Treatment

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.

Treatments for Chronic Hepatitis C

Interferons Alone and in Combination with Ribavirin. 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 2005 clinical trial of patients with chronic hepatitis C and cirrhosis found that interferon treatment reduced the risk of liver cancer and significantly improved chance of survival. The study emphasizes the importance and substantial benefits of interferon therapy.

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). Rebetol is a combination of alfa-2b and ribavirin.
• 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 also appears to be safe and effective for children. However, the combination can cause side effects, including anemia. A 2005 study suggested that some patients with hepatitis C genotypes 2 or 3 may be able to benefit from a shorter course of treatment (12 weeks) than the standard 24-week treatment duration. A shorter treatment time may reduce the risk of side effects.

PegINF combinations are proving to slow progression of scarring, and have 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.)

Investigational 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 is ongoing to find better solutions. Drugs showing promise include:

• Nucleoside analogs. Several new nucleoside analogs are in clinical development. Viramidine is a drug related to ribavirin. It is being studied in Phase III trials alone and in combination with pegylated interferon-alfa. Valopicitabine (NM283) is being tested in Phase II trials as alone and in combination with pegylated interferons.
• Albuferon. This long-acting form of interferon-alfa may have fewer side effects and require less dosing than pegylated interferons. It is currently being tested in Phase II trials for patients who have not been treated with or have not responded to standard interferon-alfa.
• IMPDH Inhibitors. Mycophenolate mofetil and VX-497 are drugs 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 (Symmetrel) is an anti-viral drug being investigated in various combinations. For example, triple therapy with amantadine, pegylated interferon, and ribavirin is showing particular promise. 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 (Zadaxin), also called thymalfasin, is a synthetic version of a peptide derived from the thymus gland (which is responsible for maturation of immune factors called 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. Novel protease inhibitors (similar to those used for HIV) are under investigation for hepatitis C patients who fail other treatments. These drugs are based on molecular therapies that target proteins involved in viral reproduction.

Other drugs 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 drugs will 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

An ounce of prevention is worth a pound of cure, and the phrase resoundingly holds true in the case of Hepatitis B. Today, a vaccine against HBV is available. It can prevent hepatitis B and, therefore, also prevent liver cancer. The American Academy of Pediatrics and the Centers for Disease Control and Prevention currently recommend that all babies born in the United States receive a hepatitis B vaccine at birth.

Five drugs are currently approved in the United States for treatment of chronic hepatitis B:

• Peginterferon alfa-2a (Pegasys)
• Interferon-alfa-2b (Intron)
• Adefovir (Hepsera)
• Lamivudine (Epivir)
• Entecavir (Baraclude)

These drugs block the replication of HBV in the body. Some also help boost the immune system. A doctor will decide which drug to prescribe based on a patient’s age, disease severity, and other factors. Each drug has various advantages and disadvantages in terms of cost, efficacy, side effects, and likelihood of drug resistance. A combination of drugs may also be prescribed.

Peginterferon alfa-2a. Peginterferon alfa-2a (Pegasys) was approved in 2005 for treatment of chronic hepatitis B. (Peginterferon is also called pegylated interferon.) The drug was previously approved in 2002 for treatment of chronic hepatitis C. Pegasys prevents the hepatitis B virus from replicating and also helps boost the immune system. It is given as a weekly injection. Peginterferon is sometimes prescribed in combination with lamivudine (Epivir).

Interferon Alpha. For many years, interferon alfa-2b (Intron) was the standard drug for hepatitis B. The drug is usually taken by injection every day for 16 weeks. (It does not appear to help 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.

Lamivudine and Entecavir. These two drugs are classified as nucleoside analogs. Lamivudine (Epivir or 3TC) is an antiretroviral drug that is used to treat human immunodeficiency virus (HIV) as well as hepatitis B. Studies suggest that lamivudine reduces viral count in over half of hepatitis B patients who take it as sole therapy for about a year. It is less expensive than interferon-alfa and has fewer side effects, but may not work as well as interferon-alfa for long-term therapy. 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. About 20% of patients who take lamivudine develop drug resistance.

In 2005, the FDA approved entecavir (Baraclude) for treatment of adults with chronic hepatitis B. In clinical trials, entecavir worked better than lamivudine for treating HBV. Entecavir appears to have less risk of drug resistance than lamivudine. Studies also suggest that it may be a good alternative treatment for patients who have developed resistance to lamivudine. Questions have been raised about the drug’s possible cancer risks. Ongoing studies are evaluating this risk

Adefovir. Adefovir (Hepsera) belongs to a class of antiviral drugs called nucleotide analogs. (Nucleotides are related to nucleosides but have a slightly different chemical structure.) Nucleotide analogs block an enzyme involved in the replication of viruses. Adefovir costs more than lamivudine, but may be effective against lamivudine-resistant strains of HBV. The drug must be taken on a long-term basis. A 2006 study indicated that when patients stopped taking adefovir after 48 weeks, the hepitatis B virus resumed replication. Patients who took the drug for a longer period (144 weeks) continued to benefit from treatment.

Drug Warnings. In 2004, the FDA issued two drug warnings for patients with HBV. The HIV drug tenofovir (Viread) should not be used to treat patients who are co-infected with HBV as the drug may increase hepatitis severity. The lymphoma drug rituximab (Rituxan) may reactivate HBV. Patients with lymphoma should be screened for HBV.

Investigational Drugs for Hepatitis B

• Emtricitabine is a nucleoside analog drug used to treat HIV and AIDS. It is being investigated for chronic HBV.
• Telbivudine is another nucleoside analog drug. It is in Phase III trials for treatment of chronic hepatitis B. Studies suggest that it may work better than lamivudine or adefovir.
• Pegylated interferon alfa-2b (Peg-Intron) is currently approved for treatment of chronic hepatitis C. It is being investigated alone and in combination with lamivudine for treatment of HBV.
• Thymosin Alpha 1 (Zadaxin), also called thymalfasin, is a synthetic version of a substance derived from the thymus gland (which is responsible for maturation of immune factors called T-cells). It appears to be safe for hepatitis B patients when used alone or in combination with interferon. It is approved in many countries, but not the United States.

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. Several 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 drugs.

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

Drugs 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.

Treatments for Other Causes of Cirrhosis

Treatment of Nonalcoholic Fatty Liver Disease (NAFLD). Weight loss is the most important method for managing NAFLD and preventing progression to nonalcoholic steatohepatitis (NASH) and, eventually, cirrhosis. Diabetes and cholesterol control are also important. Investigators are studying whether various drugs used to treat type 2 diabetes, such as metformin (Glucophage), rosiglitazone (Avandia), and pioglitazone (Actos), may help treat NAFLD and NASH. Other research is focusing on antioxidant vitamins such as vitamin E.

In 2005, the U.S. National Institutes of Health (NIH) launched two trials to study treatment of NAFLD and NASH in adults and children. Children with NAFLD will receive vitamin E, metformin, or placebo. In the adult trial, patients with NASH will receive vitamin E, pioglitazone, or placebo.

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 drugs 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.

Treatments for Liver Scarring

There are no current safe and effective therapies for liver scarring (fibrosis). However, recent insights into the cellular and molecular mechanisms responsible for scarring have led to the development of specific, antifibrotic drugs that target the primary injury and inhibit abnormal cell mechanisms. Such drugs, now in very early testing, could one day help prevent or reduce the progression of liver scarring or the progression to liver cancer.

Click the icon to see an illustrated series detailing a liver transplant.