March 2011 Hepatitis C Treated with Low Dose Naltrexone (LDN) - Dr. Zagon comments

Hepatitis C Viral load -  16,500 slightly up from the 14,679 that it was in October 2010.

ALT - 30 up from 24 in October  (6-40)

AST - 33 up from 31 in October  (10-35)


Basically the same as it has been for the last few lab tests!  Normal liver function tests and lower viral load using 3 mg. of Low Dose Naltrexone.

My platelets also went up as did my red blood cell count.  However, my IgA was back on the low side again - last labs, it was normal for the first time.

Ferritin was 43, which is down a bit from last.  Iron was also down as was total saturation.

I also saw my gastro recently and was pleasantly surprised with his attitude and manner. I had not seen him since 2009 shortly after starting LDN and he had yelled at me for taking it.

I had a new abdominal ultrasound done last week and got back the results.  The U/S report used the word unremarkable to describe most things - however, it showed "diffuse fatty infiltration of the liver" DRAT! My last u/s was done about 3-4 months following my appointment with Dr. Berkson in 2009 and my five IV ALA (alpha-lipoic-acid) treatments and it had "normal liver function" with no mention of fattly liver! Every other u/s that I have had since 2001 has had fatty something, but not the one after Dr. Berkson.  I do know that Dr. Berkson recommended a course of initial IV ALA treatments, then oral supplementation and then another round of IV ALA.  I have never had any more treatments since 2009.

So, maybe that is proof of the power of IV ALA - or as the gastro and I discussed, maybe interpreting ultrasounds is up to whoever reads it. But I would tend to think that the IV ALA did it - back in 2009 during the same time, my AFP (alpha feta protein) test went up to 6.1 (which was slightly above normal) - it had always been normal before. I remember reading at the time that liver regeneration can sometimes cause elevations in AFP. My doctor today told me that I was correct - "You have been reading". My AFP was normal for every test since then.

Fortunately for me, my own CAM doc here does ALA, so I will want to have a few. It'll probably be awhile though as I don't have the money for it now.

Anyway, it was a pleasant gastro visit - probably the only one that I've had since I was diagnosed in 2002.


NOTE!  2013 UPDATE ON DOSING - PLEASE READ POST:

Why 3mg. LDN might be best?

Back to original post:

Dr. Zagon's comments on LDN dosing

For my current labs,  I was taking the 3 mg. LDN every other night.  In the past, I had tried increasing the dosage and taking it almost every night.  Some folks in our Hepatitis Cam group had initial drops in their viral load and liver enzymes on 3 mg. but their levels seemed to go back up down the line.  When they increased their LDN dosage, their levels went back down.  I wrote to Dr. Zagon about this and this is what he said:

"You are a product of not understanding how LDN works - a classic example I might add. And most of your colleagues on the web share your misinformation.

LDN works through what is called the opioid growth factor - a native peptide (and its receptor) in your body. LDN is a decoy that fills in at the site of the receptor - the body not having the peptide makes more of it in compensation. Now the trick we discovered 30 years ago. A short time of naltrexone - low dose naltrexone is the term lay people use (but really intermittent opioid receptor blockade) increases the peptide. After the naltrexone is metabolized - optimal time is 4-6 hours for around 3 mg, the high levels of peptide and actually an increase in receptors as well can interact. This depresses cell/viral proliferation - and makes you better.

By increasing your dose of LDN you are cutting into the time you need for an optimal reaction. Hence - you feel problems.

My advice - take 3 mg/day. If you have a problem, start taking LDN once every 2 days (many folks are taking it that way - and
some every 3 days).

Dr. Zagon

A story. A lady calls me and says she has breast cancer. She is taking LDN and the cancer is growing more rapidly. I ask her how LDN is being given - she says that since LDN is so good, she is taking it several times a day. Now you know why she had a faster growing cancer - she was not allowing the opioid-receptor interaction to occur because of so much naltrexone.

And, if you block the receptors all day with naltrexone (high dose of naltrexone), we now see that wound healing is accelerated. Why, because the cells are speeding up in replication and healing the wound faster.

