Can Interferon reduce the likelihood of HCC?

Hello all

I was wondering if someone could offer some insights into the Interferon’s effectiveness to reduce the likelihood of HCC.

I’m a 43 year Chinese male living in Beijing. I have been living with HBV for 30 years and didn’t have any treatment for around 20 years between 1998 to last Aug. Before 1998 I got thymopolypeptides injection(I don’t know if it was the correct English translation) for a while, probably three to six months, after which I took Chinese herbal medicine for about a year. Since then no treatment till last August when I started the antiviral therapy with Entecavir and remains so till now. As for the family members’ medical histories, my grandfather and a uncle both from my mother’s side died of cancer. One of them may have died of liver cancer. A full history of my condition can be found at the introduction thread here: INTRODUCTION THREAD: People affected by Hep B - Introduction/Orientation - Hep B Community

Last June my results showed that my ALT was abnormal at 68 U/L and 54 in a re-test last Aug. HBV DNA also gone up to 124000 IU/ml. HBeAg negative. HBsAg II at 654 IU/ml (this figure may be kind of misleading as one doctor told me the accuracy of the result depended on the testing method). The MR result showed there were multiple small hydatoncus/cystis (I don’t know if it was the correct English translation) which my doctor said were fine, no need to worry about them.

Now I have consulted two doctors with regards to my condition. One of them strongly recommended Interferon therapy to reduce the risk of HCC/liver cancer considering my age, my latest test results and two of my family member died of cancer whilst the other doctor seemed not so keen on this idea. Both doctors are from top rank hospitals in China.

I would like to weigh statistically how much reduction of HCC risk potentially there is after Interferon injection before I make up my mind. I’ve read a few papers online but without peer review I don’t know if their conclusions are statistically decisive. What’s more what measure I should take, if I decide not to get interferon, to monitor, control or even reduce the HCC risk. It would be great if someone can share his/her experience or some research papers that were generally recognized in the science community on this subject.

Thanks
Li

Dear Bloke,

There have been studies showing that interferon can reduce HCC risk (Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma - ScienceDirect and meta-analysis here: Meta-analysis: the effect of interferon on development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection | SpringerLink), but these have been analysed comparing untreated to interferon treated. I guess the real question is what the risk is if you are on ETV or TDF/TAF compared to interferon added with that.

I think the data is perhaps less clear on this, though there are a few studies showing good benefit from interferon (Interferon-based treatment is superior to nucleos(t)ide analog in reducing HBV-related hepatocellular carcinoma for chronic hepatitis B patients at high risk: Expert Opinion on Biological Therapy: Vol 18, No 10, https://academic.oup.com/jid/article/213/6/966/2459472?login=true, Comparison of Interferon-α-based therapy and nucleos(t)ide analogs in preventing adverse outcomes in patients with chronic hepatitis B - ScienceDirect).

Probably some practicing @HealthExperts will be able to provide more context.

Thomas

Dear Bloke,

Thomas is correct that most of the data on interferon reducing HCC risk is comparing people treated with interferon to untreated patients. There are similar data now that treating with an oral nucleus(t)ide analogue like Entecavir also reduces HCC risk, which is one of the reasons we use these drugs to treat hepatitis B.

I am not aware of any good data that adding interferon reduces this risk further.
There is some evidence that treating initially with interferon can increase the rates of immune clearance, particularly in young people with HBeAg positive hepatitis B and evidence of HBV flares, but even this is controversial.

The most important thing is for you to receive ongoing treatment and entecavir is an excellent choice for most people. This will suppress the virus and reduce your risk of developing cirrhosis and/or HCC. I would also recommend 6 monthly HCC screening with liver ultrasound +/- AFP, which you are probably doing.

I would not usually recommend adding interferon as well, but if your doctor recommends it strongly and you can tolerate it there may be some theoretical benefits, although there is no strong evidence to support this approach.

Best wishes
Mark Douglas (Infectious Diseases specialist and virologist)

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It is well known that IFN reduces HCC and liver related complications in responders. However the number of long-term responders is low. I think it will be very difficult to compare the long-term benefits of IFN vs NUC for several reasons, included the fact that patients are different

PL

Prof. Pietro Lampertico, MD, PhD

Full Professor of Gastroenterology

Head of Gastroenterology and Hepatology Division

Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico

University of Milan

Via Francesco Sforza 35

20122- Milan

Italy

Phone +390255035432

Fax +390250320410

Email pietro.lampertico@unimi.it

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@ThomasTu @MarkDouglas @PLampertico

Thank you all for the inputs.

I’m aware of the fact that some studies in China showed positive results concerning this subject. But as controversial as this Interferon strategy is, it is essential for me, before I decide to go ahead, to know that those positive results, the method by which the patients were sampled and those studies were conducted, were peer reviewed and recognized by the medical research community. There are considerations too but that is another story for another time.

@PLampertico I would be appreciated if you could elaborate on the last part of your words. Or point me to the papers on this subject.

Again thank you all. Your inputs were really helpful to me.

Li

I think what Prof Lampertico was talking about is that if you take interferon and you respond well (e.g. your viral load goes down and/or go from HBeAg-positive to HBeAg-negative), your cancer risk is reduced.

However, not many people respond well after taking interferon. On average it’s around 20%, depending on many factors, including: virus genotype (e.g. Genotype C responds worse than Genotype A) or current ALT level (better response rates if these are higher). Because some of these factors also overlap with cancer or disease progression risk, it’s actually quite hard to know what is driving the differences in outcomes between groups (e.g. interferon responders vs. non-responders).

Hope this helps a bit.

Thomas

Thanks Thomas. That was what I was looking for: to have a balanced view towards the interferon.

I went for a test two days ago. The results seemed quite good. My previous test was done between last June and August and I started taking Entecavir since then. My latest results showed that ALT down from 54 to 20, HBsAg from 654 IU/ml to 627, HBV DNA from 124000 IU/ml to undected. But my CHOL was up to 5.72mmol/L. I wonder if it was a side effect of Entecavir. I will see what my doctor makes of it.

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