What is treatment of hepatitis?
Acute infection with hepatitis B usually does not require treatment. In rare cases, however, the infection may cause life-threatening liver failure. Patients with liver failure due to acute hepatitis B should be evaluated for liver transplantation. Small studies suggest that the drug lamivudine (Epivir) may be effective in this setting.
If a person is chronically infected with hepatitis B and has few signs or symptoms of complications, medications usually are not used. These patients are watched carefully and are advised to go for certain blood tests. One test measures the ‘viral load,’ that is, the amount of viral DNA in the blood. Doctors will recommend treatment if there are signs that the virus is beginning to cause damage or if the viral load is high. Another reason to prescribe medication is if the patient has a positive test for the Hepatitis B e-antigen (HBeAg) in the blood. HBeAg is associated with an increased risk of progression of liver disease and its complications.
In chronic hepatitis B, the goal of treatment is to reduce the risk of complications including cirrhosis and liver failure. Tests like the viral load or liver function tests are used to evaluate if medicines are working. People who have large amounts of the virus in their blood are at highest risk to get cirrhosis. Up to one-third of people with very high viral loads (more than one million viral copies per milliliter of blood) will develop cirrhosis over a decade, compared to only 4.5% of those with low viral loads (less than 300 viral copies per milliliter).
Medications can reduce the number of viruses in the body and may be able to eliminate the virus from the bloodstream. Logically, this should lead to them having a low rate of progression to cirrhosis (<1% per year). Even in people who clear the virus from their blood, low numbers of viruses still live in the liver and other cells. Thus, the medications do not cure the disease, but they can prevent or delay complications. People who have a good response to treatment can still transmit the virus. Doctors may also recommend liver biopsies to evaluate if the medications are effective.
The medications in current use for chronic hepatitis B include the interferons and nucleoside/nucleotide analogues. New agents are being developed although they are still under investigation and considered experimental. There are no accepted guidelines that tell how every patient should be treated. As a result, treatment is individualized according to ones experience.
Interferon-alpha has been used to treat hepatitis B for more than 20 years. Interferon-alpha is a naturally occurring protein that is made in the body by white blood cells to fight viral infections. In addition to its direct anti-viral effects, interferon works against the hepatitis B virus by stimulating the body’s immune system to clear the virus. Compared to older interferon alpha agents, pegylated interferon alpha, marketed as Pegasys or Pegintron, has a more convenient dosing schedule, more effective and suppresses the virus for a longer period of time. Pegylated interferon alpha is given once a week for 48 weeks.
- A significant reduction in the viral load or elimination of detectable viral DNA from the blood occurs in two-thirds of persons during treatment.
- Blood tests for liver functions normalize in approximately 40% people treated with interferon.
- People who have significant abnormalities in liver function before therapy are more likely to respond to treatment.
- Those who have normal liver blood tests before treatment are less likely to respond to interferon therapy.
- Liver biopsy results show improvement in about one-third of patients.
Only 27%-32% of persons who have Hepatitis B e-antigen (HBeAg) in their blood will be able to eliminate HBeAg and produce antibodies against the HBe antigen after treatment with interferon. Relapse may occur after treatment is stopped.
Sustained viral response (undetectable viral load in the blood, normal liver function tests) occurs in approximately 15% to 30% of patients after the drug is stopped. Although this is not a cure (some virus still lives in the liver and elsewhere), people with sustained response are at low risk for complications of liver disease. If the responder’s immune system is compromised, for example through the use of steroids or acquiring HIV, the disease can recur. Periodic monitoring of blood tests can help confirm that the response continues to be sustained.
Interferon side effects
Interferon causes several side effects including:
- Fatigue, generalized muscle aches, fever, chills and loss of appetite. These flu-like symptoms occur in approximately 80% of treated patients;
- mood swings, depression, anxiety
- thyroid gland abnormalities resulting in hypothyroidism (decrease thyroid hormone)
- Suppression of the bone marrow and production of blood cells
- hair loss
The side effects may be severe enough that the patient is unable to continue treatment. During treatment, the normal immune response to the virus is stimulated and may cause worsening inflammation in the liver. This is normally a good sign showing that the interferon is working, but more extreme responses may cause liver failure but this is very rare. So, physicians should monitor blood tests closely during therapy. Persons with unstable liver disease due to cirrhosis usually should not take interferon because of the increased risk of liver failure.