Below is what I wrote to Dr. Zagon:

I have been on 3 mg. LDN for over a year for my HCV with terrific results - viral load dropped from 1,400,000 to 11,200 on my April 2010 labs and lft's are normal. I was on 3 mg. every other night,then every night. I recently increased my dosage in an attempt to lower my viral load even more - went up to 3.5 and then to 4 mg. taking it every night. However, I have had small outbreaks of shingles and HHV2 on the 4 mg. dosage. I did not take the LDN for a couple of nights and started again last night at 3.5. I am going togo back to every other night dosing for now.

So after Dr. Zagon's first response, I wrote back to him and explained about our Hepatitis Cam group's database and how most folks lft's and viral load went down when they increased their LDN dosage.  This was his reply:

First, science is science. If these individuals are having to go up on dosage to evoke a positive response, that is potentially meaningful. My interpretation is that these patients are exhibiting a tolerance that builds to LDN. Very interesting. Our initial recommendation was 3-10 mg of LDN daily.

Second, your story does not conform to what others may be
seeing - tolerance. If anything, you are encountering a sensitivity. I would certainly try 3 mg every other day and see what happens.

Third, this entire LDN business is empirical right now -
you have to be in the frontier of just plain trying things out. In
your case, lower is the best. It may be that in some individuals
their pharmacology is far different than yours - they might be
building a tolerance and need more. Alternatively, the LDN is either breaking down over time and loses potentcy, or is not or high quality or is being mixed in with "fillers" that are negating the action of the LDN.


That correspondence took place over last summer (2010) - now, I ponder why my viral load seems to be staying the same (though slowly creeping higher) and not getting any lower, or thankfully, not skyrocketing back up to where it was pre-LDN - which was over 1 million.  What can I do to get it even lower?  So, despite what Dr. Zagon says, I am going to start taking the LDN every night and perhaps slightly increasing the dosage in an attempt to lower my viral load even more.  He has added a bit of confusion into the mix, I must say.   Or look into TLR's (Toll Like Receptors) - there has been a lot of research of late about them, particularly in HCV.  Dosing of LDN 2 x a day is also another possibility - I will update after more research.

Treating Hepatitis C with Low Dose Naltrexone (LDN)

3 mg. LDN next to Advil

UPDATE 2013 LDN DOSING - WHY 3 MG LDN MIGHT BE BEST -

Treating Hepatitis C with Low Dose Naltrexone (LDN)

UPDATE - JUNE 2014 -

The original post below was written back in 2010 but I have since edited it to reflect the newer research regarding using the lowest dose possible of LDN.

Please also see:   Why 3 mg Low Dose Naltrexone Might Be Best


After being on 3mg Low Dose Naltrexone for 5 years now, my HCV viral load still remains low and my liver enzymes are still normal.  And even though I imagine that in the next year or so, I will do the newest non-interferon treatment - minus the ribavirin, I still plan on taking Low Dose Naltrexone for the rest of my life - virus or no virus.  Meanwhile, now that a possible real cure for HCV has come along, most folks cannot afford it at this time.  So the best bet is to take Low Dose Naltrexone, use good quality supplements that help support one's liver and immune system and to eat as healthily as possible.  A paleo type diet and one that does not involve grains or any kind, particularly wheat.



I am successfully managing my Hepatitis C virus by using LDN - Low Dose Naltrexone, supplements, diet and exercise and have attempted to share my experiences on my blog, Nola Hepper. Now, I have tried to include all of this information in one place.

I was diagnosed in 2002 with Hepatitis C, genotype 1b. A biopsy revealed minor inflammation with Grade 0-1, Stage 0-1 and my lab work showed slightly elevated liver enzymes. Despite being urged to due interferon/ribavirin treatment back then, I chose to make healthy life style changes instead while waiting for "something else" to come along and learned as much as I could about the HCV virus. My health remained about the same for several years until 2005, when my Hurricane Katrina experience caused me to start having severe side effects. I developed fibromyalgia, shingles, severe chemical sensitivities and terrible IBD. My doctors told me that all of these problems were being caused by the Hep C and again urged me to do treatment.

