© Springer International Publishing Switzerland 2017Kia Saeian and Reza Shaker (eds.)Liver Disordersdoi.org/10.1007/978-3-319-30103-7_10
10. Viral Hepatitis: Hepatitis B (& D)
Division of Gastroenterology & Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
KeywordsHBVHepatitis BHBsAgAnti-HBcAnti-HBeVaccineOccult hepatitis BHepatocellular carcinomaCirrhosisPregnancy
What Is the Significance of Having Both Hepatitis B Surface Antibody and Hepatitis B Surface Antigen at the Same Time?
Seroconversion of the HBs antigen and emergence of HBs antibody are associated with clearance of HBV virus and emergence of immunity. However, in approximately 3–5 % of patients with chronic hepatitis B, HBsAg persists despite development of the protective antibody [1, 2]. This is thought to be due to the rise of immune variants which have an altered anti-HBs-binding site. Thus, despite seroconversion, viral replication is able to persist due to failure of recognition by the host immune system. These individuals are at risk for progressive liver disease due to active HBV replication and chronic hepatitis . Chronic infection in such individuals may also be missed if the mutated HBsAg is not detected or screened for. To avoid misdiagnosis, HBsAg, anti-HBs, and anti-HBc antibodies should be checked during routine HBV screening .
What Is the Risk of Reactivation ?
Patients who are inactive HBsAg carriers and those who have previously recovered from HBV infection are at risk for reactivation during chemotherapy, immunosuppression following organ transplantation, and treatment with corticosteroids or immune-modulating agents . Reactivation can be severe, leading to acute liver failure or chronic hepatitis . Delay of treatment until elevation of HBV DNA levels is dangerous and not recommended. Groups at high risk for reactivation include individuals being treated with B-cell-depleting agents particularly rituximab , anthracycline derivates, or 10 mg or greater of prednisone daily for 4 or more weeks. Antiviral prophylaxis for these individuals should be provided for at least 6 months following completion of the immunosuppressive therapy and at least for 12 months following B-cell-depleting agents . To date, there has been insufficient evidence to guide recommendations regarding the role of anti-HBs status in prophylaxis .
In terms of treatment, a nucleotide or nucleoside analogue with a more favorable resistance profile than lamivudine should be initiated for the necessary duration of time . Entecavir has recently been shown to be a more effective prophylactic agent in decreasing the risk of HBV reactivation and hepatitis flares when compared to lamivudine in patients undergoing chemotherapy for diffuse large B-cell lymphoma .
How Do You Distinguish Acute Hepatitis B Infection from Recurrence or Flare of Chronic Hepatitis B Infection?
Acute HBV infection is classified by appearance of HBsAg and anti-HBc IgM . HBV infection persisting for greater than 6 months is considered chronic . In addition to checking for the presence of anti-HBc IgM, distinction between acute hepatitis and flare of chronic hepatitis can be made by looking at sera from both patient groups. Patients with chronic hepatitis demonstrate higher levels of anti-HBe as well as HBeAg/anti-HBe and HBsAg/anti-HBs immune complexes compared to patients with acute hepatitis .
Upon resolution of HBV infection, patients demonstrate both anti-HBc and anti-HBs antibodies. Anti-HBc antibodies persist for life and do not develop in individuals who develop immunity through HBV vaccinations .
Should Patients with Isolated Hepatitis B Core Antibody Be Considered for Vaccination ?
Isolated presence of anti-HBc is not specific and can be indicative of either the “window period” during acute hepatitis B infection, chronic carrier state where HBsAg is unable to be detected, past infection with waning immunity, or presence of a cross-reacting antibody [9, 10]. In the literature, a wide range (up to 20 %) of patients have been reported to be isolated hepatitis B core antibody carriers. Vaccination for hepatitis B in such individuals can help determine the significance of the isolated anti-HBc as well as provide protection to nonimmune individuals .
In previously immune patients, administration of the HBV vaccine would generate an early, high anti-HBs response. The same result would not, however, be observed in individuals who are chronic nonimmune carriers or who have not previously received the HBV vaccine. A follow-up anti-HBs antibody should be ordered 2 weeks after the administration of the HBV vaccine to evaluate response. In individuals with a falsely positive anti-HBc, full immunity would be expected after the administration of the standard three-dose vaccine series .
Do I Need a Liver Biopsy If I Have Hepatitis B and My Viral Load Is Low?
