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HBF is pleased to connect our blog readers to Christine Kukka’s monthly HBV Journal Review that she writes for the HBV Advocate. The journal presents the latest in hepatitis B research, treatment, and prevention from recent academic and medical journals. This month, the following topics are explored: Continue reading
Posted in Adults, Hep B Treatment, Hepatitis B news, Living with Hep B, Pediatrics, Research
Tagged HBV, HBV Advocate, Hepatitis B
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In the last chronic hepatitis B stages blog, we looked at the immune tolerant phase.
At some point the immune system recognizes the hepatitis B virus and the chronically infected person will enter a phase referred to as the immune clearance ( also know as the immune active, or immune reactive HBeAg–positive phase). During this phase blood work will show that you are HBeAg positive, with lower levels of HBV DNA when compared to the immune tolerant stage, and increased ALT levels. (Remember, it is not at all unusual for kids to have viral loads in the millions or even billions.) During this “clearance” phase the immune system is actively attacking infected liver cells. This is both good and bad. On the good side, if the immune system is able to “beat” the virus, the person will go through HBeAg seroconversion and lose the HBeAg antigen. This means that HBeAg will go from positive to negative and the HBeAb antibody, or anti-HBe will go from negative to positive. This results in significant decrease in the hepatitis B virus level, often to an undetectable level, and normalization of ALT and other liver function labs. Successful HBe serconversion moves you into the inactive HBsAg carrier phase.
When the immune system activates and starts attacking infected liver cells, it not only kills the virus, but also the host liver-cells. You probably won’t feel any of this, but your ALT (SGPT) and AST (SGOT) lab values will be elevated. These enzymes are released when there is inflammation caused by liver cells that are injured or killed. Your doctor may see a mild, moderate or high levels of ALT elevation reflecting damage done in the liver. Ultimately the problem is how much liver damage occurs during the process of HBeAg seroconversion?
It is possible a person will quickly and spontaneously move into and out of the immune clearance phase, and with a limited amount of liver damage. However, some people may cycle for years with intermittent flares, which are evidenced by ALT elevations which may be as high as 10 times above the upper limits of normal (normal is 30 IU/mL for men and 19 IU/mL for women) when clearance is attempted. While the immune system attacks infected liver cells, viral replication will decrease and ALT levels will elevate as infected liver cells die in the battle. If successful, the immune system response will result in HBe seroconversion – losing HBeAg, gaining the HBe antibody, decline of the virus to very low or undetectable levels, and normalization of ALT/AST levels.
Unfortunately that might not be enough, and the immune system may not be able to put up a big enough fight permitting HBe seroconversion. Evidence of this are ALT levels that go back down, and viral replication that goes back up. (Note the above diagram.) This cycling up and down over time will be reflected in lab work if a liver specialist monitors you regularly. If you are not having your ALT levels regularly monitored (every few months), then you may miss these cycles of intermittent flares over time. It is during these flares that liver damage occurs, and you will likely be completely unaware, unless you have lab work done during a flare, or you wait until there are symptoms and significant liver damage.
It is during the immune clearance phase when treatment is typically recommended. It is true that a chronically infected person will eventually serconvert HBe spontaneously – without treatment, but most liver specialists choose to treat in order to prevent years of flares and damage to the liver.
Next time, next stage … Inactive Carrier, Reversion, or HBe Mutation?
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An interesting study published in Healio Hepatology: “High HBV viral load tied to low serum vitamin D levels” discusses the relationship between the HBV viral load and vitamin D levels. In fact is shows seasonal fluctuations of HBV viral load associated with vitamin D levels. Vitamin D has been on the radar for years, but this interesting correlation between HBV virus flucuations and vitamin D levels warrants additional research to investigate how adequate vitamin D levels can positively impact treatment for those living with chronic HBV. Please refer to earlier blogs, Hepatitis B and Vitamin D and Got HBV? Adding Vitamin D to Your Diet for additional information. As always, please talk to your doctor and have your serum vitamin D levels checked before making any drastic changes to your diet or supplements you may be taking. Don’t forget that vitamin D is the sunshine vitamin, so be sure to keep in mind the impact of the seasons on your levels.
Patients with chronic hepatitis B who also were vitamin D deficient had significantly higher HBV DNA levels than patients with adequate vitamin D concentrations in a recent study.
In a retrospective study, researchers measured the serum levels of 25-hydroxyvitamin D (25OHD) in 203 treatment-naive patients with chronic hepatitis B seen between January 2009 and December 2012. Patients with 25OHD levels less than10 ng/mL were considered severely deficient, levels below 20 ng/mL were considered deficient, and levels of 20 ng/mL or greater were considered adequate. Patients’ samples were collected upon initial presentation, except 29 participants whose samples were taken at antiviral therapy initiation.
The mean 25OHD concentration for the cohort was 14.4 ng/mL. Forty-seven percent of participants were considered 25OHD deficient; 34% were severely deficient. 25OHD levels were similar between Caucasians (14.38 ng/mL) and non-Caucasians (14.59 ng/mL) (P=.7).
An inverse correlation was observed between levels of HBV DNA and 25OHD (P=.0003). Multivariate analysis indicated that HBV DNA was strongly predictive of low 25OHD levels (P=.000048), and vice versa (P=.0013). Patients with HBV DNA levels less than 2,000 IU/mL had 25OHD concentrations of 17 ng/mL; those with 2,000 IU/mL or higher had concentrations of 11 ng/mL (P<.00001 for difference). Participants who tested positive for hepatitis B e antigen (HBeAg; n=26) had significantly lower 25OHD levels than HBeAg-negative participants (P=.0013); this association was significant only under univariate analysis.
