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Tag Archives: Coinfection

The Medical Community Wakes Up to a Dangerous Threat to People with Hepatitis B – Coinfection with Hepatitis D

hep DBy Christine Kukka

In the U.S. and around the world, the medical community is finally acknowledging a hidden threat to people with hepatitis B – a virulent liver coinfection that requires the presence of the hepatitis B surface antigen (HBsAg) to survive.
Hepatitis D (Delta), which causes the most severe liver infection known to humans, infects between 15 to 20 million people worldwide and an estimated 20,000 people living with chronic hepatitis B in the U.S.
For years, health officials assumed hepatitis D did not threaten Americans and occurred primarily in Central Asia and Sub-Saharan Africa. However, recent U.S. Centers for Disease Control and Prevention (CDC) studies found 4 to 5 percent of Americans with chronic hepatitis B are also infected with hepatitis D.
As a result of these findings, researchers including Hepatitis B Foundation‘s Medical Director Dr. Robert Gish, are now pushing medical organizations to establish hepatitis D testing and monitoring guidelines so doctors will start testing patients for this dangerous liver disease.
Recently, the foundation sponsored a webinar, attended by dozens of healthcare providers, patients and officials from around the world, in which Dr. Gish outlined whom should be tested for hepatitis D, and how it should be treated. A new webinar that examines hepatitis D prevalence in the U.S. is scheduled for 3 p.m. (EST), Wednesday, June 28. To register for the webinar click here.
How do people get infected with hepatitis D? Infection occurs when people are exposed to blood and body fluids from someone with an active hepatitis D infection. Basically, they get both hepatitis B and D in one exposure. This is called an acute coinfection. Some healthy adults are able to clear both infections, but they often experience serious liver damage during the clearance or recovery phase.

Another way to become infected is if someone infected with chronic hepatitis B is exposed to someone with hepatitis D. This is called a superinfection, and in 90 percent of cases, people with chronic hepatitis B will also develop chronic hepatitis D.

Who is at risk of hepatitis D? Anyone with chronic hepatitis B who themselves or their family comes from Sub-Saharan Africa, China, Russia, Middle East, Mongolia, Romania, Georgia, Turkey, Pakistan and the Amazonian River Basin should be tested. Hepatitis D rates in some of these countries can reach up to 30 percent in people infected with chronic hepatitis B.

Banner CurveWhat medical conditions suggest hepatitis D? Anyone with chronic hepatitis B who is not responding to antiviral treatment, or who has signs of liver damage even though they have a low viral load (HBV DNA below 2,000 IU/mL) should be tested. Fatty liver disease (caused by obesity) and liver damage from alcohol or environmental toxins should be ruled out before testing for hepatitis D.
Often, people with hepatitis D have low viral loads (even if they are hepatitis B “e” antigen HBeAg-positive), but they have signs of liver damage, including elevated liver enzyme (ALT/SGPT) levels.

Do hepatitis B antivirals work against hepatitis D? No. The hepatitis D virus (HDV) is structurally different from the hepatitis B virus (HBV) and does not respond to tenofovir and entecavir used to treat hepatitis B. Hepatitis B antivirals will lower HBV DNA, but they don’t reduce HBsAg, which HDV need to thrive and reproduce.

How is hepatitis D treated? The only proven hepatitis D treatment is pegylated interferon. Interferon cures hepatitis D 15 to 25 percent of the time after one year of treatment. Once interferon clears hepatitis D, doctors treat patients who continue to be infected with HBV with antivirals. There are dozens of research companies now looking into hepatitis D treatment, and if researchers can find a cure for hepatitis B that eradicates HBsAg, it will also be effective against hepatitis D.

How should people with hepatitis D be monitored? According to Dr. Gish, doctors should:

  • Monitor patients’ ALT/SGPT and liver function at least every six months
  • Perform an ultrasound of the liver and conduct a liver cancer biomarker panel (including AFP, AFPL3% and DCP) every six months;
  • And, perform viral load (HBV DNA) and HDV RNA testing every six months.

How is hepatitis D prevented? The hepatitis B vaccine prevents hepatitis D infection, as does use of safe sex and safe injection practices. According to Dr. Gish, all hepatitis B-positive pregnant women should be tested for hepatitis D if they or their families are from a country with high rates of hepatitis D, or if they have signs of liver damage — even if they do not come from a region with high hepatitis D rates.

