Hepatitis C is an
infectious diseaseAn infectious disease is a clinically evident disease resulting from the presence of pathogenic microbial agents, including pathogenic viruses, pathogenic bacteria, fungi, protozoa, multicellular parasites, and aberrant proteins known as prions...
affecting the
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, caused by the
hepatitis C virusHepatitis C virus is a small , enveloped, positive sense single strand RNA virus in the family Flaviviridae. Although Hepatitis A virus, Hepatitis B virus, and Hepatitis C virus have similar names , these are distinctly different viruses both genetically and clinically.-Structure:The hepatitis C...
(HCV). The infection is often
asymptomaticIn medicine, a disease is asymptomatic if a patient carries a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical infections...
, but once established, chronic infection can progress to scarring of the liver (
fibrosisFibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue....
), and advanced scarring (
cirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrous scar tissue as well as regenerative nodules , leading to progressive loss of liver function...
) which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure or other complications of cirrhosis, including
liver cancerHepatocellular carcinoma is a primary malignancy of the liver. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis...
.
The hepatitis C virus (HCV) is spread by blood-to-blood contact. Most people have few, if any symptoms after the initial infection, yet the virus persists in the liver in about 85% of those infected. Persistent infection can be treated with
medicationA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
, peginterferon and
ribavirinRibavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...
being the standard-of-care therapy. 51% are cured overall. Those who develop cirrhosis or liver cancer may require a liver transplant, and the virus universally recurs after transplantation.
An estimated 270-300 million people worldwide are infected with hepatitis C. Hepatitis C is a strictly human disease. It cannot be contracted from or given to any animal. Chimpanzees can be infected with the virus in the laboratory, but do not develop the disease, which has made research more difficult. No vaccine against hepatitis C is available. The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proved conclusively in 1989. It is one of five known
hepatitisHepatitis implies injury to the liver characterized by the presence of inflammatory cells in the tissue of the organ. The name is from ancient Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
viruses:
AHepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , which is most commonly transmitted by the fecal-oral route via contaminated food or drinking water. Every year, approximately 10 million people worldwide are infected with the virus...
, B, C,
DHepatitis D, also referred to as Hepatitis D virus and classified as Hepatitis delta virus, is a disease caused by a small circular RNA virus. HDV is considered to be a subviral satellite because it can propagate only in the presence of another virus, the Hepatitis B virus...
, and
EHepatitis E is a viral hepatitis caused by infection with a virus called hepatitis E virus . HEV is a positive-sense single-stranded RNA icosahedral virus with a 7.5 kb genome. HEV has a fecal-oral transmission route...
.
Acute
Acute hepatitis C refers to the first 6 months after infection with HCV. Between 60% to 70% of people infected develop no symptoms during the acute phase. In the minority of patients who experience acute phase symptoms, they are generally mild and nonspecific, and rarely lead to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection include decreased appetite, fatigue,
abdominal painAbdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
,
jaundiceJaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia...
, itching, and flu-like symptoms.
The hepatitis C virus is usually detectable in the blood within one to three weeks after infection by PCR, and antibodies to the virus are generally detectable within 3 to 15 weeks. Spontaneous FUZZ WAS HERE. <3
viral clearance rates are highly variable and between 10–60% of persons infected with HCV clear the virus from their bodies during the acute phase as shown by normalization in liver enzymes (
alanine transaminaseAlanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
(ALT) &
aspartate transaminaseAspartate transaminase also called serum glutamic oxaloacetic transaminase or aspartate aminotransferase is similar to alanine transaminase in that it is another enzyme associated with liver parenchymal cells.-Function:It facilitates the conversion of aspartate and alpha-ketoglutarate to...
(AST)), and plasma HCV-RNA clearance (this is known as
spontaneous viral clearance). However, persistent infections are common and most patients develop
chronicIn medicine, a chronic disease is a disease that is long-lasting or recurrent. The term chronic describes the course of the disease, or its rate of onset and development. A chronic course is distinguished from a recurrent course; recurrent diseases relapse repeatedly, with periods of remission in...
hepatitis C, i.e., infection lasting more than 6 months.
Previous practice was to not treat acute infections to see if the person would spontaneously clear; recent studies have shown that treatment during the acute phase of
genotypeThe genotype is the genetic constitution of a cell, an organism, or an individual usually with reference to a specific character under consideration...
1 infections has a greater than 90% success rate with half the treatment time required for chronic infections.
Chronic
Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months. Clinically, it is often asymptomatic (without symptoms) and it is mostly discovered accidentally.
The natural course of chronic hepatitis C varies considerably from one person to another. Although almost all people infected with HCV have evidence of inflammation on
liver biopsyLiver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.-History:...
the rate of progression of liver scarring (fibrosis) shows significant variability among individuals. Accurate estimates of the risk over time are difficult to establish because of the limited time that tests for this virus have been available.
