Reactivation of Hepatitis B
- (('m wondering if I should worry about this? )
Reactivation of Hepatitis B
Hepatitis B is a chronic viral infection that may lead to cirrhosis and hepatocellular cancer. During the course of HBV infection, the virus goes through cyclical phases of replication, and nonreplication. Approximately 50% of patients will experience acute reactivations during the natural history of their disease. These reactivations may present as an acute event, may be asymptomatic, and are often spontaneous; these also may occur after cancer chemotherapy or the use of corticosteroid therapy.
HBV reactivation may present as acute hepatitis with symptoms of malaise and fatigue; the average ALT elevation is 300 IU/L but may reach into the thousands. Serum bilirubin may range from mild to marked elevations. Male patients with baseline ALT levels greater than 200 IU/L are three times more likely to develop a reactivation than patients with lower ALT levels. The HBcAb-IgM (the marker for acute hepatitis B) is present in about 60% of patients. Although hepatitis B viral DNA is expected to be present in high concentrations, it may be absent in 50% of patients at the time of peak ALT levels. Reactivation of chronic HBV infection may last weeks to months. A patient's underlying liver disease usually worsens during reactivation, and if cirrhosis is present, decompensation may occur with ascites, variceal bleeding, and liver failure in about 10% with mortality rates of 5%-10%.
Patients with a history of hepatitis B who receive cancer chemotherapy are at risk for HBV reactivation. The virologic and clinical events in these patients offer some insight about the pathogenesis of the disease. The current view is that immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell function in the liver. When the cycle of chemotherapy is completed, the reconstituted immune system recognizes enhanced HBV antigen expression on the hepatocyte membrane leading to cell necrosis, which can sometimes be massive. About 50% of HBsAg positive patients, and as many as 6% of HBsAg negative but core positive (HBcAb) patients undergoing chemotherapy, may have experienced such a reactivation.
Corticosteroid therapy should be avoided in patients with chronic hepatitis B except as a life-saving treatment. HBV reactivation following cancer chemotherapy is managed by continuing corticosteroid therapy between courses and by very slow tapering of the dose, while monitoring ALT and HBV DNA levels during steroid withdrawal, which may last several months.
The treatment of spontaneous reactivation is not well defined. Interferon is not considered a useful treatment and is not recommended in patients who deteriorate during a reactivation. Lamivudine (3TC, Epivir) is an attractive choice because of its potent suppression of HBV replication. Since viral replication resumes within three months of discontinuing lamivudine in most patients, one is committed to long-term treatment once drug therapy starts. The role of other drugs such as Famciclovir (Famvir) needs to be defined.
-- -- Maurizio Bonacini, M.D.
[Non-text portions of this message have been removed]
- --- Patricia Jean <patriciajean@...> wrote:
> (('m wondering if I should worry about this? )I think in your case you have less to worry about. First, you already
know that you didn't have any liver damage at all. Second, even
though you have cancer, you are not on the type of cancer fighting
drugs they are talking about, true chemotherapy drugs. Interferon is
an immune system modulator, and it enhances your immune system, not
supresses it. Interferon is a biological medicine, not a chemical
medicine. I think Interferon is sometimes used to treat HBV. However,
it did mention immune supression drugs like corticosteroids, so those
you should maybe avoid. They are not good for the hepatitis C either.
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- If interferon helps our immune system, why do I get more infections when
- -- Patricia Jean <patriciajean@...> wrote:
> If interferon helps our immune system, why do I get more infectionsI guess each person is different. The only infections I had more of
> when taking interferon?
while on treatment were yeast infections. And if your WBC drop really
low that increases your suseptibility to infections. So, I can't
explain it - but I can post info on how interferon works! Maybe that
Interferon, any of a group of antiviral proteins
produced by animals, including humans, in response to
infection by viruses. First recognized in chick embryo
cells by British virologist Alick Isaacs and his Swiss
colleague Jean Lindenmann in 1957, interferons were
found to block further viral infection of body cells.
The active antiviral substance is not the interferons
themselves, but proteins that interferons cause other
cells to produce. Some of these proteins have been
identified, but their manner of operation is not yet
well understood. It is clear, however, that
interferons play a role in the body's most important
defenses against viruses, and that they help fight
bacteria and other disease-causing agents.
Interferons may be grouped into three categories.
Alpha (leukocyte) interferons are made by white blood
cells, beta (fibroblast) interferons by skin cells,
and gamma (immune) interferons by lymphocytes after
stimulation by antigens.
