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Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). It is difficult for the human immune system to eliminate the virus from the body, and infection with HCV usually becomes chronic. Over decades, chronic infection with HCV damages the liver and can cause liver failure in some people. In the U.S., the number of new cases of infection with HCV has declined over the last 10 years from a peak of some 200,000 annually to about 19,000 in 2006. When the virus first enters the body, there usually are no symptoms, so these numbers are estimates. Up to 85% of newly infected people fail to clear the virus and become chronically infected.. Infection is most common among people who are 40 to 60 years of age, reflecting the high rates of infection in the 1970s and 1980s. There are 8,000 to 10,000 deaths each year in the U.S. related to HCV. HCV is the leading cause of liver transplantation in the U.S and is a risk factor for liver cancer.
Nature of the Hepatitis C Virus:
HCV is a member of the Flaviviridae family of viruses. Other members of this family of viruses include those that cause yellow fever and dengue.
Viruses belonging to this family all have ribonucleic acid (RNA) as their genetic material. All hepatitis C viruses are made up of an outer coat (envelope) and contain enzymes and proteins that allow the virus to reproduce within the cells of the body, in particular, the cells of the liver. Although this basic structure is common to all hepatitis C viruses, there are at least six distinctly different strains of the virus which have different genetic profiles (genotypes). In the U. S., genotype 1 is the most common form of HCV. Even within a single genotype there may be some variations (genotype 1a and 1b, for example). Genotyping is important to guide treatment because some viral genotypes respond better to therapy than others.
People who may be at risk for hepatitis C are those who:
- Have been on long-term kidney dialysis
- Have regular contact with blood at work (for instance, as a health care worker)
- Have unprotected sexual contact with a person who has hepatitis C (this is much less common, but the risk is higher for those who have many sex partners, already have a sexually transmitted disease, or are infected with HIV)
- Inject street drugs or share a needle with someone who has hepatitis C
- Received a blood transfusion before July 1992
- Received a tattoo or acupuncture with contaminated instruments (the risk is very low with licensed, commercial tattoo facilities)
- Received blood, blood products, or solid organs from a donor who has hepatitis C
- Share personal items such as toothbrushes and razors with someone who has hepatitis C (less common)
- Were born to a hepatitis C-infected mother (this occurs in about 1 out of 20 babies born to mothers with HCV, which is much less common than with hepatitis B)
Signs and Symptoms:
AcuteAcute hepatitis C refers to the first 6 months after infection with HCV although symptoms may appear within a day if infection was caused by any method of intravenous injection. Between 60% and 70% of people infected develop no symptoms during the acute phase unless infection was caused by direct access to the blood stream as crossing the blood brain barrier is then made up to 100 times easier. Main symptoms consist of general cold and flu like symptoms with increased loss of senses. In the minority of patients who experience acute phase symptoms, they are generally mild and nonspecific, and rarely lead to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms. Hepatitis C genotypes 2A and 3A have the highest cure rates, at 81% and 74% respectively.
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.
ChronicChronic 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 (e.g. usual 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, 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 (blood sample) are coming, with FibroTest and ActiTest, respectively estimating liver fibrosis and necrotic inflammation.
Signs and Tests:
The following tests are done to help diagnose hepatitis C:
- EIA assay to detect hepatitis C antibody
- Hepatitis C RNA assays to measure virus levels (viral load)
- Hepatitis C genotype. Six genotypes exist. Most Americans have genotype 1 infection, which is the hardest to treat.
- Albumin level
- Liver function tests
- Prothrombin time
Receive antiviral therapy for hepatitis C virus?Patients at risk for cirrhosis should be considered for treatment of HCV. According to a consensus statement from the National Institutes of Health (NIH) these include persons with:
- HCV infection and persistent elevation of ALT (alanine aminotransferase, a liver enzyme in the blood)
- High levels of HCV RNA in the blood
- HCV infection and evidence of fibrosis (scarring) on liver biopsy
- HCV infection and evidence of at least moderate inflammation and liver cell injury (necrosis) on liver biopsy
Individuals who should not be treated with antiviral therapy include those who are unable to comply with the treatment schedule, should not take the specific medications (for example, allergy), and have reversible serious untreated conditions such as unstable heart disease, uncontrolled high blood pressure, or untreated major depression.
The hepatitis C virus induces chronic infection in 50%-80% of infected persons. Approximately 50% of these do not respond to therapy. 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.
Medications (interferon and ribavirin)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 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 trials . 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 patients must be treated for one to benefit (number needed to treat = 16.7; click here to adjust these results for patients at higher or lower risk of sustained virological response). However, this study’s results may be biased due to uncertain temporality of association, selective dose response.
Treatment is generally recommended for patients with proven hepatitis C virus infection and persistently abnormal liver function tests.
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.
Special factors affecting patients
Host factorsFor 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-?/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.
Viral factors:The basis for the differential response to treatment between viral genotypes is still being worked out. Mutations in the core arginine70glutamine (R70Q) and in the nonstructural protein 5A within its interferon sensitivity determining region have been associated with responsiveness at weeks 12 and 4 respectively.
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 babies ridding themselves the HCV in the first 12 months.
In a mother who also has HIV, the rate of transmission can be as high as 19%. There are currently no data to determine whether antiviral therapy reduces perinatal transmission. 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 performed after 15 months of age.
A review of the scientific evidence on 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.
Prevention may include:
- 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
- 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 insufflation
No vaccine protects against contracting hepatitis C, or helps to treat it. Vaccines are under development and some have shown encouraging results.