- by Dr. Andreas Lambrianides
- General Surgeon
- Hepatitis C virus (HCV) can and does cause acute hepatitis, but due to the mild nature
or subclinical cause of this illness, most cases go unrecognized. Acute hepatitis C is
symptomatic in only 25 - 35 percent of cases, with an incubation period of 6 - 10 weeks
with a range of 3 - 20 weeks, and it is shortest after a large inoculum.
The clinical features include malaise, nausea; right upper quadrant pain, pale stools,
dark urine and jaundice. These symptoms are usually mild but may be variable. Fulminant
Hepatitis is rare with HCV but when it occurs is usually in immunosuppressed patients.
Hepatocellular injury is invariable. Over 80% of acute HCV infected patients have a
greater than 10- fold elevation of alanine aminotransferase (ALT) levels. The rise in ALT
begins after four weeks and peaks at eight weeks. The rise usually precedes the onset of
The most commonly used test for diagnosis of acute Hepatitis C is anti HCV antibodies
which can be detected in 50 - 70% of patients at the onset of symptoms and in
approximately 90% of patients 3 months after the onset of infection. With the current
third generation anti HCV tests, antibodies do not become detectable before 7 - 8 weeks
The ideal test for early detection of infection with HCV is the HCV RNA polymerase chain
reaction, which becomes detectable within one to two weeks after exposure. Acute self
limiting Hepatitis C occurs in less than twenty percent of cases. The persistence of HCV
RNA indicates the development of chronic hepatitis C. The single feature that
distinguishes Hepatitis C from other hepatic viral infections is the tendency to become
chronic, the term relating specifically to the duration of infection and not to the
severity of the disease.
Globally the prevalence of chronic hepatitis C infection is estimated to be at 3 percent,
with four million carriers in the USA and 5 million in Western Europe. In the USA, 0.5
percent of blood donors are anti HCV positive but 1.8 percent of the population is
positive on random testing. A higher incident has been found in Africa. Up to 15 percent
of the population in Egypt are anti HCV positive. With the availability of HCV screening
serological tests after 1989, acute infection was found to be the cause of more than 80
percent of cases of post transfusion Hepatitis. After screening for HCV, the incidence of
acute hepatitis which had reached a peak in the 1980s of 180 000 cases per year, fell to
less than 30 000 by 1995. With current screening techniques the risk has now fallen to one
in a hundred thousand units transfused or 0.001 %. A small risk of acquiring HCV from
blood products remains because HCV antibodies take time to become positive after an
individual is exposed to the virus. The use of more sensitive testing would reduce the
risk even further. Currently the majority of hepatitis C infection occurs in patients with
parenteral exposure from drug use and needle sharing and constitutes the major cause of
transmission in the USA.
Risk factors associated with acute Hepatitis C include, injections associated with drug
use 43%, sexual contact 15%, cocaine snorting 5% and occupation 4%. Cocaine snorting
results in nasal ulceration and bleeding which serves as a source of HCV transmission.
Sexual activity is a less frequent cause, (15 %) with hepatitis C as compared to 50% with
Approx 25% of cases of Acute hepatitis C are jaundiced and the mortality rate is less than
1 %. The rate of subclinical infections is high and the onset of hepatitis C is more
insidious as compared to hepatitis B. Approx 15 - 20 % of patients following infection
with HCV will clear the virus. 80 - 85 % will develop chronic hepatitis C. Of all patients
with Hepatitis C, 20 % will not develop significant liver damage and 60 - 65 % will
develop liver disease after an average of 13 years. Of all the patients that develop liver
disease, 20 - 25 % will develop cirrhosis after an average of twenty years. The most
susceptible patients are those that are acquired HCV over the age of 40, male patients,
those patients that consume large amounts of alcohol, failure to respond to interferon
treatment, and those infected with a 1b genotype virus. Of all the cirrhotic patients,
after an average of 15 - 25 years, 5 - 10 % will develop liver failure and 1 - 4 % will
develop hepatocellular carcinoma (HCC).
The more significant clinical features of cirrhosis, include ascites, low levels of serum
albumim, muscle wasting, hepatic encephalopathy, upper gastrointestinal bleeding from
oesophageal or gastric varices, and hypersplenism. In patients with HCV cirrhosis, the
annual risk of developing HCC is 1 - 6 %. In some retrospective studies an incidence of
1.4 % was found, while in some prospective studies the annual incidence was found to be
2.5 percent. HCC occurs more frequently in patients over 60 years of age and with Child's
Chronic Hepatitis C is one of the major causes of cirrhosis in the USA and the most common
indication for liver transplantation in adults. Chronic hepatitis C is also the major
cause of HCC worldwide.
