Management of Hepatitis B: Our Practice and How It Relates to the Guidelines
2013; Elsevier BV; Volume: 12; Issue: 1 Linguagem: Inglês
10.1016/j.cgh.2013.04.036
ISSN1542-7714
AutoresSuna Yapalı, Nizar Talaat, Anna S. Lok,
Tópico(s)Liver Disease Diagnosis and Treatment
ResumoSeven drugs have been approved for the treatment of chronic hepatitis B. Antiviral treatment has been shown to be effective in suppressing hepatitis B virus replication, decreasing inflammation and fibrosis in the liver, and preventing progression of liver disease. However, current medications do not eradicate hepatitis B virus; therefore, a key question is which patients need to start treatment and which patients can be monitored. Professional societies have developed guidelines to assist physicians in recognition, diagnosis, and optimal management of patients with chronic hepatitis B. These guidelines suggest preferred approaches, and physicians are expected to exercise clinical judgment to determine the most appropriate management based on the circumstances of the individual patient. This article reviews recommendations in hepatitis B guidelines and the basis for those recommendations, and we discuss what we do in our practice to illustrate factors that may influence decisions regarding hepatitis B management. Seven drugs have been approved for the treatment of chronic hepatitis B. Antiviral treatment has been shown to be effective in suppressing hepatitis B virus replication, decreasing inflammation and fibrosis in the liver, and preventing progression of liver disease. However, current medications do not eradicate hepatitis B virus; therefore, a key question is which patients need to start treatment and which patients can be monitored. Professional societies have developed guidelines to assist physicians in recognition, diagnosis, and optimal management of patients with chronic hepatitis B. These guidelines suggest preferred approaches, and physicians are expected to exercise clinical judgment to determine the most appropriate management based on the circumstances of the individual patient. This article reviews recommendations in hepatitis B guidelines and the basis for those recommendations, and we discuss what we do in our practice to illustrate factors that may influence decisions regarding hepatitis B management. The advent of sensitive assays for the detection of hepatitis B virus (HBV) and the availability of potent antiviral agents have improved the management of patients with chronic hepatitis B (CHB); however, current treatment cannot eradicate the virus. Because of the high cost and risk of adverse events, as well as drug resistance with long-term treatment, the most important question regarding the management of hepatitis B is which patients need to be treated now and which patients can be monitored and have treatment deferred. The American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL) have developed clinical practice guidelines to assist physicians in recognition, diagnosis, and optimal management of patients with CHB.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar These guidelines suggest preferred approaches and physicians are expected to exercise clinical judgment to determine the most appropriate management based on the circumstances of the individual patient. Recommendations of the 3 guidelines vary slightly because of differences in timing when the guidelines were issued and also differences in available resources. This article reviews recommendations in hepatitis B guidelines and the basis for those recommendations and we discuss what we do in our practice to illustrate factors that may influence the management of CHB. The natural course of chronic HBV infection consists of 4 phases; however, patients may not experience all phases (Figure 1).4Lok A.S. Navigating the maze of hepatitis B treatments.Gastroenterology. 2007; 132: 1586-1594Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Host, viral, and environmental factors influence progression of HBV-related liver disease. Recent studies have focused on the importance of HBV replication as an independent predictor of cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths.5Chen C.J. Yang H.I. Su J. et al.Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.JAMA. 2006; 295: 65-73Crossref PubMed Scopus (2508) Google Scholar, 6Iloeje U.H. Yang H.I. Su J. et al.Predicting cirrhosis risk based on the level of circulating hepatitis B viral load.Gastroenterology. 2006; 130: 678-686Abstract Full Text Full Text PDF PubMed Scopus (1308) Google Scholar However, other factors including sex, age, HBV genotype, co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus, increased alanine aminotransferase (ALT) level, and alcohol and tobacco use also contribute to cirrhosis and HCC. Practice guidelines recommend that the treatment decision be made based on clinical status, serum HBV DNA and ALT levels, hepatitis B e antigen (HBeAg) status, and liver histology if available.