N-acetyl-cysteine and Liver Transplantation:
Jacob Schor, ND
It was recently suggested in our clinical support network that N-acetylcysteine (NAC) might be a useful supplement to use in patients undergoing liver transplants. I have done a literature search and read through what abstracts I could find related to this subject. The use of NAC appears to have sparked the interest of a number of research groups. The focus of the research has been whether or not NAC could decrease the amount of damage that occurs to the transplanted liver. NAC is the classic antidote for acetominophen poisoning[1. 2] and it also appears to be particularly useful for protecting the liver and is recommended ("This study suggests that N-acetyl-cysteine administration should be considered in all patients with acute liver failure.") in cases of hepatic failure[.3]
There have been a number of studies looking at whether NAC could improve the outcomes in liver transplants.
In January of 1995 American researchers published an experiment using pig livers that suggested that pretreatment of the liver with NAC improved outcome of transplantation. ("ATP recovery, bile output, and survival were all better in the treatment groups than in the control group. Pretreatment with NAC helps maintain hepatic glutathione during warm ischemia; given after ischemia, NAC is effective in replenishing depleted glutathione stores. Adjunctive use of NAC was associated with improved glutathione homeostasis, improved bile output and ATP regeneration, and increased survival.") 
In August of 1995, French doctors reported that NAC appeared useful in a rat experiments.[ 5]
In May of 1996 German Researchers published findings that NAC was useful in a rat model. ("We conclude that high-dose therapy with NAC in OLT attenuates manifestations of microvascular perfusion failure early after reperfusion and should be considered as a means to reduce reperfusion injury.") 
In July, 1996, French Researchers reported that NAC was useful in protecting Rat livers from injury during transplantation("....the NAC pretreatment also significantly reduced hepatocellular as well as sinusoidal oxidative stress, resulting in improvement of hepatocellular integrity relative to a control dextrose.")
This was followed by a Japanese report in February 1998, again using rats. (".... NAC prevented hepatic injury and improved liver integrity after a cold ischaemic-reperfusion injury, by acting not as a substrate for glutathione synthesis but as a direct free radical scavenger.") In 1998 an pilot study of 30 human liver transplant patients and an equal number of controls reported that: "In the NAC group we observed a distinct reduction in ischemia/reperfusion injury and improved liver function with less elevated peak transaminases, better macrocirculation, improved liver synthesis function and a lower incidence of primary nonfunction compared with the control group. We conclude that NAC is a very promising substance for reducing graft dysfunction in clinical liver transplantation." Not all the studies have been positive. Several have been unsuccessful at showing benefit to using NAC.[10 11 12 13]
None of the studies have demonstrated any harm in using it.
None of the studies have used oral NAC.
In the Thies study, the study using human subjects, it is unclear from the abstract how the NAC was administered and at what amounts. This is one journal article worth looking up in its entirety.
So how does this apply to what naturopathic physicians can do to help their patients as they undergo liver transplants (or other organ transplants for that matter)? I'm not sure. Here's what IÕm thinking. If I have any control of the person who will donate the liver prior to surgery, I'll try to have them take supplemental NAC. What dose? Probably as much as they can. I donÕt know whether giving NAC to the recipient will do much good, but it won't hurt so I'll suggest the same just before surgery and ASAP post surgery.
In looking for these abstracts I stumbled through a few other interesting references on the same subjects.
1. Liver transplant patients typically get cardiovascular problems. No surprise but they have high homocysteine levels which respond to the standard, B-12 and folic acid combination. Is it surprising that a liver transplant might deplete B-12 stores?
2. Use of NAC for MIs seems to accepted practice in some parts of the world as reported in an Australian nursing journal: "Previously administered in cases of acetaminophen toxicity, N-Acetylcysteine (NAC) is now also being used in the management of acute myocardial ischemia and reperfusion injury. NAC potentiates the beneficial effects of nitrates such as nitroglycerin and reduces oxidative stress on the heart. The critical care nurse plays an important role in optimizing the therapeutic benefits of NAC and minimizing its potential harmful effects."
3. One method being investigated or used to help protect the liver before it is transplanted is called ischemic preconditioning. Apparently subjecting the liver to short ischemic episodes prior to the transplant hardens the liver making it more resistant to damage. This apparently is due to increasing Nitrous Oxide (NO) production. Arginine seems to increase the production of NO and increases the effectiveness of the preconditioning. (" ..... L-arginine synergized with short-term ischemic pre conditioning..... to increase the survival of rats that received a liver graft ....").