Recent data suggest that among untreated patients, roughly one-third progress to liver cirrhosis in less than 20 years. Another third progress to cirrhosis within 30 years. The remainder of patients appear to progress so slowly that they are unlikely to develop cirrhosis within their lifetimes. In contrast the NIH consensus guidelines state that the risk of progression to cirrhosis over a 20-year period is 3-20 percent.
Factors that have been reported to influence the rate of HCV disease progression include age (increasing age associated with more rapid progression), gender (males have more rapid disease progression than females), alcohol consumption (associated with an increased rate of disease progression), HIV coinfection (associated with a markedly increased rate of disease progression), and fatty liver (the presence of fat in liver cells has been associated with an increased rate of disease progression).
Symptoms specifically suggestive of liver disease are typically absent until substantial scarring of the liver has occurred. However, hepatitis C is a systemic disease and patients may experience a wide spectrum of clinical manifestations ranging from an absence of symptoms to a more symptomatic illness prior to the development of advanced liver disease. Generalized signs and symptoms associated with chronic hepatitis C include fatigue, flu-like symptoms, joint pains, itching, sleep disturbances, appetite changes, nausea, and depression.
Once chronic hepatitis C has progressed to
cirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrous scar tissue as well as regenerative nodules , leading to progressive loss of liver function...
, signs and symptoms may appear that are generally caused by either decreased liver function or increased pressure in the liver circulation, a condition known as portal hypertension. Possible signs and symptoms of liver cirrhosis include
ascitesIn medicine , ascites is an accumulation of fluid in the peritoneal cavity. Although most commonly due to cirrhosis and severe liver disease, its presence can portend other significant medical problems...
(accumulation of fluid in the abdomen), bruising and bleeding tendency,
varicesVarices in general refers to distended veins. It derives from the Latin word for twisted, "varix".Types of varices include:* Varicose veins of lower extremities* Gastrointestinal varices** Esophageal varices** Gastric varices** Intestinal varices...
(enlarged veins, especially in the stomach and esophagus),
jaundiceJaundice, also known as icterus , is a yellowish discoloration of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia...
, and a syndrome of cognitive impairment known as
hepatic encephalopathyHepatic encephalopathy is a potentially-reversible neuropsychiatric abnormality in the setting of liver failure, whether chronic or acute...
. Hepatic encephalopathy is due to the accumulation of ammonia and other substances normally cleared by a healthy liver.
Liver enzyme tests show variable elevation of
ALTAlanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
and
ASTAspartate transaminase also called serum glutamic oxaloacetic transaminase or aspartate aminotransferase is similar to alanine transaminase in that it is another enzyme associated with liver parenchymal cells.-Function:It facilitates the conversion of aspartate and alpha-ketoglutarate to...
. Periodically they might show normal results. Usually prothrombin and
albuminSerum albumin, often referred to simply as albumin, is the most abundant plasma protein in humans and other mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular compartments and body tissues...
results are normal, but may become abnormal, once cirrhosis has developed. The level of elevation of liver tests do not correlate well with the amount of liver injury on biopsy. Viral genotype and viral load also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring and inflammation. Radiographic studies such as ultrasound or CT scan do not always show liver injury until it is fairly advanced. However, non-invasive tests (blood sample) are coming, with
FibroTestFibroTest, known as FibroSure in the US, is a patented biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases...
and ActiTest, respectively estimating liver fibrosis and necrotico-inflammatory. These tests are validated and recommended in Europe (FDA procedures initiated in USA)
Chronic hepatitis C, more than other forms of hepatitis, can be associated with extrahepatic manifestations associated with the presence of HCV such as
porphyria cutanea tardaPorphyria cutanea tarda is the most common subtype of porphyria. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the body's organs...
,
cryoglobulinemiaCryoglobulinaemia is a medical condition in which the blood contains large amounts of cryoglobulins - proteins that become insoluble at reduced temperatures. Cryoglobulins typically precipitate at temperatures below normal body temperature and will dissolve again if the blood is heated...
(a form of small-vessel
vasculitisVasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels.Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis....
) and
glomerulonephritisGlomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys. It may present with isolated hematuria and/or proteinuria ; or as a nephrotic syndrome, a nephritic syndrome, acute...
(inflammation of the kidney), specifically
membranoproliferative glomerulonephritisMembranoproliferative glomerulonephritis , also known as mesangiocapillary glomerulonephritis, is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane thickening, activating complement and damaging the glomeruli.MPGN accounts for approximately 4%...
(MPGN). Hepatitis C is also rarely associated with sicca syndrome (an autoimmune disorder),
thrombocytopeniaThrombocytopenia is the presence of relatively few platelets in blood.Generally speaking, in humans, a normal platelet count ranges from 150,000 and 450,000 per mm3. These limits, however, are determined by the 2.5th lower and upper percentile, and a deviation does not necessarily imply...
