Hepatitis C
Encyclopedia
Hepatitis C is an infectious disease
primarily affecting the liver
, caused by the hepatitis C virus
(HCV). The infection is often asymptomatic
, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis
, which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure or other complications, including liver cancer
or life-threatening esophageal varices
and gastric varices
.
The hepatitis C virus 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 medication; peginterferon and ribavirin
are the current standard therapy. Overall, between 51-80% of treated patients are cured. Those who develop cirrhosis or liver cancer may require a liver transplant, and the virus universally recurs after transplantation.
An estimated 180 million people worldwide are infected with hepatitis C. Hepatitis C is not known to cause disease in other animals. No vaccine against hepatitis C is currently available. The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proven in 1989.
, itching, and flu-like symptoms.
The hepatitis C virus is usually detectable in the blood by PCR within one to three weeks after infection, and antibodies to the virus are generally detectable within three to 15 weeks. Spontaneous viral clearance rates are highly variable; between 10 and 60% of persons infected with HCV clear the virus from their bodies during the acute phase, as shown by normalization of the liver enzymes alanine transaminase
(ALT) and aspartate transaminase
(AST), and plasma HCV-RNA clearance (this is known as spontaneous viral clearance). However, persistent infections are common and most patients develop chronic
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 genotype
1 infections has a greater than 90% success rate, with half the treatment time required for chronic infections.
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 biopsy
, 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 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 cirrhosis
, 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 ascites
(accumulation of fluid in the abdomen), bruising and bleeding tendency, varices
(enlarged veins, especially in the stomach and esophagus), jaundice
, and a syndrome of cognitive impairment known as hepatic encephalopathy
. 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 ALT
and AST
. Periodically, they might show normal results. Usually prothrombin and albumin
results are normal, but may become abnormal, once cirrhosis has developed. The levels 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, noninvasive tests are coming, with FibroTest
and ActiTest, respectively estimating liver fibrosis and necrotic inflammation. These tests are validated and recommended in Europe (FDA procedures initiated in USA).
, cryoglobulinemia
(a form of small-vessel vasculitis
) and glomerulonephritis
(inflammation of the kidney), specifically membranoproliferative glomerulonephritis
(MPGN). Hepatitis C is also rarely associated with sicca syndrome (an autoimmune disorder), thrombocytopenia
, lichen planus
, diabetes mellitus
and with B-cell lymphoproliferative disorders.
in size), enveloped, single-stranded, positive sense RNA virus
. It is the only known member of the hepacivirus genus in the family Flaviviridae
. There are six major genotypes of the hepatitis C virus, which are indicated numerically (e.g., genotype 1, genotype 2, etc.). Based on the NS5 gene there are three major and eleven minor genotypes. The major genotypes diverged about 300–400 years ago from the ancestor virus. The minor genotypes diverged about 200 years ago from their major genotypes. All of the extant genotypes appear to have evolved from genotype 1 subtype 1b.
The hepatitis C virus 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 route 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 transmitted
, 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.
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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, heterosexual vaginal intercourse is thought to be a rare means of transmission of hepatitis C infection. The following are the currently known modes of transmission. There may be other, as yet unknown, means of transmission.
as their delivery route for drugs are at increased risk for getting hepatitis C because they may be sharing needles or other drug paraphernalia
(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 reduction
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.
The main risk factor for HCV infection is intravenous drug using. Many studies showed that imprisonment
is an important predictor of HBV, HCV and HIV infection. Prison conditions increase the risk of transmission of infections, including blood-borne viral infections; the risk is further increased by the use of unsterile equipment used for injection.Intravenous drug users (IDUs) are at a potential risk for acquiring
blood-borne infections by parenteral and sexual routes.
During the VA Testimony before the Subcommittee on Benefits Committee on Veterans’ Affairs, U.S. House of Representatives on April 13 2000, Gary A. Roselle, M. D., Program Director for Infectious Diseases, Veterans Health Administration, Department of Veterans Affairs, stated "One in 10 US Veterans are infected with HCV, a rate five times greater than the 1.8% infection rate of the general population." A study conducted in 1999 by the Veterans Health Administration (VHA) involving 26,000 veterans showed that up to 10% of all veterans in the VHA system tested positive for hepatitis C.
Of the total number of persons who were hepatitis C antibody positive, and reported an era of service, 62.7% were noted to be from the Vietnam War. The second most frequent group is listed as post-Vietnam War at 18.2%, followed by 4.8% Korean War, 4.3% post-Korean War, 4.2% from WWII, and 2.7% Persian Gulf era veterans.
, blood products, or organ transplantation prior to implementation of HCV screening (in the U.S., this would refer to procedures prior to 1992) are all risk factors for hepatitis C.
A cDNA
clone from the hepatitis C virus genome 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 Prevention
reported the risk of HCV infection from a unit of transfused blood in the United States is less than one per million transfused units.
instruments, 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. Limitations in the implementation and enforcement of stringent standard precautions in public and private medical and dental facilities is known to be the primary cause of the spread of HCV in Egypt
, the country with highest rate of infection in the world.
People can be exposed to HCV through accidental exposure to blood through needle sticks or blood spatter to the eyes or open wounds at work. Universal precautions
to protect against such accidental exposures significantly reduce the risk of exposure to HCV.
