Management of chronic hepatitis B infection: current treatment guidelines, challenges, and new developments

Abstract

Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB.

Keywords: Antiviral resistance; Chronic hepatitis B virus infection; Clinical trials; Interferon; National institute for health and care excellence; Nucleos(t)ide analogues; Pegylated interferon; Rescue therapy; Treatment guidelines.

Figure 1

Hepatitis B viral replication cycle. The hepatitis B virus virion enters the hepatocyte via endocytosis. Viral nucleocapsids are uncoated and transported into the nucleus, where viral DNA is transformed into covalently closed circular DNA (cccDNA). Replication subsequently occurs through reverse transcription. The mature nucleocapsids are responsible for mediating viral persistence, and may be released to infect neighbouring hepatocytes. HBsAg: Hepatitis B surface antigen.

Figure 2

National Institute for Health and Care Excellence algorithm for initiation of treatment in chronic hepatitis B infection. Current indications for treatment are based on a combination of levels of serum hepatitis B virus (HBV) DNA, serum alanine transaminase (ALT), and the severity of liver disease. Specifically, patients with a transient elastography score ≥ 11 kPa are likely to have cirrhosis and confirmation by liver biopsy is not needed. Abnormal ALT, measured by two consecutive tests conducted 3 mo apart, is defined as ≥ 30 IU/mL in males, and ≥ 19 IU/mL in females.