,
lichen planusLichen planus is a chronic mucocutaneous disease that affects the skin and the oral mucosa, and presents itself in the form of papules, lesions or rashes...
,
diabetes mellitusDiabetes mellitus —often referred to simply as diabetes—is a condition in which the body either does not produce enough, or does not properly respond to, insulin, a hormone produced in the pancreas. Insulin enables cells to absorb glucose in order to turn it into energy...
and with B-cell lymphoproliferative disorders.
Virology
The Hepatitis C virus (HCV) is a small (50 nm in size), enveloped, single-stranded, positive sense
RNA virusAn RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
. It is the only known member of the
hepacivirus genus in the family
FlaviviridaeThe Flaviviridae are a family of viruses that are primarily spread through arthropod vectors . The family gets its name from Yellow Fever virus, a type virus of Flaviviridae; flavus means yellow in Latin...
. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.).
The hepatitis C virus (HCV) is transmitted by blood-to-blood contact. In developed countries, it is estimated that 90% of persons with chronic HCV infection were infected through transfusion of unscreened blood or blood products or via injecting drug use or sexual exposure. In developing countries, the primary sources of HCV infection are unsterilized injection equipment and infusion of inadequately screened blood and blood products. There has not been a documented transfusion-related case of hepatitis C in the United States for over a decade as the blood supply is vigorously screened with both EIA and PCR technologies.
Although injection drug use is the most common routes of HCV infection,
any practice, activity, or situation that involves blood-to-blood exposure can potentially be a source of HCV infection. The virus may be
sexually transmittedA sexually transmitted disease , also known as sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans or animals by means of sexual contact, including vaginal intercourse, oral sex, and anal sex...
, although this is rare, and usually only occurs when an STD that causes open sores and bleeding is also present and makes blood contact more likely..
Transmission
Sexual activities and practices were initially identified as potential sources of exposure to the hepatitis C virus. More recent studies question this route of transmission. Currently it is felt to be a means of rare transmission of hepatitis C infection. These are simply the current known modes of transmission and due to the nature of Hepatitis there may be more ways that it is transmitted than the current known methods.
Injection drug use
Those who currently use or have used
drug injectionDrug injection of recreational drugs is a method of introducing the drug into the body with a hollow needle and a syringe which is pierced through the skin into the body . This act is often colloquially referred to as shooting or banging...
as their delivery route for drugs are at increased risk for getting hepatitis C because they may be sharing needles or other
drug paraphernaliaDrug paraphernalia is any equipment, product, or material that is modified for making, using, or concealing illegal drugs such as cocaine, heroin, marijuana, and methamphetamine...
(includes cookers, cotton, spoons, water, etc.), which may be contaminated with HCV-infected blood. An estimated 60% to 80% of intravenous recreational drug users in the United States have been infected with HCV.
Harm reductionHarm reduction, or harm minimisation, refers to a range of pragmatic and evidence-based public health policies designed to reduce the harmful consequences associated with drug use and other high risk activities ....
strategies are encouraged in many countries to reduce the spread of hepatitis C, through education, provision of clean needles and syringes, and safer injecting techniques. For reasons that are not clear transmission by this route currently appears to be declining in the USA.
Blood products
Blood transfusionBlood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery...
, blood products, or organ transplantation prior to implementation of HCV screening (in the U.S., this would refer to procedures prior to 1992) is a decreasing risk factor for hepatitis C.
The virus was first isolated in 1989 and reliable tests to screen for the virus were not available until 1992. Therefore, those who received blood or blood products prior to the implementation of screening the blood supply for HCV may have been exposed to the virus. Blood products include clotting factors (taken by hemophiliacs), immunoglobulin, Rhogam, platelets, and plasma. In 2001, the
Centers for Disease Control and PreventionThe Centers for Disease Control and Prevention is a United States federal agency under the Department of Health and Human Services based in Atlanta, Georgia. It works to protect public health and safety by providing information to enhance health decisions, and it promotes health through...
reported that the risk of HCV infection from a unit of transfused blood in the United States is less than one per million transfused units.
Iatrogenic medical or dental exposure
People can be exposed to HCV via inadequately or improperly sterilized medical or dental equipment. Equipment that may harbor contaminated blood if improperly sterilized includes needles or syringes, hemodialysis equipment,
oral hygieneTeeth cleaning is the removal of dental plaque from teeth, to prevent cavities , gingivitis, and periodontitis. It is part of a complete program of oral hygiene.-Brushing:...
instruments, and jet air guns, etc. Scrupulous use of appropriate sterilization techniques and proper disposal of used equipment can reduce the risk of iatrogenic exposure to HCV to virtually zero.