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.
, or use of sex toys). For these reasons, condom use is highly recommended for those who engage in anal sex play or other sex acts likely to cause bleeding or damage mucosal linings.
performed either before the mid 1980s, "underground," or nonprofessionally are of particular concern, since sterile techniques in such settings may have been insufficient to prevent disease; sharing unsterilized tattooing equipment (for example, in the prison
system) has an obvious increased risk of acquiring HCV. The U.S. Centers for Disease Control and Prevention's position on this subject states that, "Whenever tattoos or body piercings are performed in informal settings or with nonsterile instruments, transmission of hepatitis C and other infectious diseases is possible." Despite these risks, it is rare for tattoos in an approved facility to be directly associated with HCV infection
, such as canker sores
, cold sores, and immediately after flossing.
HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils.
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 delivery
or breastfeeding
.
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. 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 history
(particularly if there is any history of IV drug abuse or inhaled substance usage such as cocaine), a history of piercings or tattoo
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 donation
(blood donors are screened for numerous blood-borne diseases including hepatitis C) or contact tracing
.
Hepatitis C testing begins with serological
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 value
for exposure to the hepatitis C virus, but may miss patients who have not yet developed antibodies (seroconversion
), or have an insufficient level of antibodies to detect. Immunocompromised individuals infected with HCV may 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 transaminases
in someone with risk factors for hepatitis C). However, liver function tests
alone are not useful in predicting the severity of infection and normal results do not exclude the possibility of liver disease.
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.
HCV can also be spread infrequently through
Strategies such as the provision of new needles and syringes, and education about safer drug injection procedures, greatly decrease 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.
In May 2011, the Food and Drug Administration
approved 2 drugs for hepatitis C. The first one is boceprevir
and the other is telaprevir
(Incivek). Both drugs block an enzyme that helps the virus reproduce. The drugs are intended to improve on standard treatments using the injected drug pegylated interferon alpha
and the pill ribavirin
.
for a period of 24 or 48 weeks, depending on hepatitis C virus genotype
. In a large multicenter randomized control study among genotype 2 or 3 infected patients (NORDymanIC), patients achieving HCV RNA below 1000 IU/mL by day 7 who were treated for 12 weeks demonstrated similar cure rates as those treated for 24 weeks.
Pegylated interferon-alpha-2a plus ribavirin
may increase sustained virological response among patients with chronic hepatitis C as compared to pegylated interferon-alpha-2b plus ribavirin according to a systematic review
of randomized controlled trial
s . The relative benefit increase was 14.6%. For patients at similar risk to those in this study (41.0% had sustained virological response when not treated with pegylated interferon alpha 2a plus ribavirin), this leads to an absolute benefit increase of 6%. About 16.7 people need to be treated for one to benefit.
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 gastroenterology
, hepatology
or infectious disease
.
The treatment may be physically demanding, particularly for those with a prior history of drug or alcohol abuse. It can qualify for temporary disability
in some cases. A substantial proportion of people 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 anemia
, cardiovascular events
and psychiatric problems such as suicide
or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the patient.
is a protease inhibitor
that binds to the HCV nonstructural 3 (NS3) active site on hepatitis C genotype 1. There have been several recent randomized double-blinded clinical trials studying boceprevir in conjunction with peginterferon-ribavirin as therapy for untreated chronic HCV genotype 1 infection and previously treated chronic HCV genotype 1 infection. These studies have shown improved sustained virologic response at 44 weeks compared to therapy with peginterferon-ribavirin therapy alone. Anemia was a common side effect in these two studies.
Boceprevir was approved by the FDA on May 13, 2011 for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin. The indication is for adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.
and Africa.
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 some patients who have a sustained virological response still appear to have actively replicating virus in their liver and peripheral blood mononuclear cells.
Similarly, baseline pretreatment plasma levels of IP-10 (also known as CXCL10) are elevated in patients chronically infected with hepatitis C virus (HCV) of genotypes 1 or 4 who do not achieve a sustained viral response (SVR) after completion of antiviral therapy. IP-10 in plasma is mirrored by intrahepatic IP-10 mRNA, and both strikingly predict the first first phase decline during interferon/ribavirin therapy for all HCV genotypes. And combining both pre-treatment levels of IP-10 and IL28B polymorphism further improves prognostication of therapeutic outcome.
Increased levels of ferritin
pre treatment seem to be associated with a poor response to treatment.
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. Ribavirin and interferons are contraindicated during pregnancy. However, avoiding fetal scalp monitoring and prolonged labor after rupture of membranes
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 diagnosis
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 be 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.
are claimed by their proponents to be helpful for hepatitis C, or are being researched to see if they can be effective treatments. Among them are milk thistle, ginseng
, colloidal silver
, licorice root (or its extract glycyrrhizin
), lactoferrin
, TJ-108 (a mixture of herbs used in Japanese Kampo
medicine), schisandra
, and oxymatrine (an extract from the sophora root).
In March 2011, the United States National Center for Complementary and Alternative Medicine (NCCAM) wrote:
Alcoholic beverage
consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more likely; insulin resistance
and metabolic syndrome
may similarly worsen the hepatic prognosis. There is also evidence that smoking increases the fibrosis (scarring) rate.
