COMMENTARY

Can Aggressive Albumin Use Reduce Mortality in Cirrhosis?

David A. Johnson, MD

Disclosures

January 09, 2019

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

We all know albumin is used for maintaining oncotic pressure, and that we treat our patients with chronic liver disease, hepatorenal syndrome, or spontaneous bacterial peritonitis with intravenous (IV) albumin as the standard of care. But can albumin provide us with much more than just that? To answer that, I want you to put on your thinking caps, expand your mind a little bit, and consider this translational message that's certainly changed the way I practice.

Firstly, we recognize IV albumin as a volume expander, but the key is to also recognize that it has immunologic function. Cirrhotics have an increase in prostaglandin E2 (PGE2). This is important to understand, because of the pleiotropic immunomodulatory function of PGE2. It has negligent effects on the patient with cirrhosis, particularly as it relates to immune function, because it reduces the immune cell trafficking to tissue compartments. Think about your patients with spontaneous bacterial peritonitis, in whom you want to get the white cells to the ascitic fluid; this reduces immune cell trafficking.

Secondly, it blunts cell antimicrobial helper T cells, which are the things that are trying to aid us as we fight infection.

Thirdly, it suppresses bactericidal activity. It actually inhibits phagocytosis and oxygenated burst bacterial killing.

So PGE2 has a significant effect as it relates to the immune function in our cirrhotic patients.[1] We also know that PGE2 is elevated in cirrhosis, and this drives susceptibility to immunosuppression and infection.

What's the leading cause of death in cirrhotic patients? It's not end-stage liver disease and fulminant hepatic failure. It's infection.

What is also really important to understand is that PGE2 has an additional effect on kidney function. There are actually four renal receptors that have direct regulation on renal perfusions. When we talk about IV albumin for hepatorenal syndrome, I don't think any of us—and certainly not me—recognized the renal receptors for PGE2 in cirrhosis as it relates to the negative effect for the reduction of renal perfusion.

Lo and behold, this is all attenuated by IV albumin. I want you think about IV albumin as a "sink" for circulating PGE2. What does that mean in clinical parameters? It's an important tool suggesting that it should modulate immunity, enhance renal perfusion, and rescue immune function.

Looking for an ANSWER

The ANSWER trial from Italy was just recently published in the Lancet.[2] This study included 431 patients with cirrhosis and uncomplicated ascites (ie, no spontaneous bacterial peritonitis or hepatic encephalopathy) treated with antialdosteronic drugs (≥ 200 mg/day) and furosemide (≥ 25 mg/day). Patients were randomized to receive either standard medical treatment (SMT) or SMT plus long-term human albumin in an IV administration of 40 g twice a week for 2 weeks and then 40 g thereafter weekly.

The study's primary endpoint was death at 18 months, which favored the group receiving SMT plus IV albumin versus SMT alone by 11%. That means the number needed to treat for death reduction is 9! I have never seen a trial that had this kind of implication as it relates to absolute risk reduction for death in a short period of time.

There were additional risk reductions as it relates to spontaneous bacterial peritonitis, repeat need for paracentesis, and hepatic encephalopathy. There was no reduction as it relates to variceal bleeding, but there was also reduction in absolute 67% reduction in spontaneous bacterial peritonitis (SBP), as well as a 30% reduction in non-SBP infection.

Remaining Questions and Conclusions

There are recognizable intrinsic costs, both direct and indirect, involved with IV albumin. Patients have to come to you to receive it, and there may be a bit of a challenge getting it approved by your pharmacy and therapeutics committee. However, we have to recognize that keeping cirrhotics out of the hospital is the best thing for the health system. Certainly, the more we could do that, the better the healthcare economics will be.

We also don't know what the target threshold amounts are for the IV albumin. Is it 3 or 3.5? I'm using 3.5 in my practice for now until I see evidence otherwise from forthcoming trials.

But for now, it makes sense that IV albumin should be considered as a translational message for such patients. Consider it as a PGE2 "sink." It's unquestionably changed my practice, and I think it should also change yours, or at the very least warrant your thoughtful consideration.

I'm Dr David Johnson. I look forward to chatting with you again soon. Thanks again for listening.

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