Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. In some areas the prevalence of hepatitis C is extremely high, as in Egypt, Saudi Arabia, the Phillipines and Papua New Guinea. The prevalence of hepatitis C antibody in volunteer blood donors is generally estimated at between 0.4% and 1%.
HCV has been described as the "shadow epidemic" because of the insidious nature of the infection which is generally asymptomatic and persists for life in 85% of patients infected with the virus.
HCV has tremendous genetic diversity and this enables it to escape the surveillance of the immune system of infected individual thus leading to chronic infection. In the same light, there are difficulties in vaccine development.
How is HCV transmitted?
HCV is largely transmitted parenterally ie by blood and blood products. Therefore, HCV infections may be acquired via the following means:
- Intravenous drug abuse
- Accidental needlestick injury
- Hemodialysis in patients with kidney failure
- Organ and semen donation from a HCV carrier
- HCV can also be transmitted by snorting drugs like cocaine ( blood from damaged nasal mucosa and transmitted by sharing straws).
- Vertical transmission ( mother to infant ) during childbirth is possible if the mother has a high HCV viral load, co-infection with HIV (AIDS) and has acute hepatitis C during pregnancy. There is a 6% transmission rate by this method.
- Sexual transmission is possible if one engages in promiscuous sexual activity.
- Rarely, household ( non sexual ) transmission is possible through the sharing of razors and toothbrushes.
What is the clinical course after a HCV infection?
The onset of infection is often unrecognised and the early course is generally indolent. The natural history of HCV infection is dependant upon on geography, alcohol use, viral characteristics ( different genetic types, viral load ), co-infection with other viruses and some as yet unidentified factors.
After exposure to the virus, detectable viral genetic material called HCV RNA is seen in the blood in 1 - 3 weeks. Nearly all patients show evidence of liver injury because blood tests for liver enzymes become elevated. However, only 25% patients manifest symptoms like lassitude, anorexia and some became jaundiced (yellowing of eyes and skin). Rapid progression to liver failure due to fulminant hepatitis is a rare occurrence.
The majority of patients (85%) fail to clear the virus within 6 months and develop chronic hepatitis C. These patients are relatively well in the first 2 decades after acquiring the infection. However in 20% of these carriers, there may be intermittent symptoms of fatigue and malaise.
Generally, symptoms only appear once advanced liver damage has occurred.
These signs and symptoms are features of liver cirrhosis ("hardening of the liver tissue") which results from persistence of the hepatitis C virus. These include ascites (swelling of the abdomen with fluid), jaundice, deterioration of mental state (hepatic encephalopathy), vomiting blood or passing out altered blood in the stools. Of course, there is the dreaded complication of liver cancer.
Generally, cirrhosis appears in at least 20% of patients within 20 years of infection. Cirrhosis can be accelerated by concomitant alcohol use.
Liver cancer develops after 30 years and occurs only in a background of liver cirrhosis.
It is interesting to note that hepatitis C has clinical manifestions beyond the liver. These are as a result of it's effect on the immune system, and are called extrahepatic manifestions. The extrahepatic manifestions include :
- Joint swelling and pain ( arthritis )
- Eye inflammation ( keratoconjuretivitis sicca )
- Skin and oral manifestions ( lichen planus which appears as a characteristic rash and oral inflammation ).
- Inflammation of kidneys ( glomerulonephritis )
- Essential mixed cryoglobulinemia - this last rare manifestion is in itself a rare disease which affects the blood and various other body systems. Major symptoms may include unusual response to cold, skin abnormalities, weakness and blood problems. There may be joint pain, inflammed blood vessels and kidney problems.
Of interest is the fact that the origins of this virus is obscure, and had eluded identification for many years. A blood test for HCV identification was developed in 1990 and refined in 1992.
The various blood tests available for HCV diagnosis are based on detection of antibody against HCV (EIA or enzymeimmunoassay and Recombinant immunoblot assays ( RIBAs ). Positive results means previous exposure to the hepatitis C virus. There are tests which detect the genetic material of the virus directly (polymerase chain reaction or PCR method) and this is a much more accurate blood test than antibody based test. EIA is inexpensive, reproducible and has been automated. It is a useful screening test. It's main failing is that is may not always be specific enough and false positive results can occur. This means positive results even the individuals do not have the infection. In a low risk population like in Singapore, a negative EIA test is sufficient to rule out infection. However if EIA is positive, RIBA is used to confirm the diagnosis of HCV infection.