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar All guidelines recommend starting treatment as soon as possible in patients with life-threatening liver disease: acute liver failure, decompensated cirrhosis, or severe exacerbation of CHB regardless of HBV DNA and ALT levels. Although data from randomized controlled trials in these settings are lacking, in case series antiviral treatment has been shown to be beneficial with little or no adverse effects. In addition, for patients requiring liver transplantation, viral suppression decreases the risk of HBV recurrence after transplant.7Papatheodoridis G.V. Cholongitas E. Archimandritis A.J. et al.Current management of hepatitis B virus infection before and after liver transplantation.Liver Int. 2009; 29: 1294-1305Crossref PubMed Scopus (65) Google Scholar The AASLD and APASL guidelines recommend antiviral therapy in patients with compensated cirrhosis and serum HBV DNA level greater than 2000 IU/mL regardless of ALT level.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar For patients with increased ALT levels, the AASLD guidelines recommend treatment regardless of HBV DNA level.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar The EASL guideline recommends treatment of patients with any detectable level of serum HBV DNA.2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar There is growing evidence that long-term treatment with nucleos(t)ide analogues (NUCs) not only prevents disease progression but also reverses fibrosis and cirrhosis. In a double-blind, randomized, placebo-controlled study of 651 patients with advanced fibrosis or cirrhosis, who were HBeAg-positive or had high levels of HBV DNA (>150,000 IU/mL), lamivudine therapy was shown to decrease progression of liver disease.8Liaw Y.F. Sung J.J. Chow W.C. et al.Lamivudine for patients with chronic hepatitis B and advanced liver disease.N Engl J Med. 2004; 351: 1521-1531Crossref PubMed Scopus (1984) Google Scholar A follow-up report of the phase 3 tenofovir vs adefovir trial including 348 patients who had paired biopsies at baseline and year 5 showed that 51% of patients had a decrease in fibrosis stage by 1 or more and 71 of 96 (74%) patients with cirrhosis on initial biopsy had regression of cirrhosis.9Marcellin P. Gane E. Buti M. et al.Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study.Lancet. 2013; 381: 468-475Abstract Full Text Full Text PDF PubMed Scopus (1208) Google Scholar All guidelines agree that treatment should be initiated in noncirrhotic patients with serum HBV DNA levels greater than 20,000 IU/mL and persistently increased ALT levels and/or histologic evidence of moderate/severe inflammation or fibrosis. However, cut-off values of HBV DNA and ALT levels and the need for liver biopsy in determining treatment indications vary slightly among the guidelines (Table 1). The AASLD guideline suggests an arbitrary HBV DNA level of 20,000 IU/mL for initiating treatment.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar The APASL guideline recommends an HBV DNA threshold of 20,000 IU/mL for HBeAg-positive patients and 2000 IU/mL for HBeAg-negative patients, whereas the EASL guideline recommends a cut-off value of 2000 IU/mL irrespective of HBeAg status.2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar All guidelines agree that serial HBV DNA and ALT level is more important than a single value in making treatment decisions. For patients who fulfill the criteria for HBV DNA, the EASL recommends treating patients with ALT levels greater than the upper limit of normal (ULN) if the liver biopsy (or noninvasive markers validated in HBV-infected patients) shows moderate-severe inflammation and/or at least moderate fibrosis, whereas the APASL and AASLD recommend treatment for patients with an ALT level greater than 2 times the ULN. The AASLD guideline suggested lower values be used to define the ULN for an ALT level of 30 U/L for men and 19 U/L for women, and a liver biopsy should be performed in patients with mildly increased ALT levels, particularly in patients older than age 40.