Hepatitis C

Hepatitis C is a liver disease. Hepatitis (HEP-ah-TY-tis) makes your liver swell and stops it from working right. Hepatitis C is a virus that often silently attacks your liver. Most people infected with the hepatitis C virus (HCV) have no symptoms at all. In fact, most people don't know they have the disease until liver damage shows up, decades later, during routine medical tests.

Hepatitis C is one of six identified hepatitis viruses the others are A, B, D, E and G. All cause the liver to become inflamed, which interferes with its ability to function. Hepatitis C is generally considered to be among the most serious of these viruses.

Over time, if you have a hepatitis C infection, it can lead to liver cancer, liver failure or cirrhosis irreversible and potentially fatal scarring of the liver. Unlike HIV, the virus that causes AIDS, the hepatitis C virus usually isn't transmitted through sexual contact. Instead, you're more at risk if you're exposed to contaminated blood through needles shared during drug use or through blood transfusions.

Although vaccines exist for hepatitis A and B, no vaccine for hepatitis C has been developed. Researchers hope to find a medication that will slow or stop the growth of the virus and prevent long-term complications, such as cirrhosis and cancer, from developing.

What causes hepatitis C?

Hepatitis C is caused by a virus.

A virus is a germ that causes sickness. (For example, the flu is caused by a virus.) People can pass viruses to each other. The virus that causes hepatitis C is called the hepatitis C virus.

Hepatitis C Causes:

• HCV is not related to the other viruses that cause hepatitis. Like the other hepatitis viruses, however, it is contagious. The hepatitis C virus is transmitted mainly by contact with blood or blood products.

• Sharing of contaminated needles among IV drug users is the most common mode of transmission. Using a needle to inject recreational drugs, even once several years ago, is a risk factor for hepatitis C.

• Transfusion with infected blood or blood products, hemodialysis, or transplantation of organs from infected donors was once a common mode of transmission but is now rare.

• In 1992, a test became available for checking blood for HCV. Blood and blood products are now tested to ensure that they are not contaminated. As a result, cases of hepatitis C related to transfusion, hemodialysis, or transplantation have dropped to almost zero since then. Transfusion of blood or blood products before 1992 is a risk factor for hepatitis C.

• Less common causes of HCV transmission include the following.

• From mother to infant at the time of childbirth

• Through sexual intercourse with an infected person: Having multiple sex partners is a risk factor.

• Needle sticks with HCV-contaminated blood: This is mostly seen in health care workers. The risk of developing HCV infection after a needle stick is about 5-10%.

• You cannot get hepatitis C by living with, being near, or touching someone with the disease. You can get the disease by sharing a razor, nail clippers, or other such items with an infected person.

• The source of transmission is unknown in about 10% of people with acute hepatitis C and in about 30% of people with chronic hepatitis C.

How could I get hepatitis C?

You could get hepatitis C by:

• Hepatitis C is spread by contact with an infected person's blood.

• You could get hepatitis C by haring drug needles.

• Sharing drug needles.

• getting pricked with a needle that has infected blood on it (hospital workers can get hepatitis C this way).

• Having sex with an infected person, especially if you or your partner has other sexually transmitted diseases.

• Being born to a mother with hepatitis C.

• In rare cases, you could get hepatitis C by getting a tattoo or body piercing with un sterilized, dirty tools.

You can NOT get hepatitis C by:

shaking hands with an infected person.   hugging an infected person.   kissing an infected person.   sitting next to an infected person.

Could I get hepatitis C from a blood transfusion?

If you had a blood transfusion or organ transplant before 1992, you might have hepatitis C. Before 1992, doctors could not check blood for hepatitis C, and some people received infected blood. If you had a blood transfusion or organ transplant before 1992, ask a doctor to test you for hepatitis C. (See "What are the tests for hepatitis C?")

A doctor can test you for hepatitis C.

What are the symptoms?