A liver biopsy may be helpful in establishing the extent of liver damage in patients with chronic hepatitis who may otherwise not meet guidelines for treatment . ALT is a convenient marker when assessing liver injury; however, ALT levels can exhibit great variability along the course of the HBV infection. In patients with normal liver transaminases and low HBV viral load, treatment is generally not recommended. However, when a liver biopsy was performed on HBeAg-negative patients with HBV viral loads equal to or less than 10,000 copies/mL (equivalent to 2000 IU/mL) and normal ALT levels, severe hepatic fibrosis was noted in 12 % of patients and mild-to-moderate necroinflammation in 26 % of patients . In this case, a liver biopsy was able to identify individuals with progressive liver disease who should receive hepatitis B treatment. Thus, particularly in patients who are HBeAg(−) who have a borderline low viral load and ALT levels <2× the upper limits of normal, consideration should be given to a liver biopsy to help assess whether treatment should be implemented.
When Do I Need to Worry About Occult Hepatitis B?
Occult hepatitis B infection is defined as the presence of viral HBV DNA in liver tissues in individuals who test negative for HBsAg . Occurrence of occult HBV is highest among hepatitis C carriers. It is a significant issue for blood banks and those involved in organ transplantation in which case HBV can be transmitted to the recipient. Though post-transfusion hepatitis remains a rare occurrence in Western countries, in case of orthotopic liver transplantation (OLT) , rates of HBV transmission have been estimated to be between 17 and 94 % from HBsAg-negative/anti-HBc-positive donors . Similarly, individuals with occult hepatitis B undergoing OLT may develop reinfection of their graft with concomitant complications and need for therapy. Another concern is the potential for reactivation of occult hepatitis B during periods of immunosuppression leading to acute severe hepatitis as well as acceleration of chronic liver disease and development of HCC, especially in individuals simultaneously co-infected with HCV . Thus, a high level of suspicion and liberal virologic testing must be performed to detect this rare but real issue associated with hepatitis B particularly in those from endemic areas.
What If I Miss a Dose of the Hepatitis B Vaccine Series? Do I Have to Repeat all the Shots?
Primary vaccination for HBV consists of three doses of the intramuscular hepatitis B vaccine administered at 0, 1, and 6 months of age to individuals born in the USA. Typically, a protective antibody response is seen in 30–55 % of individuals less than 40 years of age after the first dose, in approximately 75 % of individuals after the second dose, and in greater than 90 % of individuals after the third dose . Age, smoking, obesity, and immune suppression can contribute to decreased vaccine response . No significant effect is seen on development of immunity by increasing the time between the administrations of the first two vaccine doses. The third dose acts primarily as a booster and provides maximal long-term protection. Thus, it is not necessary to repeat all the shots in a vaccination series if a single dose of the vaccine is missed. However, by increasing the time interval between the doses, there is increased risk of acquiring HBV infection in individuals who have a delayed or incomplete response to vaccination .
Though follow-up testing after completion of the vaccination series is not necessary, it is recommended for persons who are at high risk of infection such as healthcare workers, infants of HBsAg-positive mothers, and sexual partners of those with chronic HBV infection .
How Do I Prevent Transmission of Hepatitis B to My Baby If I Am Pregnant?
Infants born to HBV-positive mothers should be given hepatitis B immune globulin (HBIG) and hepatitis B vaccine within 12 h of delivery . Combination of HBIG and hepatitis B vaccine has been shown to be up to 95 % effective in preventing transmission of HBV through birth . Furthermore, both the European Association for the Study of Liver Disease and the Asian Pacific Association for the Study of Liver Disease recommend initiation of antiviral therapy during the third trimester for HBsAg-positive mothers with greater than five million copies/mL and ten million copies/mL of HBV DNA, respectively. Lamivudine , telbivudine , or tenofovir should be started between 28 and 32 weeks, or earlier if the viral load is greater than 108 copies/mL . Telbivudine and tenofovir both carry the advantage of being pregnancy category B drugs . Antiviral therapy should be stopped within 3 months of delivery or immediately after birth if the mother plans to breastfeed her child .
What Is the Risk of Passing HBV to Those I Live With?
Patients with HBV need to be informed regarding the risk of HBV transmission to others. Hepatitis B can be transmitted by close person-to-person contact through open cuts and sores, direct contact with mucosal surfaces, as well as exposure to blood and infectious body fluids such as serum, saliva, and semen . It is recommended that persons with HBV cover up open wounds, clean blood stains with detergent or bleach, and not share toothbrushes or razors . In fact, hepatitis B virus can remain stable at room temperatures for greater than 7 days . Sexual partners also need to be vaccinated against HBV. If a sexual partner is not vaccinated then barrier protection should always be used.