I was able to get Social Security disability and Medicare and this allowed me to see a very good integrative doctor. She tested me for everything and suggested a course of action for me, which included several new supplements and diet changes. She also gave me a paper written by Dr. Burt Berkson, another integrative doctor who had done extensive work using ALA - Alpha-Lipoic-Acid. His work seemed very promising, so I began to do his protocol of ALA, Milk Thistle (although I had already been taking milk thistle for years), Selenium, and B Complex along with the other supplements that my doctor had recommended for me.

One of the diet changes that my doctor mentioned was to cut down or eliminate wheat - she said that most people cannot really digest it or are sensitive to it. I was a bit skeptical but after researching it, I decided to try it out. And the results were amazing! Within days it seemed that my IBD and bloating had greatly improved. Soon, I noticed that my fibromyalgia had gotten much better as had my chemical sensitivities - I didn't' seem to be quite so sensitive to smells anymore - and you must understand. It had been to the point where going to the grocery was an ordeal - I had to hold my breath going down the detergent or bug spray aisles. This also was much improved! Gluten (one of the proteins found in wheat) is a big problem to most folks with liver disease, particularly those who undergo interferon treatment, as it is a known trigger for celiac disease and can cause elevated liver enzymes.

After researching more about diet and nutrition, which included an appointment with a Certified Clinical Nutritionist, I took things a step further and ordered a food sensitivity/intolerance panel through a company called Alletess as they took my Medicare insurance. This test revealed that I had sensitivities to cow's milk, yeast and some shellfish. Upon eliminating these foods, my IBD really seemed to completely go away and my other health issues got much better as well.

However, my latest liver lab work (January 2009) was frustrating - my HCV viral load test was 1,400,000 - ALT was 174 and AST at 105 - other labs were pretty much in the normal range with a few blips here and there. I had exchange emails with a couple of folks who had seen Dr. Berkson and they said that they liked him and were seeing great improvements in their health - they also mentioned that he had put them both on Low Dose Naltrexone or LDN. So I decided to go out to New Mexico to see him myself.

I started on 3 mg. of LDN in mid-February 2009 while at Dr. Berkson's clinic but after I got back, I started having an upset stomach due to the lactose filler that the pharmacy in New Mexico used in their compounding mixture. I went off of the LDN for about 2 weeks until I got a new prescription mixed with acidophilus - probably March 1st, 2009. I had new labs done in late April 2009 and the results were remarkable. Viral load dropped from the 1,400,000 to 48,000! ALT from 174 to 22 and AST from 105 to 30!. My integrative doctor was amazed as I was but my traditional gastro actually yelled at me, saying that LDN was not "supposed" to treat Hepatitis C and that the labs had to be a mistake. I've never gone back to him.

This is about the time that I became an advocate for LDN and started posting more on my blog and on several LDN yahoo groups and various Hepatitis C, health sites, etc. How could I not with the results that I have had? Since that time, I have played around with the LDN dosage and have used my lab results as a kind of rough guide in doing so. Currently I am back on 3 mg. that I take most every night. My May 2010 lab work showed a viral load of 11,400 - ALT at 25; AST at 30.  (note - 2014 LDN dosage is 3mg taken every other night or every third night)

Ideally, it is best to work with a doctor who is familiar with the workings of LDN and who can prescribe it. And to get the LDN from a reputable compounding pharmacy such as Skip's Pharmacy. However, one can also order the 50 mg. tablets and make the solution themselves without a prescription.

If you already have a prescription for LDN, it is probably in a capsule form. If you want to start off at a different dose than whatever your prescription is for, it is better to mix the LDN with water than to simply take a third or half of the capsule alone. The reason being is that one can never be sure where the LDN is in the capsule and if you mix it with water, it is a more accurate dose. For example, I take my 3 mg. capsule and dump it into a dark colored vial (I got a 12 ml (cc) vial at Whole Foods for a couple of bucks). Use a 1 cc (ml) or 3 cc (mg.) syringe and measure in 3 ml. of distilled or bottled water - not tap water. Measure out the needed dose and store the rest in the fridge. For 4.5, simply increase to 4.5 cc's (ml's) of water.


