Medication Summary
Certain patients may benefit from pharmacologic therapy. For chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections in particular, the goals of therapy are to reduce liver inflammation and fibrosis and to prevent progression to cirrhosis and its complications.
In addition to the medications listed below (eg, interferons [IFNs], antivirals, and corticosteroids), the nucleoside analogues lamivudine and adefovir have shown promising results in the treatment of patients with chronic hepatitis B. Other antiviral agents that are being studied for treatment of chronic hepatitis B are entecavir and tenofovir. Besides being active against HBV, lamivudine, adefovir, and tenofovir are also active against human immunodeficiency virus (HIV) and thus are potentially useful in the treatment of patients with HBV-HIV coinfection.
For patients with chronic HCV infection, one current treatment option is combination therapy with pegylated IFN (PEG-IFN) and the antiviral ribavirin. This regimen may be recommended for a certain subset of patients with moderate or severe inflammation or fibrosis. The combination of the two drugs provides a more sustained clearance of HCV RNA from the serum of infected individuals than monotherapy does.
Other therapeutic options are being explored for treatment of chronic HCV with the goals of increasing efficacy and decreasing toxicity. These include protease inhibitors, ribozymes, and viral vaccines.
Interferons
Class Summary
IFNs are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. IFN alfa, beta, and gamma may be given topically, systemically, and intralesionally.
Interferon alfa 2b (Intron A)
IFN alfa-2b is a protein product manufactured by recombinant DNA technology. The adult dosage is 3 million units subcutaneously (SC) 3 times weekly. Modulation of host immune response by IFN may play an important role in the treatment of viral diseases.
Interferon alfacon 1 (Infergen)
This product was discontinued in September 2013. IFN alfacon is a protein product manufactured by recombinant DNA technology. Modulation of host immune response by IFN may play an important role in the treatment of viral diseases. This product is synthesized by combining the most common amino acid sequences from all 12 naturally occurring IFNs. The adult dosage is 9 mcg SC 3 times weekly.
Peginterferon alfa 2b (PEG Intron, PegIntron Redipen, Sylatron)
PEG-IFN consists of IFN alfa-2b attached to a single 12-kd PEG chain. It is excreted by the kidneys. PEG-IFN has sustained absorption, a slower rate of clearance, and a longer half-life than unmodified IFN, which permits more convenient once-weekly dosing and significantly improves the quality of life for patients. The adult dose is 1.5 mcg/kg SC.
Pegylated interferon alfa-2a (Pegasys)
PEG-IFN alfa-2a consists of IFN alfa-2a attached to a 40-kd branched PEG molecule. It is predominantly metabolized by the liver. The adult dosage is 180 mcg/kg SC once weekly.
Antivirals
Class Summary
Antiviral agents inhibit viral replication.
Famciclovir (Famvir)
Famciclovir is a prodrug that, when biotransformed into active metabolite penciclovir, may inhibit viral DNA synthesis or replication.
Entecavir (Baraclude)
Entecavir is a guanosine nucleoside analogue with activity against HBV polymerase. It competes with the natural substrate, deoxyguanosine triphosphate, to inhibit HBV polymerase activity (ie, reverse transcriptase). It is less effective for lamivudine-refractory HBV infection. Entecavir is indicated for treatment of chronic HBV infection. It is available as a tablet and as an oral solution (0.05 mg/mL; 0.5 mg = 10 mL).
Ribavirin (Rebetol, Virazole, Copegus)
Ribavirin is an antiviral nucleoside analogue. Its chemical name is D-ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. Given alone, ribavirin has little effect on the course of hepatitis C. Given with IFN, it significantly augments the rate of sustained virologic response. The adult dosage is 10.6 mg/kg orally once daily or in 2 divided doses.
Boceprevir (Victrelis)
NS3/4A protease inhibitors interfere with the ability of HCV to replicate by inhibiting a key viral enzyme, NS3/4A serine protease. Boceprevir inhibits replication of the hepatitis C virus by binding reversibly to nonstructural protein 3 (NS 3) serine protease. Boceprevir must be administered in combination with PGN-INF alfa and ribavirin. The dosage is 800 mg orally 3 times daily. This is not currently used in the United States.