Worldwide, it is estimated that 130-170 million people are living with chronic hepatitis C infection (~3% of the world's population), that it infects 3-4 million people per year, >10% of these people will develop liver cirrhosis or cancer over time and that more than 350,000 people die from hepatitis C related diseases each year. Countries with particularly high rates of infection include Egypt (22%), Pakistan (4.8%) and China (3.2%). 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. Coinfection with HIV
is common, and rates among HIV positive populations are higher. Annual deaths from HCV in the United States range from 10,000 to 20,000; 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 a 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 Africa
and Asia
. Egypt
has the highest seroprevalence
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 schistosomiasis
, 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.
are coinfected with the hepatitis C virus, mainly because both viruses are blood-borne and are present in similar populations. 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 coinfection
.
In a study involving 21 HIV coinfected patients (DICO), pretreatment baseline plasma levels of IP-10 predicted the reduction of HCV RNA during the first days of interferon/ribavirin therapy (“first phase decline”) for HCV genotypes 1-3, as is also the case in HCV monoinfected patients. Pretreatment IP-10 levels below 150 pg/mL are predictive of a favorable response, and may thus be useful in encouraging these otherwise difficult-to-treat patients to initiate therapy.
, Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the National Institutes of Health
, and his research team demonstrated how most post transfusion
hepatitis cases were not due to hepatitis A
or B viruses. Despite this discovery, international research efforts to identify the virus, initially called non-A, non-B hepatitis (NANBH), failed for the next decade. In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation
, collaborating with Dr. D.W. Bradley from CDC
, used a novel molecular cloning
approach to identify the unknown organism and develop a diagnostic test. In 1988, the virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April 1989, the discovery of the virus, renamed hepatitis C virus (HCV), was published in two articles in the journal Science. The discovery led to significant improvements in diagnosis and improved antiviral treatment.
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.
In 2000, Drs. Alter and Houghton were honored with the Lasker Award for Clinical Medical Research
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 the company hinders the fight against hepatitis C by demanding too much money for its technology.
, which is a prodrug
of ribavirin
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 interferons
, 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 inhibitors
(including telaprevir
/VX 950), entry inhibitors
(such as SP 30 and ITX 5061) and polymerase inhibitors (such as RG7128, PSI-7977
and NM 283), but development of some of these is still in the early phase. VX 950, also known as telaprevir was approved by the FDA in 2011.
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 and Zadaxin. Antisense phosphorothioate oligos
have been targeted to hepatitis C. Antisense Morpholino
oligos have shown promise in preclinical studies however, they were found to cause a limited viral load reduction.
Some studies have shown that HCV viral replication is dependent upon the host factor miR-122
. As a result, pharmaceutical companies are developing potential HCV drugs that target miR-122. HCV therapies that target this host factor necessary for viral replication, rather than the virus itself, are promising, as they show little to no potential for viral resistance.
One such drug is miravirsen, developed by Santaris Pharma a/s
, a locked nucleic acid
based miR-122 antagonist in Phase II clinical trials as of late 2010.
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. needle sticks). They do have a limited role in transplant
patients.
In addition to the standard treatment with interferon and ribavirin, some studies have shown higher success rates when the antiviral drug amantadine
(Symmetrel) is added to the regimen. Sometimes called "triple therapy", it involves the addition of 100 mg of amantadine twice a day. Studies indicate 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 and when it is a risk due to their liver deterioration.
Bristol-Myers Squibb has obtained promising Phase II results for its experimental drug, BMS-790052, an NS5A replication complex inhibitor, in combination with peginterferon alfa and ribavirin.
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
primarily affecting the liver
Liver
The 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 virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
(HCV). The infection is often asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for 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...
, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to 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, including liver cancer
Hepatocellular carcinoma
Hepatocellular carcinoma is the most common type of liver cancer. Most cases of HCC are secondary to either a viral hepatitide infection or cirrhosis .Compared to other cancers, HCC is quite a rare tumor in the United States...
or life-threatening esophageal varices
Esophageal varices
In medicine , esophageal varices are extremely dilated sub-mucosal veins in the lower esophagus...
and gastric varices
Gastric varices
Gastric varices are dilated submucosal veins in the stomach, which can be a life-threatening cause of upper gastrointestinal hemorrhage. They are most commonly found in patients with portal hypertension, or elevated pressure in the portal vein system, which may be a complication of cirrhosis...
.
The hepatitis C virus 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 medication; peginterferon and ribavirin
Ribavirin
Ribavirin 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...
are the current standard therapy. Overall, between 51-80% of treated patients are cured. Those who develop cirrhosis or liver cancer may require a liver transplant, and the virus universally recurs after transplantation.
An estimated 180 million people worldwide are infected with hepatitis C. Hepatitis C is not known to cause disease in other animals. No vaccine against hepatitis C is currently available. The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proven in 1989.
Acute infection
During the first 12 weeks after infection with HCV, most people suffer no symptoms. For those who do, the main manifestations of acute infection are generally mild and vague, and rarely point to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal pain, jaundiceJaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, itching, and flu-like symptoms.