There are slightly different instructions for the 50 mg. tablet but it is the same principal - 50 cc's (ml's) of water mixed with the tablet - obviously you would need a vial large enough for that amount - more detailed instructions are included in one of the links above or here: "How to Obtain Low Dose Naltrexone"

"Once you have a supply of 50 mg Naltrexone tablets, you can convert them as needed to LDN. To do so, fill a graduated cylinder with 50 ml of distilled water (unlike tap or spring water, distilled water contains no impurities that could potentially react with and thus reduce Naltrexone's effectiveness). Pour the water from the graduate into a 4 oz amber glass jar with a tight-fitting lid. Then add a 50 mg Naltrexone tablet. The tablet will mostly dissolve in about five to ten minutes. Since not all of the tablet is soluble in water, instead of yielding a clear solution, the result will be a cloudy suspension. It must be shaken each time before use to evenly disperse all the undissolved particles. One ml of the (shaken) suspension will contain one mg of Naltrexone. Use a graduated baby medicine dropper to measure out the dose you need."


Dosing is very individualized. I am finding that the biggest mistake that doctors are making with LDN is to prescribe the 4.5 dosage in the beginning, particularly to their patients with liver disease - some folks can tolerate this dosage, but in most it is a guarantee of initial side effects - sleep disorders being the most frequent. There are different theories on dosing, depending on what doctor or researcher you listen to. Dr. Berkson starts everyone off at 3 mg. but he prescribes sleep medications in the first month to counteract these sleep problems. Most savvy doctors and LDN veterans know to recommend that people start off at a very low dose such as 1 mg. Start at 1 mg. and stay on it for a week or so then move up to 1.5 or 2 for another week or so until you get to 3 mg. At this point, you can either work your way up to 4.5 or stay at the 3 mg. dosage until you get your first post LDN labs done. Again, dosing is very individual - up to that person's make up, medical problems, etc.  - some folks do well on 3 mg and have great results while others need more or less of the Low Dose Naltrexone - some folks take it every other night or less.  It really depends greatly on what disorder or multiple disorders the person has along with other factors.


Why LDN might not work -  According to several sites and personal accounts, yeast infections seem to be triggered or made worse when first starting LDN.  It is very important to have any candida, or other mold/yeast problems cleared up as having them can interfere with how well the LDN works.

The link below covers this as well as other side effects - note - the site was written by someone with MS, but it is still good info:


Side Effects & Dosing of Low Dose Naltrexone (LDN)


Dr. McCandless ( Children with Starving Brains )  has written about the dietary aspect when using LDN:


Dr McCandless, seldom is LDN stand-alone treatment



There is much more LDN info on other sites:

LDNers.org site - Resouces page


I have covered supplements in another area of the blog -  Supplements 

a quick recap.  The most important supplements for the liver are those that help generate more glutathione,  - usually ALA - alpha-lipoic-acid, with  NAC - N-acetyl cysteine, SAMe, whey protein (gluten-free) and others.

Silymarin (Milk Thistle) is extremely important as is Vitamin D3.  Most folks are very deficient in Vitamin D3, particularly in those with HCV.   A multi vitamin without iron! (capsule form is best and more easily absorbed than tablet), vitamins C & E.

One of the most critical things is to keep one's ferritin levels below 100.  Ferritin is basically the iron storage in the liver - and it is the iron that does all of the damage!!!  Not the HCV virus as most docs and literature would have one believe.  See Iron Ferritin and the Liver for more.

Low Dose Naltrexone (LDN) and the Liver

note - this post title really should be "Naltrexone and the Liver" as the studies below all are based on full strength naltrexone and not LDN.

Low Dose Naltrexone, or LDN, is an FDA approved medication.
"Naltrexone itself was approved by the FDA in 1984 in a 50mg dose for the purpose of helping heroin or opium addicts, by blocking the effect of such drugs. By blocking opioid receptors, naltrexone also blocks the reception of the opioid hormones that our brain and adrenal glands produce: beta-endorphin and metenkephalin."

Although naltrexone itself is an FDA-approved drug, the varied uses of LDN still await application to the FDA after related scientific clinical trials. LDN (in the 3mg or 4.5mg dosage) has not yet been submitted for approval because the prospective clinical trials that are required for FDA approval need to be funded at the cost of many millions of dollars.