Although hepatitis C damages the liver, 80% of people with the disease do not have symptoms. In those who do, symptoms may not appear for 10-20 years, or even longer. Even then, the symptoms usually come and go and are mild and vague. Unfortunately, by the time symptoms appear, the damage may be very serious. 

• A minority of people have symptoms during the early acute phase of the infection. These symptoms typically develop 5-12 weeks after exposure to HCV. Some people describe the symptoms as being flu like. The symptoms may last a few weeks or months.

• Nausea

• Vomiting

• Diarrhea

• Loss of appetite

• Fatigue

• Pain over the liver (on the right side of the abdomen, just under the rib cage)

• Jaundice - A condition in which the skin and the whites of the eyes turn yellow

• Dark-colored urine (may look like cola or tea)

• Stools become pale in color (grayish or clay colored)

• Prolonged nausea and vomiting can cause dehydration. If you have been vomiting repeatedly, you may notice the following symptoms:

• Fatigue or weakness

• Confusion or difficulty concentrating

• Headache

• Not urinating

• Irritability

• Chronic hepatitis C can lead to cirrhosis of the liver in many people, a condition traditionally associated with alcoholism. Cirrhosis is a condition in which healthy liver tissue is replaced by fibrous tissue, followed by scarlike hardening. As this happens, the liver gradually begins to fail, or lose its ability to carry out its normal functions. Eventually, symptoms develop. Symptoms of cirrhosis include the following:

• Fluid retention causing swelling of the belly (ascites), legs, or whole body

• Persistent jaundice

• Fatigue

• Disturbances in sleeping

• Itchy skin

• Loss of appetite, weight loss, wasting

• Vomiting with blood in the vomit

Mental disturbances such as confusion, lethargy, extreme sleepiness, or hallucinations (hepatic encephalopathy).

How is hepatitis C treated?

Hepatitis C is treated through shots of medicine.

Hepatitis C is treated with a drug called peginterferon, usually in combination with the drug ribavirin. You may need surgery if you have hepatitis C for many years. Over time, hepatitis C can cause your liver to stop working. If that happens, you will need a new liver. The surgery is called a liver transplant. It involves taking out the old, damaged liver and putting in a new, healthy one from a donor.

How can I protect myself?

You can protect yourself and others from hepatitis C.

If you inject drugs, use your own needles.

Prevention

There is no vaccine to prevent hepatitis C, but you can reduce your risk of becoming infected if:

• You do not share needles to inject drugs. If you are injecting drugs, the best way to protect yourself is by not sharing needles or other equipment (such as cotton, spoons, and water) with others. Many cities have needle exchange programs that provide free, sterile needles so that you do not have to share needles. If you want to stop using drugs, ask your doctor or someone you trust to help you find out about drug treatment programs.

• You work in a health care setting and you follow your institution's safety guidelines. You wear protective gloves and clothing and dispose of needles and other contaminated sharp objects properly.

• You make sure the practitioner sterilizes the instruments and supplies if you get a tattoo, have your body pierced, or have acupuncture.

• If you have hepatitis C, you can help prevent spreading it to others if.

• You do not share needles or other equipment such as cotton, spoons, and water if you continue to use needles to inject drugs.

• You keep cuts, scrapes, and blisters covered to prevent others from coming in contact with your blood and other body fluids. You also throw out any blood-soaked items such as used Band-Aids.

• You do not donate blood or sperm.

• You wash your hands and any object that has come in contact with your blood-thoroughly with water and soap.

• You do not share your toothbrush, razor, nail clippers, diabetes supplies, or anything else that might have your blood on it.

Breast-feeding mothers who have hepatitis C can continue to breast-feed their babies because hepatitis C cannot be spread through breast milk. If you are breast-feeding, you should try to avoid having cracked nipples, which might pose a risk of spreading the virus to your baby.