Investigators also noted fluctuations in HBV DNA and 25OHD levels according to season. Significantly lower HBV DNA levels were observed among samples taken during spring or summer than in autumn or winter (P=.01).
“The present study demonstrates a profound association between higher levels of HBV replication and low [25OHD] serum levels in chronic hepatitis B patients,” the researchers wrote. “At least in patients without advanced liver disease … HBV DNA viral load appears to be the strongest determinant of low [25OHD] serum levels. … Future studies to evaluate a therapeutic value of vitamin D and its analogs in HBV infection may be justified.”
Posted in Adults, Blood Tests, General Hep B info, Hep B Awareness, Hep B Treatment, Living with Hep B, Pediatrics, Research
Tagged HBV, Hepatitis B, vitamin D
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The study published by Healio Hepatology, March 8, 2013 discusses the increased risk of mother-to-infant transmission in HBV positive moms who are HBeAg positive and have a high viral load. Current prophylaxis, where infants of HBsAg+ moms receive the first shot of the HBV vaccine and a shot of HBIG within 12 hours of birth, is successful greater than 90% of the time. However, according to the study, HBeAg+ pregnant moms with a viral load above 107 cp/mL(10,000,000 cp/mL) will transmit the virus to their infant despite prophylaxis. Since a particularly elevated viral load appears to determine the failure of current prophylaxis, the need for additional screening for these women and revised intervention strategies is necessary to prevent transmission to their babies at birth.
If you are a pregnant mom that is HBsAg+, please see a liver specialist for further evaluation to determine your HBeAg status and your HBV DNA viral load. If you are HBeAg + and have a high viral load, (a viral load near the 10,000,000 cp/ml threshold) you will want to talk to your liver specialist to determine if you and your baby would benefit from antiviral therapy in order to prevent transmission of HBV to your newborn. Although there are no official guidelines or recommendations, Registry data shows medications for hepatitis B appear safe during pregnancy. Talk to your doctor to see if this is a good option for you and your baby.
If you are a pregnant woman, please read and print HBF’s Chronic Hepatitis B in Pregnancy, and give it to the doctor who will be caring for you during your pregnancy. Sadly, IOM data shows HBV+ women in the U.S. are not always identified and educated about their HBV, and an opportunity for prophylaxis may be missed despite CDC recommendations that ALL infants receive the first dose of the HBV vaccine prior to hospital discharge.
If you live in a developing country, there may be no guidelines in place that automatically screen pregnant women for hepatitis B. Once again, read and print a copy of “Chronic Hepatitis B in Pregnancy” for your doctor. Insist you are screened for HBV, and if you are HBsAg+, please be sure prophylaxis will be available at the hospital where you will give birth to your baby. If you find you are HBeAg+, with a high viral load, please speak to a liver specialist to see if an antiviral is an option for you to prevent HBV transmission to your baby. Don’t’ forget to have your baby tested at 18 months to ensure your baby is HBV free.
*Please note you can convert copies per milliliter (cp/ml) to IU/mL for the article below using WHO’s international standard where 1 IU/mL = 5.2 copies/mL. Please ask your doctor or your lab if you have specific questions regarding the conversion.
Infants born to mothers with a high hepatitis B viral load, particularly those positive for hepatitis B e antigen, are at high risk for contracting hepatitis despite immunoprophylaxis, according to recent results.
Researchers evaluated 303 mother-infant pairs in which mothers tested positive for hepatitis B surface antigen (HBsAg). Maternal viral load and hepatitis B e antigen (HBeAg) status were determined, and children were tested for HBsAg at ages 4 to 8 months (n=250) and/or 1 to 3 years (n=53 for an initial test; n=183 for a follow-up test). All children received HBV vaccine within the first week of birth and at 1 and 6 months, with a 100% completion rate; children born to mothers who tested positive for HBeAg received hepatitis B immunoglobulin within 24 hours of birth.
HBeAg-positive mothers (81 cases) had higher viral loads than those who did not (7.4 ± 1.9 log10 copies/mL vs. 2.7 ± 1.4 log10 copies/mL; P<.0001 for difference). Chronic HBV infection was identified in 10 children, all born to HBeAg-positive mothers with high viral loads (range 6.5-9.5 log10 copies/mL), and all with the same HBV genotypes and subtypes as their mothers.
Investigators identified a significant association between maternal viral load and a child’s risk for infection via multivariate analysis, after adjusting for factors including age; birth type; infant gender, weight and gestational age, and feeding practices (adjusted OR=3.49; 95% CI, 1.63-.7.48 per log10 copy/mL increase). Predictive rates for maternally transmitted HBV infection were found to be statistically significant at 7 (6.6%; P=.033), 8 (14.6%; P=.001), and 9 (27.7%; P<.001) log10 copies/mL.
“High maternal viral load is the most important factor causing maternally transmitted HBV infection, and is significantly correlated with maternal HBeAg status,” the researchers wrote. “Our predictive model including multiple risk factors showed that children with a maternal viral load above 10,000,000 to 100,000,000 copies/mL (or would have a significant risk of infection despite immunoprophylaxis. Our data provide important information for the rational design of future screening and intervention strategies to further reduce maternally transmitted HBV infection.”
Wen W-H. J Hepatol. 2013;doi:10.1016/j.jhep.2013.02.015.
March 8, 2013
Posted in HBV Awareness, Hep B Prevention, Living with Hep B, Pediatrics, Pregnancy and HBV
Tagged HBV, Hepatitis B, pregnant
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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.
What happens when you move into the immune clearance phase? Read more.
Posted in Adults, Blood Tests, General Hep B info, Hep B Diagnosis, Living with Hep B, Pediatrics
Tagged HBV, Hepatitis B, immune tolerant, natural history