HEPATITIS
C
Hepatitis
C is the most important cause of chronic liver disease in the
world. Latest estimates from the CDC indicate that nearly 4
million people in the USA are infected. There are 8-10,000 deaths
yearly from this disease, and it is suggested that the number
of patients who will develop cirrhosis and complications, as
well as liver cancer, will escalate in the next decade to astronomical
proportions. Initially, this RNA viral infection was thought
to occur only following blood product transfusion. We now know
since 1993 and the development of widespread blood bank screening
policies, that the majority of infections today are the result
of intravenous drug use. The majority of patients seen today
are 30-50 years of age, who are noted by their primary care
physician to have abnormal liver function tests. This often
leads to referral to a gastroenterologist or hepatologist for
more detailed work-up. Close to 75% of patients who are exposed
to the Hepatitis C virus will develop chronic hepatitis, and
the natural history reveals that close to 25% of these chronics
will develop cirrhosis, usually over the span of 15-20 years.
Hepatitis C and resulting cirrhosis are the most common cause
or indication for liver transplant in the USA today.
EPIDEMIOLOGY
Of
the five well-defined viruses (A, B, C, D, E) that can cause
liver disease, Hepatitis B and C are the most ominous. Both
can cause chronic hepatitis (abnormal liver tests for more than
6 months). Hepatitis B is clearly falling in prevalence in the
last 10 years as a result of blood bank screening and vaccination.
Hepatitis C is transmitted via blood to blood contact. Intravenous
drug use, nasal cocaine, body piercing, tattoos, acupuncture,
ear piercing, or sharing razors or toothbrushes of infected
victims are means of transmission. If you have tried drugs,
even once, you are at risk. Sexual contact, especially with
those that may be promiscuous, is another less common route
of infection. If you believe you may have had contact, or may
be at risk, seek screening blood work with your primary care
physician.
CLINICAL
PRESENTATION
For
many patients, chronic viral hepatitis is clinically silent,
especially early before established chronic hepatitis or cirrhosis
develops. Fatigue that worsens during the day is common. Others
may experience right upper abdominal pain, nausea, skin rash,
joint pain, loss of appetite, malaise, low grade fever, mood
alterations, weight fluctuations, or jaundice (yellowing of
the skin and eyes). Some experience itching, sleep habit changes,
and marked irritability.
DIAGNOSIS
The
physical exam done by your physician is usually unremarkable.
Chronic hepatitis is diagnosed via laboratory tests that sort
out all the causes of chronic hepatitis, and then can confirm
Hepatitis C and begin the staging process. Liver enzymes may
or may not be elevated in this disease, and the degree of elevation
does not always coincide with the degree of liver involvement.
Antibody to Hepatitis C will not appear in the blood until nearly
8 weeks after infection. We now have third generation lab tests
that confirm infection and utilize polymerase chain reaction
(PCR) to quantify the amount of virus present in the blood.
There are a number of conditions that can lead to a "false-positive"
Hepatitis C antibody test, so it is important that your physician
do the proper confirmatory tests. Hepatitis C RNA can be detected
in the blood as early as 2 weeks after exposure, and the PCR
can detect as few as 10 copies per milliliter of blood. Once
the diagnosis is established, it may be necessary to have an
ultrasound of the liver to view its internal character and size.
A liver biopsy is often next, and this should be a rather simple
out-patient procedure done by the hepatologist or radiologist.
The biopsy is taken utilizing a local anesthetic, and some IV
sedation. The biopsy helps us determine whether cirrhosis is
present, and allows the physician to properly stage your disease
prior to therapy.
TREATMENT
The
goal of treatment is viral eradication. Patients between the
age of 18-65 should be considered candidates for therapy with
"combination" regimens of alpha-Interferon and Ribavirin, a
nucleoside analogue. Interferon is an anti-viral that needs
to be injected three times a week, and Ribavirin is a pill that
is taken daily. Therapy ranges from 6-12 months depending on
the so-called genotype of the virus. The drugs are fraught with
many potential side-effects, including fever, nausea, malaise,
joint pain, fatigue. mood swings, and periods of manic or depression.
The flu-like symptoms usually lessen or disappear after 3-4
weeks of therapy. Most patients can still work and carry on
their lives, while some need to be disabled to complete the
regimen. Ribavirin can cause a serious anemia (low red cell
count), and female patients cannot consider pregnancy during
treatment. The cost of this therapy is $10-15,000 a year, yet
covered by most insurance carriers. The response rate for a
year of therapy in patients with genotype 1 is in the range
of 35-40%. For those with non-genotype 1, the rates elevate
to 60-80%.
THERAPIES
ON THE HORIZON
All
of us look forward to the release of pegylated Interferon, which
is due by January, 2001. This form of Interferon is structured
so as to be injected just once a week, avoiding some of the
peaks and valleys with Rebetron that we now use. The response
rates also look more encouraging, approaching 55% in genotype
1 (nearly 75% of Americans are type 1). A variety of other agents
are being worked on, including Thymosin, Amantadine, protease,
and helicase inhibitors, ribozymes, other interferons, and the
interleukins to name a few. We forecast that in the next 2-3
years, there will be a group of three to four agents to attack
this virus, similar to our success with HIV. Please stay tuned
to this web page for more information.