Naltrexone is a prescription drug, so your physician would have to give you a prescription after deciding that LDN appears appropriate for you.

http://www.lowdosenaltrexone.org/

Many doctors will not prescribe LDN, as they are not aware that it is FDA approved and that various clinical trials for various disorders have been done or are in progress. The other reason is because of the "Black Box Warning" for full strength Naltrexone due to adverse liver effects on obese patients using 300mg.

Full-dose naltrexone (50mg) carries a cautionary warning against its use in those with liver disease. This warning was placed because of adverse liver effects that were found in experiments involving 300mg daily. The 50mg dose does not apparently produce impairment of liver function nor, of course, do the much smaller 3mg and 4.5mg doses.

Further studies have shown that LDN is actually beneficial to the liver in low doses - however, most of the studies done used much higher doses of Low Dose Naltrexone.

Study of hepatotoxicity of naltrexone in the treatment of alcoholism.
Since a black box warning was issued by the Food and Drug Administration regarding the use of the opiate antagonist naltrexone (NTX), many clinicians have been concerned about current labeling of the potential hepatotoxicity risk of NTX in the treatment of opiate dependence and alcoholism. Despite many reports that demonstrated that the use of NTX did not cause elevation of liver enzymes, controversy concerning whether NTX is hepatotoxic continues. The current study monitored 74 alcoholic patients who received 25mg of NTX daily in the first week and then 50mg of NTX daily for the rest of the 12-week period. After the 12-week treatment, levels of the hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) did not show any elevation, except in one subject, and the results strongly support that NTX did not induce abnormalities in liver function tests or elevate the liver enzymes. Instead, a statistical significance of decreasing levels of ALT and AST in the liver was shown throughout the study. These findings provide further support that NTX is not hepatotoxic at the recommended daily dose and may be beneficial for patients with elevated liver enzymes.
PMID: 16839858 [PubMed - indexed for MEDLINE]

Effects of long-term treatment with naltrexone on hepatic enzyme activity.Mean plasma levels of hepatic enzymes did not show significant modification in the course of treatment with naltrexone.

PMID: 1686854 [PubMed - indexed for MEDLINE]
Naltrexone: report of lack of hepatotoxicity in acute viral hepatitis, with a review of the literature.
Many clinicians appear to be concerned about the potential hepatotoxicity of the opiate antagonist naltrexone (NTX) and this may be one reason why it is not used more widely in treating both heroin and alcohol abusers. Some much-quoted early studies noted abnormalities in liver function tests (LFTs) in very obese patients taking high doses, although there was no evidence of clinically significant liver dysfunction.

We describe a heroin abuser in whom clinical and laboratory manifestations of acute hepatitis B and C appeared a few days after the insertion of a subcutaneous naltrexone implant. A decision was made not to remove the implant but the hepatitis resolved completely and uneventfully well within the normal time-scale. A review of the literature indicates that even when given at much higher doses than are needed for treating heroin or alcohol abusers, there is no evidence that NTX causes clinically significant liver disease or exacerbates, even at high doses, serious pre-existing liver disease.

PMID: 15203443 [PubMed - indexed for MEDLINE]

Naltrexone protects against lipopolysaccharide/D-galactosamine-induced hepatitis in mice.
Results demonstrated that post-treatment with naltrexone (20 mg/kg, i.p.) significantly attenuated the deleterious liver function in mice treated with LPS/D-gal. It was also found that naltrexone significantly inhibited the elevation of plasma tumor necrosis factor-alpha (TNF-alpha) caused by LPS/D-gal. The overproduction of nitric oxide (NO) and superoxide anions induced by LPS/D-gal were also significantly reduced by naltrexone. Moreover, infiltration of neutrophils into the liver of mice 12 h after treatment with LPS/D-gal was also decreased by naltrexone. In conclusion, the beneficial effects of naltrexone on LPS/D-gal-induced hepatitis result from its inhibition of pro-inflammatory factors and antioxidant effects. Thus, naltrexone is of therapeutic potential for treating liver injury.

PMID: 19023176 [PubMed - indexed for MEDLINE

Lack of hepatotoxicity with naltrexone treatment.
In summary, chronic administration of naltrexone in doses up to 300 mg/day for periods up to 36 months does not significantly change hepatic function, as measured by SGOT and SGPT levels.

PMID: 7983232 [PubMed - indexed for MEDLINE]

Opioid receptor blockade reduces Fas-induced hepatitis in mice.

