WHAT ARE THE TREATMENTS FOR CONDITIONS THAT CAUSE CIRRHOSIS?
Treating Alcoholism
The only treatment for alcoholic cirrhosis is to stop drinking. Individuals with
alcoholic cirrhosis are typically malnourished and require increased calories
and rigorous nutritional support, which can improve survival rates. [For more
information, see Well-Connected Report #56 Alcoholism.]
Treatments for Chronic Hepatitis C
Interferons Alone and in Combination with Ribavirin for Hepatitis C. Pegylated
(PEG) interferon combined with ribavirin (a nucleoside analogue), is now the
gold standard for treating for chronic hepatitis C. Interferons are natural
proteins that activate certain immune functions in the body and have antiviral
properties. Ribavirin is poor at inducing initial responses alone but it can
double sustained response rates when combined with an interferon. A number of
natural and synthetic interferons are available:

Natural interferons were the first used for HCV and include interferon
alpha-2a (Intron) and Interferon alpha-2b (Roferon). Rebetron is the combination
of interferon alpha-2b and ribavirin.
Pegylated interferons (PegINF) are long-acting formulations of interferon.
They include alfa-2b (Peg-Intron) or alfa 2a (Pegasys). Both are now available
in combination with ribavirin. (Rebetol is the alfa-2b combination.)
Alfacon-1 (Infergen), also called consensus interferon, is a genetically
modified interferon. A combination of alfacon-1 with ribavirin is proving to
help some patients who had been resistant to ribavirin with interferon.

The combination of pegylated interferon alfa-2b with ribavirin (Rebetol) has
achieved the best success rates to date of all interferons and their
combinations. It has achieved responses of up to 51% with genotype 1 and nearly
80% with genotype 2 and 3. According to a 2002 comparison study, the Pegasys
combination may even produce better results.

PegINF combinations are proving to slow progression of scarring, and has even
achieved improvement in some patients who already have cirrhosis. Whether the
combination treatment protects against future liver cancer is still unclear. (A
higher total dose, rather than a longer duration of treatment, may be the
critical factor for protection.)

[For more information on treatments and other aspects of Hepatitis C, see
Well-Connected Report # 59 Hepatitis.]
Investigative Drugs for Hepatitis C
The current drugs used for HCV still do not meet the needs of all patients. They
are expensive, have significant side effects, do not work in half the patients
who take them, and are unsuitable in many others. Investigation then is ongoing
to find better solutions. Some showing promise include the following:

IMPDH Inhibitors. Mycophenylate mofetil and VX-497 are agents that inhibit an
enzyme known by its brief name, IMPDH, which may block replication of the
hepatitis C virus. If effective, they would most likely be used in combination
with interferon and ribavirin.
Amantadine. Amantadine (Symmetrel) is an antiviral agent being investigated
in various combinations. Early studies using amantadine with interferon
indicated better success rates than interferon alone. Of greater interest are
studies using triple therapy with amantadine, pegylated interferon, and
ribavirin. In some cases, the side effects of amantadine can be severe, and
include vertigo, insomnia, nervousness, and depression. They are particularly
disabling among older patients who receive inappropriately high doses.
Thymosin Alpha 1. Thymosin alpha 1 (Zadaxin), also called thymalfasin, is a
synthetic version of a peptide derived from the thymus gland (which is
responsible for maturation of immune factors call T-cells). It is being used for
hepatitis B and is under investigation for hepatitis C in combinations with
natural interferons and pegylated interferon.
Protease Inhibitors. Protease inhibitors (similar to those used for HIV) are
under investigation for hepatitis C patients who fail other treatments. These
agents are based on molecular therapies that target proteins involved in viral
reproduction.

Other agents under investigation include vaccines, genetic therapies known as
antisense oligonucleotides or monoclonal antibodies, and drugs that will help
prevent or reduce progression of liver scarring or progression to liver cancer.
Even if successful, none of these agents would be available for some years.

Of interest are studies using phlebotomy (which is simply drawing blood) to
reduce iron levels. In one study, maintenance therapy with this procedure
reduced liver inflammation and possible slowed progression of cirrhosis.
Treatments for Chronic Hepatitis B
Interferon alpha and nucleoside analogues are the important treatments at this
time for hepatitis B. At this time interferon alpha-2b is the standard agent but
experts expect the nucleoside analogue lamivudine to replace it as the primary
agent. Lamivudine is not only effective, it also less expensive than the
interferon. Most likely, the best approach in the future will be combinations of
these and other agents to achieve the greatest possible viral reduction and to
minimize the chances of drug resistance. [For more information on treatments and
other aspects of Hepatitis B, see Well-Connected Report # 59 Hepatitis.]

Interferon Alpha for Hepatitis B. Interferon alpha-2b (Intron) is the standard
drug for hepatitis B. It has eliminated the virus and sustained significant
remission in 25% to 40% of patients with chronic hepatitis B. The drug is
usually taken by injection every day for 16 weeks. (It does not appear to be
effective for hepatitis D.) Unfortunately, even in hepatitis B, the virus recurs
in almost all cases, although this recurring mutation may be weaker than the
original strain.

