Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance

Abstract

Potential conflict of interest: Dr. Hwang received grants from Merck and Gilead. Dr. Chang advises Arbutus. Dr. Lok received grants from Gilead and Bristol‐Myers Squibb. Dr. Jonas consults for Gilead and received grants from Bristol‐Myers Squibb and Roche. Dr. Brown consults and received grants from Gilead. Dr. Bzowej received grants from Gilead, Allergan and Cirius. Dr. Terrault received grants from Gilead and Bristol‐Myers Quibb. Dr. Wong is a member of the United States Preventive Services Task Force (USPSTF). This article does not necessarily represent the views and policies of the USPSTF. The funding for the development of this Practice Guidance was provided by the American Association for the Study of Liver Diseases. This practice guidance was approved by the American Association for the Study of Liver Diseases on December 4, 2017. Purpose and Scope of the Guidance This AASLD 2018 Hepatitis B Guidance is intended to complement the AASLD 2016 Practice Guidelines for Treatment of Chronic Hepatitis B1 and update the previous hepatitis B virus (HBV) guidelines from 2009. The 2018 updated guidance on chronic hepatitis B (CHB) includes (1) updates on treatment since the 2016 HBV guidelines (notably the use of tenofovir alafenamide) and guidance on (2) screening, counseling, and prevention; (3) specialized virological and serological tests; (4) monitoring of untreated patients; and (5) treatment of hepatitis B in special populations, including persons with viral coinfections, acute hepatitis B, recipients of immunosuppressive therapy, and transplant recipients. The AASLD 2018 Hepatitis B Guidance provides a data‐supported approach to screening, prevention, diagnosis, and clinical management of patients with hepatitis B. It differs from the published 2016 AASLD guidelines, which conducted systematic reviews and used a multidisciplinary panel of experts to rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations Assessment, Development and Evaluation system in support of guideline recommendations.1 In contrast, this guidance document was developed by consensus of an expert panel, without formal systematic review or use of the Grading of Recommendations Assessment, Development, and Evaluation system. The 2018 guidance is based upon the following: (1) formal review and analysis of published literature on the topics; (2) World Health Organization guidance on prevention, care, and treatment of CHB5; and (3) the authors’ experience in acute hepatitis B and CHB. Intended for use by health care providers, this guidance identifies preferred approaches to the diagnostic, therapeutic, and preventive aspects of care for patients with CHB. As with clinical practice guidelines, it provides general guidance to optimize the care of the majority of patients and should not replace clinical judgement for a unique patient. This guidance does not seek to dictate a “one size fits all” approach for the management of CHB. Clinical considerations may justify a course of action that differs from this guidance. Interim Data Relevant to the AASLD 2018 Hepatitis B Guidance Since the publication of the 2016 AASLD Hepatitis B Guidelines, tenofovir alafenamide (TAF) has been approved for treatment of CHB in adults. TAF joins the list of preferred HBV therapies, along with entecavir, tenofovir disoproxil fumarate (TDF), and peginterferon (peg‐IFN; Tables 1 and 2)6 (section: Updated Recommendations on the Treatment of Patients With Chronic Hepatitis B). Additionally, studies on the use of TDF for prevention of mother‐to‐child transmission led to TDF being elevated to the level of preferred therapy in this setting (section 1C of Screening, Counseling, and Prevention of Hepatitis B). Table 1 - Approved Antiviral Therapies in Adults and Children Drug Dose in Adultsa Use in Childrena Pregnancy Categoryb Potential Side Effectsb Monitoring on Treatmentc Preferred Peg‐IFN‐α‐2a (adult) IFN‐α‐2b (children) 180 mcg weekly ≥1 year dose: 6 million IU/m2 three times weeklyd C Flu‐like symptoms, fatigue, mood disturbances, cytopenia, autoimmune disorders in adults, anorexia and weight loss in children Complete blood count (monthly to every 3 months) TSH (every 3 months) Clinical monitoring for autoimmune, ischemic, neuropsychiatric, and infectious complications Entecavir 0.5 mg dailye ≥2 years dose: weight‐based to 10‐30 kg; above 30 kg: 0.5 mg dailye C Lactic acidosis (decompensated cirrhosis only) Lactic acid levels if there is clinical concern Test for HIV before treatment initiation Tenofovir dipovoxil fumarate 300 mg daily ≥12 years B Nephropathy, Fanconi syndrome, osteomalacia, lactic acidosis Creatinine clearance at baseline If at risk for renal impairment, creatinine clearance, serum phosphate, urine glucose, and protein at least annually Consider bone density study at baseline and during treatment in patients with history of fracture or risks for osteopenia Lactic acid levels if there is clinical concern Test for HIV before treatment initiation Tenofovir alafenamide 25 mg daily — There are insufficient human data on use during pregnancy to inform a drug‐associated risk of birth defects and miscarriage. Lactic acidosis Lactic acid levels if clinical concern Assess serum creatinine, serum phosphorus, creatinine clearance, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate Test for HIV before treatment initiation Nonpreferred Lamivudine 100 mg daily ≥2 years dose: 3 mg/kg daily to max 100 mg C Pancreatitis Lactic acidosis Amylase if symptoms are present Lactic acid levels if there is clinical concern Test for HIV before treatment initiation Adefovir 10 mg daily ≥12 years C Acute renal failure Fanconi syndrome Lactic acidosis Creatinine clearance at baseline If at risk for renal impairment, creatinine clearance, serum phosphate, urine glucose, and urine protein at least annually Consider bone density study at baseline and during treatment in patients with history of fracture or risks for osteopenia Lactic acid levels if clinical concern Telbivudine 600 mg daily — B Creatine kinase elevation and myopathy Peripheral neuropathy Lactic acidosis Creatine kinase if symptoms are present Clinical evaluation