Nucleoside/nucleotide analogues (NAs) are synthetic chemicals that mimic the nucleosides and nucleotides that are used for making DNA. When the virus tries to use the analogues to make its own DNA, it is unable to create the DNA and, therefore, cannot reproduce. Examples of these agents include adefovir (Hepsera), entecavir (Baraclude), lamivudine (Epivir-HBV, Heptovir, Heptodin), telbivudine (Tyzeka) and tenofovir (Viread).
- In patients who have HBeAg in their blood, Nucleoside analogues reduce the viral load, causing the virus to become undetectable in 21% to 67% of patients.
- Normalization of blood liver function tests occurs in 40% to 77%, and loss of HBeAg occurs in about 12% to 22% of cases after one year of treatment.
- Results are better in patients who do not have HBeAg in their blood, with 50% to 90% having non-detectable virus and 60% to 80% having normalization of liver function tests.
In a 2004 study in people who already had cirrhosis from hepatitis B, treatment with lamivudine decrease the risk of liver cancer and progressive liver failure by more than 50%. Newer NAs such as entecavir (Baraclude) and telbivudine (Tyzeka) seems to have higher response rates than older agents such as lamivudine (Epivir-HBV, Heptovir), but there is less experience with these newer agents.
Unfortunately, the hepatitis B virus may become resistant to NAs over time (see below). Adefovir may be effective against strains of virus that have become resistant to lamivudine and may be added to lamivudine when resistance appears. Simply switching from one NA to another is not recommended because this leads to formation of virus strains that are resistant to multiple medications.
Patients with HBeAg may be treated until six months after the HBeAg disappears from the blood and is replaced by antibodies (anti-HBe), if this occurs. In persons without HBeAg, the endpoints are less clear. Some experts advocate treating until the viral load (viral DNA) is undetectable and the surface antigen (HbsAg) has been cleared from the blood. Others suggest continuing medications for prolonged periods to suppress the virus. All of these strategies are hindered by the risk of the virus becoming resistant to the medications. Patients who discontinue treatment with NAs should be monitored carefully for recurrent hepatitis, which may be severe.
Why does hepatitis B virus become resistant to nucleoside/nucleotide analogues?
The major challenge associated with long-term therapy with NAs is the development of viral resistance to the NAs. This resistance results from a change (mutation) in the genetic material of the virus.
- For lamivudine (Epivir-HBV, Heptovir, Heptodin), the incidence of resistance is 25% after one year and as high as 50% after three years of treatment.
- With telbivudine (Tyzeka), resistance rates are 5% to 11% after one year.
Therefore, some guidelines do not recommended lamivudine or telbivudine alone as the first treatment for chronic hepatitis B.
For other NAs such as adefovir (Hepsera), resistance is less common after one year of therapy but rises to 30% after five years. Early results with entecavir (Baraclude) suggest that resistance may be uncommon with this agent. When resistance occurs, the viral load may rise or blood liver tests may become abnormal.
What is the role of liver transplantation in hepatitis B infection?
Liver transplantation has been successful in patients who have irreversible, life-threatening complications of hepatitis B. This includes patients with liver failure due to end-stage cirrhosis or uncommonly severe (fulminant) hepatitis. Liver transplantation does not cure hepatitis B, and hepatitis may occur in the new liver. The incidence of recurrent hepatitis has been reduced to less than 10% through use of lamivudine and HBIG in transplant recipients. Use of these agents has also improved long-term survival, with 75% to 85% 5 year survival rate.
What are the effects of alcohol on hepatitis B virus?
Agents that damage the liver are particularly harmful in patients who already have hepatitis B. For this reason, it is recommended that persons with hepatitis B avoid drinking alcohol.
What are the effects of immunosuppressive medications on hepatitis B virus?
Even in people with chronic hepatitis B, the immune system is working to suppress the virus. Medications that suppress the immune system allow the virus to reproduce in large numbers and may cause the hepatitis to flare.
Examples of medications that suppress the immune system are:
- prednisone: used to treat many diseases, including asthma, inflammatory bowel disease, certain types of skin disease and arthritis
- methotrexate (Rheumatrex, Trexall): used to treat certain types of skin disease, arthritis, and cancer;
- Cyclophosphamide (Cytoxan): used to treat some cancers.
If an immunosuppressant drug is stopped, the body’s immune system’s activity may rebound and cause severe inflammation of the liver.