Occupational exposure to blood
Medical and dental personnel, first responders (e.g., firefighters, paramedics, emergency medical technicians, law enforcement officers), and
military combat personnelCombat medics are trained military personnel who are responsible for providing first aid and frontline trauma care on the battlefield. They are also responsible for providing continuing medical care in the absence of a readily available physician, including care for disease and battle injury...
can be exposed to HCV through accidental exposure to blood through accidental needlesticks or blood spatter to the eyes or open wounds.
Universal precautionsUniversal 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....
to protect against such accidental exposures significantly reduce the risk of exposure to HCV.
Recreational exposure to blood
Contact sports and other activities, such as "slam dancing" that may result in accidental blood-to-blood exposure are potential sources of exposure to HCV.
Sexual exposure
Sexual transmission of HCV is considered to be rare. Studies show the risk of sexual transmission in heterosexual, monogamous relationships is extremely rare or even null. The CDC does not recommend the use of condoms between long-term monogamous discordant couples (where one partner is positive and the other is negative). However, because of the high prevalence of hepatitis C, this small risk may translate into a non-trivial number of cases transmitted by sexual routes. Vaginal penetrative sex is believed to have a lower risk of transmission than sexual practices that involve higher levels of trauma to anogenital mucosa (anal penetrative sex,
fistingFisting is a sexual activity that involves inserting a hand into the vagina or rectum. Typically, fisting does not involve forcing the clenched fist into the vagina or rectum. Instead, all five fingers are kept straight and held as close together as possible , then slowly inserted into a...
, use of sex toys).
Body piercings and tattoos
Tattooing dyes, ink pots, stylets and piercing implements can transmit HCV-infected blood from one person to another if proper sterilization techniques are not followed. Tattoos or
piercingsBody piercing is the practice of puncturing or cutting a part of the human body, creating an opening in which jewellery may be worn. Body piercing is a form of body modification. The word piercing can refer to the act or practice of body piercing, or to an opening in the body created by this act...
performed before the mid 1980s, "underground," or non-professionally are of particular concern since sterile techniques in such settings may have been or be insufficient to prevent disease. Despite these risks, it is rare for tattoos to be directly associated with HCV infection and the U.S. Centers for Disease Control and Prevention's position on this subject states that, "no data exist in the United States indicating that persons with exposures to tattooing alone are at increased risk for HCV infection."
Shared personal care items
Personal care items such as razors, toothbrushes, cuticle scissors, and other manicuring or pedicuring equipment can easily be contaminated with blood. Sharing such items can potentially lead to exposure to HCV. Appropriate caution should be taken regarding any medical condition which results in
bleedingBleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
such as
canker soresAn aphthous ulcer, also known as a canker sore, is a type of oral ulcer, which presents as a painful open sore inside the mouth or upper throat caused by a break in the mucous membrane...
, cold sores, and immediately after flossing.
HCV is
not spread through casual contact such as hugging, kissing, or sharing eating or cooking utensils.
Vertical transmission
Vertical transmissionVertical transmission, also known as Mother-to-child transmission refers to transmission of an infection, such as HIV, hepatitis B, or hepatitis C, from mother to child during the perinatal period, the period immediately before and after birth...
refers to the transmission of a communicable disease from an infected mother to her child during the birth process. Mother-to-child transmission of hepatitis C has been well described, but occurs relatively infrequently. Transmission occurs only among women who are HCV RNA positive at the time of delivery; the risk of transmission in this setting is approximately 6 out of 100. Among women who are both HCV and HIV positive at the time of delivery, the risk of transmitting HCV is increased to approximately 25 out of 100.
The risk of vertical transmission of HCV does
not appear to be associated with method of
deliveryChildbirth is the culmination of a human pregnancy or gestation period with birth of one or more newborn infants from a woman's uterus...
or
breastfeedingBreastfeeding is the feeding of an infant or young child with breast milk directly from human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk...
.
Diagnosis
The diagnosis of "hepatitis C" is rarely made during the acute phase of the disease because the majority of people infected experience no symptoms during this phase of the disease. Those who
do experience acute phase symptoms are rarely ill enough to seek medical attention. The diagnosis of chronic phase hepatitis C is also challenging due to the absence or lack of specificity of symptoms until advanced liver disease develops, which may not occur until decades into the disease.
Chronic hepatitis C may be suspected on the basis of the
medical historyThe medical history or anamnesis of a patient is information gained by a physician by asking specific questions, either of the patient or of other people who know the person and can give suitable information , with the aim of obtaining information useful in formulating a diagnosis and providing...
(particularly if there is any history of IV drug abuse or inhaled substance usage such as cocaine), a history of piercings or
tattooA tattoo is a marking made by inserting ink into the layers of skin to change the pigment for decorative or other reasons. Tattoos on humans are a type of decorative body modification, while tattoos on animals are most commonly used for identification or branding.Tattooing has been practiced...
s, unexplained symptoms, or abnormal liver enzymes or liver function tests found during routine blood testing. Occasionally, hepatitis C is diagnosed as a result of targeted screening such as
blood donationA blood donation occurs when a healthy person voluntarily has blood drawn. The blood is used for transfusions or made into medications by a process called fractionation....