If a pregnant woman is infected with either hepatitis B and/or hepatitis D, immunizing her newborn with the first dose of the hepatitis B vaccine within 12 hours of birth and giving the baby a dose of HBIG (hepatitis B antibodies) will prevent both infections.

Bottom line, if you are infected with chronic hepatitis B, you should be tested for hepatitis D if:

  • You or your family comes from a region with high rates of hepatitis D; and/or
  • You have a low viral load, but you continue to have signs of liver damage, indicated by elevated ALT/SGPT or an ultrasound exam of your liver, if your doctor has ruled out fatty liver, NASH or alcohol-related liver damage.

Talk to your doctor about getting tested. Click here for a hepatitis D fact sheet to give to your doctor and click here for a patient-oriented fact sheet. An affordable hepatitis D test has recently become available in the U.S. For more information, click here.

  • Find answers to frequently-asked-questions about hepatitis D here.
  • To watch the webinar featuring Dr. Gish discussing the hidden, hepatitis D epidemic, click here.

Your Doctor Not Screening You for Liver Cancer? Time for a Talk

Image courtesy of FreeDigitalPhotos.net
Image courtesy of FreeDigitalPhotos.net

The longer we have hepatitis B, the higher our risk of developing liver cancer. With every decade of life, our liver cancer risk increases 2.7-times, according to a report on Viral Hepatitis in the Elderly published in the American Journal of Gastroenterology.

But current medical guidelines don’t spell out exactly when liver cancer testing should begin in many hepatitis B patients who don’t have liver damage (cirrhosis) or a family history of liver cancer, and are not of Asian or African descent.

Age is clearly an important factor when it comes to liver cancer, “… but current guidelines only provide age-specific recommendations for (liver cancer) surveillance in hepatitis B carriers of Asian ethnicity (men over age 40 and women over age 50),” a team of University of Miami and Veterans Affairs researchers wrote in the journal article. Continue reading "Your Doctor Not Screening You for Liver Cancer? Time for a Talk"

Hepatitis D Coinfection with Hepatitis B

Hepatitis D virus (HDV) – the “D” is for delta – is a viral enigma that doesn’t act like a normal virus. It is helpless – that is, it can’t infect a cell – without its viral accomplice, the hepatitis B virus (HBV), and makes infection with HBV worse.

Delta virus can only cause illness in those already infected with HBV, said Timothy Block, Ph.D., President and Co-Founder of the Hepatitis B Foundation, Professor and Director, Drexel University Institute for Biotechnology and Virology Research.

“It can take quiescent HBV and turn it into an acute, lethal viral infection,” Block said. “Liver disease – cirrhosis, liver failure – that might take decades to develop or could only take a year or two. Delta virus converts HBV infection into an emergency situation.”

“It’s one of the most severe forms of human viral hepatitis,” said Jeffrey Glenn, MD, Ph.D., Associate Professor of Medicine at Stanford Cancer Institute.

“Delta virus is a parasite of HBV because it encodes its own genome and coat-like protein but it doesn’t make its own envelope protein,” Glenn explained. “It steals that from HBV. It needs the B envelope protein to make its own, and this provides a means to infect new cells and subsequently make a fully formed viral particle to get out of those cells to infect others.”

Individuals can acquire delta virus two ways: Either after infection with HBV, which is called a “superinfection” and more likely to stay chronic, or a “co-infection”, which entails becoming infected with both viruses at the same time. In the latter, acute infections are more severe and increase the likelihood of developing liver disease much more quickly.

Worldwide, more than 15 million are infected, though fewer than 100,000 in the U.S. have the virus. It is concentrated in particular regions worldwide. Mediterranean areas such as southern Italy and southern Greece, for example, have larger than usual numbers of affected individuals, and in Turkey it is endemic. There are eight reported genotypes of HDV, which vary by geographical distribution and pathogenicity. Some believe that HDV’s incidence is declining. This is likely due to the hepatitis B vaccined and the resulting decrease in HBV carriers.

Because HDV is not a huge problem in the U.S., it flies under the radar screen of public awareness. Screening for HDV is not routinely ordered; however, infection with delta virus should always be considered when a patient with chronic liver disease suddenly gets worse.

Researchers have been frustrated in their attempts to develop effective treatments against HDV. Newer antiviral drugs that keep down levels of HBV DNA don’t do much against delta virus because they don’t affect the HBV envelope protein. The response rate to pegylated interferon alpha is typically poor.

