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Hemochromatosis: Treatment, the Liver, and Hepatitis B

Genetic conditions can be an unfortunate part of life, but with information and support, some can be managed. By sharing your family health history and learning about genetic disorders that run in the family, measures can be taken to prevent damage and help your loved ones stay healthy!

Hereditary hemochromatosis is one of the most common genetic disorders. The Centers for Disease Control and Prevention (CDC) reports that approximately 80-90% of hemochromatosis cases are from the hereditary form of the condition1. Due to a mutation in the HFE gene, the body begins to produce too much iron – a process

Northern European Countries

called iron overload. Iron overload can cause complications in the liver, heart, and pancreas2. According to the National Organization for Rare Disorders (NORD), hereditary hemochromatosis has several names that all refer to the same disorder: bronze diabetes, classic hemochromatosis, hemochromatosis type I, hemosiderosis, HFE-related hemochromatosis, HH, and primary hemochromatosis. The two non-hereditary forms of hemochromatosis are secondary hemochromatosis and neonatal hemochromatosis. Both are considered to be rare. Although the hereditary form is common, the exact number of patients worldwide is unknown. Globally, it is estimated that 1 in 227 individuals of Northern European descent is living with hemochromatosis. In the U.S, an estimated 1 million individuals are impacted as well 2

Not everyone who has the mutant gene develops hemochromatosis. These individuals are known as “carriers”; they can pass the gene on without suffering from the symptoms. Symptoms include joint pain, fatigue, abdominal pain, unexplained weight loss, and a bronze or grey skin color. For most patients, symptoms do not appear until middle age (40-60) because it takes time for the iron to build up in the body. Males tend to be affected more often than women and experience symptoms at a younger age as well 3,2. Some carriers for the mutant gene may develop a more severe version of the disorder called juvenile hemochromatosis. With juvenile hemochromatosis, patients experience an excessive amount of iron overload that can lead to liver and heart damage between the ages of 15 and 30.

Hemochromatosis, the Liver, and Hepatitis B

While the body needs a certain amount of iron to function, iron overload can be dangerous.  Hemochromatosis can lead to two major liver issues: hepatomegaly and cirrhosis. Hepatomegaly is the enlargement of the liver and cirrhosis is the scarring of the liver. Both issues can impair the liver’s ability to function and filter out toxins that enter the body. They can also increase a person’s risk of developing liver cancer. Recently, two major studies by the University of Exeter and the U.K. University of Connecticut, and the U.S. National Institute on Aging have found that a person living with hemochromatosis has four times the risk of developing a liver disease than a person who is living with the disorder.

For individuals living with hepatitis B, it is extremely important to understand any behaviors or conditions that may have a negative impact on your liver. Since one liver disease can increase your risk of another liver disease, it is important to identify the disorder as early as possible, especially if you have any of the following risk factors:

Risk Factors for Hereditary Hemochromatosis:

  • Men or postmenopausal women
  • Of Northern European descent
  • Having a relative with hemochromatosis

Risk Factors for Secondary Hemochromatosis:

  • Alcoholism
  • Family history of diabetes, heart disease, or liver disease
  • Taking iron or vitamin C supplements

Hepatitis B patients do not have an increased risk of developing hemochromatosis4. However, if you have any of the above risk factors, it is important to get tested. Hemochromatosis can easily be identified by a comprehensive look at a person’s family health history, a physical exam, and a simple blood sample. Your doctor will then use the blood sample to run a series of tests that may include transferrin saturation (TS), serum ferritin, or liver function tests. In certain cases, the doctor may also perform genetic testing to see if the mutant HFE gene is present.

Treatment

Treatment for hemochromatosis is available! Based up tests results, family history, medical history, and the appearance of symptoms, the doctor may suggest a few different treatment methods. In therapeutic phlebotomy – the most common treatment method – a patient undergoes regular blood draw to lower the amount of iron in the body. This method is effective, affordable, and typically lasts for an extended period of time. Through iron chelation therapy, patients can either receive an injection or orally consume a medication that will lower the amount of iron in your blood. Finally, some doctors may suggest changes to your diet, such as eating less vitamin C, avoiding alcohol and shellfish, and not taking iron supplements. Dietary changes are mainly used to prevent liver damage.

For more information on HH, you can visit the National Heart, Lung, and Blood Institute.

References:

  1. Grosse, S. (2017). A New Public Health Assessment of the Disease Burden of Hereditary Hemochromatosis: How Clinically Actionable is C282Y Homozygosity? [Blog]. Retrieved from https://blogs-origin.cdc.gov/genomics/2017/08/16/a-new-public-health-assessment/
  2. National Organization for Rare Disorders. (2019). Classic Hereditary Hemochromatosis. Retrieved from https://rarediseases.org/rare-diseases/classic-hereditary-hemochromatosis/#general-discussion
  3. National Institute of Diabetes and Digestive and Kidney Diseases. (2019). Hemochromatosis. Retrieved from https://www.niddk.nih.gov/health-information/liver-disease/hemochromatosis
  4. Beaton, M., & Adams, P. (2007). The Myths and Realities of Hemochromatosis. Canadian Journal Of Gastroenterology, 21(2), 101-104. doi: 10.1155/2007/619401

Doctors Get a New Tool to Improve Hepatitis B Treatment and Monitoring

Photo courtesy of CDC.
Photo courtesy of CDC.

