Immunocompetent patients who are already positive for hepatitis B (HBV) are treated with INF-µ. Patients who have had a recent exposure should immediately be treated with hepatitis B immunoglobulin (HBIg). Interestingly, HBIg may have a variety of other applications for HBV infected patients. For example, it can be administered to infants born to HBV positive mothers within 24 hours of birth to prevent neonate infection.
Perhaps the most interesting application, is that of the case of post-transplant patients. Immunosuppressed transplant patients may be treated with INF-µ2b to prevent allograft re infection. However, if allograft reinfection does occur, INF-µ2b can cause rejection, as was the case in a 1997 clinical trial of the drug. Discouragingly, if patients who are transplanted for chronic active infections do not receive any kind of post-transplant antiviral therapy, average estimated survival times range from only 1 – 5 years.
Treatment with HBIg in immunosuppressed post-transplant patients has been remarkably successful. HBIg has been shown to prevent allograft reinfection by maintaining anti-HBs titers at a level >250IU/L. This is so successful that it even prevents reinfection in patients with actively replicating viral infections!
Though this treatment is extremely effective, it is also expensive. For the first year of HBIg treatment, patients may be looking at a cost around $38,000! For every year after that, patients can expect to pay around $15,000 annually. It seems extremely unfair that such effective treatment is reserved only for those who are able to afford it…
Great post Christine. As you stated, HBIg treatment can be pretty pricey. However, alternative treatment methods have been suggested not only to reduce HBV recurrence in the post transplant patient, but to reduce the overall cost of HBIg treatment as well.
ReplyDeleteFor many patients that receive liver transplant due to HBV infection, the likelihood of reinfection is a function of the serum HBV levels at transplant. As such, many transplant hepatologists won't list a HBV (or HCV) infected individual for transplant until a viral load-reducing treatment has been administered. So the idea is to use an anti-viral medication pre-transplant to reduce the serum HBV level. Combination therapy with an anti-viral medication and a reduced dose of HBIg is then used post-transplant.
The benefit is two-fold. First, lower levels of serum HBV pre-transplant decreases the likelihood of reinfection. Second, the overall cost of treatment should be less. The cost of administering an anti-viral medication pre-transplant and using combination therapy (an anti-viral plus a reduced dose of expensive HBIg) post-transplant should be lower than the cost of conventional HBIg treatments.
Hi Christine. Is that really supposed to be IFN "mu"? As far as I know the treatment for HepB is IFN alpha.
ReplyDeleteWould this type of treatment be efficacious for chronic patients? I noticed that you said people who have been recently exposed, so I am just wondering if this has been shown to work in people who have progressed from acute to chronic infection?
ReplyDeleteHi everyone! Thanks for your posts!
ReplyDeleteBrianL7630: Agreed! The cost of HBIg is definitely lower than a transplant - especially when you factor in immunosuppressants, steroids, etc post transplant!
So I'm curious, if physicians won't list patients for a transplant unless they've completed some viral load reducing treatment, what do you think about MELD scores? Because a MELD score of >14 makes you a candidate for transplant. Is it wrong to wait to list patients with a qualifying MELD score just because they haven't tried an antiviral course? Many HBV+ people are asymptomatic for many years, and don't even realize they have HBV until they're stage 4 and their enzymes are going crazy.
Dr. Cohen: To my knowledge, INF - alpha is something that is used to treat HCV patients exclusively (right not INF alpha + ribavirin is is the standard of treatment in all HCV drug clinical trials). Some studies have been done, showing that using INF gamma can actually help the antiviral activity of INF alpha if they are used together in HCV patients, however...
Interferon-(gamma) Improves Response To Interferon-(alpha) In Hepatitis C.
Hepatitis Weekly. February 18, 2002
To treat HBV patients, it is possible to use either INF alpha or INF gamma. However, it is believed that treatment with INF gamma more effectively prevents hepatocellular fibrosis (about 40% more effectively than INF alpha) in patients with the HBs-Ag (the less infectious version of the virus). To my knowledge (that doesn't mean they're not out there) there haven't been any studies done in patients with the highly infectious antigen, HBe-Ag.
TanyaC7630:HBIg is efficacious for chronic patients - however it's a time commitment. Some people receive IV HBIg treatments monthly! This is costly, and it wipes you out (for at least a day).
If you have recently been exposed to HBV, the hepatitis immunoglobulin (HBIg) can prevent infection in about 97% of people if you get it within 24 hours (12 is better) of being exposed to infected fluid. This is also given to babies born to HBV+ mothers at birth.
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ReplyDeleteChristine, great question regarding MELD scores. Most patients that are transplanted have MELD scores that are in the mid 20's. Patients that are in the top 10 on the transplant list here at CU (meaning they are seriously being considered for transplant) usually aren't transplanted until they hit a MELD in the upper 20’s (one of the transplant surgeons quoted me ~29 as the average). So while a patient may be eligible to be listed for transplant once they have a MELD >14, they won't be eligible to receive a liver until they make their way up the list. As you may have guessed, how quickly they do that is a function of their particular disease state and assessment by the hepatologists and transplant surgeons.
ReplyDeleteThat being said, many patients that are listed for HBV (or HCV) have had some sort of treatment to attempt to reduce viral load. For most patients anti-viral treatment will have been initiated before a transplant is even considered in an effort to avoid transplant altogether. If the patient is sick enough for transplant, i.e. their MELD is >14, and has not had treatment, they may receive treatment after they have been listed and are waiting for a liver. Not having had anti-viral treatment prior to listing does not preclude a patient from being listed.
Though it is ideal to attempt to reduce HBV viral load prior to transplant, certainly the overall condition of the patient is assessed extensively when they are evaluated for listing. For patients that are quite sick and have progressed to say, Stage 4 liver disease, a decision may be made to move them to the top of the list (obviously the degree to which they are sick should be reflected in their MELD score). Case in point, there is an individual that has been HBV+ for years and was diagnosed with cirrhosis less than eight weeks ago. This individual was not previously listed for transplant and was just put at the top of the list with a MELD well above 30.