The hepatitis C virus is usually detectable in the blood by PCR within one to three weeks after infection, and antibodies to the virus are generally detectable within three to 15 weeks. Spontaneous viral clearance rates are highly variable; between 10 and 60% of persons infected with HCV clear the virus from their bodies during the acute phase, as shown by normalization of the liver enzymes alanine transaminase
Alanine transaminase
Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
(ALT) and aspartate transaminase
Aspartate transaminase
Aspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...
(AST), and plasma HCV-RNA clearance (this is known as spontaneous viral clearance). However, persistent infections are common and most patients develop chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
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 genotype
Genotype
The genotype is the genetic makeup 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 infection
Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months. Clinically, it is often asymptomatic, and it is mostly discovered accidentally, following the investigation of elevated liver enzyme levels discovered during a standard checkup.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 biopsy
Liver biopsy
Liver 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 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 cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to 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 ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
(accumulation of fluid in the abdomen), bruising and bleeding tendency, varices
Varices
Varices may refer to:In lower extremities* Varicose veins, large tortuous veins usually found on legsIn the digestive system* Sublingual varices* Esophageal varices, also known as Oesophageal varices* Gastric varices* Intestinal varices...
(enlarged veins, especially in the stomach and esophagus), jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, and a syndrome of cognitive impairment known as hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
. 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 ALT
Alanine transaminase
Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
and AST
Aspartate transaminase
Aspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...
. Periodically, they might show normal results. Usually prothrombin and albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
results are normal, but may become abnormal, once cirrhosis has developed. The levels 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, noninvasive tests are coming, with FibroTest
FibroTest
FibroTest, 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 necrotic inflammation. These tests are validated and recommended in Europe (FDA procedures initiated in USA).
Extrahepatic manifestations
Chronic hepatitis C can be associated with signs and symptoms in organs besides the liver, such as porphyria cutanea tardaPorphyria cutanea tarda
Porphyria 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...
, cryoglobulinemia
Cryoglobulinemia
Cryoglobulinemia 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 vasculitis
Vasculitis
Vasculitis 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 glomerulonephritis
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
(inflammation of the kidney), specifically membranoproliferative glomerulonephritis
Membranoproliferative glomerulonephritis
Membranoproliferative 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), thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, lichen planus
Lichen planus
Lichen planus is a chronic mucocutaneous disease that affects the skin, tongue, and oral mucosa. The disease presents itself in the form of papules, lesions, or rashes. Lichen planus does not involve lichens, the fungus/algae symbionts that often grow on tree trunks; the name refers to the dry and...
, diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
and with B-cell lymphoproliferative disorders.
Virology
The hepatitis C virus is a small (50 nmNanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...
in size), enveloped, single-stranded, positive sense RNA virus
RNA virus
An 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 Flaviviridae
Flaviviridae
The 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.). Based on the NS5 gene there are three major and eleven minor genotypes. The major genotypes diverged about 300–400 years ago from the ancestor virus. The minor genotypes diverged about 200 years ago from their major genotypes. All of the extant genotypes appear to have evolved from genotype 1 subtype 1b.
The hepatitis C virus 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 route 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 transmitted
Sexually transmitted disease
Sexually transmitted disease , also known as a sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans by means of human sexual behavior, 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
Injection drug use
Those who currently use or have used drug injectionDrug injection
In substance dependence and recreational drug use, drug injection is a method of introducing a drug into the body with a hollow needle and a syringe which is pierced through the skin into the body...
as their delivery route for drugs are at increased risk for getting hepatitis C because they may be sharing needles or other drug paraphernalia
Drug paraphernalia
Drug paraphernalia is a term used, often with a slightly negative connotation due to its use in criminal law field e.g. "possession of drug paraphernalia", to denote any equipment, product, or material that is modified for making, using, or concealing drugs, typically for recreational purposes...
(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 reduction
Harm reduction
Harm reduction refers to a range of public health policies designed to reduce the harmful consequences associated with recreational 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.
The main risk factor for HCV infection is intravenous drug using. Many studies showed that imprisonment
is an important predictor of HBV, HCV and HIV infection. Prison conditions increase the risk of transmission of infections, including blood-borne viral infections; the risk is further increased by the use of unsterile equipment used for injection.Intravenous drug users (IDUs) are at a potential risk for acquiring
blood-borne infections by parenteral and sexual routes.
During the VA Testimony before the Subcommittee on Benefits Committee on Veterans’ Affairs, U.S. House of Representatives on April 13 2000, Gary A. Roselle, M. D., Program Director for Infectious Diseases, Veterans Health Administration, Department of Veterans Affairs, stated "One in 10 US Veterans are infected with HCV, a rate five times greater than the 1.8% infection rate of the general population." A study conducted in 1999 by the Veterans Health Administration (VHA) involving 26,000 veterans showed that up to 10% of all veterans in the VHA system tested positive for hepatitis C.
Of the total number of persons who were hepatitis C antibody positive, and reported an era of service, 62.7% were noted to be from the Vietnam War. The second most frequent group is listed as post-Vietnam War at 18.2%, followed by 4.8% Korean War, 4.3% post-Korean War, 4.2% from WWII, and 2.7% Persian Gulf era veterans.