By Christine Kukka

A recently-approved test now allows doctors to measure exactly how much hepatitis B surface antigen (HBsAg) people with chronic hepatitis B have in their blood; so why should patients get this test and how will it help the millions of people around the world infected with hepatitis B?

According to experts, including the Hepatitis B Foundation’s Medical Director Robert Gish, knowing a patient’s HBsAg levels gives doctors:

  • A better understanding of what stage of hepatitis B a patient is in;
  • A more accurate assessment of a patient’s liver cancer risk; and
  • Essential information to judge if it’s time to start or stop treatment.

And in the future, this test may be critical to finding a cure.

Don’t labs already test for HBsAg? HBsAg, the protein that makes up the surface of the virus, is what labs look for in a blood sample to determine if a person is currently infected with hepatitis B.

Historically, labs determined only if HBsAg was present or not, which is why patients either tested positive or negative for HBsAg. Recently, countries outside the U.S. began measuring HBsAg quantities in blood samples and late last year became available in the U.S. as a federally-approved (CLIA) lab test from Quest Diagnostics.

Hepatitis B Foundation President Timothy Block
Hepatitis B Foundation President Timothy Block

“The strange thing about HBsAg, is that each hepatitis B virus requires only about 100 HBsAg molecules to provide its envelope protein, but the virus produces about 100- to 1 million-times more HBsAg than is needed, leaving millions of HBsAg circulating in the bloodstream,” explained Timothy Block, president of the Hepatitis B Foundation and the Baruch S. Blumberg Institute, the foundation’s research arm.

That over-abundance of HBsAg is why people continue to test positive for HBsAg even if they have an undetectable viral load (HBV DNA).

Why is there so much HBsAg? Researchers, including Block, suspect that in addition to covering the virus’ surface, HBsAg also serves as a decoy to “exhaust” or deflect our immune system’s:

  • T-cells, so they can’t attach to and attack the virus,
  • And B-cells, so they don’t generate the antibodies needed to destroy the viral antigens that make up the virus.

So when HBsAg levels decline–either due to treatment or a strong immune response to the infection–researchers know a patient is on the road to clearing the infection. Bottom line: A low or undetectable HBsAg level means patients are winning the war against hepatitis B and their risk of liver damage is greatly reduced. 

When should doctors measure HBsAg? According to Quest Diagnostics, which created the test, measuring HBsAg levels better identifies which patients are at risk of hepatitis B reactivation.

For example, a patient may be HBeAg-negative and have normal liver enzymes (ALT/SGPT) that indicate a liver is “healthy,” but if HBsAg remain high, doctors know a patient remains at risk of reactivation and hasn’t really entered the safer, “inactive” stage.

Quest maintains that measuring HBsAg and viral load (HBV DNA) together, “…improves the ability to differentiate the phases in HBeAg-negative patients and HBeAg-positive disease and results in a diagnostic accuracy of 70 to 94 percent.

According to Quest, patients with HBV genotype B or C who have low HBV DNA levels (less than 2,000 IU/mL) and HBsAg levels below 1,000 IU/mL have lower risk of liver damage and cancer. In fact, if HBsAg is under 100 IU/mL, patients may be on their way to clearing HBsAg from their blood.

Dr. Robert Gish
Dr. Robert Gish

Knowing for sure when treatment is working: HBsAg levels also reflect the amount of virus protein produced by infected liver cells and if treatment is effectively stopping the virus from producing these proteins. If a patient is treated with pegylated interferon, a decline in HBsAg during the first 12 weeks indicates a successful response to the drug. No change in HBsAg levels indicates interferon will not be effective.

HBsAg changes may also determine if antivirals are working. “In HBeAg-negative patients, low (HBsAg) levels at the end of treatment are associated with sustained virologic response,” Quest officials noted.

If patients have been treated with antivirals for many months or years and achieve undetectable viral load and low HBsAg levels, doctors may consider taking them off the drug.

Dr. Gish considers this new test an essential tool that providers should employ and patients should ask for to get an accurate picture of their infection state and liver cancer risk.

“I use it today to determine when to start treatment, assess a patient’s prognosis while on treatment, enhance patient compliance and determine when treatment can be stopped or should be continued,” he explained. “And this will also be an extremely helpful tool for drug developers in the future to identify promising treatments.”

Because lowering or eradicating HBsAg appears essential to stopping chronic infection and empowering the immune system to fight this complex infection, researchers around the world are working to develop treatments that inhibit HBsAg.

“I am a big believer in finding drugs that suppress HBsAg,” Dr. Block noted. Two of these surface antigen eradicator products are currently in Phase II trials.