Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection

Hepatitis B infection is caused by the hepatitis B virus (HBV), an enveloped DNA virus that infects the liver, causing hepatocellular necrosis and inflammation.

HBV infection can be either acute or chronic, and the associated illness ranges in severity from asymptomatic to symptomatic, progressive disease. Chronic hepatitis B (CHB) – defined as persistence of hepatitis B surface antigen
(HBsAg) for six months or more – is a major public health problem. Worldwide, there are an estimated 240 million chronically infected persons, particularly in low- and middle-income countries (LMICs). The major complications of CHB are cirrhosis and hepatocellular carcinoma (HCC). Between 20% and 30% of those who become chronically infected will develop these complications, and an estimated 650 000 people will die annually due to CHB. The majority of people are unaware of their HBV infection, and therefore often present with advanced disease. Universal hepatitis B immunization programmes that target infants, with the first dose at birth, have been highly effective in reducing the incidence and prevalence of hepatitis B in many endemic countries. However, these programmes will not have an impact on HBV-related deaths until several decades after their introduction.

Antiviral agents active against HBV are available, and have been shown to suppress HBV replication, prevent progression to cirrhosis, and reduce the risk of HCC and liver-related deaths. However, currently available treatments fail to eradicate the virus in most of those treated, necessitating potentially lifelong treatment. In addition, these drugs are not widely available or used in LMICs, and therefore timely intervention to prevent the onset of advanced liver disease does not occur.

These are the first World Health Organization (WHO) guidelines for the prevention, care and treatment of persons living with CHB infection, and complement similar recent published guidance by WHO on the prevention,
care and treatment of infection due to the hepatitis C virus (HCV). In contrast to several recent international guidelines on the management of CHB infection from the United States, Europe, Asia-Pacific and the United Kingdom (UK), the primary audience for these WHO guidelines is country programme managers in
all settings, but particularly in

LMICs to help plan the development and scale up of hepatitis B prevention, care and treatment. These guidelines are also intended for health-care providers who care for persons with CHB in these settings.

The recommendations are structured along the continuum of care for persons with CHBa, from initial assessment of stage of disease and eligibility for treatment, to initiation of first-line antiviral therapy and monitoring for disease progression, toxicity and HCC, and switch to second-line drugs in persons with treatment failure. They are intended for use across age groups and adult populations.

The recommendations in these guidelines are covered in Chapters 5 to 10, and promote the use of simple, non-invasive diagnostic tests to assess the stage of liver disease and eligibility for treatment; prioritize treatment for those with most advanced liver disease and at greatest risk of mortality; and recommend the preferred use of nucleos(t)ide analogues with a high barrier to drug resistance (tenofovir and entecavir, and entecavir in children aged 2–11 years) for first- and second-line treatment. These guidelines also recommend lifelong treatment in those with cirrhosis; and regular monitoring for disease progression, toxicity of drugs and early detection of HCC. An additional chapter highlights management considerations for specific populations, including those coinfected with HIV, HCV
and hepatitis D virus (HDV); children and adolescents; and pregnant women.

Recommendations for the treatment of HBV/HIV-coinfected persons are based on the WHO 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, which will be updated in 2015. The use of interferon or pegylated interferon as antiviral therapy was excluded from consideration in these guidelines, as their use is less feasible in LMICs due to their high cost and significant adverse effects requiring careful monitoring.

Existing recommendations for the prevention of HBV transmission from relevant WHO guidelines are summarized in Chapter 10. These include prevention of perinatal and early childhood HBV infection through infant hepatitis B
vaccination; catch-up vaccination and other prevention strategies in key affected populations, including persons who inject drugs, men who have sex with men, and sex workers; as well as prevention of HBV transmission in health-care
settings. The use of alcohol reduction interventions to reduce progression of liver disease in those with CHB is also highlighted.

Several key topics were not included in the scope of work for these guidelines, but will be covered in future guidelines as well as planned consolidated guidelines on persons with chronic hepatitis B and C infection for publication in 2016. These include hepatitis B and C testing algorithms and strategies on who to screen; updated recommendations on hepatitis C treatment; diagnosis and management of acute hepatitis B and C; and management of advanced liver disease. Updated recommendations on the use of hepatitis B vaccination will be considered and issued by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) a Defined as persistence of hepatitis B surface antigen (HBsAg) for six months or more. The term chronic hepatitis B (CHB) is used to mean chronic infection with HBV throughout these guidelines in 2015. There will also be a need for future operational guidance on strategies to
improve retention in care and adherence to antiviral therapy as well as delivery of hepatitis care, including opportunities to integrate with maternal and child health clinics, tuberculosis clinics, and services that treat HIV and drug dependence.

The development of these guidelines was conducted in accordance with procedures established by the WHO Guidelines Review Committee. Clinical recommendations in the guidelines were formulated by a regionally
representative Guidelines Development Group at a meeting held in June 2014, and are based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to reviewing evidence and formulating recommendations. This includes assessment of the quality of evidence, consideration of the overall balance of benefits and harms (at individual and population levels), patient/health worker values and preferences, resource use, cost–effectiveness and feasibility.

As with other WHO guidelines on the use of antiretroviral therapy, these guidelines are based on a public health approach to the use of antiviral drugs for the treatment of CHB, which considers feasibility and effectiveness across a
variety of resource-limited settings, including where access to specialized tests such as measurement of HBV DNA viral load or liver biopsy for staging of liver disease is limited. The process has also identified key gaps in knowledge that will guide the future research agenda. Most of the evidence was based on studies in adults from Asia, North America and western Europe, and there is a striking lack of data to inform management from sub-Saharan Africa, and in children. These recommendations provide opportunities to save lives, improve clinical outcomes of persons living with CHB, reduce HBV incidence and transmission, and stigma due to disease, but they also pose practical challenges to policymakers and implementers in LMICs. Chapter 12 covers implementation considerations across the health system for national programmes in adopting the key recommendations. These address the necessary decision-making and planning for the development of hepatitis treatment programmes in the context of HBV epidemiology, health systems capacity, laboratory services and supply systems for drugs and other commodities, as well as available financial resources, and ethical and human rights considerations. There are particular challenges to the implementation of lifelong care and treatment programmes for persons with CHB in LMICs, particularly in sub-Saharan Africa, where there is currently very limited access to diagnostic assays, antiviral therapies and appropriate infrastructure.

To read the fool text of the “GUIDELINES FOR THE PREVENTION, CARE AND TREATMENT OF PERSONS WITH CHRONIC HEPATITIS B INFECTION”, please refer to the following document.

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