Blood products
Blood transfusionBlood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
, blood products, or organ transplantation prior to implementation of HCV screening (in the U.S., this would refer to procedures prior to 1992) are all risk factors for hepatitis C.
A cDNA
Complementary DNA
In genetics, complementary DNA is DNA synthesized from a messenger RNA template in a reaction catalyzed by the enzyme reverse transcriptase and the enzyme DNA polymerase. cDNA is often used to clone eukaryotic genes in prokaryotes...
clone from the hepatitis C virus genome 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 Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
reported 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 hygieneOral hygiene
Teeth cleaning is part of oral hygiene and involves the removal of dental plaque from teeth with the intention of preventing cavities , gingivitis, and periodontal disease. People routinely clean their own teeth by brushing and interdental cleaning, and dental hygienists can remove hardened...
instruments, 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. Limitations in the implementation and enforcement of stringent standard precautions in public and private medical and dental facilities is known to be the primary cause of the spread of HCV in Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...
, the country with highest rate of infection in the world.
Occupation
People can be exposed to HCV through accidental exposure to blood through needle sticks or blood spatter to the eyes or open wounds at work. Universal precautions
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 practice was introduced in 1985–88. In 1987, the practice of universal precautions was...
to protect against such accidental exposures significantly reduce the risk of exposure to HCV.
Recreation
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 nil. The government does not recommend condom use to prevent hepatitis C transmission in long-term mutually monogamous relationships. However, for not well understood reasons, the risk of transmission is higher if one has multiple sex partners and condom use is recommended. 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
Fisting is a sexual activity that involves inserting a hand into the vagina or rectum. Once insertion is complete, the fingers either naturally clench into a fist or remain straight. In more vigorous forms of fisting, such as "punching", a fully clenched fist may be inserted and withdrawn slowly...
, or use of sex toys). For these reasons, condom use is highly recommended for those who engage in anal sex play or other sex acts likely to cause bleeding or damage mucosal linings.
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
Body piercing, 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. The word piercing can refer to the act or practice of body piercing, or to an opening in the body created by this act or practice...
performed either before the mid 1980s, "underground," or nonprofessionally are of particular concern, since sterile techniques in such settings may have been insufficient to prevent disease; sharing unsterilized tattooing equipment (for example, in the prison
Prison
A prison is a place in which people are physically confined and, usually, deprived of a range of personal freedoms. Imprisonment or incarceration is a legal penalty that may be imposed by the state for the commission of a crime...
system) has an obvious increased risk of acquiring HCV. The U.S. Centers for Disease Control and Prevention's position on this subject states that, "Whenever tattoos or body piercings are performed in informal settings or with nonsterile instruments, transmission of hepatitis C and other infectious diseases is possible." Despite these risks, it is rare for tattoos in an approved facility to be directly associated with 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
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
, such as canker sores
Aphthous ulcer
An aphthous ulcer , also known as a canker sore, is a type of mouth ulcer which presents as a painful open sore inside the mouth or upper throat characterized by a break in the mucous membrane. Its cause is unknown, but they are not contagious...
, cold sores, and immediately after flossing.
HCV is not spread through casual contact, such as hugging, kissing, or sharing eating or cooking utensils.
Vertical
Vertical transmissionVertical transmission
Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period. A pathogen's transmissibility refers to its capacity for vertical transmission...
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 delivery
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...
or breastfeeding
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
.
Diagnosis
Chronic hepatitis C may be suspected on the basis of the medical history
Medical history
The 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 tattoo
Tattoo
A tattoo is made by inserting indelible ink into the dermis layer of the skin to change the pigment. Tattoos on humans are a type of body modification, and tattoos on other animals are most commonly used for identification purposes...
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 donation
Blood donation
A blood donation occurs when a person voluntarily has blood drawn and 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 tracing
Contact tracing
In 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 serological
Serology
Serology is the scientific study of blood serum and other bodily fluids. 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 value
Positive predictive value
In statistics and diagnostic testing, the positive predictive value, or precision rate is the proportion of subjects with positive test results who are correctly diagnosed. It is a critical measure of the performance of a diagnostic method, as it reflects the probability that a positive test...
for exposure to the hepatitis C virus, but may miss patients who have not yet developed antibodies (seroconversion
Seroconversion
Seroconversion 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. Immunocompromised individuals infected with HCV may 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 transaminases
Elevated transaminases
In 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). However, liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
alone are not useful in predicting the severity of infection and normal results do not exclude the possibility of liver disease.
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.
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)
- Needle stick 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)
- Sharing drug products via insufflationInsufflation (medicine)Insufflation is the practice of inhaling a substance. Insufflation has limited medical use, but is a common route of administration with many respiratory drugs used to treat conditions in the lungs and paranasal sinus .The technique is common for many recreational drugs and is also used for some...
Strategies such as the provision of new needles and syringes, and education about safer drug injection procedures, greatly decrease 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.
Treatment
The hepatitis C virus induces chronic infection in 50%-80% of infected persons. Approximately 20-50% of these do not respond to therapy, depending on the genotype they are infected with. 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.In May 2011, the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approved 2 drugs for hepatitis C. The first one is boceprevir
Boceprevir
Boceprevir is a protease inhibitor used as a treatment for hepatitis C genotype 1. It binds to HCV nonstructural 3 active site....
and the other is telaprevir
Telaprevir
Telaprevir , marketed as the brand name Incivek, is a pharmaceutical drug for the treatment of hepatitis C co-developed by Vertex and Johnson & Johnson. It is a member of a class of antiviral drugs known as protease inhibitors...
