BMJ | 6 JULY 2013 | VOLUME 347 31 PRACTICE 1 National Clinical Guideline Centre, Royal College of Physicians of London, London NW1 4LE, UK 2 Sydney Emerging Infections and Biosecurity Institute and School of Public Health, University of Sydney, Australia 3 Section of Hepatology and Gastroenterology, Department of Medicine, Imperial College, London Correspondence to: G Sarri Grammati.sarri@rcplondon.ac.uk Cite this as: BMJ 2013;346:f3893 doi: 10.1136/bmj.f3893 This is one of a series of BMJ summaries of new guidelines based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists. Further information about the guidance, a list of members of the guideline development group, and the supporting evidence statements are in the full version on bmj.com. Chronic hepatitis B describes a spectrum of disease result- ing from chronic hepatitis B virus (HBV) infection. About a third of the world’s population has serological evidence of past or present HBV infection, and 350-400 million peo- ple have chronic HBV infection. 1 In the UK about 326 000 people are thought to have chronic hepatitis B. 2 In some people, chronic hepatitis B may cause liver fbrosis, cirr- hosis, and hepatocellular carcinoma; in others it is inactive and does not lead to important health problems. 3 Antiviral therapy suppresses HBV replication and decreases the risk of progressive liver disease. 4 This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on the diagnosis and management of chronic hepatitis B in children, young peo- ple, and adults. 5 Recommendations NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost efectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are in the full version of this article on bmj.com. Assessment and referral in primary care Children, young people, and adults who are seropositive for HBV surface antigen (HBsAg) •  Refer to a paediatric or adult hepatologist, gastroenterologist, or infectious disease specialist with an interest in hepatology. •  Arrange the following tests and include test results with the referral: - Hepatitis B e antigen (HBeAg, an indirect marker of high levels of viraemia and infectivity) or antibody status (anti-HBe, an indirect marker of lower levels of viraemia and infectivity) - HBV DNA level (quantitative direct measure of level of viraemia and infectivity) - IgM antibody to hepatitis B core antigen (IgM anti-HBc, evidence of recent infection with HBV) - Hepatitis C virus antibody (anti-HCV) - Hepatitis delta virus antibody (anti-HDV) - HIV antibody (anti-HIV) - Hepatitis A virus antibody (anti-HAV) - Alanine aminotransferase (ALT) or aspartate aminotransferase, γ-glutamyltransferase, serum albumin, total bilirubin, total globulins, full blood count, and prothrombin time - Tests for hepatocellular carcinoma, including hepatic ultrasound and α fetoprotein testing. GUIDELINES Diagnosis and management of chronic hepatitis B in children, young people, and adults: summary of NICE guidance Grammati Sarri, 1 Maggie Westby, 1 Sarah Bermingham, 1 Grant Hill-Cawthorne, 2 Howard Thomas, 3 on behalf of the Guideline Development Group Pregnant women who test positive for HBsAg at antenatal screening •  Refer pregnant women as above for assessment within six weeks of receiving the screening test result in order to allow treatment in the third trimester. Assessment of liver disease in secondary specialist care Throughout the following sections, “abnormal ALT” is defned as ≥30 IU/mL alanine aminotransferase for males and ≥19 IU/mL for females measured by two consecutive tests conducted three months apart. Adults with chronic hepatitis B •  Ofer transient elastography as the initial test to assess severity of liver disease and need for treatment: - For a transient elastography score ≥11 kPa, ofer antiviral treatment (as below) without liver biopsy (as such patients are very likely to have cirrhosis and confrmation by liver biopsy is not needed). - For a transient elastography score between 6 and 10 kPa, consider liver biopsy to confrm the level of fbrosis and ofer antiviral treatment (as below). Natural course of chronic hepatitis B virus (HBV) infection Time (years) HBV DNA level ALT level Upper limit of normal Risk of cirrhosis Immune tolerance phase Immune control phase Immune escape phase Immune clearance phase HBeAg positive Risk of cirrhosis HBeAg negative, anti-HBe antibody positive HBV is not cytopathic; it is the patient’s immune response to infected hepatocytes that results in progressive liver injury. The four phases of chronic hepatitis B result from variation in this immune response to viral antigens: Immune tolerance phase – HBeAg positive with high levels of viraemia (HBV DNA) with normal alanine aminotransferase (ALT) levels and minimal liver necro-inflammation. Immune clearance phase – Falling levels of HBe antigen and viraemia with elevated fluctuating ALT levels resulting from a developing antiviral response. There is a risk of progressive liver fibrosis. Immune control phase – HBeAg negative with very low or undetectable viraemia, normal ALT levels, and minimal necro-inflammation or fibrosis progression. Immune escape phase – HBeAg negative, positive for anti-HBe antibodies, increasing viraemia, elevated ALT levels, and necro-inflammation with progressive fibrosis. Adapted from: Chu CM, Karayiannis P, Fowler MJ, Monjardino J, Liaw YF, Thomas HC. Natural history of chronic HBV infection in Taiwan: studies of hepatitis B virus DNA in serum. Hepatology 1985;5:431-4