During the 1960s physicians attempted to use
interferons to treat virus-caused human diseases,
especially colds, but the therapy was determined
impractical due to the enormous cost of obtaining
minute quantities of interferons from human white
blood cells. Researchers then tried to stimulate the
body to make its own interferons with inducers such as
synthetic nucleic acids. These chemicals worked, but
the body quickly became tolerant of them, and they
lost their effect. In 1980, however, interferons were
made available in sufficient quantities through
genetic engineering techniques, and trials testing
dosage levels and side effects were begun the
Thus far only some alpha interferons have been tested,
but they have shown promise against a host of viral
diseases. The use of interferons against such cancers
as malignant melanoma and renal cell cancer has
produced mixed results. The side effects accompanying
interferons can range from mild to life-threatening.
Beta and gamma interferons have not yet been tested in
quantity, but may prove more useful than alpha
any of several related proteins that are produced by
the body's cells as a defensive response to viruses.
They are important modulators of the immune response.
Interferon was named for its ability to interfere with
viral proliferation. The various forms of interferon
are the body's most rapidly produced and important
defense against viruses. Interferons can also combat
bacterial and parasitic infections, inhibit cell
division, and promote or impede the differentiation of
cells. They are produced by all vertebrate animals and
possibly by some invertebrates as well.
Interferons are categorized as cytokines, small
proteins that are involved in intercellular signaling.
Interferon is secreted by cells in response to
stimulation by a virus or other foreign substance, but
it does not directly inhibit the virus's
multiplication. Rather, it stimulates the infected
cells and those nearby to produce proteins that
prevent the virus from replicating within them.
Further production of the virus is thereby inhibited
and the infection is stemmed. Interferons also have
immunoregulatory functions�they inhibit B-lymphocyte
(B-cell) activation, enhance T-lymphocyte (T-cell)
activity, and increase the cellular-destruction
capability of natural killer cells.
Three forms of interferon�alpha (a), beta (b), and
gamma (g)�have been recognized. These interferons have
been classified into two types: type I includes the
alpha and beta forms, and type II consists of the
gamma form. This division is based on the type of cell
that produces the interferon and the functional
characteristics of the protein. Type I interferons can
be produced by almost any cell upon stimulation by a
virus; their primary function is to induce viral
resistance in cells. Type II interferon is secreted
only by natural killer cells and T lymphocytes; its
main purpose is to signal the immune system to respond
to infectious agents or cancerous growth.
Another group of proteins that provide protection are
the interferons, which inhibit the replication of
many�but not all�viruses. Cells that have been
infected with a virus produce interferon, which sends
a signal to other cells of the body to resist viral
growth. When first discovered in 1957, interferon was
thought to be a single substance, but since then
several types have been discovered, each produced by a
different type of cell. Alpha interferon is produced
by white blood cells other than lymphocytes, beta
interferon by fibroblasts, and gamma interferon by
lymphocytes. All interferons inhibit viral replication
by interfering with the transcription of viral nucleic
acid. Interferons exert additional inhibitory effects
by regulating the extent to which lymphocytes and
other cells express certain important molecules on
their surface membranes and by stimulating the
activity of natural killer cells, which are described
Nonspecific responses to infection
Infection often results in tissue damage, which may
trigger an inflammatory response. The signs of
inflammation include pain, swelling, redness, and
fever, which are induced by chemicals released by
macrophages. These substances promote blood flow to
the area, increase the permeability of capillaries,
and induce coagulation. The increased blood flow is
responsible for redness, and the leakiness of the
capillaries allows cells and fluids to enter tissues,
causing pain and swelling. These effects bring more
phagocytic cells to the area to help eliminate the
pathogens. The first cells to arrive, usually within
an hour, are neutrophils and eosinophils, followed a
few hours later by macrophages. Macrophages not only
engulf pathogens but also help the healing process by
disposing of cellular debris which accumulates from
destroyed tissue cells and neutrophils that
self-destruct after ingesting microorganisms. If
infection persists, components of specific
immunity�antibodies and T cells�arrive at the site to
fight the infection.
NATAP - www.natap.org
How Does Interferon Work in Your Body
Overview of Pharmacodynamic Properties
Excerpted from full report from Adis Intl., written by Caroline Perry
and Blair Javis; www.adis.com; report supported by grant from Roche,
manufacturer of Pegasys
The interferons are a family of naturally occur-ring proteins with
nonspecific regulatory activity. These cytokines are secreted by many
mammalian cells and influence cell growth and differentiation,
modulate the immune response and inhibit the replication of a number
of viruses including hepatitis B and C. Although the antiviral,
immunomodulatory and anti-inflammatory properties of interferon-a are
thought to contribute towards its beneficial effects in patients with
chronic hepatitis C, the exact mechanism of action of this cytokine
in hepatitis C has yet to be established.  The mechanisms of
action of interferon-a have been reviewed in detail elsewhere;
[21-23] this section therefore provides a brief overview of its
putative antiviral activity in patients with chronic hepatitis C.
