COMMUNICABLE THROUGH BLOOD PRODUCTS OR NEEDLE PRICKS & THROUGH SEX ONLY, NOT BY ORAL ROUTE.
Medical Care: Therapy is currently recommended for patients with evidence of chronic active disease (ie, high levels of the aminotransferases, positive HBV DNA findings, HBeAg). Currently, interferon alfa (IFN-a), lamivudine, and adefovir dipivoxil are the main drugs approved globally, although ongoing trials are investigating new types of medications such as entecavir, tenofovir disoproxil, emtricitabine, BL-thymidine (L-dT), DAPD, clevudine (l-FMAU), thymosin, and therapeutic vaccines. No clearcut guidelines are available as to which medication should be chosen.
Patients who have lost HBeAg and in whom HBV DNA is undetectable have an improved clinical outcome (ie, slower rate of progression, prolonged survival without complications, reduced rate of HCC, and clinical and biochemical improvement after decompensation).
Special attention must be given to patients on transplantation lists. Initiation of treatment with lamivudine or adefovir is of cardinal importance before and after liver transplantation in order to achieve viral suppression and prevent recurrence of the disease after the procedure.
" Interferon alfa
o Published reports indicate that after IFN-a treatment with 5 million U/d or 10 million U 3 times per week subcutaneously for 4 months, the HBV DNA levels and HBeAg become undetectable in 30-40% of patients. In addition, 10% of patients seroconvert from HBsAg to HBsAb. Unfortunately, 5-10% relapse after completion of treatment. A transient "flare" (ie, increased aminotransferase levels during the beginning of treatment) can be identified, and this represents the impact of the activated cytolytic T cells on the infected hepatocytes.
o High levels of aminotransferases, a low viral load, and infection with the wild type are good prognostic factors for response to IFN-a treatment.
o Asian patients and patients with the precore mutant virus tend to not respond to IFN-a treatment.
o Special attention must be given to patients with HBV-decompensated cirrhosis (eg, ascites, encephalopathy) who are taking IFN-a because of the fact that although they occasionally may respond, they also can deteriorate further.
o The adverse effects of IFN-a sometimes can be severe, even devastating. Some patients cannot complete treatment. A flulike syndrome, myelosuppression (eg, leukopenia, thrombocytopenia), nausea, diarrhea, fatigue, irritability, depression, thyroid dysfunction, and alopecia are among the adverse effects that may occur.
" Lamivudine
o A nucleoside analogue inhibiting the viral polymerase, lamivudine has been associated with a 4-log reduction of the viral load. Lamivudine treatment (100 mg/d) has been associated with a 16-18% seroconversion rate from HBeAg to HBeAb, a 30-33% rate of HBeAg loss, a 40-50% normalization of the value of the aminotransferases, and a 1-2% HBsAg seroconversion rate.
o Histologic improvement (ie, reduction of histologic activity index of >2 points) has been noticed in approximately 50% of patients taking this medication. The adverse effects are negligible.
Lamivudine appears to be effective for patients who do not respond to IFN-a treatment (eg, patients infected by the precore mutant virus). A transient elevation of aminotransferases can be noticed shortly after starting treatment.
o The duration of treatment is 12 months, but the HBeAg seroconversion rate has been shown to possibly increase to 27% after 2 years, 40% after 3 years, and 47% after 4 years of treatment in patients with a viral load of less than 104 pg/mL.
Lamivudine treatment also has been shown to dramatically improve the condition of patients with decompensated disease due to HBV reactivation.
o The emergence of viral variants is the major complication. Approximately 15-30% of patients develop a mutation of the viral polymerase gene (the YMDD variants) after 12 months of treatment, and approximately 50% develop a mutation after 3 years of treatment. However, continued treatment after the breakthrough with the variant type has been associated with lower HBV DNA levels, less aminotransferase activity, and histologic improvement. Discontinuation of treatment for these patients is accompanied by a reversion to a wild type of HBV and a flare of the disease.
" Adefovir dipivoxil
o This agent is a nucleoside analogue, a potent inhibitor of the viral polymerase. The efficacy of this drug has been tested in HbeAg-positive, HbeAg-negative, and lamivudine-resistant patients with encouraging results.
o The estimated rate of resistance to adefovir and the development of mutations (rtN236T and rtA181V) is approximately 4-6% after 3 years of treatment.
o The optimal dose seems to be 10 mg/d. Higher doses are nephrotoxic.
o The results of 2 multicenter trials using adefovir for 48 weeks were published recently.
" In HBeAg-positive subjects who received 10 mg of adefovir daily, a median 3.52 log reduction of the viral load (HBV DNA) level was noted. In 48% of the subjects, normalization of the aminotransferases level was reported. Histologic improvement was noticed in 53% of the subjects who received this regimen. The HBeAg seroconversion rate was 12%.