if symptoms are present Lactic acid levels if there is clinical concern aDose adjustments are needed in patients with renal dysfunction.bIn 2015, the U.S. Food and Drug Administration replaced the pregnancy risk designation by letters A, B, C, D, and X with more specific language on pregnancy and This is being in and to TAF includes is not approved for children with chronic hepatitis B, is approved for treatment of chronic hepatitis may using this for children with chronic The of treatment in is is 1 mg daily if the is or if Table - of Approved Antiviral Therapies in Adults with Chronic Hepatitis B and Tenofovir Tenofovir to loss — — loss 3 years 1 Entecavir Tenofovir Tenofovir to loss 6 3 years 6 of of 3 years of years of for for and tenofovir disoproxil for tenofovir for for and tenofovir disoproxil for tenofovir by and for and is a that of to HBV TAF is more TDF in and the to more a to used with and renal and bone 3 of hepatitis B patients with to TAF 25 mg daily or TDF 300 mg daily in a with serum HBV in in loss in and hepatitis B loss in in the TAF and TDF that and serum HBV and and and in TAF and TDF a 3 of patients with to TAF 25 mg daily or TDF 300 mg daily in a in in the TAF and TDF in serum HBV in of TAF patients and of TDF with 1 The approved of TAF is 25 mg with needed creatinine clearance is In 3 TAF TDF in bone density and renal at of In the in the rate was for TAF the was in TDF patients In the in the rate was in TAF the for TDF patients was In and bone density the in bone density for TAF TDF was for patients and in patients In human virus TAF TDF therapy for to that TAF a on bone density and renal with patients on TAF TDF or treatment of renal complications data in patients are with to the on clinical as renal and fracture the of TAF with evidence of led to the preferred HBV for patients studies of from TDF to TAF from the HIV In studies of to a to TAF TDF treatment of an was with in renal the and bone studies that TAF has a TDF and in studies of to 1 Screening, Counseling, and Prevention of Hepatitis B The of the of hepatitis B. Chronic acute is by the of for at least 6 The of with of persons as as to and as In developed the is from or and in with HBV is by and and by by and children in In HBV is transmission the of chronic transmission in the United in children of not appropriate HBV at The majority of children and with CHB in the United States are or HBV the for The risk of chronic HBV acute from in of to in and children to in In persons are more to chronic HBV acute Table 3 at risk for CHB should for HBV and if and to hepatitis B should used for to hepatitis B for as as are for and to from previous HBV HBV does not to Table 3 - at for HBV in of or HBV of and and and and of and of and and and and and and persons not as an in with HBV with immunosuppressive therapy, including to and for or with elevated or of of or with renal including and to with chronic with and of are not in a during the previous 6 evaluation or treatment for a Health care and at risk for to blood or and of for to with or of HBV are the of blood or that of persons with are years of for with are should hepatitis B if Table - of for HBV Test Chronic hepatitis B and management needed HBV management or or immunosuppressive therapy HBV or HBV if if not from of or and not persons may for not may or may not with the on or the risk The of for and for a of to populations, the is previous to HBV the majority of persons from acute HBV in and to been with HBV for before In the the risk of or cirrhosis to HBV is In the persons are at risk of with an rate that to to with chronic HBV with levels more if are if are and are in with of HBV or HIV or hepatitis C virus with more specific may a in persons from with risk for HBV and more may the of HBV during the of acute hepatitis persons should for of to of the risk for HBV for in blood if in Since the the of has to in blood and in with HIV or to or immunosuppressive therapy are at risk for if HBV and should for The majority of for not HBV with specific to or to hepatitis B and HBV with a HBV a HBV does not levels of HBV in blood in an on the and of the used and HBV in the study the of patients an to HBV with the majority a to hepatitis B to persons without HBV for all in Table should HBV to HBV with to levels 3 or data that may the of using an with HBV the of hepatitis B transmission the clinical of the patient. persons are for for are at risk of HBV the risk or immunosuppressive are or in Screening, Counseling, and Prevention of Hepatitis B, all persons are for or without should at risk for HBV in this Guidance on for Hepatitis B should using and is in all persons in with a of persons not as in with HBV persons immunosuppressive therapy, and the in Table persons should for to is not is an in patients HIV are to or and immunosuppressive or renal and in blood if Screening, Counseling, and Prevention of Hepatitis B, B, Patients with chronic HBV should and prevention of transmission as as the of specific been to on the of CHB syndrome and to of more of for and more for are with risk of cirrhosis and the risk of of are the approach is to or with CHB should hepatitis if not persons should transmission to Table of risk of HBV and should if for HBV serological or not been or not the should of HBV from health care to patients has been to in persons with CHB are the for and Prevention that should seek and from an expert review If serum HBV therapy is and of is if serum HBV is to and that Since the U.S. of has that it is for and to are to special to for children in the in and Table - 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at of in with of and with with or HIV with or history of with elevated or with or HBV list is not The of treatment is the of which is by of levels and a in on patients with elevated of HBV and of the for or The of cirrhosis may treatment as is the in HBV are not in patients with or HBV patients with levels may including during treatment of and if the levels treatment with preferred or is of HBV may to which should a on The approved treatment of chronic hepatitis is is the of without in or Treatment as from to the virological The of with does not the of an virological with to of In the study of