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Medication

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 the 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 the treatment of chronic HCV with the goals of increasing efficacy and decreasing toxicity. These include protease inhibitors, ribozymes, and viral vaccines.

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)

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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)

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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)

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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)

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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.

Class Summary

Antiviral agents inhibit viral replication.

Famciclovir (Famvir)

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Famciclovir is a prodrug that, when biotransformed into active metabolite penciclovir, may inhibit viral DNA synthesis or replication.

Entecavir (Baraclude)

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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)

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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)

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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.

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

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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)

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Prednisolone decreases autoimmune reactions, possibly by suppressing key components of immune system. This agent does not need to undergo hepatic metabolism.

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)

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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)

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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).

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)

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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.

Questions

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Media Gallery

Viral Hepatitis. Hepatitis A virus as viewed through electron microscopy.
Viral Hepatitis. Liver biopsy specimen showing ground-glass appearance of hepatocytes in a patient with hepatitis B.
Viral Hepatitis. Liver biopsy with hematoxylin stain showing stage 4 fibrosis (ie, cirrhosis) in a patient with hepatitis B.
Viral Hepatitis. Liver biopsy with trichrome stain showing stage 3 fibrosis in a patient with hepatitis B.
Viral Hepatitis. Hepatic carcinoma, primary. Large multifocal hepatocellular carcinoma in an 80-year-old man without cirrhosis.
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.

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Table 1. Diagnostic Tests for Hepatitis B

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.

Table 2. Histologic Grading for Hepatitis C–Induced Liver Disease

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

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Author

Naga Swetha Samji, MD Physician, Bellin Clinic, Bellin Health Systems

Naga Swetha Samji, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, Wisconsin Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Adrienne M Buggs, MD, FACEP, FAAEM Medical Policy Advisor, Office of Merchant Mariner Credentialing, United States Coast Guard

Adrienne M Buggs, MD, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Praveen K Roy, MD, MSc Clinical Assistant Professor of Medicine, University of New Mexico School of Medicine

Praveen K Roy, MD, MSc is a member of the following medical societies: Alaska State Medical Association, American Gastroenterological Association

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

Eugene Hardin, FAAEM, FACEP Former Chair and Associate Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science; Former Chair, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center

Disclosure: Nothing to disclose.

Douglas M Heuman, MD, FACP, FACG, AGAF Chief of GI, Hepatology, and Nutrition at North Shore University Hospital/Long Island Jewish Medical Center; Professor, Department of Medicine, Hofstra North Shore-LIJ School of Medicine

Douglas M Heuman, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Physicians, and American Gastroenterological Association

Disclosure: Novartis Grant/research funds Other; Bayer Grant/research funds Other; Otsuka Grant/research funds None; Bristol Myers Squibb Grant/research funds Other; Scynexis None None; Salix Grant/research funds Other; MannKind Other

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Joseph K Lim, MD Associate Professor of Medicine, Director, Yale Viral Hepatitis Program, Section of Digestive Diseases, Yale University School of Medicine

Joseph K Lim, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Robert M McNamara, MD, FAAEM Chair and Professor, Department of Emergency Medicine, Temple University School of Medicine

Robert M McNamara, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Association, Pennsylvania Medical Society, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Rajeev Vasudeva, MD, FACG Clinical Professor of Medicine, Consultants in Gastroenterology, University of South Carolina School of Medicine

Rajeev Vasudeva, MD, FACG is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy, Columbia Medical Society, South Carolina Gastroenterology Association, and South Carolina Medical Association

Disclosure: Pricara Honoraria Speaking and teaching; UCB Consulting fee Consulting

David C Wolf, MD, FACP, FACG, AGAF Medical Director of Liver Transplantation, Westchester Medical Center; Professor of Clinical Medicine, Division of Gastroenterology and Hepatobiliary Diseases, Department of Medicine, New York Medical College

David C Wolf, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, and American Gastroenterological Association

Disclosure: Nothing to disclose.

Viral Hepatitis Medication

Medication Summary

Interferons

Class Summary

Interferon alfa 2b (Intron A)

Interferon alfa 2b (Intron A)

Interferon alfacon 1 (Infergen)

Interferon alfacon 1 (Infergen)

Peginterferon alfa 2b (PEG Intron, PegIntron Redipen, Sylatron)

Peginterferon alfa 2b (PEG Intron, PegIntron Redipen, Sylatron)

Pegylated interferon alfa-2a (Pegasys)

Pegylated interferon alfa-2a (Pegasys)

Antivirals

Class Summary

Famciclovir (Famvir)

Famciclovir (Famvir)

Entecavir (Baraclude)

Entecavir (Baraclude)

Ribavirin (Rebetol, Virazole, Copegus)

Ribavirin (Rebetol, Virazole, Copegus)

Boceprevir (Victrelis)

Boceprevir (Victrelis)

Corticosteroids

Class Summary

Prednisone

Prednisone

Prednisolone (Orapred ODT, Prelone, Millipred)

Prednisolone (Orapred ODT, Prelone, Millipred)

Vaccines, Viral, Prevention

Class Summary

Hepatitis b vaccine (Engerix B, Heplisav-B, Recombivax HB, PreHevbrio)

Hepatitis b vaccine (Engerix B, Heplisav-B, Recombivax HB, PreHevbrio)

Hepatitis A vaccine, inactivated, and hepatitis B vaccine (Twinrix)

Hepatitis A vaccine, inactivated, and hepatitis B vaccine (Twinrix)

Immune Globulins

Class Summary

Hepatitis B immune globulin (HBIG) (H big, Hep B Gammagee, HepaGam B)

Hepatitis B immune globulin (HBIG) (H big, Hep B Gammagee, HepaGam B)

Viral Hepatitis Medication

Medication Summary

Interferons

Class Summary

Interferon alfa 2b (Intron A)

Interferon alfacon 1 (Infergen)

Peginterferon alfa 2b (PEG Intron, PegIntron Redipen, Sylatron)

Pegylated interferon alfa-2a (Pegasys)

Antivirals

Class Summary

Famciclovir (Famvir)

Entecavir (Baraclude)

Ribavirin (Rebetol, Virazole, Copegus)

Boceprevir (Victrelis)

Corticosteroids

Class Summary

Prednisone

Prednisolone (Orapred ODT, Prelone, Millipred)

Vaccines, Viral, Prevention

Class Summary

Hepatitis b vaccine (Engerix B, Heplisav-B, Recombivax HB, PreHevbrio)

Hepatitis A vaccine, inactivated, and hepatitis B vaccine (Twinrix)

Immune Globulins

Class Summary

Hepatitis B immune globulin (HBIG) (H big, Hep B Gammagee, HepaGam B)

References

Tables

Contributor Information and Disclosures

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