Dr. Widjaja Luman
Consultant Gastroenterologist and General Physician
B Sc (St. Andrews), MB ChB (Man), MRCP (UK), M.D. (Edin),
CCST (UK), FRCP (Edin)
(Ahli penyakit pencernaan dan hepar)
Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. Prevalence of hepatitis C is extremely high in some parts of the world such as 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 by the parenteral route i.e. by blood and blood products. Therefore, HCV infections may be acquired via the following means :-
- Intravenous drug abuse, tattooing, body-piercing, and accidental needle stick injury through contaminated needles
- 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 1-2% transmission rate by this method. This mode of transmission is much lower than in hepatitis B.
- 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 are the symptoms and course of disease?
The onset of infection is often unrecognized and the early course is generally indolent. 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 lethargy, anorexia and even less often some may develop jaundiced (yellowing of eyes and skin). Rapid progression to liver failure due to fulminant hepatitis is a rare occurrence in this early stage of infection.
The majority of patients (85%) fail to clear the virus within 6 months after acute infection and go on to develop chronic hepatitis C ( carriers). These patients are relatively well in the first 2 decades after acquiring the infection and are not aware they have chronic hepatitis C unless they undergo laboratory tests. About 20% of these carriers may feel mild fatigue and malaise.
Generally, symptoms only appear once advanced liver damage has occurred. This stage is called “deceompensated cirrhosis”. Cirrhosis is “ hardening of the liver ”. The hardening of liver is caused by scarring from long term inflammation of liver cells caused by persistent hepatitis C virus. Early stage of cirrhosis without symptoms is termed as “compensated cirrhosis”. More advanced cirrhosis with symptoms is termed as “decompensated cirrhosis”.
The signs and symptoms of “decompensated cirrhosis” are ascites ( swelling of the abdomen with fluid ), jaundice, deterioration of mental state ( hepatic encephalopathy ), vomiting blood or passing out altered blood in the stools from dilated veins in the oesophagus (oesophageal varices). Of course, there is the dreaded complication of liver cancer. Liver cancer developes after 30 years and occurs only in a background of liver cirrhosis.
Generally, cirrhosis appears in at least 20% of patients within 20 years of infection. Progression to cirrhosis can be accelerated by concomitant alcohol use, co-infection with chronic hepatitis B or HIV (human immunodeficiency virus) and co-existent non-alcoholic fatty liver disease (NAFLD) .
Hepatitis C can cause symptoms beyond the liver. Chronic hepatitis C causes disruption of the immune system, and the immunological effects can cause damage outside the liver. These damaging effects are not due to direct invasion of the hepatitis C virus (unlike its effect in the liver) and are thus called extra-hepatic manifestations.
These extra-hepatic manifestations are :-
- Joint swelling and pain ( arthritis )
- Eye inflammation ( keratoconjunctivitis )
- Skin and oral manifestations ( lichen planus which appears as a characteristic rash and oral inflammation ).
- Inflammation of kidneys ( glomerulonephritis ) with loss of protein in the urine.
- Essential mixed cryoglobulinemia
This last manifestation of essential mixed cryoglubulinaemia is in itself a rare condition. It affects the blood and various other body systems. Major symptoms include unusual response to cold, skin abnormalities, weakness and blood problems. There may be joint pain and inflammation of blood vessels (vasculitis) and kidney problems.
How is HCV infection diagnosed ?
The blood tests for detection of HCV diagnosis is based on detection of antibody against HCV (anti HCV IgG). Positive results mean previous exposure to the hepatitis C virus. This is a cheap and good screening test. However, positive results have to be followed by confirmatory test as there is a false positive rate of 30%. This means positive results in individuals who do not have the infection. This is due to technical issue of the immunological test. In a low risk population like in Singapore, a negative antibody test is sufficient to rule out infection.
In order to confirm current active infection, there are tests which detect the genetic material of the virus directly (polymerase chain reaction or PCR method for HCV RNA test) and this is a much more accurate blood test than antibody based test. This test is called HCV RNA (qualitative or quantitative) test.
If HCV RNA test is positive, HCV genotypes test will be carried out prior to starting therapy. There are several genotypes of hepatitis C and some may require more prolonged therapy. However, genotyping test will be obsolete soon as we now have highly effective pan genotypic medicine.
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.
Ultrasound scan of the liver shows presence of cirrhosis and tumour in liver. Ultrasound scan is similar to the scan performed for pregnant women. Your doctor may order Transient elastography or magnetic resonance elastography. These two tests are for determining stiffness of liver, or degree of fibrosis and scarring.
It may be necessary to extract a small sample of the liver by a process known as a liver biopsy to assess the degree of inflammation and damage to liver. However, liver biopsy is seldom carried out as we have highly effective treatment nowadays.
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 recipients
- Share instruments for cocaine usage (eg. straws for snorting cocaine)
Can hepatitis C infection be prevented?
There is no vaccine available to protect people from getting infected with hepatitis C. Hepatitis C is a blood borne pathogen. So people can prevent infection by reducing exposure through healthy life style practices such as barrier contraception during sexual intercourse if your partner is known to be a carrier. Secondly, avoid sharing household utensil which can be exposed to infected person’s blood such as toothbrush, razor blades, needle, nail cutter.
Can I get pregnant?
Pregnancy is not contraindicated in HCV carriers. The chance of vertical transmission to new born baby is low. However, the child should be tested for antibodies against HCV at 1 year of age.
How is chronic hepatitis C treated ?
Similar to hepatitis B, hepatitis C can lead to chronic hepatitis (liver inflammation), cirrhosis, liver failure and liver cancer. Previously, a combination of ribavirin and interferon was used to treat chronic hepatitis C. This treatment regime had success rate of only 30% in eradicating the virus with adverse side effects (lethargy, fever, nausea, hair loss, blood disorders). Only certain individuals were indicated for therapy at that time. Since the introduction of Direct acting antiviral drugs (DAAs) in 2013, all infected individuals are considered for therapy. DAA’s attack the viral components directly thereby preventing viral replication. These drugs have much better success rates (above 95%) and are much better tolerated than interferon based therapy. Some of the newer drugs are:
- ledipasvir-sofosbuvir (Harvoni)
- glecaprevir-pibrentasvir (Mavyret)
- sofosbuvir – velpatasvir (Epclusa)
- sofosbuvir – velpatasvir – voxilaprevir (Vosevi)
The tablets are taken for 8 to 12 weeks. Occasionally your physician may add ribavirin in addition to DAA’s. The length of treatment depends on the stage of liver disease and the types of hepatitis C. Your physician will discuss with you as to the choice of medication and duration of therapy. Undetectable HCV RNA 12 weeks after the end of therapy confirms successful eradication.
For patients who have developed complications of cirrhosis such as ascites (water retention in abdomen) or variceal bleeding, successful eradication may improve liver function. However, the liver failure may be too advanced for some patients and liver transplant may be the only option. In these cases, DAA’s will be prescribed after liver transplant.
For patients who have reached the stage of cirrhosis, they will still need regular surveillance for liver cancer even with successful eradication of hepatitis C virus. This is because they still have a low risk of development of liver cancer, albeit at lower risk than before therapy. They should have six monthly blood tests with alpha-foeto protein and ultrasound scan. They should avoid excessive drinking of alcohol and getting overweight with NAFLD.
How can HCV transmission be prevented?
- HCV positive carriers should avoid donating blood, tissue, organs or semen.
- Safer sexual practices should be strongly encouraged in persons with multiple sexual partners e.g. by using latex condoms.
- Avoid sharing razors and tooth brushes 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 1 year of age.