They play an indispensable role in the vaccination and management of complex regimens.
Hepatitis is a disease characterized by liver inflammation, with hepatitis A, B, and C being the 3 most common viral hepatitis types in the United States.
Each type of hepatitis elicits similar symptoms, despite differences in the route of transmission. Hepatitis A is spread via the fecal-oral route, whereas hepatitis
B and C are transmitted mainly through bodily fluids, such as blood. Prevention with universal vaccination remains essential, with pharmacists playing an integral part in this endeavor. Vaccinations exist for hepatitis A and B but not for hepatitis C. By contrast, there are effective pharmacologic treatments for hepatitis B and C, but only supportive care is available for hepatitis A infection. Prevention and appropriate treatment of viral hepatitis decreases associated morbidity, mortality, and transmission.1 It is vital for pharmacists to be familiar with the common types of viral hepatitis to encourage appropriate vaccination, recognize key considerations, and understand treatment options for viral hepatitis.
Vaccinations are Key
Hepatitis A and B immunizations can prevent the morbidity and mortality associated with viral hepatitis. Hepatitis B and C viruses (HBV, HCV) persist as the most significant global risk factors for hepatocellular carcinoma.2 Despite the efforts of the Advisory Committee on Immunization Practices (ACIP), the CDC, and the World Health Organization, vaccination rates are suboptimal, and adherence to completing the entire series is a concern. The COVID-19 pandemic reduced vaccination rates for both ACIP-recommended childhood vaccinations and adult vaccinations in at-risk populations.3 Routine hepatitis A vaccination in children aged 12 to 23 months caused a 95.5% reduction in reported acute hepatitis A infections between 1999 and 2011. A 2-dose series is recommended for hepatitis A in children, adults who have not been vaccinated, and those traveling to endemic areas. Outbreaks of hepatitis A have been attributed to low vaccination rates, which substantiates the need for health care professionals to promote appropriate vaccinations.4,5 The ACIP recommends HBV vaccinations be given at birth, during early childhood, to those who are at risk of infection, and to those who have been exposed and qualify for postexposure prophylaxis.6 Patients who are immunocompromised and have significant renal impairment may not have seroconversion with standard doses. Specific guidelines can be found in the ACIP HBV vaccination recommendation.7
Examples and Significance
The CDC recommends one-time HCV testing of all adults as well as HBV screening in those who are at an increased risk of acquiring HBV. Those with risk factors, such as individuals who inject drugs and undergo hemodialysis, should be tested regularly. Coinfection prevalence with HIV and viral hepatitis varies substantially according to risk group.8 In 2009, approximately 21% of adults with HIV were also positive for HCV, emphasizing the need to rule out other coharbored infections.9 Up to 82% of individuals who inject drugs are coinfected with HCV and HIV.9 Early detection and screening ensures improved clinical outcomes and helps clinicians initiate adequate therapy. It also provides an opportunity to counsel patients about hepatitis and mitigation of risky behaviors and to emphasize the need for vaccinations.
Despite available treatment and vaccinations, there is no cure for chronic hepatitis B (CHB), as covalently closed circular DNA remains in the liver, posing a lifelong risk for reactivation. Treatment goals are to reduce morbidity and mortality through functional cure, defined as the loss of hepatitis B surface antigen (HBsAg) and sustained HBV DNA.10 Therapies for CHB include direct-acting antivirals and interferon alpha. Therapy limitations consist of drug resistance, which is related to adherence; HBsAg loss; and toxicities.11
New drugs targeting different stages in the HBV life cycle are in development. Bulevirtide (Hepcludex), a novel entry inhibitor, was recently approved in Europe for treatment of chronic hepatitis D (CHD). Additionally, the results of one study showed that combination therapy with bulevirtide and tenofovir disoproxil (Viread) reduced HBsAg without serious adverse events.12 In a phase 2 trial, vebicorvir (ABI-H0731), an oral capsid assembly modulator, combined with entecavir (Baraclude) in treatment-naïve patients with CHB showed higher HBV DNA and RNA decline at 12 weeks compared with the placebo.13 Finally, the OSPREY trial (NCT05123599) is investigating the reduction of HBsAg with therapeutic vaccination once every 4 weeks combined with nucleoside analogues.14
The therapeutic drug pipeline for CHB is expanding, which may lead to the identification of a cure. The HCV treatment landscape has dramatically changed, with therapies offering a complete cure. To review a comprehensive guideline on specialty populations, therapy selection, and drug interaction management, visit the American Association for the Study of Liver Diseases website.15
Pharmacists play a key role in treating viral hepatitis by administering important vaccinations and educating patients about screening and vaccination. Expanding their knowledge on the resources for managing the disease enhances their understanding of emerging and existing antiviral therapies.