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar Besides HBV replication status, ALT levels, and liver histology, all guidelines recommend that patient age, HBeAg status, family history of HCC, occupational requirements, family planning, and patient preference should be considered in making treatment decisions.Table 1Comparison of AASLD, APASL, and EASL Guideline Recommendations Regarding Treatment of Hepatitis B1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google ScholarAASLD(2009)APASL(2012)EASL(2012)HBV DNA cut-off level, IU/mL HBeAg-positive20,00020,0002000 HBeAg-negative2000–20,00020002000ALT cut-off level, U/L30 for men, 19 for womenTraditional cut-off value of 40 U/LTraditional cut-off value of 40 U/LRecommendations for treatment and monitoring Noncirrhotic patients HBeAg-positiveHBV DNA >20,000 IU/mL, ALT >2× ULNMonitor for 3–6 moTreat if no spontaneous HBeAg lossLiver biopsy before treatment is optionalHBV DNA >20,000 IU/mL, ALT >2× ULNMonitor for 3–6 moTreat if no spontaneous HBeAg lossLiver biopsy before treatment is optionalHBV DNA >2000 IU/mL, ALT >ULNMonitor for 3–6 moLiver biopsy (or noninvasive markers of fibrosis) is recommendedTreat if no spontaneous HBeAg loss and biopsy shows moderate-severe inflammation and/or at least moderate fibrosisHBV DNA >20,000 IU/mL, ALT ≤2× ULNMonitor every 3–6 moConsider biopsy in patients >40 y, ALT persistently 1–2× ULN, or with family history of HCCTreat if biopsy shows moderate/severe inflammation or significant fibrosisHBV DNA >20,000 IU/mL, ALT 1–2× ULNMonitor every 1–3 moConsider biopsy in patients >40 y, ALT persistently 1–2× ULN, or with family history of HCCTreat if biopsy shows moderate/severeinflammation or fibrosisHBV DNA >20,000 IU/mL, ALT 30 y, ALT persistently 1–2× ULN, or with family history of HCCTreat if biopsy shows moderate-severe inflammation or significant fibrosis HBeAg-negative patientsHBV DNA >20,000 IU/mL, ALT >2× ULNTreatment is clearly indicated, liver biopsy is optionalHBV DNA >2000 IU/mL, ALT >2× ULNTreatment is clearly indicated, liver biopsy is optionalHBV DNA >20,000 IU/mL, ALT >2× ULNTreatment is clearly indicated, liver biopsy is optionalHBV DNA 2000–20,000 IU/mL, ALT 1–2× ULNConsider liver biopsyTreat if liver biopsy shows moderate/severe inflammation or significant fibrosisHBV DNA >2000 IU/mL, ALT 1–2× ULNMonitor ALT and HBV DNA every 1–3 moConsider liver biopsy if patient is ≥40 yTreat if biopsy shows moderate/severe inflammation or fibrosisHBV DNA >2000 IU/mL, ALT >ULNLiver biopsy (or noninvasive markers of fibrosis) is recommendedTreat if biopsy shows moderate-severe inflammation and/or at least moderate fibrosisHBV DNA ≤2000 IU/mL, ALT ≤ULNMonitorHBV DNA ≤2000 IU/mL, ALT ≤ULNMonitorHBV DNA ≤2000 IU/mL, ALT ≤ULNMonitor Cirrhosis CompensatedHBV DNA >2000 IU/mLTreat regardless of ALT levelHBV DNA >2000 IU/mLTreat regardless of ALT levelHBV DNA detectableTreat regardless of ALT levelHBV DNA ULNHBV DNA ULN DecompensatedRegardless of HBV DNA or ALT levelTreat and refer for liver transplantationRegardless of HBV DNA or ALT levelTreat and refer for liver transplantationRegardless of HBV DNA and ALT levelTreat and refer for liver transplantation HCC surveillanceUS every 6 monthsUS and AFP every 6 monthsUS every 6 monthsUS, ultrasound. Open table in a new tab US, ultrasound. All guidelines recommend 3 to 6 months of observation in HBeAg-positive patients and treatment if there is no spontaneous HBeAg seroconversion, but a period of pretreatment observation is not necessary in HBeAg-negative patients who meet criteria for treatment. Recommendations for treatment of noncirrhotic HBeAg-positive and HBeAg-negative patients are summarized in Figures 2 and 3.Figure 3Algorithm showing guideline recommendations for the treatment of patients with HBeAg-negative CHB. *EASL indicates treatment may be initiated in patients with normal ALT level if the biopsy shows moderate-severe inflammation or fibrosis.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In our practice, we initiate treatment as soon as we recognize that the patient has acute liver failure or severe acute hepatitis B (prolonged jaundice or coagulopathy), severe exacerbation of CHB, or decompensated cirrhosis, regardless of ALT or HBV DNA levels. For patients with compensated cirrhosis, we follow the AASLD guidelines, although increasingly we initiate treatment even in patients with HBV DNA levels less than 2000 IU/mL. We have become more liberal in treating patients with compensated cirrhosis because of the high barrier to resistance of the newer antiviral agents entecavir and tenofovir, the established safety of these drugs, and the difficulty in predicting which patient with cirrhosis will develop HCC. For patients without cirrhosis, we follow the AASLD guidelines and recommend treatment if HBV DNA level is greater than 20,000 IU/mL and ALT level is greater than 2 times the ULN. For both HBeAg-positive and HBeAg-negative patients in the gray zone, we recommend liver biopsy particularly if they are older than age 40. We inform the patients that a histologic finding of moderate/severe inflammation/fibrosis will urge us to treat, but the absence of these findings does not rule out the risk of HCC. For patients who decline a liver biopsy, we rely on a combination of ultrasound and laboratory tests including the aspartate-aminotransferase-platelet-ratio index to assess stage of liver disease because liver stiffness measurement is not readily available in the United States. All guidelines agree that treatment is not required in the immune tolerance phase because liver injury is mild and the likelihood of response (in particular HBeAg seroconversion) to available treatment is low.