The aetiological agent for Hepatitis C was identified in 1989 using advanced molecular
biology techniques. Molecular cloning, sequencing and analysis of the hepatitis C genome
have enabled classification of the virus. Electron microscopic studies of virions purified
from the serum of the HCV infected individuals have confirmed HCV to be an enveloped virus
less than 80 nm in diameter, with a lipid envelope and strongly associated with the
lipoprotein fraction of the serum. Each HCV particle contains a single RNA molecule of
approximately 9500 nucleotides that contain a single gene. This encodes a polyprotein of
3008 - 3037 amino acids. The core and envelope proteins are structural proteins that form
the viral particle, while the remainder, the non-structural proteins are required for
virus replication. The structural proteins are derived from the
5 'end of the genome. The virus circulates in the blood as a population composed of a
master sequence and a large number of minor variants. This occurs because of random
mutations during viral replication and also the selection pressure exerted by the host's
immune response. This mixed population of viral particle is referred to as quasispecies
and is the basis of the variation found in the HCV genome. The virus is sub classified
into 6 distinct genotypes.
The management of viral hepatitis involves general measures to reduce physical and
psychosocial morbidity, anti viral therapy and interventions for complications.
Hepatitis A and B vaccinations should be offered to all patients with hepatitis C who do
not have protective antibodies, to minimize the risk of decompensation of liver disease
associated with a second hepatitis infection. No effective vaccine has yet been developed
to protect contacts of those infected with hepatitis C. Immune serum globulin does not
confer protection. There is much interest in dietary therapy, homeopathy, vitamins and
other alternative therapies, and most patients are taking herbal remedies. There is no
evidence that such measures affect the natural history of hepatitis and the patients are
vulnerable to exploitation. In addition while most herbal remedies are safe, Chinese
herbal medicines have occasionally being associated with severe hepatotoxicity.
Antiviral therapy is the only effective means at our disposal in the fight against
hepatitis C. The short-term aim is to stop viral replication and to reduce liver cell
inflammation and necrosis, so that progressive fibrosis does not occur. The long-term
objective is to prolong survival by decreasing cirrhosis, liver failure and HCC.
Interferons are naturally occurring antiviral proteins that inhibit growth and replication
by stimulating the host's immune response. The original report for the use of alpha
interferon was in 1986.
The response to interferon at 12 weeks is an important point. Patients who fail to respond
at that time are unlikely to respond to further treatment. The most promising new
treatment is the combination of two antiviral drugs - Interferon and Ribavirin. Ribavirin
is a Guanosine analogue, but is not effective if given alone. Results show a significant
advantage for combination therapy as compared to interferon alone. In addition the effect
of genotype is demonstrated: 65% of patients with genotype, 2 or 3 need only 6 months of
combination therapy to attain viral clearance while 1 or 4 require a full 12 months
treatment to achieve a 30 % SR rate.
Complications of interferon include systemic problems, neurological, psychological,
cardiac, induction of autoimmunity, myelosuppression and susceptibility to infection.
Ribavirin complications include hematological problems, respiratory, dermatological and
Although interferon has been shown to be effective in the treatment of chronic hepatitis
C, recent trials indicate effectiveness for Acute Hepatitis C. At the end of 24 weeks
therapy with interferon and a further 24 weeks follow up, 98 % had undetectable levels of
Hepatitis C virus RNA in the serum and normal ALT levels. Early treatment of acute
hepatitis C with interferon Alpha - 2b alone prevented the development of chronic HCV in
almost all patients. This particular finding is important in health care workers with
infection concerns due to needle stick or surgical injuries.
Available therapies for HCC include surgical resection, which is only suitable for small
tumors and has carries a recurrent rate of 50 - 80% at 5 years.
Systemic chemotherapy has no proven benefit and liver transplantation is only suitable for
small tumors in patients with portal hypertension and/or liver failure.
Embolisation may decrease the size of large tumors but does not increase survivor.
Discovering that a patient has hepatitis C is a shocking and traumatic experience for most
patients. Many feel isolated just when strong support from family and friends is needed.
When treatment is not successful, patients with hepatitis C often see themselves as having
failed treatment when in fact treatment has failed them.