Getting cured from Hepb after years of taking medication

Living With Hep B Treatment and Monitoring
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Hi all,

When this forum was still on old website years ago, I could remember an old guy telling his story that after years of taking viral medicine he eventually got cured in old age, the virus was really dead or something.
Any people in this forum experienced this also ? Just curious.

Br,
Jp

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Dear HepB1,

I’m presuming the person was on long term nucleoside analog therapy (tenofovir, entecavir, etc…). If so, it is possible for very long term therapy (typically a decade or longer) to induce clearance of HBV. It is quite rare, with only a few percent of people on therapy for that long clearing the virus, but it can happen. It is most likely that viral clearance was actually accomplished by the person’s immune system. However, we don’t know why the immune system suddenly “woke up” in those patients and cleared the virus. Knowing that would help guide development of curative therapies.

John

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So I was thinking about this, maybe you know the answer, so if you are on medication, the virus load can drop to undetectable, but one of the virus component will always be present, indicating that you still have the virus, it is the Hbsag test or something else ? If you are on medication, how will you know you are really cured, is by measuring this component right ?

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@hepb1,
There is no clear answer on this. Some experts will say you have to clear hep b surface antigen, undetectable viral load etc but others do not support this idea. Here is information on this from the Hepatitis B Foundation’s website on this issue:

"Late last year, hepatitis B experts from the American Association for the Study of Liver Disease (AASLD) tackled this question and reviewed recent studies that followed patients who stopped antivirals after losing HBeAg. They found no clear answers and made clear their recommendations were “conditional” because the quality of evidence found in the studies was “low.” But here is what they recommend for patients who lost HBeAg during antiviral treatment and now have normal ALT levels:

  • Experts “suggest” that adults who don’t have cirrhosis (severe liver scarring) who lost HBeAg and developed “e” antibodies may stop treatment after a minimum of 12 months of normal ALT levels and undetectable viral load.
  • However, they recommend a longer “consolidation” treatment period might be better to reduce patients’ risk of relapse and a return of HBeAg after treatment stops. They suggested that an alternative approach would be to stay on antivirals until patients lose the hepatitis B surface antigen (HBsAg)."

Source: I've Lost the Hepatitis B "e" Antigen (HBeAg), So When Can I Stop Treatment? - Hepatitis B Foundation
Best, Bansah1.

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Hi Bansah1,

We simply don’t know when it is safe for most folks to stop HBV treatment. This is a complex question that is influenced by the sensitivity of our assays for HBV products, patient variability in a lot of parameters (degree of fibrosis, ALT levels, genetics, immune status…), plus I’m sure a number of things that we don’t understand yet. The clinical researchers are working hard on this question, but a firm answer is not available yet.

John

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This is a major research question for which there is no clear answer. Currently the clinical “functional cure” definition relies on absence of HBs and HBV DNA in blood at least 6 months after stopping treatment. However, we know that both of these measures are flawed. Assays for both viral products are sensitive , but they have lower limits of detection where the HBV product can be present but be unable to be detected. Also, most HBs in blood in HBeAg-negative individuals comes from HBV DNA integrated into the person’s own DNA, and that is not affected by clearing or permanently inactivating the cccDNA, which is the real, mechanistic definition of a “functional cure”. Unfortunately, we do not have better markers of cccDNA clearance/inactivation (and we may never find them), so the current assays focusing on HBs and DNA are the best we can do for now.

As to what HBV components remain in people whose DNA and HBs are suppressed below detection: It is known that the viral cccDNA is present in at least a large fraction of people with a “functional cure” or who have cleared an acute infection. We know very little about that residual cccDNA. Because there is no HBs or HBV DNA in the blood, the cccDNA must be very minimally active, or fully repressed, presumably by the immune system. Other viral components, including the HBV polymerase, RNAs, HBs, and HBc, may be present at very low levels in a few cells because viral replication can resurge upon immune suppression in some people who appear to have cleared HBV, and those products are needed for viral replication. Because we know so little about how/where the cccDNA is maintained in these individuals, we also know essentially nothing about whether the cccDNA is completely inactive (= true viral latency), or if there is very low viral gene expression and viral replication in a few isolated cells (= very low chronic infection leading to clinical latency).

These are really tough issues. We’ll need a very good, immunocompetent animal model for HBV to figure them out, and the ones we have are not good enough yet. WHV in woodchucks is the best we have for this question, but it has a number of limitations that may prevent it from giving us the answer that is applicable to people.

I hope this helps.

John

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