Saturday, August 9, 2008


Hepatitis C Virus


Although its means of transmission is fairly well documented, the hepatitis C virus itself largely remains a mystery. Hepatitis C is extremely small, even for a virus - it is only about 50 nanometers in diameter. A nanometer is one billionth of a meter - if you placed 200,000 hepatitis C viruses end to end, they would be only a single centimeter long. However, what is known about hepatitis C underscores the type of threat that it poses.

Hepatitis C is an RNA virus - which means that it mutates frequently. Once an infection has begun, hepatitis C creates different genetic variations of itself within the body of the host. The mutated forms are frequently different enough from their ancestors that the immune system cannot recognize them. Thus, even if the immune system begins to succeed against one variation, the mutant strains quickly take over and become new, predominant strains. As a result, the development of antibodies against HCV does not produce immunity against the disease like it does with most other viruses. More than 80% of the individuals infected with HCV will progress to a chronic form of the disease.

As a result of this, hepatitis C is usually not self-limited as a disease. In more than 85% of all cases, whether they progress to chronic liver disease or not, the infected individual carries the virus for life. This means that they also remain contagious for a lifetime, able to transmit the virus to others. And because of the long progression of the illness, even patients who will eventually die as a result of hepatitis C carry the virus for decades before it takes their lives. Most epidemics are self-limiting - they spread rapidly, but over a short period of time the affected population either dies or develops immunity to the disease, and it stops spreading. Not so with hepatitis C. Much like HIV and AIDS, it lasts a lifetime, and kills slowly - giving the virus plenty of time to spread.

There are six basic genotypes of HCV, with 15 recorded subtypes, which vary in prevalence in different regions of the world. Each of these major genotypes can differ significantly in their biological effects - in terms of replication, mutation rates, type and severity of liver damage, and detection and treatment options. However, these differences are not yet clearly understood.

The 21 current variations in genotype, complicated by the constant mutation of the virus within infected individuals, represents a major challenge for the development of treatments and vaccines against HCV - and even for reliable detection of the virus. There is no guarantee that a treatment, test, or vaccine against one strain will be effective against all of them. Moreover, individuals cured of one strain will be prone to re-infection by any of the other strains.

The infection is often asymptomatic, and can often lead to chronic infection and cause inflammation of the liver (chronic hepatitis). This condition can progress to scarring of the liver (fibrosis), and advanced scarring (cirrhosis). In some cases, those with cirrhosis will go on to develop liver failure or other complications of cirrhosis, including liver cancer. No effective vaccine against hepatitis C is available. The symptoms of infection can be medically managed, and a proportion of patients can be somewhat cleared of the virus by a course of anti-viral medicines. Although early medical intervention is helpful, people with HCV infection can experience mild symptoms, and consequently do not seek treatment. (Approximately 150-200 million or more) people are infected with hepatitis C world wide.

Although HCV is not known to efficiently be transmitted sexually, persons at risk for infection through injection drug use might seek care in STD treatment facilities, HIV counseling and testing facilities, prisons/and or correctional facilities, drug treatment facilities, and other public health settings where STD and HIV prevention and control services are available.

Sixty to 70% of persons newly infected with HCV typically are usually asymptomatic or have a mild clinical illness. HCV RNA can be detected in blood within 1–3 weeks after exposure. The average time from exposure to antibody to HCV (anti-HCV) seroconversion is 8–9 weeks, and anti-HCV can be detected in >97% of persons by 6 months after exposure. Chronic HCV infection develops in 70%–85% of HCV-infected persons; 60%–70% of chronically infected persons have evidence of active liver disease. The majority of infected persons might not be aware of their infection because they are not clinically ill. However, infected persons serve as a source of transmission to others and are at risk for chronic liver disease or other HCV-related chronic diseases decades after infection.

HCV is most efficiently transmitted through large or repeated percutaneous exposure to infected blood (e.g., through transfusion of blood from non screened donors or through use of injecting drugs). Although much less frequent, occupational, Perinatal, and sexual exposures also can result in transmission of HCV.

Since the clinical characteristics are similar for all types of acute viral hepatitis, the specific viral cause of illness cannot be determined solely on the basis of signs, symptoms, history, or current risk factors, but must be verified by specific serologic testing.