Epidemiology

In America, since HBsAg screening was introduced, the incidence of post-transfusion hepatitis has a declined, but a significant number of cases remained. At least 95% of post-transfusion hepatitis was caused by non-A non-B. Worldwide, there are thought to be 100 million carriers of hepatitis C. It is particularly prevalent in Japan, where it is thought to be responsible for the majority of cases of hepatocellular carcinoma. There are 175,000 new cases of hepatitis C in the US per year. In the US, NANBH infection is more common than HBV infection amongst IVDA and those given blood transfusions. NANBH is usually transmitted parenterally. Sexual transmission can occur albeit considerable less efficient for HBV. There were recent reports of vertical infection.

Risk Groups for hepatitis C in the U.S.A.

1. IVDA 35%

2. Blood transfusion 5%

3. Promiscuity 7%

4. Household contacts 8%

5. Health care workers 20%

6. Unidentified sources 43%

The highest HCV antibody prevalence is found in haemophiliac patients who have received untreated blood or blood products where up to 85% of such patients in the UK have antibodies. A large proportion of cases occur in people with no known risk factors. The evidence for and against sexual spread is confusing. It is noteworthy though that 20% of non-drug using female partners of IV drug users with hepatitis C are positive for anti-HCV. In general, the mode of HCV transmission is similar to HBV.

Health care workers experiencing needlestick injuries are also at risk of acquiring HCV infection. In one study, 3% of health workers with a needlestick exposure in which the source patient was anti-HCV positive converted to anti-HCV. Accumulating evidence indicates that HCV is transmitted from mother to infant; however the actual risk is unknown. Anti-HCV seroconversion has only been rarely documented among infants born to anti-HCV positive mothers unless their mothers were also infected with HIV. However, in studies using PCR, HCV transmission apparently occurred without anti-HCV seroconversion.

In common with other RNA viruses, wide genetic variation of hepatitis C exist in nature. On the basis of phylogenetic analysis, HCV has been classified into six major genotypes (types 1 to 6) of which four (types 1 to 4) contain several more closely related subtypes (e.g. a, b and c). In West-ern Europe and the USA, the predominant geno-types are la, lb, 2b and 3a, with some variation in frequency. In Japan and Taiwan types lb, 2a and 2b are seen most frequently. Elsewhere in Asia, genotype 3 is the most common, and genotype 4 is found frequently in the Middle East and Africa. Type 5 is mainly found in Southern Africa and type 6 in SE Asia. There is increasing evidence demonstrating a link between HCV genotype and disease severity and re-sponsiveness to interferon therapy. Genotype lb was found significantly more often in cases of severe liver disease such as cirrhosis and hepatocellular carcinoma. It was also associated with a longer disease duration and a higher level of viraemia than other genotypes. Individuals infected with genotype 1b are less likely to respond to interferon therapy.

What are the tests for hepatitis C?

The doctor will take some blood to check for hepatitis C.

To check for hepatitis C, the doctor will test your blood.

These tests show if you have hepatitis C and how serious it is.

The doctor may also do a liver biopsy.

A biopsy (BYE-op-see) is a simple test. The doctor removes a tiny piece of your liver through a needle. The doctor checks the piece of liver for signs of hepatitis C and liver damage.

Laboratory Diagnosis

1. Serology: the first generation ELISA kits relied on a fusion protein antigen produced from a original 5-1-1 clone with a few adjoining clones. The antigen was denoted as the C100 antigen. The problem with the first generation kits was that the antigen used was non-structural and thus may not pick up all cases of HCV. Furthermore, antibodies against this antigen could not be detected until 15 weeks after the onset of hepatitis. Therefore, HCV infection cannot be excluded in those whose serum is antibody-negative up to 6 months after the onset of symptoms. The first generation kits had also been demonstrated to have a poor specificity. Second and third generation assays are now used for serological diagnosis. Second generation assays incorporate C22 core antigen as well as NS4 (C-100-3) and NS3 antigens. The newer third generation assays incorporate NS5 as an additional antigen. However this increase in sensitivity is offset by a slight decrease in specificity. They reduce the "diagnostic window" down to 4 weeks after initial infection.

