for hepatitis C of which half were unaware that they had it. As part of a bid to eradicate hepatitis C by 2025 NHS England conducted a large procurement exercise in 2019.
Merck Sharp & Dohme Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for Merck Group, founded in Germany in 1668, of whom it was once the American arm. The company does business as Merck Sharp ...
,
Gilead Sciences Gilead Sciences, Inc. () is an American biopharmaceutical company headquartered in Foster City, California, that focuses on researching and developing antiviral drugs used in the treatment of HIV/AIDS, hepatitis B, hepatitis C, influenza, and C ...
, and
Abbvie AbbVie is an American publicly traded biopharmaceutical company founded in 2013. It originated as a spin-off of Abbott Laboratories. History On October 19, 2011, Abbott Laboratories announced its plan to separate into two publicly traded compani ...
were awarded contracts, which, together, are worth up to £1 billion over five years. The total number of people with this infection is higher in some countries in
Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
and
Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...
. Countries with particularly high rates of infection include Pakistan (4.8%) and China (3.2%). Since 2014, extremely effective medication have been available to eradication the disease in 8–12 weeks in most people. 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. These numbers differ by country and improved in 2016, with some countries achieving higher cure rates than new infection rates (mostly high income countries). By 2018, twelve countries are on track to achieve HCV elimination. While antiviral agents will curb new infections, it is less clear whether they impact overall deaths and morbidity. 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).


History

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 The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
, and his research team demonstrated how most post- transfusion hepatitis cases were not due to
hepatitis A Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
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 Qui-Lim Choo is a Singapore-born scientist, who along with Michael Houghton, George Kuo and Daniel W. Bradley, co-discovered and cloned Hepatitis C in 1989. He also co-discovered the Hepatitis D genome in 1986. The discovery of Hepatitis C led ...
, and
George Kuo George Ching-Hung Kuo is a Taiwanese-born scientist, who along with Michael Houghton, Qui-Lim Choo and Daniel W. Bradley, co-discovered and cloned the hepatitis C virus in 1989. Kuo graduated from the National Taiwan University in 1961 and comple ...
at
Chiron Corporation Chiron Corporation ( ) was an American multinational biotechnology firm founded in 1981, based in Emeryville, California, that was acquired by Novartis on April 20, 2006. It had offices and facilities in eighteen countries on five continents. ...
, collaborating with
Daniel W. Bradley Daniel W. Bradley (born 13 July 1941) is an important American virologist who, along with Michael Houghton, Qui-Lim Choo and George Kuo at Chiron Corporation, worked to help isolate the Hepatitis C virus in 1989. He graduated from San José Stat ...
at the
Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
, used a novel
molecular cloning Molecular cloning is a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their DNA replication, replication within Host (biology), host organisms. The use of the word ''cloning'' re ...
approach to identify the unknown organism and develop a diagnostic test. In 1988, Alter confirmed the virus by verifying its presence in a panel of NANBH specimens, and Chiron announced its discovery at a Washington, DC 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 Emperor , commonly known in English-speaking countries by his personal name , was the 124th emperor of Japan, ruling from 25 December 1926 until his death in 1989. Hirohito and his wife, Empress Kōjun, had two sons and five daughters; he was ...
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 invented the term "Hepatitis C" in November, 1988 in Tokyo news reports publicizing the testing of the Emperor's blood. Chiron managed to sell a screening order to the Japanese health ministry in November 1988, earning the company $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 Science is a systematic endeavor that builds and organizes knowledge in the form of testable explanations and predictions about the universe. Science may be as old as the human species, and some of the earliest archeological evidence for ...
''. Chiron filed for several patents on the virus and its diagnosis. 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 coinventor, and receive damages and royalty income. He dropped the suit in 1998 after losing before an appeals court. 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. In 1992, the San Francisco Chronicle reported the virus had never been observed under an electron microscope. 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 AstroTurf is an American subsidiary of SportGroup that produces artificial turf for playing surfaces in sports. The original AstroTurf product was a short-pile synthetic turf invented in 1965 by Monsanto. Since the early 2000s, AstroTurf has m ...
" patient advocacy groups to raise awareness (and fear) of the disease. Hepatitis C was finally "discovered" in 2005 when a Japanese team was able to propagate a molecular clone in a cell culture called
Huh7 Huh7 is an immortalised cell line and may be grown in the laboratory for research purposes. According to the web site huh7.com, it is "a well differentiated hepatocyte-derived carcinoma cell line, originally taken from a liver tumor in a 57-year ...
. 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,
Sovaldi Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken by mouth. Common side effects include fatigue, headache, nausea, and trouble sleeping. Side effects are generally more common i ...
, 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. 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 1970's mass chemotherapy campaign to eliminate
snail fever Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody ...
. On October 5, 2020, Houghton and Alter, together with
Charles M. Rice Charles Moen Rice (born August 25, 1952) is an American virologist and Nobel Prize laureate whose main area of research is the Hepatitis C virus. He is a professor of virology at the Rockefeller University in New York City and an adjunct profess ...
, were awarded the
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
for their work.