(Incivek). Both drugs block an enzyme that helps the virus reproduce. The drugs are intended to improve on standard treatments using the injected drug pegylated interferon alpha
Pegylated interferon alpha
Pegylated interferon alpha can refer to:* Pegylated interferon-alpha-2a* Pegylated interferon-alpha-2b...
and the pill ribavirin
Ribavirin
Ribavirin 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...
.
Medications
Treatment is generally recommended for patients with proven hepatitis C virus infection and persistently abnormal liver function tests. 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
Ribavirin 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 genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
. In a large multicenter randomized control study among genotype 2 or 3 infected patients (NORDymanIC), patients achieving HCV RNA below 1000 IU/mL by day 7 who were treated for 12 weeks demonstrated similar cure rates as those treated for 24 weeks.
Pegylated interferon-alpha-2a plus ribavirin
Ribavirin
Ribavirin 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...
may increase sustained virological response among patients with chronic hepatitis C as compared to pegylated interferon-alpha-2b plus ribavirin according to a systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
of randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s . The relative benefit increase was 14.6%. For patients at similar risk to those in this study (41.0% had sustained virological response when not treated with pegylated interferon alpha 2a plus ribavirin), this leads to an absolute benefit increase of 6%. About 16.7 people need to be treated for one to benefit.
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 gastroenterology
Gastroenterology
Gastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. The name is a combination of three Ancient Greek words gaster , enteron , and logos...
, hepatology
Hepatology
Hepatology is the branch of medicine that incorporates the 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 disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...
.
The treatment may be physically demanding, particularly for those with a prior history of drug or alcohol abuse. It can qualify for temporary disability
Disability
A disability may be physical, cognitive, mental, sensory, emotional, developmental or some combination of these.Many people would rather be referred to as a person with a disability instead of handicapped...
in some cases. A substantial proportion of people 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 anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, cardiovascular events
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
and psychiatric problems such as suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
or suicidal ideation. The latter are exacerbated by the general physiological stress experienced by the patient.
Boceprevir
BoceprevirBoceprevir
Boceprevir is a protease inhibitor used as a treatment for hepatitis C genotype 1. It binds to HCV nonstructural 3 active site....
is a protease inhibitor
Protease inhibitor (pharmacology)
Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...
that binds to the HCV nonstructural 3 (NS3) active site on hepatitis C genotype 1. There have been several recent randomized double-blinded clinical trials studying boceprevir in conjunction with peginterferon-ribavirin as therapy for untreated chronic HCV genotype 1 infection and previously treated chronic HCV genotype 1 infection. These studies have shown improved sustained virologic response at 44 weeks compared to therapy with peginterferon-ribavirin therapy alone. Anemia was a common side effect in these two studies.
Boceprevir was approved by the FDA on May 13, 2011 for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin. The indication is for adult patients (18 years of age and older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.
Cure rates by genotype
Responses can vary by genotype. Approximately 80% of hepatitis C patients in the United States have genotype 1, and genotype 4 is more common in the Middle EastMiddle East
The Middle East is a region that encompasses Western Asia and Northern Africa. It is often used as a synonym for Near East, in opposition to Far East...
and Africa.
| Genotype | Description |
|---|---|
| 2 and 3 | 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. Patients achieving HCV RNA below 1000 IU/mL by day 7 (i.e. just prior to the second dose of pegylated interferon) may be treated for as little as 12 weeks with retained sustained cure rates. |
| 1 | Sustained response is about 50% in patients with HCV genotype 1 given 48 weeks of treatment. 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%. |
| 4 | Sustained response is about 65% in those with genotype 4 given 48 weeks of treatment. |
| 6 | 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. |
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 some patients who have a sustained virological response still appear to have actively replicating virus in their liver and peripheral blood mononuclear cells.
Host factors
For genotype 1 hepatitis C treated with pegylated interferon-alpha-2a or pegylated interferon-alpha-2b combined with ribavirin, 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 likely to achieve sustained virological response after the treatment than others. A later report from Nature demonstrated the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus. It has subsequently been reported that polymorphisms in IL28B are strongly associated with the elimination of HCV RNA during the first days of peginterferon-α/ribavirin therapy (“first phase decline”), irrespective of HCV genotype.Similarly, baseline pretreatment plasma levels of IP-10 (also known as CXCL10) are elevated in patients chronically infected with hepatitis C virus (HCV) of genotypes 1 or 4 who do not achieve a sustained viral response (SVR) after completion of antiviral therapy. IP-10 in plasma is mirrored by intrahepatic IP-10 mRNA, and both strikingly predict the first first phase decline during interferon/ribavirin therapy for all HCV genotypes. And combining both pre-treatment levels of IP-10 and IL28B polymorphism further improves prognostication of therapeutic outcome.
Increased levels of ferritin
Ferritin
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
pre treatment seem to be associated with a poor response to treatment.
