WHO Guidelines for Prevention, Care and Treatment of Individuals Infected with HBV: A US Perspective

Abstract

The prevalence of chronic hepatitis B (CHB) differs globally. CHB is responsible for 30% of all deaths from cirrhosis and 40% from hepatocellular carcinoma. The WHO developed guidelines in 2015 on prevention, care, and treatment of chronic HBV infection targeted to program managers in all health care settings, particularly in low- and middle-income countries. Several of the recommendations differ from those of the major Liver Societies, including the American Association for the Study of Liver Diseases (AASLD). This review highlights key differences between the AASLD and WHO guidelines and discusses the impact on management of CHB.

Keywords: AASLD guidelines; Chronic hepatitis B virus Infection; WHO guidelines.

Figure 1:. Global Estimates of the Prevalence of HBsAg.

HBsAg Hepatitis B surface antigen. From Schweitzer A, Horn J, Mikolajczyk RT. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386:1546–55, with permission.

Figure 2:. Countries Providing Hepatitis B Birth Dose (HepB-BD) in 2014

In 2014 only, half of all countries globally had adopted HepB-BD as part of their national immunization program and less than 38% of babies born worldwide received HepB-BD within the recommended time frame. Adapted from Schweitzer A, Horn J, Mikolajczyk RT. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386:1546–55, with permission.

Figure 3:. Algorithm of WHO Recommendations on the Management of Persons with Chronic Hepatitis B Infection

Treatment and monitoring algorithm for patients with CHB based upon WHO guidelines. Adapted from Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection, WHO 2015. WHO: World Health Organization; HBsAg Hepatitis B surface antigen NITs non-invasive tests, ALT alanine aminotransferase level, APRI aspartate aminotransferase-to-platelet-ratio index Chronic hepatitis B defined as persistence of HBsAg for six months or more. ^aClinical features of decompensated cirrhosis: ascites, variceal hemorrhage and hepatic encephalopathy), coagulopathy or jaundice. Other clinical features of cirrhosis include hepatomegaly, splenomegaly, pruritus, fatigue, arthralgias, palmar erythema, peripheral edema. ^bThe age cutoff of >30 years is not absolute and some persons with CHB less than 30 years may also meet criteria for antiviral treatment. ^cALT levels fluctuate in persons with chronic hepatitis B and require longitudinal monitoring to determine the trend. Upper limits for normal ALT have been defined as below 30 U/L for men and 19 U/L for women, though local laboratory normal ranges should be applied. Persistently normal/abnormal may be defined as three ALT determinations below or above the upper limit of normal, made at unspecified intervals during a 6–12-month period or predefined intervals during 12-month period. ^dWhere HBV DNA testing is not available, treatment may be considered based on persistently abnormal ALT levels, but other common causes of persistently raised ALT levels such as impaired glucose tolerance, dyslipidemia and fatty liver should be excluded. ^eAll persons with CHB should be monitored regularly for disease activity/progression and detection of HCC, and after stopping treatment for evidence of reactivation. More frequent monitoring maybe required in those with more advanced liver disease, during the first year of treatment or where adherence is a concern, and in those with abnormal ALT and HBV DNA levels >2000 IU/mL, not yet on treatment. ^fBefore initiation, assessment should be done of renal function (serum creatinine level, estimated glomerular filtration rate, urine dipsticks for proteinuria and glycosuria, and risk factors for renal dysfunction (decompensated cirrhosis, CrCl <50 mL/min, poorly controlled hypertension, proteinuria, uncontrolled diabetes, active glomerulonephritis, concomitant nephrotoxic drugs, solid organ transplantation, older age, BMI <18.5 kg/m2 (or body weight <50 kg), concomitant use of nephrotoxic drugs or a boosted protease inhibitor (PI) for HIV). Monitoring should be more frequent in those at higher risk of renal dysfunction.

Figure 4:. (A) AASLD Guidelines on Management of Persons with HBeAg positive chronic hepatitis B (B) AASLD Guidelines on Management of Persons with HBeAg negative chronic hepatitis B.

Treatment algorithm for patients with HBeAg positive and HBeAg negative chronic hepatitis B based upon AASLD guidelines. Adapted from NA Terrault, AS Lok, BJ McMahon, et al. Update on Prevention, Diagnosis, and Treatment and of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Hepatology. 2018 Apr; 67(4): 1560–1599, with permission.

Figure 4:. (A) AASLD Guidelines on Management of Persons with HBeAg positive chronic hepatitis B (B) AASLD Guidelines on Management of Persons with HBeAg negative chronic hepatitis B.

Treatment algorithm for patients with HBeAg positive and HBeAg negative chronic hepatitis B based upon AASLD guidelines. Adapted from NA Terrault, AS Lok, BJ McMahon, et al. Update on Prevention, Diagnosis, and Treatment and of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance. Hepatology. 2018 Apr; 67(4): 1560–1599, with permission.