Hepatitis C virus
medical conditions

Hepatitis C virus

Explore the available health information, treatment context, and integrative evidence for Hepatitis C virus.

Background
  • Hepatitis is defined as inflammation of the liver. Viral infections are the most common cause of hepatitis. A type of hepatitis known as hepatitis C is caused by the hepatitis C virus (HCV). This virus is made up of a single strand of ribonucleic acid (RNA) surrounded by two layers (envelopes), one consisting of proteins and the other of lipids (fat). RNA is a nucleic acid that helps in protein synthesis, which is important for the growth and maintenance of the body.
  • Hepatitis C virus belongs to the Flaviviridae family, which includes viruses that mainly spread through arthropod vectors such as ticks and mosquitoes. Dengue fever, an infectious disease transmitted to humans by mosquitoes, and Japanese encephalitis, an infection that affects the nervous system which is also transmitted by mosquitoes, are some of the diseases caused by the Flaviviridae family of organisms.
  • In the mid 1970s, researchers found that a particular type of hepatitis that develops in a person after receiving a blood transfusion was not caused by hepatitis A or B viruses. They named the new virus non-A, non-B hepatitis (NANBH). The unknown organism was identified by scientists in 1987, and it was renamed the hepatitis C virus (HCV) in 1989.
  • HCV causes a liver disease known as hepatitis C. The incubation period, which is the period between infection and the onset of clinical symptoms, ranges from 15 to 150 days. Humans and chimpanzees are the only two species that are susceptible to HCV, and a similar disease process has been observed in both species.
  • According to the World Health Organization, an estimated 170 million people are chronically infected with HCV, with 3 to 4 million new infections occurring every year. The distribution of HCV types varies globally. For example, HCV type 1 is the most common and accounts for 70% of the HCV infections in the United States.
Risk Factors and Causes
  • HCV can be passed to others through blood and bodily fluids such as vaginal secretions and semen. It is commonly spread through blood transfusions, in which blood is transferred from one person to another, or by sharing needles contaminated with the virus, particularly among street drug and steroid users. It is advisable to check for HCV in people who received a blood transfusion or organ transplant before 1992, when there were no tests to identify the virus. The infection cannot spread by hugging, kissing, or shaking hands with an infected person.
  • Equipment used for procedures such as tattooing, body piercing, and acupuncture may transmit HCV infection. In rare cases, transmission may occur through contaminated (infected) dialysis equipment. Dialysis is a procedure used to filter harmful wastes from blood in people with impaired kidney function. The virus may also be transmitted from infected mothers to their infants, although this is uncommon.

HCV rapidly replicates, or produces multiple copies of itself, with nearly 1 trillion particles produced every day in an infected individual. Its high mutation rate helps the virus elude the host's immune response. A mutation is a change within a gene, specifically a change in the sequence of base pairs in the DNA that make up a gene. Several studies indicate that HCV replicates within liver cells. Circulating HCV particles enter the liver cells by initially binding to specific surface receptors. These receptors are protein molecules to which the viral particle attaches itself to gain entry into the cell. Because of the high mutation rate of the HCV, the liver cell perceives the mutated or genetically altered viral RNA as its own RNA and proceeds to replicate it. Because the viral RNA is assumed to be the body's own RNA, there is no immune response generated. Thus, the viral RNA is successful in avoiding attack by the host's immune system.