PMID: 15389866 [PubMed - indexed for MEDLINE]

Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats.

CONCLUSIONS: This is the first study to demonstrate that administration of an opioid antagonist prevents the development of hepatic fibrosis in cirrhosis. Opioids can influence liver fibrogenesis directly via the effect on HSCs and regulation of the redox sensitive mechanisms in the liver.

PMID: 16543289 [PubMed - indexed for MEDLINE]

Opioid system blockade decreases collagenase activity and improves liver injury in a rat model of cholestasis.
CONCLUSION: Opioid receptor blockade improved the degree of liver injury in cholestasis, as assessed by plasma enzyme and liver MMP-2 activities. The beneficial effect of naltrexone may be due to its ability to increase liver SAM level and restore the SAM : SAH ratio.

PMID: 17295775 [PubMed - indexed for MEDLINE]

Effect of oral naltrexone on pruritus in cholestatic patients.

CONCLUSION: Naltrexone can be used in the treatment of pruritus in cholestatic patients and is a safe drug showing few, mild and self-limited complications.

PMID: 16534857 [PubMed - indexed for MEDLINE]

Opioid peptides and primary biliary cirrhosis.
Patients with liver disease have increased plasma concentrations of the endogenous opioid peptides methionine enkephalin and leucine enkephalin. As an initial investigation to determine whether opioid peptides contribute to any of the clinical manifestations of hepatic disease nalmefene, a specific opioid antagonist devoid of agonist activity, was given to 11 patients with cirrhosis. They all experienced a severe opioid withdrawal reaction on starting the drug. In the nine patients with primary biliary cirrhosis pruritus was greatly alleviated, fatigue seemed to improve, and plasma bilirubin concentration, which had been rising, showed a modest fall in all except one patient. These results indicate that blocking opioid receptors has an effect on some of the metabolic abnormalities of liver disease.

PMID: 3147046 [PubMed - indexed for MEDLINE]
Pharmacokinetics of long-acting naltrexone in subjects with mild to moderate hepatic impairment.

Long-acting naltrexone is an extended-release formulation developed with the goal of continuous naltrexone exposure for 1 month for the treatment of alcohol dependence. The influence of mild and moderate hepatic impairment on naltrexone pharmacokinetics following long-acting naltrexone 190-mg administration was assessed. Subjects with mild (Child-Pugh grade A) and moderate (Child-Pugh grade B) hepatic impairment (n = 6 per group) and matched control subjects (n = 13) were enrolled. Naltrexone and 6beta-naltrexol concentrations were determined over a period of 63 days following a single intramuscular dose. Naltrexone and 6beta-naltrexol concentrations were detected in all subjects through 28 days. Total exposure (AUC(0-infinity)) of naltrexone and 6beta-naltrexol was similar across all groups. The long apparent half-lives of naltrexone and 6beta-naltrexol (5-8 days) were attributed to the slow release of naltrexone (long-acting naltrexone exhibits absorption rate-limited elimination or "flip-flop" kinetics); elimination was not altered in subjects with hepatic impairment. Based on pharmacokinetic considerations, the dose of long-acting naltrexone does not need to be adjusted in patients with mild or moderate hepatic impairment.

PMID: 16239359 [PubMed - indexed for MEDLINE]

High-dose naltrexone and liver function safety.






























Studies have found naltrexone useful in the treatment of diseases other than opiate addiction in which endogenous opioids presumably play a role, such as alcoholism and eating disorders. Some of these studies involve high doses (100-200 mg bid). Because investigational studies with high doses (300 mg/day) reported clinically significant increases in liver enzyme levels, the authors measured a spectrum of liver function parameters in response to high doses of naltrexone in a double-blind, crossover trial (100 mg bid) followed by an open-label period (200 mg bid). They observed no adverse clinical or laboratory changes in liver function in association with high-dose naltrexone therapy in eating disorders.

PMID: 9097868 [PubMed - indexed for MEDLINE]

Effect of liver cirrhosis on the systemic availability of naltrexone in humans.

