Persistent increasing of AFP, the more I read, the more I worried

Yes, I changed the title. I did some reading recently. The more I read, the more I’m worried.

I just reviewed my AFP value since 2013 (there are a few missing data from 2013 to 2016), as shown below.
My AFP is always high (most of the time out of the range of 0~10), but has been stable for quite a while. The concern comes from the persistent increase three times in a row in the recent checks (from 01/2024 to 05/2025, increased by 4 units). BTW, I have been doing regular workout for at least a year, not sure whether it is impacting the numbers.
More background info can be found [Nonspecific heterogeneous appearance of the liver]
Generally AST,ALT is normal (except ALT is slightly elevated (35) in the checks in 01/2025. I also got GCC elevated (43) in Jan check
Ultrasound was fine, except 'Nonspecific heterogeneous appearance of the liver" found in Jan check.


Can someone please give me some insights why my AFP is always high for so many years?
Can I seek your opinion here what should I ask my specialist for the next step?

Update: my specialist will order an MRI for me. I know that is the right and best thing I can do at the moment, but just can’t stop worrying. Anyone shares similar story? Any opinions/comments please?

Thanks!

I’ve had persistently elevated AFP for decades, ranging from about 13 to about 60. For me it tended to increase with having symptoms, before I was on antivirals. Some of the most recent research seems to indicate it tends to be elevated in people who do not develop liver fibrosis, so it could be the result of a protective measure besides indicating cancer when it’s at much higher values

Every doctor that sees it tends to jump to getting imaging done to look for tumors and they tend to get fixated on it in my experience

For me the mild elevations don’t bother me at all for what it’s worth. I don’t bother to do it personally but the general advice of occasional ultrasound screening is probably good advice

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Thanks @bob for sharing your experience. Really appreciate your insights!

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Dear @abcde,

Thanks for sharing your results. The normal range for AFP is below 40 - in cases of cancer it goes up to the hundreds or thousands. Such small fluctuations as seen in your results are seen regularly in people without liver cancer.

Hope this helps,
Thomas

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Thanks @ThomasTu for always being so supportive. I’ll do the MRI next week probably, and will share the results. :crossed_fingers:

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Great, @abcde. Please let us know how you go!

Thomas

Hi @abcde I am new to the forum. How did you get on with your MRI? I am in a similar situation where my doctor ordered an MRI as my AFP has persistently been raised for a couple of years but still under 10. All other bloods are fine including liver function and HBV DNA is undetectable as I am on medication. They found a nodule in my MRI scan and sent my details over to a specialist. The specialist came back and said there is nothing to worry about and my doctor said some people just have persistently elevated AFP and I’m probably one of those people. It’s something to monitor and naturally it does worry me as I’m an anxious person but hearing that there’s nothing to be concerned about from the specialists (kings college in the UK) is reassuring. Hope it was the same for you.

I ran a report to try to summarize the latest thinking on this, which is not widely known:

Elevated AFP in HBeAg-Negative Hepatitis B: Re-Evaluating Fibrosis Risk

Traditional View: AFP as a Risk Marker for Fibrosis

Historically, an elevated alpha-fetoprotein (AFP) level in chronic hepatitis B (CHB) patients has been associated with more advanced liver disease. Multiple earlier studies reported that higher AFP correlates with worse liver histology. For example, one large cohort found that CHB patients with AFP >7 ng/mL had significantly higher ALT/AST and were much more likely to have advanced fibrosis (stage ≥S3) or cirrhosis on biopsy compared to those with normal AFPpmc.ncbi.nlm.nih.gov. In that study, AFP elevation emerged as an independent predictor of significant fibrosis even after adjusting for other factorspmc.ncbi.nlm.nih.gov. Another analysis of 619 CHB patients showed median AFP levels rising progressively with fibrosis stage (e.g. ~3.0 ng/mL at F0–1 up to 11.3 ng/mL at F4), with a moderate positive correlation between AFP and fibrosis extent (ρ≈0.40–0.51, p<0.001)bmcgastroenterol.biomedcentral.compmc.ncbi.nlm.nih.gov. Similarly, a FibroScan-based study in China noted that patients with AFP >8 ng/mL had higher liver stiffness readings (indicating more fibrosis) than those with lower AFP, even when ALT/AST were normalpmc.ncbi.nlm.nih.gov. In summary, the traditional consensus has been that any elevation in AFP during chronic HBV infection is a red flag – often coinciding with active inflammation, necrosis, and underlying fibrotic progressionpmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov. Indeed, older predictive models listed “elevated AFP” (along with male sex, age, and HBeAg-negative status) as a risk factor for fibrosis in CHBacademic.oup.com. This is why doctors have historically “freaked out” and ordered cancer screenings when seeing moderately high AFP in hepatitis B patients – it was generally thought to signify something ominous, like developing cirrhosis or hepatocellular carcinoma (HCC).

