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CHRONIC HBV Rx
CHRONIC Rx The aim of therapy in chronic HBV infection is to eradicate the virus. The two modalities of therapy available to achieve this goal have been: immune modulators (interferon alpha) and antiviral agents in the form of nucleoside analogues (e.g., lamivudine, famciclovir).
- Until recently, IFN-α has been the mainstay of therapy. Its mechanism of action is to stimulate the immune system to attack HBV-infected hepatocytes, thus inhibiting viral protein synthesis.
- A 4-month course of treatment results in a 30% to 40% response with significant reduction of serum HBV DNA, normalization of ALT, and loss of HBeAg. Seroconversion from HBeAg to HBeAb occurs in 15% to 20%.
- Factors that increase the likelihood of response to IFN-α therapy include:
- Adult onset of infection
- High baseline ALT
- Low baseline HBV DNA
- Absence of cirrhosis
- HBeAg positive
- Infrequent relapse after successful completion of therapy
- 80% of patients who lose HBeAg during therapy lose HBsAg in the decade after therapy
- >50% of patients who do not seroconvert after initial therapy develop a delayed HBeAg seroconversion months to years after therapy
- Overall incidence of cirrhosis and hepatocellular carcinoma is decreased in those treated with IFN-α
- IFN-α is successful only in patients with an active immune response; therefore it is not effective in patients with HIV infection and organ transplant patients
- Asians respond poorly to IFN-α
- Treatment with IFN-α in general is also poorly tolerated: side effects include flulike symptoms, injection-site reactions, rash, weight loss, anxiety, depression, alopecia, thrombocytopenia, granulocytopenia, thyroid dysfunction
- Nucleoside analogues block viral replication by inhibiting HBV polymerase
- Lamivudine is, to date, the only one of these agents approved for treatment of chronic HBV infection; it has been shown to rapidly reduce HBV replication and suppress HBV DNA to undetectable levels after a few weeks of treatment, and treatment for 1 yr is as effective as IFN-α with respect to loss of HBeAg seroconversion to HBeAb and loss of HBV DNA
- Adefovir dipivoxil is a nucleotide reverse transcriptase inhibitor recently shown to have antiviral activity against HBV. It is a prodrug that is converted to the active drug adefovir. It is highly active against HBV and may be useful as a salvage therapy for patients who are refractory or intolerant to lamivudine. (Nephrotoxicity is a potential concern.)
- Lamivudine is better tolerated than IFN-α
- It is easier to administer given orally
- Suppression of HBV replication regardless of sex, ethnicity, disease severity
- Other nucleoside agents under evaluation include famciclovir (found less effective than lamivudine), adefovir and ganciclovir, lobucavir, entecavir, emtricitabine
- A problem with the antiviral therapies is emergence of resistant HBV strains (YMDD variants [tyrosine-methionine-aspartate-aspartate])
- Combination therapy with two or three nucleoside analogues or combination therapy with IFN-α currently under investigation
- Liver transplantation (consider for fulminant hepatitis)
- Follow-up as outpatient
- Acute disease: usually <6 wk
- Rare fatalities (fulminant hepatitis)
- Possible chronic carrier state, cirrhosis, hepatocellular carcinoma
REFERRAL To infectious disease specialist and gastroenterologist for consultation regarding fulminant hepatitis or prolonged cholestasis, for cases of uncertain etiology, or for treatment of chronic active hepatitis PEARLS [amp ] CONSIDERATIONS COMMENTS
- Virus and HBsAg in high titers in blood for 1 to 7 wk before jaundice and for a variable time thereafter.
- Transmission is possible during entire period of HBsAg (and especially during HBeAg) in serum.
- Universal precautions should be followed for all contacts with blood or secretions/excretions contaminated with blood.
- Preventing before exposure:
- Lifestyle changes
- Meticulous testing of blood supply (although some chronically infected, infectious donors are HBsAg negative)
- Sterilization via steam or hypochlorite
- Hepatitis B vaccine for high-risk groups given IM in deltoid to induce HBsAb (response should be confirmed) is protective (>90% effective)
- Recommendation for universal childhood immunization with doses at birth, 1 mo, and 6 mo
- Prevention after exposure:
- HBV hyperimmune globulin (HBIG) given immediately after needlestick, within 14 days of sexual exposure, or at birth, followed by HBV vaccination
- Standard immune globulin: nearly as effective as HBIG