Current standard of care for chronic Hepatitis B (HBV) consists of(Type I Interferon or IFN-alpha-2a) or nucleos(t)ide analogs (NA). These two types of treatment (Rx) have different administration routes and rationale ( ),
- Given as subcutaneous injections, IFN-alpha influences the body’s immunological control of HBV.
- Taken orally, NAs directly target the virus.
- The NAs currently approved as HBV Rx aren’t all alike, with lower risk of drug resistance against (ETV) and (TDF/TAF) compared to (ADV), (LAM) and (TBV).
Further, assessing how well these Rx work is far from straightforward. This answer outlines
- Why assessment of efficacy of chronic HBV Rx is difficult.
- Standard Rx (as of 2017) for chronic HBV Rx.
Why assessment of efficacy of chronic HBV Rx is difficult
At present chronic HBV infection has no cure.
Rather than a monochrome disease with a singular, inexorable outcome, chronic Hepatitis B (HBV) has distinct phases. However, not all patients appear to go through each one of them and neither have the anti-HBV immune responses during each phase been fully characterized yet (2).
The main goal of current HBV Rx is to prevent or mitigate risk of cirrhosis and liver cancer (hepatocellular carcinoma), and decision to treat/not and if yes, then with what, is made on the basis of clinical and lab assessment of individual patient’s HBV phase (see below from).
HBV disease pattern also depends on
- Whether the patient has other liver infections such as Hepatitis C or D, HIV, has autoimmune or metabolic liver disease or is alcoholic.
- This picture is complicated by the fact that
- Though current Rx is considered safe and effective, long-term use does carry risk of complications (2).
- Patient’s individual HBV gentoype that can range from A to I (9 gentoypes plus sub-genotypes), which can influence both response to Rx as well as risk for developing resistance ( ).
While a detailed meta-analysis of 42 studies with a combined 62731 patients revealed a modest Rx benefit for chronic HBV patients with advanced fibrosis or cirrhosis (), Rx data are on the whole poor for a couple of reasons (2).
- Chronic HBV infection usually progresses slowly, with its worst outcomes (cirrhosis and cancer) usually manifesting decades later.
- Clear benefit of therapy requires a very large study that
- Should include a control group that does not get any treatment.
- Is followed for many years in order to allow time for worst outcomes to develop.
- Obviously, such a study would be both unethical and impractical.
Standard Rx (as of 2017) for chronic HBV Rx
Thus far in 2017, the European Association for the Study of the Liver (EASL) has published a thorough and detailed guideline for how to manage HBV (see below from).
1. European Association for the Study of the Liver. “EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.” Journal of Hepatology (2017).
2. Ghany, Marc G. “Current Treatment Guidelines Of Chronic Hepatitis B: The Role Of Nucleos (t) ide Analogues And Peginterferon.” Best Practice & Research Clinical Gastroenterology (2017).
3. Lok, Anna SF, et al. “Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta‐analysis.” Hepatology 63.1 (2016): 284-306.