(blood donors are screened for numerous blood-borne diseases including hepatitis C) or
contact tracingIn epidemiology, contact tracing is the identification and diagnosis of persons who may have come into contact with an infected person. For sexually transmitted diseases, this is generally limited to sexual partners but for highly virulent diseases such as Ebola and tuberculosis, a thorough contact...
.
Hepatitis C testing begins with
serologicalSerology is the scientific study of blood serum. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...
blood tests used to detect antibodies to HCV. Anti-HCV antibodies can be detected in 80% of patients within 15 weeks after exposure, in >90% within 5 months after exposure, and in >97% by 6 months after exposure. Overall, HCV antibody tests have a strong
positive predictive valueThe positive predictive value, or precision rate, or post-test probability of disease, is the proportion of patients with positive test results who are correctly diagnosed....
for exposure to the hepatitis C virus, but may miss patients who have not yet developed antibodies (
seroconversionSeroconversion is the development of detectable specific antibodies to microorganisms in the blood serum as a result of infection or immunization. Serology is used to determine antibody positivity...
), or have an insufficient level of antibodies to detect. Rarely, people infected with HCV never develop antibodies to the virus and therefore, never test positive using HCV antibody screening. Because of this possibility, RNA testing (see nucleic acid testing methods below) should be considered when antibody testing is negative but suspicion of hepatitis C is high (e.g. because of
elevated transaminasesIn medicine, the presence of elevated transaminases, commonly the transaminases alanine transaminase and aspartate transaminase , may be an indicator of liver damage...
in someone with risk factors for hepatitis C).
Anti-HCV antibodies indicate exposure to the virus, but
cannot determine if ongoing infection is present. All persons with positive anti-HCV antibody tests must undergo additional testing for the presence of the hepatitis C virus itself to determine whether current infection is present. The presence of the virus is tested for using molecular nucleic acid testing methods such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), or branched DNA (b-DNA). All HCV nucleic acid molecular tests have the capacity to detect not only whether the virus is present, but also to measure the amount of virus present in the blood (the HCV viral load). The HCV viral load is an important factor in determining the probability of response to interferon-based therapy, but does
not indicate disease severity nor the likelihood of disease progression.
In people with confirmed HCV infection, genotype testing is generally recommended. HCV genotype testing is used to determine the required length and potential response to interferon-based therapy.
Treatment
There is a very small chance of clearing the virus spontaneously in chronic HCV carriers (0.5% to 0.74% per year). However, the majority of patients with chronic hepatitis C will not clear it without treatment.
Current treatment is a combination of Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) and the antiviral drug
ribavirinRibavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...
for a period of 24 or 48 weeks, depending on hepatitis C virus
genotypeThe genotype is the genetic constitution of a cell, an organism, or an individual usually with reference to a specific character under consideration...
. Treatment is generally recommended for patients with proven hepatitis C virus infection and persistently abnormal liver function tests. Sustained cure rates (sustained viral response) of 75% or better are seen in people with HCV genotypes 2 and 3 with 24 weeks of treatment. Sustained responses are rarer with other genotypes, at about 50% in patients with HCV genotype 1 given 48 weeks of treatment and 65% in those with genotype 4 given 48 weeks of treatment. Approximately 80% of hepatitis C patients in the United States have genotype 1. Genotype 4 is more common in the
Middle EastThe Middle East is a region that spans southwestern Asia, southeastern Europe, and northeastern Africa. It has no clear boundaries, often used as a synonym to Near East, in opposition to Far East...
and Africa.
In patients with HCV genotype 1, if treatment with pegylated interferon + ribavirin does not produce a 2-log viral load reduction or complete clearance of RNA (termed "early virological response") after 12 weeks the chance of treatment success is less than 1%. Early virological response is typically not tested in non-genotype 1 patients, as the chances of attaining it are greater than 90%. The mechanism of cure is not entirely clear, because even patients who appear to have a sustained virological response still have actively replicating virus in their liver and peripheral blood mononuclear cells.
The evidence for treatment in genotype 6 disease is currently sparse, and the evidence that exists is for 48 weeks of treatment at the same doses as are used for genotype 1 disease. Physicians considering shorter durations of treatment (e.g., 24 weeks) should do so within the context of a clinical trial.
Treatment during the acute infection phase has much higher success rates (greater than 90%) with a shorter duration of treatment; however, this must be balanced against the 15-40% chance of spontaneous clearance without treatment (see Acute Hepatitis C section above).
Those with low initial viral loads respond much better to treatment than those with higher viral loads (greater than 400,000 IU/mL). Current combination therapy is usually supervised by physicians in the fields of
gastroenterologyGastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. Etymologically, the name is a combination of three Ancient Greek words gastros , enteron , and logos ....
