Online ExcluSive James A. McHugh, MD; Samuel Cullison, MD; Chronic hepatitis B infection: Joseph Apuzzio, MD; Joan M. Block, RN, BSN; Chari Cohen, MPH; Shou Ling A workshop consensus Leong, MD; W. Thomas London, MD; Robert J. McNellis, MPH, PA; Richard L. statement and algorithm Neubauer, MD, FACP; Robert Perrillo, MD; Robert Squires, MD, FAAP; Dianne Tarrant, Here, presented with an evidence-based algorithm, MSN, APRN, FNP-BC; Brian J. McMahon, MD are workshop consensus recommendations on whom Swedish Family Medicine, Seattle, Wash (Drs. McHugh and to screen for hepatitis B and when to pursue further Cullison); Maternal Fetal Medi- cine, New Jersey Medical School, evaluation and management. Newark (Dr. Apuzzio); Hepatitis B Foundation, Doylestown, Pa (Mss. Block and Cohen); Family and Community Medicine, Penn State College of Medicine, Practice creening for hepatitis B virus (HBV) infection is simple Hershey (Dr. Leong); Fox Chase and relatively inexpensive. Yet it is underused in every- Cancer Center, Philadelphia, Pa recommendations (Dr. London); American day practice, leaving some HBV-positive patients un- Academy of Physician Assistants, › Screen patients at risk of S aware and at risk for serious health consequences, including Alexandria, Va (Mr. McNellis); contracting hepatits B virus Internal Medicine, Alaska Native cirrhosis, liver failure, and hepatocellular carcinoma (HCC).1 (HBV), especially those from Medical Center, Anchorage, HBV-endemic regions of the In addition, many primary care providers do not follow exist- (Dr. Neubauer); Division of ing guidelines for HBV screening and management.2 Yet they Hepatology, Baylor University world, by testing for hepatitis B Medical Center, Dallas, Tex surface antigen and antibody are often the first, and sometimes the only, clinicians that in- (Dr. Perillo); Division of (HBsAg and anti-HBs). A fected individuals will see. Gastroenterology, Children’s z Why chronic HBV is still a problem. Although the in- Hospital of Pittsburgh, Pa › Vaccinate all infants, (Dr. Squires); University of Alaska children, and adolescents cidence of acute HBV infection has declined significantly as Anchorage School of Nursing, following guidelines of the a result of universal infant vaccination in the United States, Anchorage (Ms. Tarrant); Liver Disease and Hepatitis Program, Centers for Disease Control chronic infections are still prevalent in this country due to Alaska Native Tribal Health and Prevention and American such factors as immigration from areas where HBV is endemic, Consortium, Alaska Native Academy of Pediatrics, as well perinatal transmission, transmission among household con- Medical Center, Anchorage, (Dr. McMahon) as at-risk adults whose screen- tacts, and risky behaviors. In most adolescents and adults, ing results are negative for HBV infection leads to acute hepatitis from which they fully [email protected] both HBsAg and anti-HBs. A recover; chronic infection ensues in only 5% to 10% of cases. The workshop, convened on March › Provide periodic moni- However, 90% of infants and 25% to 50% of children younger 10-11, 2010, was funded by the Hepatitis B Foundation, from its general toring for patients who than 5 years who become infected with HBV go on to develop operating funds. The Foundation is are HBsAg-positive. While supported primarily by federal, state, lifelong infection. Most people with chronic HBV infection do and private grants and individual these patients may appear not exhibit any signs of clinical illness, which makes screening donations, and has small, unrestricted asymptomatic, they are educational grants from Bristol-Myers all the more important—particularly since effective antiviral Squibb, Gilead Sciences, Idenix, Merck, infected with HBV and require and Novartis. No commercial support treatments are available.1,3 further evaluation. A was directly provided for the workshop. To help primary care providers address the issues of › Ms. Cohen owns stock in Bristol-Myers Consult a specialist expe- screening for HBV, the Hepatitis B Foundation convened a work- Squibb and Gilead, and served on rienced in treating hepatitis the Bristol-Myers Squibb advocacy shop of prominent primary care practitioners and specialists advisory board for hepatitis B in 2010. if active liver disease is in hepatitis and liver diseases. The workshop panel reviewed Dr. Perrillo serves on the speaker’s suspected in patients with bureau for Bristol-Myers Squibb and evidence-based guidelines and reports from the American Asso- Gilead Sciences, and is a consultant chronic HBV infection who for Roche Pharmaceuticals and Gilead. ciation for the Study of Liver Diseases (AASLD), the Centers for Dr. McMahon’s spouse owns stock present with elevated alanine in GlaxoSmithKline. The