Recombinant Immunoblot assays (RIBA) were developed by Ortho whereby nitrocellulose strips were coated with discrete bands of E. coli  and yeast  cloned antigens. It is thought that this test carried a much higher specificity with equal sensitivity. Another method to increase sensitivity was to use "blocking tests". Sera positive for anti-HCV were blocked by C-100-3 antigen. Inability to be blocked is interpreted as non-specificity. Recombinant antigens are being developed based on structural proteins which should lead to serological tests with higher sensitivities. Also it is feasible that antibodies to these antigens may appear earlier and thus diagnosis of acute infection may become possible.

2. Polymerase Chain Reaction: A PCR test had been developed where the level of HCV viraemia is roughly quantified and thus infectivity of the blood. A 5' conserved non-coding region had been identified. PCR has enormous potential value in support of the anti-HCV ELISA and in the study of HCV. It can be used to diagnose acute infection as HCV viraemia occurs well before the development of anti-HCV antibodies. Evidence provided by PCR for fluctuated level of infectivity in certain individuals may play an important role in the consideration of infectivity of seropositive donors. RIBA-2 positivity appears to correlate well with PCR positivity. A branched DNA assay has also been developed for the detection of HCV-RNA.

3. Hepatitis C Antigen: Recent reports described the identification of hepatitis C antigen (HCAg) in hepatocytes of patients suffering from chronic HCV infection using a FITC polyclonal IgG obtained from patients with hepatitis C. A test for hepatitis C antigen in serum is being developed for the detection of HCV viraemia, rather like PCR.

Immunsystem und Hepatitis-C

Pathogenesis 

Each clinical form of viral hepatitis with HBV can also occur with HCV. Acute disease may lead to recovery, fulminant hepatitis, relapsing hepatitis with intervening periods of normal liver function, inapparent chronic infection, chronic active hepatitis and cirrhosis have been documented. The incubation period lies between that of HAV and HBV. HCV infection is particularly associated with high ALT levels and it was suggested that ALT levels could be used as surrogate marker for the screening of NANBH before the availability of a test for anti-HCV.

Chronic Infection: It is thought chronic infection occurs in 50- 75% of all patients infected with HCV, in contrast to 10% for adults infected with HBV. In a cohort study where patients with HCV chronic disease had been followed up for 10 years, 20% have cirrhosis, 30% made improvements, 45% remained stable, 25% have shown progression (including the development of cirrhosis).

Association with hepatocellular carcinoma: Several recent studies have established a strong association between HCV and hepatocellular carcinoma. anti-HCV antibodies, in the absence of HBV markers, were detected in 44.5% of HCC patients in Spain, 43% in Japan, 16% in Italy, 7% in South Africa. Since HBV carriers often have chronic HCV infection, it is conceivable that the 2 viruses may act together to cause HCC and epidemiological data linking HBV to HCC may require reassessment in terms of the magnitude of the risk involved with the availability of testing for chronic HCV infection. HCV may prove to be as important as HBV in the causation of hepatocellular carcinoma worldwide. It has recently been suggested that the risk of developing HCC is approximately 5% year in cirrhotic patients with chronic hepatitis C; this is greater than the risk from hepatitis B.

In chimpanzees and to a lesser extent in humans, cytoplasmic tubules (cylindrical confronting cisternae) are regularly seen under EM. The nature of these structures are unknown in particular to the part they may play in HCV replication. In HCV hepatitis, direct cytopathic damage to the hepatocytes is thought to be the mechanism of pathogenesis, in contrast to the immunopathological mechanisms in HBV.

                              HBV                            HCV

Symptomatic             50                              10-35

Chronicity                 10-15                         50-75

Hepatocyte injury CMI direct CPE.

In general, hepatitis C is a slower disease than hepatitis B. It takes 10 years to develop chronic hepatitis, 20 years to develop cirrhosis, and 30 years to develop hepatocellular carcinoma. There are certain nonhepatic disorders which are sometimes associated with chronic hepatitis C infection. eg. mixed cryoglobulinaemia, membranoproliferative glomerulonephritis, Sjogren's syndrome, sporadic porphyria cutanea tarda, and lichen planus.

Treatment

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