Hepatic Encephalopathy- Enough with the Diarrhea

 

English: Liver veins (hepatic veins, portal vein)

Hepatic encephalopathy is a common condition in those that suffer from severe cirrhosis. Their liver does not detoxify the toxins in the blood well causing severe confusion, difficulties walking, hallucinations, and in later stages can cause coma or death. Controlling it is very difficult and the main therapies now include a non-absorbable antibiotic to kill off ammonia/toxin producing gut bacteria. However this is not that effective and costs close to $1000 a month. The other medication that does work very well and is very cheap comes at a very different price. It works by causing severe diarrhea. It is called lactulose and it is basically a sugar that cannot be absorbed by the intestines drawing water into the gut and causing diarrhea. The goal is to have the patient have 3 to 4 bowel movements a day to allow the toxins to clear in the stool.

Not great choices are they? Well it turns out there are other options that are not used. Zinc is one. It was studied as far back as 1984 in the journal Lancet. They did a tiny study of only 22 patients but they were randomized to receive zinc or not and it did show improvement in the zinc group and not in the placebo group. Another study done more recently in 2010 in Japan by Dr. Takuma at Kurashiki Central Hospital was slightly bigger, also randomized and also showed a benefit. In fact one group in the Netherlands published their study of a patient that they were able to induce encephalopathy by inducing zinc deficiency by giving oral histidine. It has also been clearly shown that zinc supplementation decreases blood ammonia levels, which happens to be the lab checked by physicians to confirm if a patient is having hepatic encephalopathy. And the reason for this is well-known. Zinc increases the activity of ornithine transcarbamylase which is an enzyme in the urea cycle. And yet despite all this no large trial has ever been done and it is rarely if ever used despite being extremely safe with few if any side effects and is very cheap.

The same can be said for L-carnitine which is an amino acid usually made by the liver to help the body produce energy. But of course people with cirrhosis do not have good liver function to make L- carnitine. And guess what. Lots of small studies, all show benefit, no big studies done and hardly ever if ever used despite being very cheap with few if any side effects.

Then there are probiotics. Now if you have been paying attention you may say “wait a minute, you are using antibiotics to kill gut flora to treat encephalopathy. Why would you want to give gut flora back in pill form?” Good question, but it has to do with the type of gut flora. The bacteria used in probiotics are not the same culprits that produce ammonia and other toxins that lead to hepatic encephalopathy. The good gut flora in probiotics can help displace these bad ones and indeed the few small studies that have been done show dramatic benefit from probioitics. Yet again, small studies show benefit, no big studies done and hardly ever used despite few if any side effects and being very cheap.

Do you see a trend here? If a person with cirrhosis were to use zinc, L-carnitine, and probioitics supplements the data show they would be highly unlikely to suffer any adverse reactions and statistically speaking they are very likely to get some improvement and more likely to see dramatic improvement. All while paying very little money and not having to induce diarrhea in themselves.

These studies need to be done. I have watched hundreds of people with cirrhosis suffer from hepatic encephalopathy and it is sometimes even harder on the family. Compliance to lactulose is extremely low and patients often lie about taking it because they simply cannot stand the diarrhea that comes with it. Zinc, L-carnitine and probitics show great promise for more humane treatments and yet they go unstudied. This needs to stop.

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