Risk of hepatocellular carcinoma across a biological gradient of HBVDNA

[melcul]

can you help me interpret this study guys ? i was searching regarding of what to do in my case with a very high viral load and it seems that doctors have different opinions regarding "To treat or not to treat the "immunotolerant phase" of hepatitis B infection "

Abstract

CONTEXT:
Serum hepatitis B virus (HBV) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B.

OBJECTIVE:
To evaluate the relationship between serum HBV DNA level and risk of hepatocellular carcinoma.

DESIGN, SETTING, AND PARTICIPANTS:
Prospective cohort study of 3653 participants (aged 30-65 years), who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus, recruited to a community-based cancer screening program in Taiwan between 1991 and 1992.

MAIN OUTCOME MEASURE:
Incidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems.

RESULTS:
There were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41,779 person-years of follow-up. The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100,000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100,000 person-years for an HBV DNA level of 1 million copies/mL or greater. The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3% and 14.9%, respectively. The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant (P or =10,000 copies/mL) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg, serum alanine aminotransferase level, and liver cirrhosis

[stef2011]

any, it can directly appear

[melcul]

Does HCC starts with nodules like you had, than advance to hcc or can hcc directly appear ?

[stef2011]

immune tollerant stage, with no liver damage has no increased risk of hcc or anything.it is like if there is no virus

[melcul]

And for Tenofovir :

Participants were randomly assigned to take tenofovir alone or co-formulated tenofovir/emtricitabine. Safety and efficacy were evaluated over 96 weeks. About 90% of participants in both study arms completed all 96 weeks.

Assessments included kidney biomarkers (serum creatinine, creatinine clearance, serum phosphorus) because tenofovir can cause kidney toxicity in susceptible individuals, as well as DEXA bone density scans because the drug has been linked to bone loss in people with HIV.

Looking specifically at kidney-related side-effects, no participants saw a confirmed serum creatinine increase of 0.5 mg/dL or more from baseline. Just 1% had reduced serum phosphorus below 2 mg/dL, whilst 3% had creatinine clearance below 50 ml/min (most of whom had sub-normal kidney function at baseline).


http://www.elpa-info.org/elpa-news---reader/items/aasld-2012-tenofovir-safe-and-effective-for-long-term-hepatitis-b-treatment-with-little-bone-loss.htm

[melcul]

there are some "good news" about entecavir related to kidneys, i found a study, on 11 people with chronic kidney disseas/ end stage renal disease /transplanted kidney and showed that entecavir was safe to use with no changes in kidneys function

Mean entecavir treatment period was 2.1 +/-  0.8 years, with a mean dose of 0.24 +/- 0.3 mg/d.

Kidney function remained stable within the entire treatment period in the nonhemodialysis patients when we compared baseline and last treatment values: serum creatinine of 1.5 +/- 1.1 mg/dL (range 0.8–3.3) vs. 1.72 +/- 1.3 mg/dL (range 0.8–3.8; . There were no signifi cant changes in the other laboratory values.
There were no adverse events related to entecavir. In transplanted patients, no rejection episodes occurred under treatment.

Study Link :
http://onlinelibrary.wiley.com/doi/10.1002/dat.20485/pdf

[melcul]

Correcting, 350k in july,  380k in november, rising pretty fast. I don't know if its normal or not, if it's imunotolerant or not, fibroscan was good, but alt was 1x, 2x times higher than normal most of the time of this 6 months.this month tests are decisive, i incline to try pegint as first line of treatment...maybe it will bring down viral load and bring me some time as an imunotolerant ? Are the side effects dangerous ?, i have 24 years old, do i have higher chances by being young to have luck with the imune system?  any professional idea ?

[melcul]

350k hbsag iu, 380 iu in november, 5,6 kp . Suspected imunotolerant phase. My doctor advice me to start treatment if alt doesnt go down .this month i will go and make all the blood tests again and decide to start the meds or not. Doctor advice me to start with interferon because probably wants to try the chance if it can be stopped at any time .there are critical decisions that has to be make ...also, in my country only free nuc is entecavir, for tenofovir i have to pay which is a lot

[andrey19]

Genotype starts to matter only when viral load rises over 10^6.


Hepatocellular carcinoma risk score and risk levels stratification for chronic hepatitis B patients: an upgraded version from the REVEAL-HBV cohort study
http://onlinelibrary.wiley.com/doi/10.1111/liv.12716/full

[andrey19]

I think it is a must for you to bring down your viral load to undetectable and tenofovir can surely do that for you. Then test your hbsag in quantity and maybe add interferon over time to bring it down below 1000 iu/ml. This is probably the only way to stay on a safest possible side while waiting for cure.

"The risk of HCC was significantly increased in these patients, with an HBsAg level ≥1000 IU/ml compared to those with a level <1000 IU/ml (HR: 5.4; 95% CI: 2.1–14.2). The 10-year cumulative incidence rate of HCC was 0.2% for HBeAg-negative patients with an HBV DNA level <2000 IU/ml and an HBsAg level <1000 IU/ml, similar to the rate of non-HBV and non-HCV infected individuals [47]. "  http://onlinelibrary.wiley.com/doi/10.1111/liv.12716/full

[mike9111]

You are correctbut only in 20 percent without cirrhosis but others like stef can correct me on that. Here is my 2 cents when i first find out about my case i started my research and found that genotype D from mediterrenean most likely will have the precore mutant and this is what cause cancer and i'm genotype D and from mediterrenean. I saw one of the best professor here and she ran several tests and she said i don't need medication although my fibroscan is 7.6 kpa. In conclusion yes i'm scared of hcc with having 2 little boys to leave behond me but what can i do? I just stopped thinking about hcc and trying to be healthy. I didn't chose hbv like most of us carried it by birth so really we have little control on hcc.

[melcul]

Hepatocellular carcinoma, like any other cancer, develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and/or results in the cell avoiding apoptosis. In particular, chronic infections of hepatitis B and/or C can aid the development of hepatocellular carcinoma by repeatedly causing the body's own immune system to attack the liver cells, some of which are infected by the virus, others merely bystanders.[19] While this constant cycle of damage followed by repair can lead to mistakes during repair which in turn lead to carcinogenesis, this hypothesis is more applicable, at present, to hepatitis C. Chronic hepatitis C causes HCC through the stage of cirrhosis. In chronic hepatitis B, however, the integration of the viral genome into infected cells can directly induce a non-cirrhotic liver to develop HCC. - wikipedia

[melcul]

it's not acute, i now from 6 months, but it's chronic, that's what i'm trying to find out, if anybody has more accurate informations about hcc risk

[mike9111]

Also from what i know 20 percent only of non cirrhosis hbv will develop hcc and these are the one with fibroscan at least 8.0 kpa

[mike9111]

But you might have acute unless you did other tests that show chronic. Mine was always fluctuate bwtween 300 and 16000 iu/ml

[melcul]

I may think that with nucs and healthy diet you can somehow prevent chirosis, but is it possible to prevent hcc as well ?or is just a Russian roulette

[melcul]

My viral is high like 170 mil, alt rised by 1 or 2 times.discovered 6 months ago The fibroscan is f0  but hcc has nothing to do with fibroscan, from what i know hcc can occur at any time despite your fibroscan score if the viral load is higher than 1 mil ...

[mike9111]

What is your viral load? Did you have any treatment at all? Was your fibroscan good?

[melcul]

i extracted a study, indeed from 1991-1992 but still, i'm Trying to find the right approach and to take the best decision ..

this is the oficial page :

To treat or not to treat the "immunotolerant phase" of hepatitis B infection: A tunnel of controversy

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009478/