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. While there is no preventative treatment, there is a high probability of the baby clearing the infection 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. Ribavirin and interferons are contraindicated during pregnancy. However, avoiding fetal scalp monitoring and prolonged labor after rupture of membranes
Rupture of membranes
Rupture of membranes or amniorrhexis is a term used during pregnancy to describe a rupture of the amniotic sac. Normally, or "spontaneously", it occurs at full term 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 diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
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 be 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 medicine
Several alternative therapiesAlternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
are claimed by their proponents to be helpful for hepatitis C, or are being researched to see if they can be effective treatments. Among them are milk thistle, ginseng
Ginseng
Ginseng is any one of eleven species of slow-growing perennial plants with fleshy roots, belonging to the genus Panax of the family Araliaceae....
, colloidal silver
Colloidal silver
The medical uses of silver include its incorporation into wound dressings to treat external infections, and its use as an antiseptic and disinfectant in medical appliances...
, licorice root (or its extract glycyrrhizin
Glycyrrhizin
Glycyrrhizin is the main sweet-tasting compound from liquorice root. It is 30–50 times as sweet as sucrose . Pure glycyrrhizin is odorless....
), lactoferrin
Lactoferrin
Lactoferrin , also known as lactotransferrin , is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions...
, TJ-108 (a mixture of herbs used in Japanese Kampo
Kampo
, alternatively shortened as just , is the Japanese study and adaptation of Traditional Chinese medicine. The basic works of Chinese medicine came to Japan between the 7th and 9th centuries. Since then, the Japanese have created their own unique herbal medical system and diagnosis...
medicine), schisandra
Schisandra
Schisandra is a genus of shrub commonly grown in gardens. It is a hardy deciduous climber which thrives in virtually any soil; its preferred position is on a sheltered shady wall. It may be propagated by taking cuttings of half-matured shoots in August. Species include S. chinensis, S....
, and oxymatrine (an extract from the sophora root).
In March 2011, the United States National Center for Complementary and Alternative Medicine (NCCAM) wrote:
- A review of the scientific evidence on complementary and alternative medicine (CAM) and hepatitis C found the following:
- No CAM treatment has been scientifically proven to successfully treat hepatitis C.
- A 2003 analysis of results from 13 clinical trials testing the effects of various medicinal herbs on hepatitis C concluded that there is not enough evidence to support using herbs to treat the disease.
- Two other reviews that covered a variety of CAM modalities for hepatitis C concluded that conventional therapies are the only scientifically proven treatments for the disease.
- In a 2002 NIH consensus statement on the management of hepatitis C, a panel of medical and scientific experts concluded that "alternative and nontraditional medicines" should be studied. Participants in a 2001 NIH research workshop on the benefits and risks of CAM therapies for chronic liver disease recommended research support for related laboratory and clinical studies.
Additional recommendations
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 beverage
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
consumption accelerates HCV associated fibrosis and cirrhosis, and makes liver cancer more likely; insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
and metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
may similarly worsen the hepatic prognosis. There is also evidence that smoking increases the fibrosis (scarring) rate.
Special groups
Hemophilia and thalassemia are special group in HCV infected patients. Using the ribavirin in thalassemia group is not approved by FDA yet and hemophilia is at higher risk of complication in therapy with standard drugs.Epidemiology
Liver transplantation
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original...
in the United States. Coinfection with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
is common, and rates among HIV positive populations are higher. Annual deaths from HCV in the United States range from 10,000 to 20,000; 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 a 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 Africa
Africa
Africa 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...
and Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
. Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...
has the highest seroprevalence
Seroprevalence
Seroprevalence 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 schistosomiasis
Schistosomiasis
Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
, 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.
Coinfection with HIV
Approximately 350,000 people (35% of patients) in the USA infected with HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
are coinfected with the hepatitis C virus, mainly because both viruses are blood-borne and are present in similar populations. 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 coinfection
Coinfection
In parasitology, coinfection is the term used to describe the simultaneous infection of a host by multiple pathogen species. In virology, coinfection can also refer to the simultaneous infection of a single cell by two or more virus particles...
.
In a study involving 21 HIV coinfected patients (DICO), pretreatment baseline plasma levels of IP-10 predicted the reduction of HCV RNA during the first days of interferon/ribavirin therapy (“first phase decline”) for HCV genotypes 1-3, as is also the case in HCV monoinfected patients. Pretreatment IP-10 levels below 150 pg/mL are predictive of a favorable response, and may thus be useful in encouraging these otherwise difficult-to-treat patients to initiate therapy.
History
In the mid 1970s, Harvey J. AlterHarvey J. Alter
Harvey 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 Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
, and his research team demonstrated how most post transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
hepatitis cases were not due to hepatitis A
Hepatitis A
Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus , an RNA virus, usually spread the fecal-oral route; transmitted person-to-person by ingestion of contaminated food or water or through direct contact with an infectious person...
or B viruses. Despite this discovery, international research efforts to identify the virus, initially called non-A, non-B hepatitis (NANBH), failed for the next decade. In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation
Chiron Corporation
Chiron 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 CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
, used a novel molecular cloning
Molecular cloning
Molecular cloning refers to a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms...
approach to identify the unknown organism and develop a diagnostic test. In 1988, the virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April 1989, the discovery of the virus, renamed hepatitis C virus (HCV), was published in two articles in the journal Science. The discovery led to significant improvements in diagnosis and improved antiviral treatment.