In most of the developed countries, the people at risks of HCV infection include; Current or former injection drug users, including those who injected only once many years ago, Recipients of clotting factor concentrates made before 1987 when more advanced methods for manufacturing those products were developed, Recipients of blood transfusions or solid organ transplants before July 1992 when better testing of blood donors became available, Chronic hemodialysis patients, Persons with known exposures to HCV such as health care workers after needle sticks involving HCV-positive blood recipients of blood or organs from a donor who tested HCV-positive Persons with HIV infection, Children born to HCV-positive mothers.

Is it possible for someone to become infected with HCV and then spontaneously clear the infection?

Yes. Approximately 15%–25% of persons clear the virus from their bodies without treatment and do not develop chronic infection; the reasons for this are not well known. HCV infection becomes chronic in approximately 75%–85% of cases.

Why most persons remain chronically infected with HCV?

A person infected with HCV mounts an immune response to the virus, but replication of the virus during infection can result in changes that evade the immune response. This may explain how the virus establishes and maintains chronic infection.

What are the chances of developing chronic HCV infection/liver disease, cirrhosis, or liver cancer or dying as a result of hepatitis C.?

For every 100 persons infected with HCV, approximately 75–85 will go on to develop chronic infection 60–70 will go on to develop chronic liver disease, 5–20 will go on to develop cirrhosis over a period of 20–30 years, 1–5 will die from the consequences of chronic infection (liver cancer or cirrhosis). And persons can become infected with a different strain of HCV after they have cleared the initial infection. Prior infection with HCV does not protect against later infection with the same or different genotypes of the virus. This is because persons infected with HCV typically have an ineffective immune response due to changes in the virus during infection.

For the same reason, no effective pre- or post exposure prophylaxis (i.e., immune globulin) is available. Currently there is no vaccine for hepatitis C available. Research into the development of a vaccine is still ongoing.

Transmission and Symptoms:

How HCV is transmitted:

HCV is transmitted primarily through large or repeated percutaneous (i.e., passage through the skin) exposures to infectious blood, such as Injection drug use. Receipt of donated blood, blood products, and organs (once a common means of transmission but now rare in most developed countries, 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)

Can HCV be spread during medical or dental procedures?

Yes, therefore Standard Precautions and other infection control practices should be followed routinely and consistently. There are However cases that HCV has been spread in healthcare settings when injection equipment, such as syringes, was shared between patients or when injectable medications or intravenous solutions were mishandled and became contaminated with blood. Healthcare personnel should understand and adhere to Standard Precautions, which includes safe injection practices and other guidance aimed at reducing blood borne pathogen risks for patients and healthcare personnel. If healthcare-associated HCV infection is suspected, this should be reported to state and local public health authorities.

Can HCV be spread within a household?

Yes, but does not occur very often. If HCV is spread within a household, it is most likely a result of direct, through-the-skin exposure to the blood of an infected household member.

Signs and symptoms of acute HCV infection:

Persons with newly acquired HCV infection usually are asymptomatic or have mild symptoms that are unlikely to prompt a visit to a healthcare professional. When symptoms occur, they can include; Fever, Fatigue, Dark urine, Clay-colored And approximately 20%–30% of those newly infected with HCV experience fatigue, abdominal pain, poor appetite, or jaundice. In those persons who do develop symptoms, the average time period from exposure to symptom onset is 4–12 weeks (range: 2–24 weeks).

Signs and symptoms of chronic HCV infection:

Most persons with chronic HCV infection are asymptomatic. However, many have chronic liver disease, which can range from mild to severe, including cirrhosis and liver cancer. Chronic liver disease in HCV-infected persons is usually insidious, progressing slowly without any signs or symptoms for several decades. In fact, HCV infection is often not recognized until asymptomatic persons are identified as HCV-positive when screened for blood donation or when elevated alanine aminotransferase (ALT, a liver enzyme) levels are detected during routine examinations.

