Diagnosed With Chronic Hepatitis B? What State – Immune Tolerant?

Do you know the stage or phase of your chronic hepatitis B infection? Quite often people may refer to themselves as “hepatitis B carriers”. This statement by itself does not really say anything about your chronic HBV infection except that you are someone who tests positive for hepatitis B, and that you are HBsAg positive. The names of the stages or phases of HBV have changed a bit over the years, but they reflect the natural history of the virus. It is important for your doctor to determine if you are in the immune tolerant, immune active or clearance phase, the inactive carrier phase, have developed HBe negative chronic HBV, or if you are in an HBsAg negative phase. It may take a few months or even half a year to accurately determine the phase, and then your doctor can talk to you about possible treatment options and whether or not treatment would benefit you at this time. Remember, HBV is typically not an emergency, so try to relax with the process knowing you may not have immediate answers.

If you are acutely infected, you also follow the natural course of the virus in a matter of months (clearance of an acute HBV infection within 6 months is considered an acute HBV infection). However, at the end of 4-6 months, those acutely infected will have a resolved infection, and will no longer be HBsAg+. If you are chronically infected, you will pass through many of these phases too, but unfortunately you will likely never get to an HBsAg negative or resolved phase. The journey from phase to phase is different for each person and the time it takes to move through these phases varies along with the amount of liver damage that occurs. The importance of a good liver specialist cannot be over emphasized. These stages and phases may seem simple to understand, but not everything is black and white, and the gray between phases, time between phases, lab and other diagnostic data collected, varies with each patient. The importance of being actively involved in your hepatitis B care can also not be overstated. Tracking your lab data over time and putting it into an excel spreadsheet or graphing the data may help you understand what is happening with the virus and may even be helpful for your doctor, so don’t forget to request copies of all lab results.

Once you have confirmed that you have chronic HBV, you need further testing to determine your HBeAg status. Those with chronic HBV are either HBeAg positive or negative. If you are HBeAg positive, you have a higher HBV viral load and are more infectious to others. People who are HBeAg positive are either in the immune tolerant stage or the immune clearance stage. Additional labs will clarify this for your doctor.

If you are in the immune tolerant stage, you are HBeAg positive and have a high viral load. You will have normal or very mildly elevated ALT (SGPT) levels and mild or no inflammation or damage to the liver. This is very common with chronically infected young children who may have viral loads in the millions or even billions. During this time the virus is actively replicating in the liver, but the immune system has not recognized the virus so it is not trying to kill the infected liver cells. It is not the replication of the virus that kills liver cells, causing liver damage, but it is the response of your immune system killing these infected liver cells. So, during the immune tolerant phase the virus is happily replicating, completely unchecked by the immune system, which accounts for the high viral load and lack of liver damage during this time. People in the immune tolerant phase may remain in this phase for a couple of years, or it may be decades. Treatment is not typically recommended during this phase, but this trend seems to be changing even with children. (The idea is to prevent integration of the HBV cccDNA into the host DNA.) Certainly for those that have been in this phase for decades, treatment is something that may be recommended by your liver specialist.

HBsAg Levels Linked with Fibrosis in HBeAg-Positive Patients

Below is a publication from “Healio Hepatology, February 21, 2013 – HbsAg Levels Linked with Fibrosis in HBeAg-Positive Patients” , showing the correlation between HBsAg and HBV DNV virus levels and the risk of moderate to severe fibrosis in HBeAg positive patients.

Patients with hepatitis B who tested positive for hepatitis B e antigen were at increased risk for moderate-to-severe fibrosis with lower levels of hepatitis B surface antigen in a recent study.

Researchers evaluated serum samples and liver biopsy results from 406 treatment-naive patients with chronic hepatitis B. HBV genotype and hepatitis B e antigen (HBeAg) status were recorded along with levels of HBV DNA and hepatitis B surface antigen (HBsAg).

HBeAg-positive patients (n=101) had a higher mean fibrosis stage than HBeAg-negative patients (1.86 ± 1.18 vs. 1.40 ± 0.99; P<.001) and had greater levels of HBV DNA (7.06 ± 1.71 vs. 4.12 ± 1.67)and HBsAg (4.24 ± 0.9 vs. 3.53 ± 0.92) (P<.0001 for both). Investigators observed strong correlations between HBV DNA and HBsAg levels (r=0.44; P<.0001) and between fibrosis severity and HBsAg levels (r=0.43; P<.0001) among HBeAg-positive patients, but not among HBeAg-negative participants.

HBeAg-positive patients with moderate-to-severe fibrosis had lower HBsAg (3.84 ± 1.01 vs. 4.63 ± 0.58; P<.0001)and HBV DNA levels (6.47 ± 1.81 vs. 7.62 ± 1.40; P<.001) than those with mild or no fibrosis. HBeAg-positive patients with genotypes B, D or E had significantly higher HBsAg levels than HBeAg-negative patients, along with higher HBV DNA levels regardless of genotype.

Modeling analysis established an HBsAg cutoff of 3.85 log IU/mL-1 with a theoretical sensitivity of 100%, specificity of 86% and NPV of 100% for predicting moderate-to-severe fibrosis among HBeAg-positive patients with genotypes B or C. Investigators noted that the small cohort size used to establish this cutoff requires further validation to be clinically useful.