Another test done routinely is liver function tests. If these liver enzymes (ALT, AST) are elevated, it would indicate that there is liver inflammation. If this process is allowed to go unchecked, it will result in cirrhosis and liver cancer in the long run. Active liver disease caused by HCV requires further treatment to reduce the viral load.
It is necessary to extract a small sample of the liver by a process known as a liver biopsy, for further examination in the laboratory. By studying the liver tissue one is able to assess the degree of inflammation and damage to liver. Liver biopsy is the gold standard for assessment of the activity of chronic hepatitis C. When combined with liver function tests, one can assess the severity or activity of the disease and institute treatment if necessary.
Who should be tested for HCV infection?
Individuals who :
- Have had blood or blood product transfusion .
- Are on hemodialysis
- Have had multiple sexual partners
- Are spouses or close household contacts of hepatitis C patients
- Are organ transplant receipients
- Share instruments for cocaine usage (eg. straws for snorting cocaine)
Similar to hepatitis B, hepatitis C can lead to chronic hepatitis (liver inflammation), cirrhosis ( "liver hardening "), liver failure and liver cancer.
Treatment is aimed at eradicating the virus and to prevent / delay it's complication.
Alpha-Interferon: The current recommended regime for treatment is alpha-interferon 3 million units 3 times per week for 12 months. Interferon is administered subcutaneously. It is believed to act by obstructing viral replication and also boosting the immune system to destroy the virus.
Flu like symptoms (fever, chills, malaise, headache, bone and muscle pain, rapid heart beat rate) are common in the initial part of treatment with interferon. Later side effects are fatigue, hair loss, suppression of white and red cell production, and psychiatric complications. Occasionally these patients may become irritable and depressed to the point of suicide.
Severe side-effects occur in less than 2% of patients treated with interferon. These include thyroid problems, fits, heart and kidney failure, eye and lung problems, hearing impairment and infection. Rare deaths from liver failure or infection have occurred in some, especially those with cirrhosis.
The milder side-effects of interferon may sometimes be ameliorated by administering interferon at night or taking paracetamol (Panadol). Occasionally a dose reduction or even discontinuation of treatment may be required in those with more severe side-effects.
Following the initiation of interferon alfa therapy, the patient is monitored clinically and by blood tests. Visits to the liver specialist should be weekly initially (first month), followed by 2 to 4 weekly. If patients do not respond after 3months of therapy with interferon alone, they should be considered for combination therapy of interferon and ribavarin. Ribavarin is an oral anti-viral agent which is believed to act through inhibition of some effector of tissue damage.
The main side-effect of this drug is the breakdown of red blood cells ( hemolysis ) resulting in anaemia ( low red blood cell count ).
The response to interferon alfa therapy is between 20 & 30 percent. The goal of therapy is reduction of liver inflammation and the eradication of hepatitis C virus.
What kind of surveilance will my doctor do to detect liver cancer?
Although there is a lack of data supporting cost effectiveness, unlike in hepatitis B patients, patients with HCV cirrhosis should have a liver ultrasonography and serum alfa-fetoprotein level every 6 months for screening of liver cancer. Non-cirrhotic HCV carriers generally require 6 monthly alfa-fetoprotein levels and yearly ultrasonography of the liver.
Who should receive treatment for HCV infection?
Patients with raised liver enzymes and liver biopsy indicating active inflammation. The role for intervention is strengthened if the patient's blood shows the presence of viral RNA ( HCV RNA ).
- Patients with acute hepatitis C
- Patients with HCV infection complicated by essential mixed cryoglobulinemia.
- Patients with concurrent stable HIV infection, as these patients may have an accelerated course.
Who should not be treated with interferon?
- HCV positive carriers should avoid donating blood, tissue, organs or semen.
- Safer sexual practices should be strongly encouraged in persons with multiple sexual partners eg. by using latex condoms.
- Avoid sharing razors and toothbrushes with members of the household who are HCV carriers.
- Intravenous drug users should not share needles/syringes.
- Pregnancy is not contraindicated in HCV carriers. However the child should be tested for antibodies against HCV at one year of age.