Testing and Diagnosis HCV testing is recommended for anyone at increased risk for HCV infection, including:

Persons who have ever injected illegal drugs, including those who injected only once many years ago Recipients of clotting factor concentrates made before 1987, Recipients of blood transfusions or solid organ transplants before July 1992, Patients who have ever received long-term hemodialysis treatment.
Persons with known exposures to HCV, such as health care workers after needle sticks involving HCV-positive blood recipients of blood or organs from a donor who later tested HCV-positive

All persons with HIV infection. Patients with signs or symptoms of liver disease (e.g., abnormal liver enzyme tests), Children born to HCV-positive mothers (to avoid detecting maternal antibody, these children should not be tested before age 18 months)Several tests are performed for HCV infection,including; Screening tests for antibody to HCV (anti-HCV)enzyme immunoassay(EIA)enhanced chemiluminescence immunoassay (CIA)Recombinant immunoblot assay(RIBA)Qualitative tests to detect presence or absence of virus (HCV RNA polymerase chain reaction [PCR])Quantitative tests to detect amount (titer) of virus (HCV RNA PCR).
False-positive anti-HCV tests appear more often when persons at low risk for HCV infection (e.g., blood donors) are tested. Therefore, it is important to confirm a positive anti-HCV test with a supplemental test, such as RIBA (recombinant immunoblot assay), as most false positive anti-HCV tests are reported as negative on supplemental testing.

Persons with early HCV infection might not yet have developed antibody levels high enough that the test can measure which might result into a false negative. In addition, some persons might lack the (immune) response necessary for the test to work well. In these persons, further testing such as PCR for HCV RNA may be considered. A confirmed positive anti-HCV test is usually followed by other additional tests such as ALT (alanine aminotransferase, a liver enzyme). An elevated ALT indicates inflammation of the liver. The patient should be checked further for chronic liver disease and possible treatment. The evaluation should be performed by a medical doctor/ healthcare professional familiar with chronic hepatitis C. Also one can have a normal liver enzyme (e.g., ALT) level and still have chronic hepatitis C. It is common for patients with chronic hepatitis C to have liver enzyme levels that go up and down, with periodic returns to normal or near normal levels. Liver enzyme levels can remain normal for over a year despite chronic liver disease.

Management and Treatment:

HCV-positive persons should be evaluated (by referral or consultation, if appropriate) for presence of chronic liver disease, including assessment of liver function tests, evaluation for severity of liver disease and possible treatment, and determination of the need for hepatitis A and hepatitis B vaccination. A specialist can be consulted in the management of HCV-infected persons but, any physician who manages a person with hepatitis C should be knowledgeable and current on all aspects of the care of a person with hepatitis C; this can include some internal medicine and family practice physicians as well as specialists such as infectious disease physicians, gastroenterologists, or hepatologists.

Treatment for chronic hepatitis C:

Combination therapy with pegylated interferon and ribavirin is the treatment of choice, resulting in sustained virologic response (defined as undetectable HCV RNA in the patient's blood 24 weeks after the end of treatment) rates of 40%–80% (up to 50% for patients infected with genotype 1, and up to 80% for patients infected with genotypes 2 or 3). Combination therapy using interferon and ribavirin is approved for use in children ages 3–17 years in some countries. Treatment success rates are now being improved with the addition of polymerase and protease inhibitors to standard pegylated interferon/ribavirin combination therapy. At least six distinct HCV genotypes (genotypes 1–6) and more than 50 subtypes have been identified. It is necessary to do viral genotyping when managing a person with chronic hepatitis C. Because there are at least six known genotypes and more than 50 subtypes of HCV, genotype information is helpful in defining the epidemiology of hepatitis C and in making recommendations regarding treatment.

Knowing the genotype can help predict the likelihood of treatment response and, in many cases, determine the duration of treatment. Patients with genotypes 2 and 3 are almost three times more likely than patients with genotype 1 to respond to therapy with alpha interferon or the combination of alpha interferon and ribavirin. When using combination therapy, the recommended duration of treatment depends on the genotype. For patients with genotypes 2 and 3, a 24-week course of combination treatment is adequate, whereas for patients with genotype 1, a 48-week course is recommended. Once the genotype is identified, it need not be tested again; genotypes do not change during the course of infection. Super-infection is possible if risk behaviors (e.g., injection drug use) for HCV infection continue, but it is believed to be very uncommon.

Does chronic hepatitis C affect only the liver?