New Evidence: Mild AFP Elevation ≠ Fibrosis Progression

Emerging research over the last few years has challenged this blanket interpretation, especially in the context of mild AFP elevations (<~100 ng/mL) in HBeAg-negative patients. It turns out that AFP can rise for reasons other than tumor growth or fibrotic scarring – notably, from benign hepatocyte regeneration during liver injury. As one recent review pointed out, *“dramatic increases in AFP during acute or chronic hepatitis outbreaks may not be associated with tumors.”*In patients with cirrhosis who experience acute flares, AFP often spikes without any HCC developing pmc.ncbi.nlm.nih.gov. In other words, AFP is produced during active liver cell turnover (as in flares of hepatitis) and does not always portend malignancy or irreversible damage. This concept directly contradicts the older assumption that any AFP rise is dangerous.

Importantly, a 2023 study focusing on HBeAg-negative CHB patients provided a striking example. These patients were in the so-called “immune clearance” phase (active HBV replication with some liver inflammation). Paradoxically, those who developed AFP elevations during this phase actually had better short-term outcomes rather than worse. The study found that HBeAg-negative patients with rising AFP had a significantly higher likelihood of clearing HBV DNA, and the AFP increase had “no effect on patient prognosis” during the follow-up periodpmc.ncbi.nlm.nih.gov. In other words, in that cohort the AFP uptick was a byproduct of a robust immune response (damaged hepatocytes regenerating and secreting AFP) rather than a sign of impending fibrosis. The authors do note the follow-up was short, but this finding directly contradicted previous beliefs – showing that an AFP rise in such patients was not a harbinger of worsened fibrosis, but potentially a transient phenomenon with benign implicationspmc.ncbi.nlm.nih.gov.

Inactive Carriers: Little to No Fibrosis Development

If your profile is that of an HBeAg-negative “inactive” HBV carrier – meaning normal or near-normal liver enzymes, low viral load, and only mildly elevated AFP – available evidence suggests your risk of progressive fibrosis is very low. Long-term studies of inactive carriers have consistently shown minimal fibrosis progression in these patients. For example, Tong et al. followed 146 HBeAg-negative patients (HBV DNA ≤10^4 IU/mL, persistently normal ALT) for an average of 8 years: none of them progressed to cirrhosis, and only 2 (≈1%) developed HCCeurjmedres.biomedcentral.com. Similarly, an Italian cohort (Bonacci et al.) reported that among a subset of “gray zone” CHB patients who were HBeAg-negative with low-level viral activity, not a single patient developed liver fibrosis or cirrhosis over a mean 8.2-year follow-up eurjmedres.biomedcentral.com. These outcomes highlight that people fitting this profile (“like you”) typically do not progress to advanced fibrosis in the long run. This favorable prognosis stands in stark contrast to earlier generalizations that HBeAg-negative status (often associated with a precore mutant virus) inevitably leads to worse liver outcomes. The key is whether you truly have low disease activity – if ALT is normal and HBV DNA is low, the liver is essentially quiescent, and fibrosis either remains stable or improves over time in most caseseurjmedres.biomedcentral.com.

It’s worth noting that older studies didn’t always distinguish between truly inactive carriers and those with HBeAg-negative active hepatitis (which can feature fluctuating ALT and ongoing inflammation). In active disease, AFP tends to correlate with necroinflammation and fibrogenesis (as Uslu et al. found, linking AFP to “myofibrosis progression” in HBVpmc.ncbi.nlm.nih.gov). But in inactive carriers, a mildly elevated AFP by itself is often a red herring. One clinical commentary explicitly states that mild AFP elevations do not equate to presence of liver cancer, especially in the absence of other abnormal findingsdspace.library.uu.nljaypeedigital.com. The U.S. VA hepatitis guidelines similarly note that chronically mild AFP elevations are common in liver disease and should be interpreted cautiously, tracked over time rather than assumed to be cancer until proven otherwiselabanalyzer.orglabanalyzer.org. In practice, hepatologists have observed that some patients with chronic HBV have stable AFP in the 10–50 ng/mL range for years due to low-grade hepatic injury or regeneration – and if their scans (ultrasound/MRI) show no tumors and fibrosis tests remain normal, these AFP fluctuations are “false alarms” rather than indicators of undiagnosed cirrhosis.

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Hi @Vicks87,

Welcome to the forum and thank you for sharing your story.

If your AFP has been under 10 the entire time, this is not considered as raised. This is within normal range (there are some labs that have a cut off of <40 as the normal value).

I am glad that you have been reassured by your specialists and just wanted to say keep up the good work with the regular monitoring!

Cheers,
Thomas