With research there is always hope. Currently, there is a clinical trial of lonafarnib for the treatment of those coinfected with hepatitis B and D in the United States. It was originally developed for the treatment of different types of cancers. Perhaps additional information will come out of this year’s International Meeting on Molecular Biology of Hepatitis B Viruses. We shall soon hear.

Hepatitis D Fast facts:

—   Delta hepatitis is one of the most severe forms of viral hepatitis.

—   It is an incomplete viral particle that was discovered in 1997.

—   Approximately 15 million people are infected with HDV worldwide.

—   In the U.S., an estimated 6,000-13,000 people suffer acute HDV infection 
each year; 30,000 suffer from chronic HDV; and 1,000 Americans die 
from HDV-related diseases annually.

—   It is transmitted by blood from people already infected with hepatitis B.

—   Preventing hepatitis B, especially vaccination, will prevent HDV.

—   There is currently no effective treatment for HDV

Which is Worse Chronic Hepatitis B or C? What Do You Think?

From HBF’s expert Guest Blogger, Dr. Thomas London

If you ask doctors in the United States, or patients with liver disease, or the average person on the street, the answer that you usually get is that Hepatitis C is worse.  Hepatitis C has a bad reputation in the media and with the public. We, at the Hepatitis B Foundation, tend to think that hepatitis B is the worse disease, but until now we have not had any basis for that answer. Now we do.

Recently a group of investigators from Johns Hopkins University published a paper with the title “Comparative Risk of Liver-Related Mortality from Chronic Hepatitis B Versus Chronic Hepatitis C Virus Infection”.  The answer from this publication is that hepatitis B is more likely to cause liver related death than hepatitis C.  It is worth dwelling on how the authors came to this conclusion: unexpectedly, the AIDS epidemic triggered the studies, which made the conclusion possible.

Acquired immune deficiency disease (AIDS) was first reported in the United States in 1981. The disease appeared to be deadly, and it was thought-to-be confined to homosexual men. In fact, it was initially called Gay Related Immune Deficiency or GRID.  Although it was soon proven that this new immune deficiency disease was not limited to gay men, it is true that men who had sex with men (MSM) accounted for most of the early cases.  In the 1970’s there were several reports that MSM had a high incidence of hepatitis B.  For the initial clinical trial of the then new hepatitis B vaccine, MSM in New York City were selected as the study population because of their high risk for hepatitis B infection. In the trial about 27% of the unvaccinated population became infected with hepatitis B virus (HBV) within 18 months, whereas less than 3% of the men who received the vaccine became infected over the same time interval.  This result proved the efficacy of the vaccine.

Fast forward to 1984 before the virus causing AIDS was clearly identified, several researchers suggested that a variant of hepatitis B was the cause. A group of investigators proposed a prospective study of MSM who had been tested for hepatitis B and a newly reported anti-HIV antibody, but who did not have immune deficiency disease.  By following the men over time, the thought was that it would be possible to observe which infection – HIV or hepatitis B or a combination of both – led to AIDS.

MSM were recruited from 4 cities in the USA (Baltimore, Chicago, Pittsburgh, Los Angeles); thereafter called the Multicenter Cohort Study (MACS).  Over four time intervals from 1984 to 2002, 6972 MSM were enrolled.  The men were followed until 2010, on average for more than 8 years. Serum samples were collected every 6 months, frozen and stored.  Although the hepatitis C virus had not yet been identified in 1984, all the samples were later tested for HIV, HBV and hepatitis C virus (HCV).  All deaths were recorded as were all liver related deaths.

The results were surprising. Comparable numbers of men were infected with HBV and HCV, but MSM with chronic hepatitis B were twice as likely to die a liver related death as the men with chronic hepatitis C.  The statistical analyses were carefully done to account for the treatments of HCV, HBV, and HIV that were used during the course of the study.  Immunodeficiency further increased the risk of liver death in the men with hepatitis B over that in the men with chronic hepatitis C.

The study showed that in the two and a half decades after 1984, hepatitis B infection was more serious than hepatitis C. Now, in 2012, this difference is even greater. Chronic hepatitis C has become a curable disease.  Chronic hepatitis B is manageable, but not yet curable.  This means that hepatitis B, which was already a worse disease than hepatitis C before the new therapies for HCV, is now a much more important unsolved health problem.

– Dr. Tom London