,
hepatologyHepatology is the branch of medicine that incorporates study of liver, gallbladder, biliary tree and pancreas as well as management of their disorders. Etymologically the word Hepatology is formed of ancient Greek hepar or hepato- meaning ' liver' and suffix -logia meaning 'word' or 'speech'...
or
infectious diseaseAn infectious disease is a clinically evident disease resulting from the presence of pathogenic microbial agents, including pathogenic viruses, pathogenic bacteria, fungi, protozoa, multicellular parasites, and aberrant proteins known as prions...
.
The treatment may be physically demanding, particularly for those with a prior history of drug or alcohol abuse. It can qualify for temporary
disabilityDisability is defined by the Americans with Disabilities Act of 1990 as "a physical or mental impairment that substantially limits one or more major life activities."...
in some cases. A substantial proportion of patients will experience a panoply of side effects ranging from a 'flu-like' syndrome (the most common, experienced for a few days after the weekly injection of interferon) to severe adverse events including
anemiaAnemia is a decrease in normal number of red blood cells or less than the normal quantity of hemoglobin in the blood...
,
cardiovascular eventsCardiovascular disease or cardiovascular diseases is the class of diseases that involve the heart or blood vessels ....
and psychiatric problems such as
suicideSuicide is the intentional killing of one's self. Many dictionaries also note the metaphorical sense of "willful destruction of one's self-interest"...
or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the patient.
Current guidelines strongly recommend that hepatitis C patients be vaccinated for hepatitis A and B if they have not yet been exposed to these viruses, as infection with a second virus could worsen their liver disease.
Alcoholic beverageAn alcoholic beverage is a drink that contains ethanol . Alcoholic beverages are divided into three general classes: beers, wines, and spirits....
consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more likely;
insulin resistanceInsulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. Insulin resistance in fat cells reduces the effects of insulin and results in elevated hydrolysis of stored triglycerides in the absence of...
and
metabolic syndromeMetabolic syndrome is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. It affects one in five people, and prevalence increases with age...
may similarly worsen the hepatic prognosis. There is also evidence that smoking increases the fibrosis (scarring) rate.
Host genetic factors influencing treatment response
For genotype 1 hepatitis C treated with Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) combined with
ribavirinRibavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...
, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in response to the treatment. This finding, originally reported in Nature , showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more possibly to achieve sustained sustained virological response after the treatment than others. Later report from Nature demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.
During pregnancy and breastfeeding
If a woman who is pregnant has risk factors for hepatitis C, she should be tested for antibodies against HCV. About 4% infants born to HCV infected women become infected. There is no treatment that can prevent this from happening. There is a high chance of the baby ridding the HCV in the first 12 months.
In a mother who also has HIV, the rate of transmission can be as high as 19%. There are currently no data to determine whether antiviral therapy reduces perinatal transmission.
RibavirinRibavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...
and
interferonInterferons are natural cell-signaling proteins produced by the cells of the immune system of most vertebrates in response to challenges such as viruses, parasites and tumor cells. They belong to the large class of glycoproteins known as cytokines and are produced by a wide variety of cells in...
s are contraindicated during pregnancy. However, avoiding fetal scalp monitoring and prolonged labor after
rupture of membranesRupture of membranes or amniorrhexis is a term used during pregnancy to describe a rupture of the amniotic sac at the onset of, or during, labor...
may reduce the risk of transmission to the infant.
HCV antibodies from the mother may persist in infants until 15 months of age. If an early
diagnosisIn medicine, diagnosis is a label given for a medical condition or disease identified by its signs, symptoms, and from the results of various diagnostic procedures...
is desired, testing for HCV RNA can be performed between the ages of 2 and 6 months, with a repeat test done independent of the first test result. If a later diagnosis is preferred, an anti-HCV test can performed after 15 months of age. Most infants infected with HCV at the time of birth have no symptoms and do well during childhood. There is no evidence that breast-feeding spreads HCV. To be cautious, an infected mother should avoid breastfeeding if her nipples are cracked and bleeding.
Alternative therapies
Several
alternative therapiesIn Western culture, alternative medicine is any healing practice "that does not fall within the realm of conventional medicine", or "that which has been shown consistently to be effective." Alternative medicine is often based on the belief that a particular health regimen has efficacious effects...
aim to maintain liver functionality, rather than treat the virus itself, thereby slowing the course of the disease to retain quality of life. As an example, extract of
Silybum marianum and
Sho-saiko-toSho-Saiko-To , also known as Minor Bupleurum Formula and Xiao Chai Hu Tang in Chinese, is an herbal supplement, believed to enhance liver health. Sho-Saiko-To is a widely used prescription drug in Japan and is a listed formula in Japanese Kampo...
are sold for their HCV related effects; the first is said to provide some generic help to hepatic functions, and the second claims to aid in liver health and provide some antiviral effects.. There has never been any verifiable histologic or virologic benefit demonstrated with any of the alternative therapies.