Signs and Symptoms
  • Hepatitis C can present in two forms: acute or chronic. Acute hepatitis C occurs during the first six months following infection with HCV. Chronic hepatitis C occurs when the HCV persists beyond six months in the individual.
  • In acute infection, the virus is detected within 1 to 3 weeks after infection and the antibodies to the virus are identified 3 to 12 weeks after infection. Earlier studies have shown that about 15 to 40% of individuals infected with HCV clear the virus during the acute phase because of the successful removal of the virus from the body; however the remaining 60 to 85% of individuals develop chronic hepatitis.
  • The clinical course of chronic hepatic C varies from one person to another. The symptoms may suggest liver disease is absent only until a large amount of scarring of the liver has occurred. The patient may experience a wide range of clinical manifestations, from absence of symptoms to symptomatic illness, before the development of advanced liver disease.
  • In most cases, both acute and chronic HCV infections are without symptoms (asymptomatic). If symptoms do occur, they may include fever, loss of appetite, stomachache, fatigue, muscle pain, yellowish discoloration of skin and eyes, dark yellow urine, and light-colored stools. Manifestations of liver disease such as jaundice and enlargement of the liver and spleen may also occur. HCV infection can also present with symptoms outside the liver. These may include inflammation of the thyroid, a form of inflammation of blood vessels (cryoglobulinemia), inflammation of the kidneys, a type of inherited disease with skin and nerve complications (porphyria cutanea tarda), or Sjogren's syndrome, an inflammatory disease affecting different parts of the body.
Diagnosis
  • General: When an individual is exposed to the hepatitis C virus (HCV), his or her body produces antibodies to the virus. These antibodies remain in the HCV-infected individual throughout his or her life, even if the virus is eliminated from the body naturally or following medical treatment. Antibodies are proteins produced by the body's defense system to fight against foreign agents called antigens. An antigen is a substance that is capable of causing an immune response. Patients who recover from HCV infection have a lower risk of reinfection, although HCV antibodies do not completely prevent reinfection.
  • Diagnostic testing: HCV may be detected within 1 to 2 weeks after infection. The diagnostic tests for HCV are divided into two categories: serological assays, which detect the antibodies to HCV in the serum or plasma, and molecular assays that detect, quantify, or characterize HCV RNA in an infected patient. Both blood and tissue samples taken from the infected patient may be used to perform the molecular assays. Serum is the liquid component of blood that does not contain clotting factors. Plasma is the liquid component of blood in which blood cells are suspended.
  • Serological tests, which detect the anti-HCV antibodies, can be screening tests or confirmatory tests. Screening tests help identify blood samples that contain antibodies, while confirmatory tests confirm the presence of specific antibodies in the screened samples. The second or third line of tests is referred to as supplemental tests.
  • HCV infection is identified by screening for the presence of anti-HCV antibodies in the serum. These tests help determine whether the individual was exposed to the virus in the past, but cannot determine active viral infection. The results of these tests are indicated as positive, negative, or weakly positive. In 2003, the Centers for Disease Control and Prevention (CDC) revised the guidelines and suggested that weakly positive tests must be confirmed with a confirmatory test before reporting.
  • Either the enzyme immunoassay (EIA) or enhanced chemiluminescence immunoassay (CIA) test is usually the first test performed for screening the virus. If the result is positive, then further verification has to be done by a more specific serologic test, either by recombinant immunoblot assay (RIBA®, Chiron Corporation, Emeryville, California) or nucleic acid test (NAT) for confirmation.
  • ELISA (enzyme-linked immunosorbent assay): ELISA is a diagnostic technique used to detect the presence of an antibody or antigen in a blood sample. ELISA is most widely used as an initial blood test for screening a large number of samples on a daily basis. The third-generation ELISA test is more sensitive and accurate than the previous versions, but false-negative results may be produced in patients whose immune systems do not generate sufficient antibodies, e.g., in people with HIV (human immunodeficiency virus) and in people undergoing hemodialysis for kidney disease.
  • HCV-RIBA® (recombinant immunoblot assay): HCV-RIBA® is an additional test with a high specificity to confirm the presence of anti-HCV antibodies. Specificity refers to the ability of an assay to measure a particular organism or substance in a sample of interest. This high specificity makes it possible to confirm the presence or absence of anti-HCV antibodies in low-risk individuals who are identified as HCV-positive during routine screening. The results are interpreted as positive, negative, or indeterminate. Like the ELISA, this test can be used to determine exposure to the virus, but not the current infection status.
  • Polymerase chain reaction (PCR): PCR is an automated process that generates a number of copies of a specific DNA/RNA sequence (amplification) within a short time. PCR is done in the laboratory under a controlled environment and uses specific reagents and enzymes. This technique may be used to detect the presence of HCV, generally in individuals who have antibodies to HCV (anti-HCV positive) and who have a known risk of developing the infection. The technique can even detect low levels of HCV RNA in the serum.
  • Optimal HCV PCR assays have the ability to detect less than 100 copies of HCV RNA per milliliter of plasma or serum. Quantitative PCR, which determines the amount of virus in the blood, is one of the most sensitive tests for determining hepatitis C viral load.
  • Nucleic acid test (NAT): NAT is a supplemental test to detect HCV RNA in both acute and chronic infections. It is also used for evaluation and management of patients with chronic hepatitis C infection. NAT can detect the presence of active HCV infection and can verify the presence of antibodies to HCV. NATs must be performed in specifically designed laboratories because any variation in the manner of sample collection, storage, or processing may lead to inaccurate results.
  • COBAS AMPLICORâ„¢ HCV test: COBAS AMPLICOR (Roche Molecular Systems, Inc., New Jersey) may be used as both a qualitative and a quantitative test. It is a type of NAT that detects HCV RNA using reverse transcriptase polymerase chain reaction (RT-PCR) amplification. Reverse transcription is the process of producing double-stranded DNA from a single-stranded RNA. It is a fully automated test that facilitates greater sensitivity, reliability, and standardization. The test detects even low levels of HCV RNA.