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar Liver biopsy should be considered in patients with persistent borderline normal or slightly increased ALT levels, particularly those older than age 40 (age 30 according to the EASL guidelines), and treatment should be recommended if the biopsy shows moderate/severe inflammation and/or fibrosis. All guidelines recommend that patients in the inactive carrier phase do not require treatment.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar We do not recommend treatment of patients in the immune tolerance phase except in the context of clinical trials or in patients older than the age of 40. The rationale for treating HBeAg-positive patients who remain in the immune tolerance phase after the age of 40 is because the population-based REVEAL study, in which 67% of patients enrolled were older than age 39, showed that persistently high serum HBV DNA levels are associated with increased risk of cirrhosis, HCC, and liver-related death.5Chen C.J. Yang H.I. Su J. et al.Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.JAMA. 2006; 295: 65-73Crossref PubMed Scopus (2508) Google Scholar Other studies in Taiwan found that patients who remained HBeAg-positive after age 40 had an increased risk of HCC.6Iloeje U.H. Yang H.I. Su J. et al.Predicting cirrhosis risk based on the level of circulating hepatitis B viral load.Gastroenterology. 2006; 130: 678-686Abstract Full Text Full Text PDF PubMed Scopus (1308) Google Scholar We do not recommend treatment of patients who are confirmed to be in the inactive carrier phase after 3 or more evaluations showing persistently normal ALT level and low ( 7–8 log IU/mL).10Xu W.M. Cui Y.T. Wang L. et al.Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study.J Viral Hepat. 2009; 16: 94-103Crossref PubMed Scopus (299) Google Scholar, 11Han G.R. Cao M.K. Zhao W. et al.A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection.J Hepatol. 2011; 55: 1215-1221Abstract Full Text Full Text PDF PubMed Scopus (299) Google Scholar The EASL and APASL recommends prophylactic antiviral treatment in pregnant women with high levels of viremia. Lamivudine, telbivudine, or tenofovir may be considered. Reactivation of HBV replication in patients receiving immunosuppressive therapy can lead to severe hepatitis, liver failure, and even death. The EASL and AASLD guidelines recommend testing for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) in patients who will be receiving chemotherapy or immunosuppressive therapy.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar The APASL guideline recommends screening for HBsAg only, and additional testing for anti-HBc in patients who will be receiving biologic treatment such as rituximab or anti–tumor necrosis factor-α.3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar Prophylactic antiviral therapy has been shown to decrease the risk of HBV reactivation.12Loomba R. Rowley A. Wesley R. et al.Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy.Ann Intern Med. 2008; 148: 519-528Crossref PubMed Scopus (406) Google Scholar All 3 guidelines recommend initiating prophylactic antiviral therapy in HBsAg-positive patients who will be receiving cancer chemotherapy or immunosuppressive therapy and monitoring of HBsAg-negative, anti–HBc-positive patients and initiating antiviral therapy when serum HBV DNA level becomes detectable.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar The EASL guideline recommends prophylactic antiviral therapy in patients who will receive rituximab or stem cell transplantation.2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar We defer treatment in women who have plans to be pregnant unless they have active or advanced liver disease. We discuss the benefits and risks of prophylactic antiviral treatment with women who have serum HBV DNA level greater than 7 log IU/mL during the second trimester of pregnancy. We recommend starting antiviral treatment around week 30 if the patient agrees and prefer tenofovir in this setting. When the goal of treatment is to prevent perinatal transmission, we stop treatment immediately after delivery and emphasize the importance of monitoring for postpartum flares. We discuss the potential risk of exposing the infant to the antiviral medication