Experimental treatments
The drug
viramidineTaribavirin is an antiviral drug in Phase III human trials, but not yet approved for pharmaceutical use. It is a prodrug of ribavirin, active against a number of DNA and RNA viruses...
, which is a
prodrugA prodrug is a pharmacological substance that is administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and excretion optimization...
of
ribavirinRibavirin is an anti-viral drug indicated for severe RSV infection , hepatitis C infection and other viral infections. Ribavirin is a prodrug, which when metabolised resembles purine RNA nucleotides...
that has better targeting for the liver, and therefore may be more effective against hepatitis C for a given tolerated dose, is in phase III experimental trials against hepatitis C. It will be used in conjunction with
interferonsPegylated interferon alpha can refer to:* Pegylated interferon-alpha-2a* Pegylated interferon-alpha-2b...
, in the same manner as ribavirin. However, this drug is not expected to be active against ribavirin-resistant strains, and the use of the drug against infections which have already failed ribavirin/interferon treatment, is unproven.
There are new drugs under development like the
protease inhibitorsProtease inhibitors are a class of medications used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new...
(including
VX 950) and polymerase inhibitors (such as
NM 283), but development of some of these is still in the early phase. VX 950, also known as Telaprevir is currently in Phase 3 Trials.
One protease inhibitor,
BILN 2061, had to be discontinued due to safety problems early in the clinical testing. Some more modern new drugs that provide some support in treating HCV are
Albuferon,
Zadaxin, and
DAPY. Antisense phosphorothioate
oligosAn oligonucleotide is a short nucleic acid polymer, typically with twenty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized by polymerizing individual nucleotide precursors...
have been targeted to hepatitis C. Antisense
MorpholinoIn molecular biology, a Morpholino is a molecule used to modify gene expression. Morpholino oligomers are an antisense technology used to block access of other molecules to specific sequences within nucleic acid...
oligos have shown promise in preclinical studies however, they were found to cause a limited viral load
reduction.
Immunoglobulins against the hepatitis C virus exist and newer types are under development. Thus far, their roles have been unclear as they have not been shown to help in clearing chronic infection or in the prevention of infection with acute exposures (e.g. needlesticks). They do have a limited role in
transplantOrgan transplant is the moving of an organ from one body to another , for the purpose of replacing the recipient's damaged or failing organ with a working one from the donor site. Organ donors can be living or deceased...
patients.
In addition to the standard treatment with interferon and ribavirin, some studies have shown higher success rates when the antiviral drug
amantadineAmantadine is the organic compound known formally as 1-aminoadamantane. The molecule consists of adamantane backbone that is substituted at one of the four methyne positions with an amino group. This compound is sold under the name "Symmetrel" for use both as an antiviral and an antiparkinsonian...
(Symmetrel) is added to the regimen. Sometimes called "triple therapy", it involves the addition of 100 mg of amantadine twice a day. Studies indicate that this may be especially helpful for "nonresponders" - patients who have not been successful in previous treatments using interferon and ribavirin only. Currently, amantadine is not approved for treatment of Hepatitis C, and studies are ongoing to determine when it is most likely to benefit the patient.
Among the more novel treatments under development is the Hemopurifier(R), a first-in-class medical device that selectively removes infectious viruses and immunosuppressive proteins from the bloodstream. In HCV care, the Hemopurifier(R) inhibits viral replication through selective adsorption of circulating HCV and augments the immune response by removing toxic proteins shed from HCV to kill-off immune cells. Recent clinical data validates the mechanical removal of HCV through blood filtration in combination with SOC therapy can increase HCV cure rates by greater than 50%. Studies are ongoing at the Fortis Hospital in New Dehli, India.
Epidemiology
It is estimated that Hepatitis C has infected nearly 200 million people worldwide, and infects 3-4 million more people per year. There are about 35,000 to 185,000 new cases a year in the United States. It is currently a leading cause of cirrhosis, a common cause of hepatocellular carcinoma, and as a result of these conditions it is the leading reason for liver transplantation in the United States. Co-infection with
HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid,...
is common and rates among HIV positive populations are higher. 10,000-20,000 deaths a year in the United States are from HCV; expectations are that this mortality rate will increase, as those who were infected by transfusion before HCV testing become apparent. A survey conducted in California showed prevalence of up to 34% among prison inmates;
82% of subjects diagnosed with hepatitis C have previously been in jail,
and transmission while in prison is well described.
Prevalence is higher in some countries in
AfricaAfrica is the world's second-largest and second most-populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area. With a billion people in 61 territories, it accounts for about 14.8% of the...
and
AsiaAsia is the world's largest and most populous continent, located in the eastern and northern hemispheres. It covers 8.6% of the earth's total surface area and with approximately 4 billion people, it hosts 60% of the world's current human population.Asia is traditionally defined as part of the...
