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Reactivation of Hepatitis B

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  • Patricia Jean
    (( 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
    Message 1 of 7 , Jan 27, 2002
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      (('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]
    • claudine intexas
      ... 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
      Message 2 of 7 , Jan 27, 2002
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        --- 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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      • Patricia Jean
        If interferon helps our immune system, why do I get more infections when taking interferon? alley http://clubs.yahoo.com/clubs/happyheppers
        Message 3 of 7 , Jan 27, 2002
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          If interferon helps our immune system, why do I get more infections when
          taking interferon?

          alley
          http://clubs.yahoo.com/clubs/happyheppers
        • claudine intexas
          ... I guess each person is different. The only infections I had more of while on treatment were yeast infections. And if your WBC drop really low that
          Message 4 of 7 , Jan 28, 2002
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            -- Patricia Jean <patriciajean@...> wrote:
            > If interferon helps our immune system, why do I get more infections
            > when taking interferon?

            I guess each person is different. The only infections I had more of
            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
            will help.

            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
            following year.

            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
            interferons.

            *******************************************************


            interferon
            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
            below.

            Nonspecific responses to infection
            Inflammatory response
            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. [20] 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. [22] 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. [22] 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.
            [22]

            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. [24] 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. [24] 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, [24] 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. [24]

            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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          • martine
            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
            Message 5 of 7 , Jan 29, 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.
              god bless!!!!!!!!!
              ----- Original Message -----
              From: Patricia Jean
              To: GIWorld-Hepatitis@yahoogroups.com
              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
              taking interferon?

              alley
              http://clubs.yahoo.com/clubs/happyheppers



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            • Patricia Jean
              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 :( alley
              Message 6 of 7 , Jan 29, 2002
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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 :(

                alley
              • Gail Samples
                ... Think of it as being similar to a country that has grown too large to protect its borders. The inteferon that we use for HCV does stimulate our immune
                Message 7 of 7 , Feb 1, 2002
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                  ----------
                  >From: "Patricia Jean" <patriciajean@...>


                  > If interferon helps our immune system, why do I get more infections when
                  > taking interferon?
                  >
                  Think of it as being similar to a country that has grown too large to
                  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.

                  gail
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