Unlike many anti-HIV drugs, which target the functions of HIV
proteins, the antiviral activity of interferon-a is achieved by its
ability to alter interactions between the host and virus in a complex
manner.  After administration, interferon-a binds to high
affinity receptors on the target cell surface which activates a
cascade of reactions in the cell and triggers the activation of many
genes. The numerous cellular activities of interferon-a are mediated
by the products of these interferon-o -induciblegenes. [21,22] The
antiviral activity of interferon-a is achieved via two different but
complementary mechanisms. Firstly, interferon-a induces a nonspecific
antiviral state in the virus-infected cell [e.g. by stimulating the
2,5-oligoadenylate synthetase (OAS) system and Mx proteins] which
leads to the inhibition of HCV replication. Secondly, the drug
induces immunomodulatory effects that intensify specific host immune
responses against the virus.  The immunomodulatory effects of
interferon-a are triggered by its binding to the surface receptors of
immune cells. Activation of macrophages, natural killer cells and
cytotoxic T lymphocytes, and stimulation of the production of type 1
T-helper cells are among the many imunomodulatory effects produced by
the drug. Interferon-a also has anti-inflammatory properties, which
are achieved via inhibition of the production of tumour necrosis
factor-a , interleukin (IL)-1 and IL-8 and stimulation of the
production of IL-10, a cytokine that produces a down-regulation of
the pro-inflammatory response and modulation of hepatic fibrogenesis.
Data on the pharmacodynamic properties of peginterferon-a -2a (40kD)
(Pegasys) in humans are limited at present. However, preliminary
results of one in-vestigation showed that the pharmacological
activity of interferon-a -2a is augmented by pegylation.  The
activity of OAS, a key effector protein synthesised in response to
interferon-a stimulation and involved in interferon-mediated
inhibition of viral function, [21,22] increased with dose in
volunteers (number not reported) after single 45, 135 or 270 ug
subcutaneous doses of peginterferon-a -2a (40kD), or single 3 or 18MU
subcutaneous doses of interferon-a -2a.  Notably, maximum serum
OAS activity occurred approximately 48 hours after administration of
the dose and remained at about this level for up to 168 hours (1
week) before declining in the peginterferon-a -2a (40kD) [135ug]
treatment groups,  reaching baseline after the second week
following administration. Interferon-a -2a 3MU produced less OAS
activity than the 18MU dose and, as with the higher dose, OAS
activity declined 24 hours after administration. 
Editorial note: in the end the performance of Pegasys in humans is
what counts. In other words its ability to reduce viral load to
undetectable levels and sustain this is what counts. Pegasys is in
the FDA review process for approval. It is not yet available in the
pharmacy, only in studies. FDA approval and commercial availability
is expected in Summer 2002.
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- on you getting infections, when on interferon ,it lowers youe white blood cells,and makes you more prone to getting sick,it lowers your immune sustem.thats what my doc told me, and also your plateletes will get lower mone are 40.000 and dropping, they have had to cut my dose in half already and just been on meds for 12 wks.
----- Original Message -----
From: Patricia Jean
Sent: Sunday, January 27, 2002 10:30 PM
Subject: Re: [GIWorld-Hepatitis] Reactivation of Hepatitis B
If interferon helps our immune system, why do I get more infections when
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- thanks martine! Luckily while on combo, my blood counts never got out of
normal ranges. whew! Can't say that on the cancer interferon tho :(
>From: "Patricia Jean" <patriciajean@...>Think of it as being similar to a country that has grown too large to
> If interferon helps our immune system, why do I get more infections when
> taking interferon?
protect its borders. The inteferon that we use for HCV does stimulate our
immune system-against viral invaders. So while the body is busy with the
viral invaders, other invaders, bacterial, fungal, parasitic, etc. have a
better chance of getting by the immune system. Like a country under attack
by sea, then by air, then from a land border, then another land border, etc.
The country still has to defend itself on all sides. We are much like this
scenario-constantly being bombarded by microbial invaders, with our skin and
mucous systems providing a very decent first ine of defense. But if
something does make it past those first lines, and the body is not already
busy fighting some other infection, it can quickly attend to the invader.
If it is already busy elsewhere, then the response can be slower or weaker,
causing an illness or infeciton. This is why some infections are called
'opportunistic' infections. They are already there, but kept under control
by the immune system. When the system gets weakened (or too busy elsewhere)
by a fight with some other microbial invader, the other laid back infection,
like herpes cold sores (the little bastards), comes alive.