Summary
Introduction. Chronic hepatitis B (CHB) remains a significant global public health concern, posing a high risk of complications such as cirrhosis and primary hepatocellular carcinoma progression. Despite advancements in vaccination and antiviral therapy, sterilising cure remains difficult to achieve due to the persistence of stable covalently closed circular DNA (cccDNA) integrated into the host hepatocyte genome. Achieving realistic functional cure is considered the optimal therapeutic goal, although it is rarely attained in clinical practice.
Objective and Methods. This literature review aims to evaluate the characteristics of the hepatitis B virus (HBV), the natural course of the infection, its tendency toward chronicity, and the progression of liver disease, as well as the possibilities of achieving both realistic functional and sterilising cure. The scientific literature search was conducted using databases such as PubMed, Google Scholar, ScienceDirect, and UpToDate. Relevant keywords and their combinations were used for the search. The review includes scientific studies and guidelines published within the last 10 years.
Results. This article describes the key properties of HBV, the natural course of the disease, and the viral and host factors that contribute to infection chronicity, including the virus’s ability to evade the immune system and factors influencing functional recovery. It is highlighted that current CHB treatment strategies primarily focus on suppressing viral replication, but complete eradication of cccDNA or HBV-DNA integrated into the host genome remains unachievable. Consequently, there is a persistent residual risk of hepatocarcinogenesis. Despite effective suppression of viral replication and regression of liver cell damage, CHB treatment must be continued for a lifetime to maintain infection control. The article provides a detailed discussion of the terminology used to describe CHB treatment goals. Currently, the therapeutic target is realistic functional cure, defined as long-term loss of hepatitis B surface antigen (HBsAg), with or without seroconversion, and undetectable HBV-DNA in serum after treatment cessation. While the term “complete recovery” offers hope, a sterilizing cure for CHB remains unattainable in the near future. The article also explores novel treatment strategies aimed at enhancing the efficacy of existing therapies, including combinations of antiviral drugs with immunomodulators and new drugs targeting specific stages of the HBV replication cycle.
Conclusions. Although realistic functional cure remains an ambitious goal, ongoing research on combination therapies and the development of new antiviral drugs provides hope for more effective CHB treatment strategies in the future, ultimately bringing us closer to achieving a sterilising cure.