A small percentage of persons with chronic HCV infection develop medical conditions due to hepatitis C that are not limited to the liver. These conditions are thought to be attributable to the body's immune response to HCV infection. Such conditions can include;Diabetes mellitus, which occurs three times more frequently in HCV-infected persons, Glomerulonephritis, a type of kidney disease caused by inflammation of the kidney, Essential mixed cryoglobulinemia, a condition involving the presence of abnormal proteins in the blood, Porphyria cutanea tarda, an abnormality in heme production that causes skin fragility and blistering, Non-Hodgkins lymphoma, which might occur somewhat more frequently in HCV-infected persons, Counseling Patients.

Patients should be informed about the low but present risk for transmission with sex partners. Sharing personal items that might have blood on them, such as toothbrushes or razors, can pose a risk to others. Cuts and sores on the skin should be covered to keep from spreading infectious blood or secretions. Donating blood, organs,tissue, or semen can spread HCV to others. HCV is not spread by sneezing, hugging, holding hands, coughing, sharing eating utensils or drinking glasses, or through food or water. Patients may benefit from joining support group.

HCV-positive persons should be advised to avoid alcohol because it can accelerate cirrhosis and end-stage liver disease. Viral hepatitis patients should also check with a health professional before taking any new prescription pills, over-the counter drugs (such as non-aspirin pain relievers), or supplements, as these can potentially damage the liver.

Hepatitis C and Healthcare Personnel:

What is the risk for HCV infection from a needle stick exposure to HCV-contaminated blood?

After a needle stick or sharps exposure to HCV-positive blood, the risk of HCV infection is approximately 1.8% (range: 0%–10%).

Other than needle sticks, do other exposures, such as splashes to the eye, pose a risk to healthcare personnel for HCV transmission?

Although a few cases of HCV transmission via blood splash to the eye have been reported, the risk for such transmission is expected to be very low. Avoiding occupational exposure to blood is the primary way to prevent transmission of blood borne illnesses among healthcare personnel. All healthcare personnel should adhere to Standard Precautions. Depending on the medical procedure involved, Standard Precautions may include the appropriate use of personal protective equipment (e.g., gloves, masks, and protective eyewear).

What follow-up testing is recommended for healthcare personnel exposed to HCV-positive blood?

For the source, perform baseline testing for anti-HCV.For the person exposed to a HCV-positive source, perform baseline and follow-up testing, including baseline testing for anti-HCV and ALT activity and follow-up testing for anti-HCV (e.g., at 4–6 months) and ALT activity. If earlier diagnosis of HCV infection is desired, testing for HCV RNA may be performed at 4–6weeks. Confirmation by supplemental anti-HCV testing of all anti-HCV results reported as positive by enzyme immunoassay.

Pregnancy and HCV Infection:

Should pregnant women be routinely tested for anti-HCV?

No. Since pregnant women have no greater risk of being infected with HCV than non-pregnant women and interventions to prevent mother-to-child transmission are lacking, routine anti-HCV testing of pregnant women is not recommended. Pregnant women should be tested for anti-HCV only if they have risk factors for HCV.

What is the risk that an HCV-infected mother will spread HCV to her infant during birth?

Approximately 4 of every 100 infants born to HCV-infected mothers become infected with the virus. Transmission occurs at the time of birth, and no prophylaxis is available to prevent it. The risk is increased by the presence of maternal HCV viremia at delivery and also is 2–3 times greater if the woman is co-infected with HIV. Most infants infected with HCV at birth have no symptoms and do well during childhood. More research is needed to find out the long-term effects of Perinatal HCV infection.

Should a woman with HCV infection be advised against breastfeeding?

No. There is no evidence that breastfeeding spreads HCV. However, HCV-positive mothers should consider abstaining from breastfeeding if their nipples are cracked or bleeding.

When should children born to HCV-infected mothers be tested to see if they were infected at birth?

Children should be tested for anti-HCV no sooner than age 18 months because anti-HCV from the mother might last until this age. If diagnosis is desired before the child turns 18 months, testing for HCV RNA could be performed at or after the infant's first well-child visit at age 1–2 months. HCV RNA testing should then be repeated at a subsequent visit, independent of the initial HCV RNA test result.

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