remaining aminotransferase and HBV Disease Control and Prevention (CDC), the National Institutes authors reported no potential conflict DNA >2,000 IU/mL. B of Health (NIH), and the Institute of Medicine (IOM), as well as a of interest relevant to this article. jfponline.com Vol 60, no 9 | SEPTEMBeR 2011 | The jouRnal of family PracTice E1 TABLE 1 Phases of chronic HBV infection (HBsAg+ >6 mos)6 phase labs and histology hBV Dna >20,000 iu/ml* alT normal immune tolerant hBeag detectable no or minimal liver inflammation and fibrosis hBV Dna usually >20,000 iu/ml* immune active alT elevated hBeag may be detectable or not; anti-hBe may be present liver inflammation and fibrosis can develop hBV Dna <2000 iu/ml or undetectable* alT normal inactive hBsag carrier hBeag undetectable; anti-hBe present Screen all minimal to no liver inflammation; fibrosis may regress individuals at hBV Dna levels increase risk for HBV. Reactivation alT normal or elevated hBeag undetectable alT, alanine aminotransferase; anti-hBe, antibody to hBeag; hBsag, hepatitis B surface antigen; hBeag, hepatitis B e-antigen; hBV, hepatitis B virus. *for hBV Dna: 2000 iu/ml=104 copies/ml; 20,000 iu/ml=105 copies/ml. recent Hepatitis B Foundation publication on circulating virus, indicated by HBV DNA levels. HBV screening and management in children However, the body does not mount an immune and other relevant publications.1-5 The resul- response to the virus; there is no active liver tant algorithm and consensus recommenda- disease, and the serum ALT level is normal. tions presented here can assist primary care When the immune system recognizes providers in applying evidence-based guide- HBV as foreign, the patient enters the immune lines for HBV infection to everyday practice. active phase, wherein liver inflammation and fibrosis can develop and ALT is correspond- ingly elevated. HBV antibody (anti-HBe) may 3 phases of HBV infection: be present. What screening results mean In nearly all patients, HBeAg seroconver- Hepatitis B surface antigen (HBsAg) that is sion to HBeAg-negative/anti-HBe-positive persistently detectable in a patient’s serum status occurs spontaneously or as a result for more than 6 months signifies chronic of antiviral treatment. After seroconversion, HBV infection.1,3,4 The 3 immunologic phases most patients enter the HBsAg inactive of chronic HBV infection—immune toler- carrier phase, in which a strong cellular im- ant, immune active, and inactive carrier—are mune response is able to suppress, but not determined by serum levels of alanine ami- eliminate, the virus. This phase typically notransferase (ALT) and HBV DNA, and the features low or undetectable serum levels of presence or absence of hepatitis B e antigen HBV DNA and normal ALT levels. Over time, (HBeAg) (TABLE 1).6 liver inflammation and fibrosis improve, and All individuals with chronic HBV infec- the risk of cirrhosis and HCC declines.7 tion are initially HBeAg positive. Those in the However, some patients do not enter immune tolerant phase also have high levels of the inactive phase after HBeAg seroconver- E2 The jouRnal of family PracTice | SEPTEMBeR 2011 | Vol 60, no 9 CHRONIC HEPATITIS B INFECTION TABLE 2 FDA-approved drugs for the treatment of chronic HBV infection3 Drug labeled for use in: interferons interferon alfa-2b (intron a) adults; children >12 months peginterferon alfa-2a (pegasys) adults Nucleos(t)ide analogs lamivudine (epivir-hBV) adults; children >3 years adefovir dipivoxil (hepsera) adults; children >12 years entecavir (Baraclude) adults; children >16 years Telbivudine (Tyzeka) adults Tenofovir disoproxil fumarate (Viread) adults hBV, hepatitis B virus. Vaccinate children and sion. They instead continue to exhibit active malization of ALT. Seven drugs are approved adolescents viral replication and liver disease due to the by the U.S. Food and Drug Administration according to CDC emergence of one or more HBeAg-negative (FDA) for treatment of chronic hepatitis B in- guidelines, as viral mutants. Moreover, in as many as 20% fection (TABLE 2).3 The decision to treat must well as at-risk of those who enter the inactive HBsAg car- take into account multiple factors, including adults who test rier state, infection will reactivate and pos- phase of disease, age of the patient, extent of negative for sibly return the patient to HBeAg-positive liver involvement on biopsy, potential efficacy HBsAg and status. HBV infection is a dynamic condition: of and adverse events associated with avail- anti-HBs. Individuals can go from active disease to the able therapies, cost of long-term medication, inactive phase and then have reactivation of and, importantly, the high risk of development liver disease at any point during their life- of nucleos(t)ide analog-resistant viral