Society and culture

World Hepatitis Day World Hepatitis Day, observed on July 28 every year, aims to raise global awareness of hepatitis — a group of infectious diseases known as hepatitis A, B, C, D, and E — and encourage prevention, diagnosis and treatment. Hepatitis affec ...
, held on July 28, is coordinated by the World Hepatitis Alliance. 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 with the cost of a liver transplant costing approximately US$200,000. In Canada the cost of a course of antiviral treatment is as high as 30,000 CAD in 2003, while the United States costs are between 9,200 and 17,600 in 1998 USD. In many areas of the world, people are unable to afford treatment with antivirals as they either lack insurance coverage or the insurance they have will not pay for antivirals. In the English
National Health Service The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
treatment rates for hepatitis C are higher among wealthier groups per 2010–2012 data. Spanish anaesthetist Juan Maeso infected 275 patients between 1988 and 1997 as he used the same needles to give both himself and the patients opioids. For this he was jailed.


Special populations


Children and pregnancy

Compared with adults, infection in children is much less understood. Worldwide the prevalence of virus infection in pregnant women and children has been estimated to 1–8% and 0.05–5% respectively. 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%) and prevalence in children (15%). In developed countries transmission around the time of birth is now the leading cause of HCV infection. In the absence of virus in the mother's blood transmission seems to be rare. 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. 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. The presentation in childhood may be asymptomatic or with elevated liver function tests. While infection is commonly asymptomatic both cirrhosis with liver failure and hepatocellular carcinoma may occur in childhood.


Immunosuppressed

The rate of in immunosuppressed people is higher. This is particularly true in those with
human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immun ...
infection, recipients of
organ transplant Organ transplantation is a medical procedure in which an organ (anatomy), organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organ ...
s, and those with
hypogammaglobulinemia Hypogammaglobulinemia is a problem with the immune system in which not enough gamma globulins are produced in the blood (thus '' hypo-'' + ''gamma'' + ''globulin'' + '' -emia''). This results in a lower antibody count, which impairs the immune sys ...
. 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 Ribavirin, also known as tribavirin, is an antiviral medication used to treat RSV infection, hepatitis C and some viral hemorrhagic fevers. For hepatitis C, it is used in combination with other medications such as simeprevir, sofosbuvir, pe ...
with caution to the possible side effects.


Research

, there are about one hundred medications in development for . These include vaccines to treat hepatitis,
immunomodulators Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
, and
cyclophilin Cyclophilins (CYPs) are a family of proteins named after their ability to bind to ciclosporin (cyclosporin A), an immunosuppressant which is usually used to suppress rejection after internal organ transplants. They are found in all domains of l ...
inhibitors, among others. These potential new treatments have come about due to a better understanding of the virus. There are a number of vaccines under development and some have shown encouraging results. The combination of sofosbuvir and velpatasvir in one trial (reported in 2015) resulted in cure rates of 99%. More studies are needed to investigate the role of the preventive antiviral medication against HCV recurrence after transplantation.


Animal models

One barrier to finding treatments for 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 for the development of vaccines in poorer communities.
Chimpanzees The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close relative th ...
remain the only available living system to study, yet their use has ethical concerns and regulatory restrictions. While scientists have made use of human cell culture systems such as hepatocytes, questions have been raised about their accuracy in reflecting the body's response to infection. 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 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 evaluating antiviral compounds. Alternatively, generating inbred mice with susceptibility to HCV would simplify the process of studying mouse models.


See also

* PSI-6130, an experimental drug treatment


References


External links

* * * {{Authority control Healthcare-associated infections Infectious causes of cancer Wikipedia medicine articles ready to translate (full) Wikipedia emergency medicine articles ready to translate +C