.
EgyptEgypt , officially the Arab Republic of Egypt, is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Western Asia...
has the highest
seroprevalenceSeroprevalence is the number of persons in a population who test positive for a specific disease based on serology specimens; often presented as a percent of the total specimens tested or as a proportion per 100,000 persons tested...
for HCV, up to 20% in some areas. There is a hypothesis that the high prevalence is linked to a now-discontinued mass-treatment campaign for
schistosomiasisSchistosomiasis is a parasitic disease caused by several species of fluke of the genus Schistosoma....
, which is endemic in that country. Regardless of how the epidemic started, a high rate of HCV transmission continues in Egypt, both iatrogenically and within the community and household.
Co-infection with HIV
Approximately 350,000, or 35% of patients in the USA infected with HIV are also infected with the hepatitis C virus, mainly because both viruses are blood-borne and present in similar populations. In other countries co-infection is less common, and this is possibly related to differing drug policies. HCV is the leading cause of chronic liver disease in the USA. It has been demonstrated in clinical studies that HIV infection causes a more rapid progression of chronic hepatitis C to cirrhosis and liver failure. This is not to say treatment is not an option for those living with co-infection.
Prevention
According to Centers for Disease Control, hepatitis C virus is spread by exposure to large quantities of blood, either through the skin or by injection:
- Injection drug use (currently the most common means of HCV transmission in the United States)
- Receipt of donated blood, blood products, and organs (once a common means of transmission but now rare in the United States since blood screening became available in 1992)
- Needlestick injuries in healthcare settings
- Birth to an HCV-infected mother
HCV can also be spread infrequently through
- Sex with an HCV-infected person (an inefficient means of transmission)
- Sharing personal items contaminated with infectious blood, such as razors or toothbrushes (also inefficient vectors of transmission)
- Other healthcare procedures that involve invasive procedures, such as injections (usually recognized in the context of outbreaks)
Proponents of
harm reductionHarm reduction, or harm minimisation, refers to a range of pragmatic and evidence-based public health policies designed to reduce the harmful consequences associated with drug use and other high risk activities ....
believe that strategies such as the provision of new needles and syringes, and education about safer drug injection procedures, greatly decreases the risk of hepatitis C spreading between injecting drug users.
No vaccine protects against contracting hepatitis C, or helps to treat it. Vaccines are under development and some have shown encouraging results.
History
In the mid 1970s,
Harvey J. AlterHarvey J. Alter is an American medical researcher, virologist, and physician who is best known for his work that led to the discovery of the hepatitis C virus....
, Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the
National Institutes of HealthThe National Institutes of Health is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical and health-related research. It consists of 27 separate institutes and centers which includes the Office...
, and his research team demonstrated that most post-
transfusionBlood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery...
hepatitis cases were not due to
hepatitis AHepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , which is most commonly transmitted by the fecal-oral route via contaminated food or drinking water. Every year, approximately 10 million people worldwide are infected with the virus...
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 CorporationChiron Corporation was a multinational biotechnology firm based in Emeryville, California that was acquired by Novartis International AG on April 20 2006. It had offices and facilities in eighteen countries on five continents. Chiron's business and research was in three main areas:...
, collaborating with Dr. D.W. Bradley from
CDCThe Centers for Disease Control and Prevention is a United States federal agency under the Department of Health and Human Services based in Atlanta, Georgia. It works to protect public health and safety by providing information to enhance health decisions, and it promotes health through...
, utilized a novel
molecular cloningMolecular cloning refers to the procedure of isolating a defined DNA sequence and obtaining multiple copies of it in vivo. Cloning is frequently employed to amplify DNA fragments containing genes, but it can be used to amplify any DNA sequence such as promoters, non-coding sequences, chemically...
approach to identify the unknown organism. In 1988, the virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April of 1989, the discovery of the virus, re-named hepatitis C virus (HCV), was published in two articles in the journal
Science.
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 co-inventor, and receive damages and royalty income. He dropped the suit in 1998 after losing before an appeals court.
In 2000, Drs. Alter and Houghton were honored with the
Lasker Award for Clinical Medical ResearchThe Lasker Awards have been awarded annually since 1946 to living persons who have made major contributions to medical science or who have performed public service on behalf of medicine . They are administered by the Lasker Foundation, founded by advertising pioneer Albert Lasker and his wife Mary...
for
"pioneering work leading to the discovery of the virus that causes hepatitis C and the development of screening methods that reduced the risk of blood transfusion-associated hepatitis in the U.S. from 30% in 1970 to virtually zero in 2000."
In 2004 Chiron held 100 patents in 20 countries related to hepatitis C and had successfully sued many companies for infringement. Scientists and competitors have complained that the company hinders the fight against hepatitis C by demanding too much money for its technology.
Information and resources
Organizations and programs