" Sixty-four percent of the HbeAg-negative population experienced histologic improvement after receiving 10 mg of adefovir for 48 weeks, and 72% had normalized aminotransferase levels. The serum HBV DNA level was decreased in 51% of subjects (Hadziyannis, 2003; Marcellin, 2003). The outcomes are maintained if treatment is continued for 144 weeks, but the benefits are lost if treatment is discontinued at 44 weeks. The development of resistant mutations (rtN236T and rtA181V) has been estimated around 6% (Hadziyannis, 2005).
Surgical Care: Orthotopic liver transplantation (OLT) is the treatment of choice for patients with fulminant hepatic failure who do not recover and for patients with end-stage liver disease. The implementation of hepatitis B immunoglobulin (HBIG) during and post-OLT period, and of lamivudine or adefovir in the pre-OLT period and post-OLT period, dramatically improves the recurrence rate of HBV infection.
Diet:
" Acute and chronic hepatitis (patients without cirrhosis) - No restrictions
" Decompensated cirrhosis (prominent signs of portal hypertension or encephalopathy) - Low-sodium diet (1.5 g/d), high-protein diet, ie, white-meat protein (eg, pork, turkey, fish), and, in cases of hyponatremia, fluid restriction (1.5 L/d)
DRUG TREATMENT :
1. ANTIVIRALS :
- INTERFERON ALFA-2B
- LAMIVUDINE
- ADEFOVIR
- ENTECAVIR
- TELBIVUDINE
DRUG(S) OF CHOICE
o Chronic hepatitis B: persistent hepatitis B surface antigenemia > 6 months
? Interferon-alpha (IFN-a) and lamivudine (LAM) are equally effective.
? Goals of therapy: Decrease in HBV DNA to undetectable level; loss of hepatitis Be antigen and
appearance of anti -Hbe; loss of HBsAg from serum is seldom achieved but will be ideal.
Chronic hepatitis B therapy
HBeAg HBV-DNA ALT* Rx
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+ + + IFN, ADV or LAM
- - N Monitor
+/- + CC LAM or ADV
+/- + DC LAM or ADV; Liver transplant
+/- - CC Monitor
+/- - DC Liver transplant
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* ALT + when >2x normal
CC: compensated cirrhosis
DC: decompensated cirrhosis
Contraindications: Interferon: platelet count < 50,000. Mouse immunoglobulin, egg protein or neomycin allergy. Corticosteroids may add to morbidity/increased mortality.
Precautions:
o Other disorders of coagulation, myelosuppression, seizures, depression (esp. suicide ideation), pregnancy,
fertile age group, lactation
o Increased serum triglycerides may occur during IFN therapy; may cause abnormal ALT
o Psychiatric evaluation may be prudent prior to IFN treatment
o Lamivudine resistant mutations
ALTERNATIVE DRUGS Adefovir 10 mg qid, Famciclovir (Famvir) 500 mg tid for chronic hepatitis B
PATIENT MONITORING
o Serial measurement of serum AST/ALT
o Appropriate serum viral markers useful for evaluation of recovery or progression
o Liver biopsies in chronic disease; in acute cases if diagnosis remains in doubt
o Monitor for metabolic complications
o WBC, platelets with interferon alfa therapy
o Chronic HBV, HBV-DNA valuable for prediction of favorable response to IFN. High pretreatment ALT and
low pretreatment HBV-DNA associated with favorable response.
o Monitor for hepatic decompensation (ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, etc) in cirrhotics
PREVENTION/AVOIDANCE
o General
? Screen blood products
? Proper disposal of needles
? Good sanitation, hygiene
? Maximum infectivity 2 weeks before jaundice
? May be endemic in institutions; day care centers - vaccinate for HBV
? HBV transmitted sexually, perinatally, occupationally, and via parenteral drug use (e.g., shared needles);
also enterically.
o Specific
? Hepatitis B vaccine. A new hepatitis B vaccine to include pres, and S2 antigens will be available soon;
more effective especially in nonresponders.
? High risk groups: hepatitis B human immune globulin within 24 hr of exposure (0.06 mL/kg IM)
? HBV screening in pregnant women; vaccinate all infants at birth.
POSSIBLE COMPLICATIONS Acute or subacute necrosis, chronic active or chronic hepatitis, cirrhosis, hepatic failure; hepatocellular carcinoma (HBV, HCV)
EXPECTED COURSE/PROGNOSIS
o Recovery from acute infection in 95% of patients
o Severity of hepatic encephalopathy best predictor of poor survival in hepatic failure
o HBV (mortality 1%) and HDV (with icterus, mortality 2-20%) more severe symptoms; often leads to persistent/chronic liver disease, cirrhosis, liver failure, hepatocellular carcinoma; more severe problems if
impaired immune function. Follow treatment with HBVDNA levels.
PREGNANCY
β’ Test, in later gestation, for HBsAg
β’ HBV transmitted vertically (< 10%) as well as perinatally and produces carrier state in 30%. Give infant HBIg 0.5 mL and HBV vaccine (Recombivax HB; separate sites) within 12 hrs of birth followed by HBV vaccine, 0.5 mL IM at ages 1 and 6 months. Check HBsAg and HBsAb at age 12 months
β’ Vertical transmission increased in HIV