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HBV Management
Practical Insights on HBV Management, HDV screening, and HCC risk

Released: December 05, 2023

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Key Takeaways
  • Healthcare professionals should screen all patients who are hepatitis B surface antigen positive for hepatitis delta virus.
  • Although guidelines recommend hepatocellular carcinoma (HCC) screening for patients with chronic hepatitis B (CHB) of certain ages, there is a role for HCC screening in all individuals with CHB as they are at risk.

The following is a recap of key questions from healthcare professionals (HCPs) during a program featuring Paul Y. Kwo, MD; Ira M. Jacobson, MD; and Tatyana Kushner, MD, MSCE, discussing the treatment of patients with hepatitis B virus (HBV) and how quantitative hepatitis B surface antigen (HBsAg) testing should be used in clinical practice.

Do you recommend testing all patients with HBV for hepatitis D virus (HDV)?

Tatyana Kushner, MD, MSCE:
Yes, we should be screening all patients with chronic hepatitis B (CHB) for HDV. Current American Association for the Study of Liver Diseases (AASLD) guidance recommends only screening those who are at risk, but the European Association for the Study of the Liver (EASL) guidance states that we should screen everyone who is HBsAg positive. In my practice, I screen everyone. Ira, I imagine you do as well?

Ira M. Jacobson, MD:
Yes, we do. Although the prevalence of HDV infection is significantly lower in some subgroups of people than others, the consequences of missing an HDV infection in a patient with CHB may be severe given the pathogenicity of HDV and the differences in treatment of HDV infection from HBV monoinfection.  

What are your thoughts on proposing anti-HDV reflex testing for those who are HBsAg positive?

Tatyana Kushner, MD, MSCE:
I think the problem is that HDV is rare—it’s something that many primary care providers and other HCPs don’t see and don’t think about. Therefore, reflex testing is a solution to identifying those with HDV because not everyone will be the “typical” patient that one would expect and present with known risk factors.

What is considered adequate virologic suppression with HBV treatment? In HIV, it is ≤200 copies/mL. At what point are you satisfied with the virologic response from first-line therapies in HBV?

Ira M. Jacobson, MD:
I like to see HBV DNA less than the limit of quantification, which is usually 10 IU/mL, as opposed to the lower limit of detection (LLD), which has a lower cutoff. There is a phenomenon called viral blipping, where HBV DNA is not detected on one occasion but is detected—yet below the lower limit of quantification (LLQ)—on another occasion.  This fluctuation can occur in alternating fashion over the long term and reflects the extremely low levels of viral replication that are likely to be ongoing even in patients who take our most potent antiviral medications. The laboratory reports for these patients will at times indicate that the HBV DNA level was below LLQ (ie, <10 IU/mL), but was detected and is therefore marked as abnormal. Patients with viral blipping do well clinically, with no demonstrable differences in outcome vs patients with HBV DNA levels consistently below the LLD. Most published studies of antiviral therapy, whether older therapies or new, evaluated HBV DNA less than LLQ as the endpoint. I am most satisfied with HBV DNA levels less than LLQ and increasingly dissatisfied with HBV DNA levels >1-2 log (10-100 IU/mL).

Would you add a second agent if patients are not meeting your HBV DNA suppression target?

Ira M. Jacobson, MD:  
Certainly, if the patient’s serum HBV DNA level is above 2 log IU/mL (100 IU/mL), I will add a second agent and I would consider it in patients with an HBV DNA level ranging between 10-100 IU/mL. I like my patients’ viral load to be below LLQ. If their viral load is not suppressed well enough with antiviral therapy, medication adherence should be the first thing discussed. Patients sometimes need a little pep talk about how their viral load should decrease when taking antiviral agents. Very few patients in my practice fail to achieve viral suppression to LLQ with tenofovir or entecavir after a suitable time period on treatment. Viral suppression should be expected to take longer in patients with high baseline viral loads than in patients with low baseline viral loads, and this has to be taken into consideration.

Tatyana Kushner, MD, MSCE:
I query patients carefully and closely when their labs result in an HBV DNA level of 50 copies/mL after being undetectable at last check. Patients sometimes will say, “I might have missed a few antiviral doses.” In my experience, it’s helpful to directly ask about their antiviral adherence.

A 40-year-old patient with hepatitis B e antigen–negative CHB presents to your practice with labs showing low HBV DNA and elevated ALT. They have a family history of hepatocellular carcinoma (HCC). Would you prescribe this patient antiviral medication to further reduce their HCC risk, or would you just observe them?

Tatyana Kushner, MD, MSCE:
I do think age enters the discussion here and their family history is critical. There are multiple risk factors for this patient. If it is a first-degree relative with HCC, as opposed to a more distantly related family member, then I would be more concerned about their family history of HCC and recommend treatment.

What populations are you screening for HCC earlier than AASLD guidance suggests? And if you were to obtain an exceptionally high HBsAg level, would that influence your approach to HCC screening?

Ira M. Jacobson, MD:  
No, because I am a renegade both from an antiviral therapy and HCC screening point of view. Most HCPs with a high volume of patients with CHB have seen at least one young person with HCC and no or mild fibrosis in their liver. I certainly have. It is unusual, but I do not ever want to be in the position where I have to explain to a bereaved family that they lost their loved one because I followed the guidelines and did not screen for HCC. HCC screening is cost effective given the incidence of HCC in people with CHB and the typical cost of an ultrasound. I anticipate spending the rest of my career screening every young person with CHB for HCC.

Do you do change the HCC screening interval in younger patients?

Ira M. Jacobson, MD:  
No. If you are going to screen patients with CHB for HCC, you should do so at an interval that is adjusted to the disease and tumor growth rate, not for what you think the patient’s level of risk is. Screening is intended to catch HCC early, so if you widen the screening interval, you may not catch it early if it does happen to occur, however unlikely you might expect it to be.

Paul Y. Kwo, MD:
I think the guidelines are not sufficient in terms of their recommendations for HCC screening. I perform HCC screening in patients who are younger than the guidelines recommend. To me, it seems wrong to encounter a patient in the clinic who is 18 years old and at risk for HCC, and you say, “Great, we are going to order the next ultrasound of your liver when you are 40 or 50 years old.” Patients could potentially go 22 or 32 more years without an imaging study! There is considerable variability among hepatologists about how to approach screening for HCC in this population and I screen for HCC in younger individuals at the same interval of every 6 months. We clearly need better biomarkers to be able to identify those at risk for HCC as well as biomarkers to identify early-stage HCC.

How do you approach steatotic liver disease in patients with HBV? Is it any different than your strategies for treating a standard patient with metabolic dysfunction-associated steatotic liver disease (MASLD)?

Tatyana Kushner, MD, MSCE:  
My approach is different in the patient with HBV and MASLD because there are 2 insults to the liver. We have clear data that having 2 liver diseases leads to more rapid liver disease progression, and therefore it is important to monitor these patients closely and address both of the coexistent liver conditions. HCPs should use each disease state to emphasize the importance of controlling the other. For example, if patients have elevated liver enzymes, even if you think it is related to their MASLD, then you may have a lower threshold for initiating HBV treatment. Likewise, with MASLD, you may be more likely to initiate HBV treatment or refer to clinical trials because you can be a bit more aggressive with their disease management.

Your Thoughts?
How do you approach HDV and HCC screening in your patients with CHB? Join the conversation by posting a comment.