“To our knowledge, the current study is only the second to associate an HBsAg cutoff with the prediction of fibrosis severity in CHB patients,” the researchers wrote. “It will be of considerable interest to see whether the serum HBsAg and HBV DNA levels in the patients infected with different genotypes are significantly different from the mean values of the overall HBeAg-positive group, and if they will require the development of genotype-specific cutoffs, or whether a single cutoff is applicable to all HBV genotypes.”

Got HBV? Adding Vitamin D to Your Diet

Do you have hepatitis B, and are you considering adding vitamin D to your diet? Adding vitamin D seems to be a win-win for those with liver disease since it is a potent immune modulator, appears to aid in the prevention of cancer, and other potentially related disorders such as NAFLD, along with Type I and II Diabetes, glucose intolerance and metabolic syndrome. Before you make any big additions, be sure to talk to your doctor or liver specialist to ensure it’s safe for you with your current health status.

Vitamin D is a fat soluble vitamin (needs a little fat to digest), versus a water soluble vitamin, that is ultimately stored in the liver. There are pros and cons to this. Fat soluble vitamins are not necessarily needed on a daily basis as they are stored in fatty tissues and in the liver making it available for longer periods of time. Vitamin D is specifically stored in the liver. Unlike water soluble vitamins, excesses are not excreted through urine on a daily basis. That makes the balance a little trickier because you don’t want vitamin D accumulating in the liver and causing toxicity. Symptoms of vitamin D deficiency include osteomalacia, or softening of the bones, or perhaps less obvious bone pain and muscle weakness. Symptoms of vitamin D toxicity may include decreased appetite, nausea,vomiting, excess calcium blood levels or an accumulation of calcium in soft tissues. Too much of a good thing is NOT good for you!

Current guidelines for vitamin D intake are 600 IU or 15 mcg per day. (See table for age specific info). Natural sources of vitamin D in foods (vitamin D2, or ergocalciferol) are hard to come by, but they are out there. Mega sources include fatty fish like salmon, mackerel, and tuna. Cod liver oil is an excellent source, which is probably why we see old movies with mom spooning cod liver oil into the mouths of young children! In the U.S. many dairy products, and others such as cereals, or orange juice are fortified with vitamin D and other vitamins. (There’s a great reason for the fortification of dairy with vitamin D – absorption is enhanced in the presence of calcium.) It is also found in smaller amounts in egg yolks. Naturally all of this needs to be balanced with the concerns of farm raised fish and possible exposure to PCBs, or mercury levels found in tuna, pollution of our oceans, raising your cholesterol levels due to focusing on the yolks, possible toxic levels of vitamin A with cod liver oil (in Western countries where foods are fortified with vitamin A), or simply the bad, fishy taste associated with cod-liver oil. It’s a tough balance, but it’s important to work through some of the risks versus benefits in your own mind.

Sunshine is another readily available source of vitamin D (vitamin D3, cholecalciferol), but you need to be sure to balance it with the risk of over-exposure to the sun’s rays. And of course in the north, during the winter months, it may be difficult to get adequate sunshine to boost your vitamin D levels. You can get adequate sun exposure with 10-15 minutes in the sun, 3-5 times per week, with the exposure of face and arms. Naturally this will vary based on the sun’s intensity, how much skin is exposed and each individual’s skin tone, since the amount of necessary sun increases with the amount of melanin (pigment) in the skin. Just to confuse matters, a recent study shows a possible link of higher levels of vitamin D to non-melanoma skin cancer, even though higher levels are thought to reduce the risk of basal cell cancer. Clearly more studies need to be done, but until that time, just keep reminding yourself that balance is important.

Sometimes it’s tough to get adequate vitamin D levels from natural sources such as food and sunshine, so there is the option for vitamin D supplements. This is where my anxiety levels intensify. Bad enough I have to worry about my food sources – PCBs from farm raised fish and such things, but now I have to choose a supplement – perhaps cod liver oil in a liquid or capsule that I can take daily. Will it be in a form that is able to be absorbed? (There’s a debate on the true benefit of cod liver oil once it is processed. The same argument might apply to many available supplements.) How will I know this? Will I break the bank trying to purchase these supplements? I started to do the research on vitamin D supplementation, but like so many supplements, it’s very complex. I always feel like I’m being sold. Using supplements is a personal thing. My personal preference would be to get my vitamin D through the foods I eat, and a short duration of sunshine. However, I currently have adequate levels of vitamin D, so whatever I’m doing seems to be adequate. That’s the key: tailoring your decisions based on you, your family history, or ethnicity and things you might be prone to such as a vitamin D deficiency, or other issues.

Please don’t forget to talk to your PCP and your liver specialist before drastically changing your vitamin D intake. This is especially important if you are currently undergoing treatment for HBV. Your doctor may wish to get a general baseline of your vitamin D levels, and continue to monitor them if there are problems. Your doctor may be uncomfortable recommending a specific supplement since there is little or no regulation. Heed her advice before moving forward, and if you choose the supplementation route, be sure to do your homework to get the best quality product that is readily absorbable, without causing toxicity.