  • This test is used for patients with liver disease who test positive for HCV in screening tests. The presence of HCV RNA indicates that the virus is replicating and is therefore active. The test accurately diagnoses current infection and monitors the response to treatment. Quantification or viral load assessment is also possible for assessing treatment outcomes.
  • The viral load or quantitative HCV tests help measure the number of viral RNA particles in the blood. This type of test should be done both before and after treatment (usually after 3 months) to determine the response to the treatment. Successful treatment decreases the viral load by 99% in 4 to 12 weeks, to an undetectable level.
  • COBAS Taqman® HCV test: COBAS Taqman test (TaqMan HCV; Roche Molecular Systems Inc., Branchburg, New Jersey) is a type of nucleic acid amplification test used for quantifying HCV RNA in human serum or plasma. It may therefore be used to detect the severity of the HCV infection. The system provides quick results and is highly specific and sensitive with a broad dynamic range.
  • The dynamic range of an assay is the difference between the highest and lowest detectable amounts of a product such as HCV RNA. The highest detectable level is independent of the technique used. However, the lowest detectable amount of the product depends on the assay technique used. A large dynamic range indicates a more sensitive test because it can detect much lower quantities of the product.
  • HCV-RNA test: HCV RNA tests may be qualitative or quantitative. Qualitative tests determine the presence of HCV, whereas quantitative tests determine the amount of virus in the blood. The HCV RNA test can determine the active status of the virus and therefore helps identify currently infected individuals. It is reported as "positive" or "detected" if HCV viral RNA is found and "negative" or "not detected" if the viral RNA is not found. It is generally used after the completion of treatment to check whether the virus has been fully eliminated from the body. A positive HCV RNA test implies that the person has active hepatitis C infection.
  • Viral genotyping: Viral genotyping helps determine the type of hepatitis C, and is important in determining the patient response to standard treatment and the duration of treatment. The test is done before treatment is started to analyze the duration and success rate of the treatment.
  • Transcription-mediated amplification (TMA): TMA is a highly sensitive technique for detecting the presence of HCV RNA in serum. The test accurately measures the antiviral response at the end of treatment because it can detect even a small amount of virus present in the serum.
  • Immunostaining: Immunostaining is an antibody-based method to detect a specific protein or antigen in the tissue sample by using stains such as fluorescent dyes and peroxidase enzymes. This can be performed by antibodies to detect the presence of HCV in the liver. Although it can identify the antigens in 60 to 70% of patients with chronic hepatitis, the test is not used often because it requires special handling of liver tissue. In addition, the infection can be detected only in individuals with high levels of anti-HCV antibodies in the serum.
  • Liver biopsy: A liver biopsy may be performed to determine the extent of damage to liver cells and the best treatment option for the infected patient. During the procedure, a needle is inserted into the liver and a small piece of tissue is removed. The tissue is then analyzed under a microscope in a laboratory to detect and identify features of hepatitis C infection and liver damage. Liver biopsy may be necessary in chronically infected patients. This procedure allows doctors to grade the severity of the disease, identify the degree of fibrosis (excess fibrous connective tissue in an organ), and detect any permanent damage to the liver.
  • Liver enzymes: A blood test may be performed to check for elevated levels of liver enzymes contained in liver cells, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These enzymes leak into the bloodstream when liver cells are injured. The most common cause of elevation of ALT is chronic hepatitis C infection. Therefore, if routine blood tests reveal increased liver enzyme levels, such individuals must be clinically evaluated and tested for HCV using ELISA.
Complications
  • The major complication of HCV infection is progressive liver damage. In addition, hepatitis C worsens any underlying liver disease. For example, the progression of liver damage is rapid in people with alcoholic liver disease and HCV infection. Also, about 35% of individuals with HIV in the United States are also infected with HCV because both viruses are spread through blood contact.
  • Approximately 10 to 20% of individuals with chronic hepatitis C progress to cirrhosis within 20 years and are at a higher risk of developing complications such as end-stage liver disease and liver cancer. Cirrhosis is a condition of the liver in which the liver tissue is replaced by fibrous scar tissue.
Treatment
  • A vaccine to prevent hepatitis C is currently unavailable, but the symptoms may be medically managed by using antiviral drugs. Treatment in the acute phase yields a better success rate (greater than 90%) with a shorter duration of treatment than treatment in the chronic stage. Also, patients with low viral loads respond better to treatment than those with higher viral loads.
  • Although antiviral therapy may be beneficial, it has not been approved for children. Interferon-α therapy has not been shown to be effective in adults and has shown a sustained response in only 10 to 15% of cases. A combination of interferon-α and the antiviral drug ribavirin is effective, however, with 40 to 50% of the treated cases showing a sustained response.
  • Several integrative therapies have been used to maintain the function of the liver rather than treating the virus, thereby delaying the progression of the infection. Extracts of Silybum marianum and Sho-saiko-to have been shown to improve liver function in HCV-infected patients by their antiviral effects.
Prevention
  • Hepatitis C virus (HCV) can be passed to others through blood and bodily fluids such as vaginal secretions and semen. It is commonly spread through blood transfusions, in which blood is transferred from one person to another, or by sharing needles contaminated with the virus, particularly among street drug and steroid users. Practicing safe sex and avoiding exposure to potentially contaminated needles will decrease the risk of being infected with HCV.
  • The infection cannot spread by hugging, kissing, or shaking hands with an infected person.
References
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