About The Authors
Wiyanna K. Bruck, PharmD, BCPS, BCIDP, BCPPS, is an assistant professor of pharmacy practice at South College in Knoxville, Tennessee.
Christopher Baladad, PharmD, is a PGY-2 infectious diseases pharmacy resident at University of Florida Health in Gainesville, Florida.
1. Viral hepatitis surveillance – United States. CDC. Updated May 19, 2021. Accessed January 21, 2022. https://www.cdc.gov/hepatitis/statistics/SurveillanceRpts.htm
2. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology. 2021;73(suppl 1):4-13. doi:10.1002/hep.31288
3. DeSilva MB, Haapala J, Vazquez-Benitez G, et al. Association of the COVID-19 pandemic with routine childhood vaccination rates and proportion up to date with vaccinations across 8 US health systems in the vaccine safety datalink. JAMA Pediatr. 2022;176(1):68-77. doi:10.1001/jamapediatrics.2021.4251
4. Advisory Committee on Immunization Practices (ACIP); Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006;55(RR-7):1-23.
5. CDC. Viral hepatitis. Updated May 19, 2021. Accessed May 10, 2022. https://www.cdc.gov/ hepatitis/statistics/index.htm
6. Schillie S, Vellozzi C, Reingold A, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018;67(1):1-31. doi:10.15585/mmwr.rr6701a1
7. Amjad W, Alukal J, Zhang T, Maheshwari A, Thuluvath PJ. Two-dose hepatitis B vaccine (Heplisav-B) results in better seroconversion than three-dose vaccine (Engerix-B) in chronic liver disease. Dig Dis Sci. 2021;66(6):2101-2106. doi:10.1007/s10620-020-06437-6
8. Negro F. Hepatitis D virus coinfection and superinfection. Cold Spring Harb Perspect Med. 2014;4(11):a021550. doi:10.1101/cshperspect. a021550
9. People coinfected with HIV and viral hepatitis. CDC. Updated September 21, 2020. Accessed February 23, 2022. https://www.cdc.gov/hepatitis/populations/hiv.htm#ref0
10. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MJ, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63(1):261-283. doi:10.1002/hep.28156
11. Tang Y, Liang H, Zeng G, Shen S, Sun J. Advances in new antivirals for chronic hepatitis B. Chin Med J (Engl). 2022;135(5):571-583. doi:10.1097/CM9.0000000000001994
12. Wedemeyer H, Bogomolov P, Blank A, et al. Final results of a multicenter, open-label phase 2b clinical trial to assess safety and efficacy of Myrcludex B in combination with Tenofovir in patients with chronic HBV/HDV co-infection. J Hepatol. 2018;68(1):S3. doi:10.1016/ S0168-8278(18)30224-1
13. Ma X, Lalezari J, Nguyen T, et al. Interim safety and efficacy results of the ABI-H0731 phase 2a program exploring the combination of ABI-H0731 with Nuc therapy in treatment-naive and treatment-suppressed chronic hepatitis B patients. J Hepatol. 2019;70(1):e130. doi:10.1016/S0618-8278(19)30230-0
14. A study of JNJ-73763989, JNJ-64300535, and nucleos(t)ide analogs in virologically suppressed, hepatitis B e antigen (HBeAg)-negative participants with chronic hepatitis B virus infection (OSPREY). ClinicalTrials.gov. Updated March 16, 2022. Accessed April 8, 2022. https://clinicaltrials.gov/ct2/show/NCT05123599
15. Practice guidelines. American Association for the Study of Liver Diseases. Accessed April 8, 2022. https://www.aasld.org/publications/practice-guidelines