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.
In 2000, Drs. Alter and Houghton were honored with the Lasker Award for Clinical Medical Research
Lasker Award
The 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 the company hinders the fight against hepatitis C by demanding too much money for its technology.
Research
The drug viramidineViramidine
Taribavirin 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 prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
of ribavirin
Ribavirin
Ribavirin 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 interferons
Pegylated interferon alpha
Pegylated 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 inhibitors
Protease inhibitor (pharmacology)
Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of proteases, e.g.HIV-1 protease, enzymes used by the viruses to cleave nascent proteins for final assembly of new...
(including telaprevir
Telaprevir
Telaprevir , marketed as the brand name Incivek, is a pharmaceutical drug for the treatment of hepatitis C co-developed by Vertex and Johnson & Johnson. It is a member of a class of antiviral drugs known as protease inhibitors...
/VX 950), entry inhibitors
Entry inhibitors
Entry inhibitors, also known as fusion inhibitors, are a class of antiretroviral drugs, used in combination therapy for the treatment of HIV infection. This class of drugs interferes with the binding, fusion and entry of an HIV virion to a human cell...
(such as SP 30 and ITX 5061) and polymerase inhibitors (such as RG7128, PSI-7977
PSI-7977
PSI-7977 is an experimental drug candidate for the treatment of hepatitis C. It is under development by Pharmasset and is currently in Phase II clinical trials. It is being studied as a treatment to be used in combination with ribavirin....
and NM 283), but development of some of these is still in the early phase. VX 950, also known as telaprevir was approved by the FDA in 2011.
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 and Zadaxin. Antisense phosphorothioate oligos
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
have been targeted to hepatitis C. Antisense Morpholino
Morpholino
In molecular biology, a Morpholino is a molecule in a particular structural family that is 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.
Some studies have shown that HCV viral replication is dependent upon the host factor miR-122
MiR-122
miR-122 is a miRNA that is conserved between vertebrate species. miR-122 is not present in invertebrates, and no close paralogs of miR-122 have been detected. miR-122 expression is specific to the liver, where it has been implicated as a regulator of fatty-acid metabolism in mouse studies. Reduced...
. As a result, pharmaceutical companies are developing potential HCV drugs that target miR-122. HCV therapies that target this host factor necessary for viral replication, rather than the virus itself, are promising, as they show little to no potential for viral resistance.
One such drug is miravirsen, developed by Santaris Pharma a/s
Santaris Pharma a/s
Santaris Pharma A/S is a biopharmaceutical company founded in 2003 in Copenhagen, Denmark with a small branch in San Diego, California that opened in 2009...
, a locked nucleic acid
Locked nucleic acid
A locked nucleic acid , often referred to as inaccessible RNA, is a modified RNA nucleotide. The ribose moiety of an LNA nucleotide is modified with an extra bridge connecting the 2' oxygen and 4' carbon. The bridge "locks" the ribose in the 3'-endo conformation, which is often found in the A-form...
based miR-122 antagonist in Phase II clinical trials as of late 2010.
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. needle sticks). They do have a limited role in transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
patients.
In addition to the standard treatment with interferon and ribavirin, some studies have shown higher success rates when the antiviral drug amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
(Symmetrel) is added to the regimen. Sometimes called "triple therapy", it involves the addition of 100 mg of amantadine twice a day. Studies indicate 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 and when it is a risk due to their liver deterioration.
Bristol-Myers Squibb has obtained promising Phase II results for its experimental drug, BMS-790052, an NS5A replication complex inhibitor, in combination with peginterferon alfa and ribavirin.
See also
- HCV-HIV coinfectionHepatitis C/co-infection with HIVIn HIV–HCV co-infected patients, the Hepatitis C viral load is higher than in HCV-mono-infected patients in both the plasma and liver tissue. Patients who are HIV-positive are commonly co-infected with HCV due to shared routes of transmission: percutaneous exposure to blood, sexual intercourse,...
- List of people with hepatitis C
- PSI-6130PSI-6130PSI-6130 is an experimental treatment for hepatitis C. PSI-6130 is a member of a class of antiviral drugs known as nucleoside polymerase inhibitors that was created by chemist Jeremy L. Clark. Specifically, PSI-6130 inhibits the hepatitis C virus NS5B RNA dependant RNA polymerase.PSI-6130 is...
(experimental treatment) - World Hepatitis DayWorld Hepatitis DayWorld Hepatitis Day, observed July 28, aims to raise global awareness of hepatitis B and hepatitis C and encourage prevention, diagnosis and treatment....
Information and resources
Organizations and programs
- National Hepatitis C Program U.S. Department of Veterans Affairs
- Hepatitis C American Liver Foundation
- Hepatitis Australia Hepatitis Australia
- Hepatitis C homepage of the UK National Health ServiceNational Health ServiceThe National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
- National CIHR Research Training Program in Hepatitis C Training program for student researchers funded by the Canadian Institutes of Health Research.
- Hepatitis C Research Sphinx: European Union Framework7 Hepatitis C research programme