Corticosteroids
Class Summary
Corticosteroids may be used in cholestatic HAV. A brief course may shorten the illness; however, this may be most effective in patients with milder disease.
Prednisone
Prednisone decreases autoimmune reactions, possibly by suppressing key components of immune system. Prednisone is inactive and must be metabolized to the active metabolite prednisolone; this conversion may be impaired in patients with liver disease.
Prednisolone (Orapred ODT, Prelone, Millipred)
Prednisolone decreases autoimmune reactions, possibly by suppressing key components of immune system. This agent does not need to undergo hepatic metabolism.
Vaccines, Viral, Prevention
Class Summary
The hepatitis B vaccine is used for active immunization against disease caused by HBV.
Hepatitis b vaccine (Engerix B, Heplisav-B, Recombivax HB, PreHevbrio)
Hepatitis B vaccine is recommended by the CDC for at-risk adults who seek protection from HBV infection. Newborns should receive the vaccine within 24 hours of birth to HBsAg–negative mothers and within 12-h for HBsAg–positive mothers. Childhood catch-up and adolescent immunization schedules are also defined if a child did not receive the vaccine at birth. The vaccines are available as a 3-dose regimen over 6 months (Engerix B, Recombivax HB) for adults or children. Also, a 2-dose regimen over 1 month (Heplisav-B [adjuvanted]) and a 3-dose regimen at 0, 1, and 6 months (PreHevbrio [3-antigens]) for adults are options.
Hepatitis A vaccine, inactivated, and hepatitis B vaccine (Twinrix)
This combined hepatitis A–hepatitis B vaccine is used for active immunization of persons older than 18 years against disease caused by HAV and infection by all known subtypes of hepatitis B virus (HBV).
Immune Globulins
Class Summary
Immune globulins may be used for passive immunization against viral diseases.
Hepatitis B immune globulin (HBIG) (H big, Hep B Gammagee, HepaGam B)
This immune globulin is prepared from plasma preselected for high-titer anti-HBs. It provides passive immunization for individuals who describe recent exposure to a patient infected with HBV. HBIG is also administered after liver transplantation to persons infected with HBV in order to prevent HBV-induced damage to the liver allograft.
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Viral Hepatitis. Hepatitis A virus as viewed through electron microscopy.
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Viral Hepatitis. Liver biopsy specimen showing ground-glass appearance of hepatocytes in a patient with hepatitis B.
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Viral Hepatitis. Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in a patient with hepatitis B.
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Viral Hepatitis. Liver biopsy with trichrome stain showing stage 3 fibrosis in a patient with hepatitis B.
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Viral Hepatitis. Hepatic carcinoma, primary. Large multifocal hepatocellular carcinoma in an 80-year-old man without cirrhosis.
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Viral Hepatitis. Triple-phase computed tomography scan depicting liver cancer, revealing classic findings of enhancement during the arterial phase and delayed hypointensity during the portal venous phase.
Tables
Test |
CHB HBeAg Positive |
CHB HBeAg Negative |
Inactive Carrier |
HBsAg |
+ |
+ |
+ |
Anti-HBs |
- |
- |
- |
HBeAg |
+ |
- |
- |
Anti-HBe |
- |
+ |
+ |
Anti-HBc |
+ |
+ |
+ |
IgM anti-HBc |
- |
- |
- |
HBV DNA |
>2 × 104 IU/mL* (>105 copies/mL) |
>2 × 103 IU/mL (>104 copies/mL) |
< 2 × 103 IU/mL (< 104 copies/mL) |
ALT level |
Elevated |
Elevated |
Normal |
ALT = alanine aminotransferase; anti-HBc = antibody to hepatitis B core antigen; anti-HBe = antibody to HBeAg; anti-HBs = antibody to HBsAg; CHB = chronic hepatitis B; HBV = hepatitis B virus; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; IgM = immunoglobulin M. *Increasingly, experts in the field use IU/mL rather than copies/mL. |
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Grade |
Portal Inflammation |
Interface Hepatitis |
Lobular Necrosis |
1 – Minimal |
Mild |
Scant |
None |
2 – Mild |
Mild |
Mild |
Scant |
3 – Moderate |
Moderate |
Moderate |
Spotty |
4 – Severe |
Marked |
Marked |
Confluent |