Administering the drug for longer periods may produce sustained remission in
more patients while still being safe. Interferon is also effective in eligible
children, although long-term effects are unclear. A 2001 study suggested that it
may temporarily disrupt growth, but it should be noted that hepatitis itself,
even without interferon treatment, can compromise growth. [For a detailed
description of Interferon and eligibility, seeBox Interferons.]

Lamivudine and Other Nucleoside Analogues. Nucleoside analogues are drugs that
can block viral replication, and they are important in hepatitis B. The primary
agent used in hepatitis is lamivudine (Zeffix). It can be taken orally, has few
severe side effects, and is less expensive than interferon. Experts expect it to
become the first-line treatment for hepatitis B. Famciclovir is an alternative.
Newer nucleoside analogues, adefovir (Hepsera) and entecavir may prove to be
even more effective than the older agents.

Lamivudine has reduced viral count in over half of hepatitis B patients who have
taken it as sole therapy for about a year. It also appears to significantly
reduce the risk for liver damage and cirrhosis, and appears to be effective and
safe in patients with decompensated cirrhosis. The drug even suppresses
hepatitis B viral replication in HIV-positive patients and liver transplant
recipients. It appears to be effective for children as well as adults. It is not
yet clear if it protects against liver cancer, particularly in patients who have
harbored the virus since childhood.

A major problem with lamivudine is the development of mutated viral strains that
become resistant to the drug, particularly in areas where the virus is common.
The specific genetic hepatitis B strain may be an important marker for
predicting resistance. Other nucleosides, such as adefovir and entecavir, may be
pose less of a risk for resistance. Combinations with interferons may also be
able to help control viral breakthroughs from mutated viruses and help sustain
its effectiveness.

Lamivudine causes muscle aches and chills but does not appear to have some of
the distressing side effects of interferon, such as depression, hair loss,
weight loss, or a drop in white blood cells (leukopenia). Of some concern,
however, is eventual resistance to the drug in many patients.

Immunotherapy. A number of drugs are being studied that boost the body's own
immune system to fight the virus.

Thymosin Alpha 1. Thymosin alpha 1 (Zadaxin), also called thymalfasin, is a
synthetic version of a peptide derived from the thymus gland (which is
responsible for maturation of immune factors call T-cells). It is injected and
has few side effects. It appears to be safe for hepatitis B patients when used
alone or in combination. Combinations with interferon and nucleoside analogues
are showing promise.
Vaccines as Treatments. Some hepatitis B vaccines, including Hepagene, are
being investigated for treating as well as preventing hepatitis B.
Treatments for Primary Biliary Cirrhosis
Ursodeoxycholic Acid (UDCA) and Drugs Used to Slow Progression. At this time no
medication can cure primary biliary cirrhosis. Ursodiol, ursodeoxycholic acid
(Actigall), or UDCA has been the standard drug used for primary biliary
cirrhosis. A number of studies have reported that it slows progression and helps
prevent the need for liver transplantation.

It has no effect on symptoms, including itching and fatigue. Some drugs, such as
colchicine, corticosteroids, or immunosuppressants, are being investigated for
use in combination with UDCA. Long-term controlled trials are needed to
determine the value of UDCA alone or with other agents.

Agents for Itching. Itching is a major problem with this disease.
Cholestyramine, taken with meals, is the first choice for relieving itching. and
a number of agents have been used or investigated, including low doses of the
drug naltrexone and phototherapy.

Agents for Impaired Fat Absorption. Because primary biliary cirrhosis affects
fat absorption, patients may need high doses or injections of important
fat-soluble vitamins, including K, D, A, and E. Agents called medium-chain
triglycerides may be helpful for steatorrhea (in which the feces contain
excessive fat).
Treatments for Other Causes of Cirrhosis
Treatment of Nonalcoholic Fatty Liver Disease (NASH). Weight loss is the most
important component for managing NASH and preventing progression to liver
disease. Investigators are studying various drugs, including gemfibrozil,
vitamin E, metformin ursodiol, and betaine.

Secondary Biliary Cirrhosis. Secondary biliary cirrhosis caused by blockage in
the bile ducts can be relieved by surgery.

Autoimmune Hepatitis. Autoimmune hepatitis is treated with corticosteroids as
standard agents and also possibly immunosuppressants, such as azathioprine and
cyclosporine A.

Hemochromatosis. For hemochromatosis, weekly bleedings (phlebotomies) may be
performed until iron levels are normal, then repeated as needed. If treatment is
given before cirrhosis develops, life expectancy may be normal.
Wilson's Disease. D-penicillamine is the drug most used for Wilson's disease.



Sandra Tara Balduf (Ane)

Frontline Hepatitis Awareness

Support for patients and educational materials

http://frontline-hepatitis-awareness.com

1-866-Hep-GoGo 866-437-4646




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