if treatment is continued, but we do not advise against breastfeeding. We recommend HBsAg and anti-HBc testing of all patients who will be receiving chemotherapy or immunosuppressive therapy and prophylactic antiviral therapy in patients at high risk of HBV reactivation: all HBsAg-positive patients and HBsAg-negative, anti–HBc-positive patients with hematologic malignancies or who will require rituximab or long-term high-dose steroid therapy. All guidelines recommend that patients who are not deemed to be treatment candidates at presentation and those who decide to defer treatment should undergo monitoring. Guidelines recommend monitoring immune tolerant patients at 3-6 month intervals and more frequent monitoring if ALT levels become increased.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar For HBeAg-negative patients with normal ALT and HBV DNA levels less than 2000 IU/mL, the AASLD guideline recommends testing for ALT level every 3 months during the first year to confirm that they are truly in the inactive carrier state.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar Thereafter, patients should be monitored by ALT and HBV DNA levels every 6 to 12 months.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar, 3Liaw Y.F. Kao J.H. Piratvisuth T. et al.Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update.Hepatol Int. 2012; 6: 531-561Crossref PubMed Scopus (805) Google Scholar For patients with persistently normal ALT and HBV DNA levels between 2000 and 20,000 IU/mL, the EASL guideline recommends monitoring ALT level every 3 months and HBV DNA level every 6 to 12 months for the first 3 years.2EASL clinical practice guidelines: management of chronic hepatitis B virus infection.J Hepatol. 2012; 57: 167-185PubMed Google Scholar We emphasize to all patients that HBV infection is a chronic condition and regular monitoring is critical. We follow up young (<30 y) patients in the immune tolerance phase every 6 to 12 months and older patients every 3 to 6 months. We monitor HBeAg-negative patients every 3 months over a 1-year period before determining they are truly in the inactive carrier phase, at which time we decrease monitoring to every 6 to 12 months. We ask patients to inform us if they have unexplained fatigue or if they are diagnosed with cancers or other medical conditions that require long-term steroid or other immunosuppressive therapy. The AASLD guideline recommends HCC surveillance for HBV carriers who are Asian men older than age 40 and Asian women older than age 50, persons with cirrhosis, persons with a family history of HCC, first-generation African Americans older than age 20, and any carrier older than age 40 with persistent or intermittent ALT increases and/or HBV DNA levels greater than 2000 IU/mL.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar Surveillance with ultrasonography at 6-month intervals is recommended by the EASL and AASLD guidelines.1Lok A.S. McMahon B.J. Chronic hepatitis B: update 2009.Hepatology. 2009; 50: 661-662Crossref PubMed Scopus (2399) Google Scholar, 13Bruix J. Sherman M. Management of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (6549) Google Scholar, 14EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2012; 56: 908-943PubMed Google Scholar The APASL recommends a combination of ultrasound and α-fetoprotein (AFP) testing every 6 months.15Omata M. Lesmana L.A. Tateishi R. et al.Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma.Hepatol Int. 2010; 4: 439-474Crossref PubMed Scopus (830) Google Scholar We follow the AASLD guidelines regarding which patients should undergo HCC surveillance, but we rely on both AFP and ultrasound. Although AFP has limited sensitivity and specificity, the reliability of ultrasound in the surveillance of HCC is suboptimal and operator-dependent. Studies have shown that AFP and ultrasound are complementary. We evaluate absolute as well as delta AFP values. Approved medications for chronic HBV infection include interferon (IFN), either standard or pegylated IFN (PEG-IFN), and NUCs, lamivudine, adefovir dipivoxil, telbivudine, entecavir, and tenofovir disoproxil fumarate. Rates of response and resistance to these medications are summarized in Table 2.16Scaglione S.J. Lok A.S. Effectiveness of hepatitis B treatment in clinical practice.Gastroenterology. 2012; 142 (e1361): 1360-1368Abstract Full Text Full Text PDF PubMed Scopus (117) Google ScholarTable 2Response Rates and Genotypic Resistance Rates to Approved Therapies in HBeAg-Positive and HBeAg-Negative Patients18Marcellin P. Lau G.K. Bonino F. et al.Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B.N Engl J Med. 2004; 351: 1206-1217Crossref PubMed Scopus (1053) Google ScholarTreat
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