CONCLUSIONS: Our data suggest the occurrence of important changes in the systemic availability of naltrexone and 6 beta-naltrexol in liver cirrhosis; such alterations are consistent with lesser reduction of naltrexone to 6 beta-naltrexol and appear to be related to the severity of liver disease. This must be considered when administering naltrexone in conditions of liver insufficiency.
PMID: 9314128 [PubMed - indexed for MEDLINE]

Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics.

RESULTS: There were no significant differences in alanine aminotransferase, aspartate aminotransferase, or bilirubin levels between the study groups at study initiation or at subsequent assessments. Gamma-glutamyltransferase in the XR-NTX 380 mg group was lower compared with placebo at weeks 4, 8, 12, and 20. Both high (>3 times the upper limit of normal) liver chemistry tests (LCTs) and hepatic-related adverse events were infrequent in all study groups. In patients who were drinking heavily throughout the study, obese subjects, or those taking nonsteroidal anti-inflammatory drugs, there was no increase in frequency of high LCTs or hepatic-related adverse events in patients receiving XR-NTX (either dose) compared with placebo. CONCLUSION: Extended-release formulation of naltrexone does not appear to be hepatotoxic when taken at the recommended clinical doses in actively drinking alcohol-dependent patients.

PMID: 18241321 [PubMed - indexed for MEDLINE]

Changes in transaminases over the course of a 12-week, double-blind nalmefene trial in a 38-year-old female subject.










A gradual return to normal in ALT and AST, while treatment with nalmefene continued, does not support the role of nalmefene as an hepatotoxin. Relapse to drinking was excluded because of normal values for the gamma-glutamyltransferase, and verification of sobriety by self-report, significant other, and breathalyzer. A virology panel ruled out the presence of viral hepatitis. Dietary intake before the elevation in LFTs contained elements that have established association with hepatocellular changes. The routine prescription of serial LFTs in alcoholism pharmacotherapy trials may be expected to reveal clinically nonsignificant elevations that could potentially be related to exogenous factors, such as dietary composition and should not be reflexively attributed to medication under investigation and/or drinking.

PMID: 7847604 [PubMed - indexed for MEDLINE]
Effects of long-term treatment with naltrexone on hepatic enzyme activity.




The influence of naltrexone on liver function in heroin addicts was studied, with respect to the metabolizing function by using the antipyrine clearance and to cellular damage by monitoring plasma levels of hepatic enzymes. The clearance of antipyrine was not affected by naltrexone treatment, and, during the study period, the use and withdrawal of benzodiazepines and alcohol did not change this parameter; moreover, there was no relationship between changes in plasma hepatic enzymes and antipyrine half-life. Mean plasma levels of hepatic enzymes did not show significant modification in the course of treatment with naltrexone.

PMID: 1686854 [PubMed - indexed for MEDLINE]

Effects of acute administration of naltrexone on cardiovascular function, body temperature, body weight and serum concentrations of liver enzymes in autistic children.




The effects of acute, orally administered naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg), a potent opiate receptor antagonist, on auscultated heart rate, systolic blood pressure and axillary body temperature were investigated before and about 1 h postdrug in 5 autistic children (4-12 years of age). In addition, an electrocardiogram was recorded on each child before and about 3 h after placebo or 2.0 mg/kg of naltrexone. Finally, the serum concentrations of the liver enzymes glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) were measured 24 h following placebo or naltrexone administration. Naltrexone had no statistically significant effects on any of these measures in comparison with baseline or placebo levels. Thus, these data provide preliminary evidence for the safety of acute administration of naltrexone in children.

PMID: 2721334 [PubMed - indexed for MEDLINE]

Naltrexone hydrochloride (Trexan): a review of serum transaminase elevations at high dosage.




In summary, evidence is presented associating typically asymptomatic and reversible elevations of serum transaminase values with high daily dosages of naltrexone. Statistical significance was found only between placebo and the 300 mg dosage. Subjects aged 40 years and over were significantly more likely to develop this finding than younger subjects. All subjects with significant elevations of transaminase values in these studies took daily naltrexone dosages higher than recommended for opioid addiction. The daily dosage of naltrexone recommended for opioid addiction did not cause abnormalities of serum transaminase values in these studies.

PMID: 3092099 [PubMed - indexed for MEDLINE]

Opioid receptor blockade improves mesenteric responsiveness in biliary cirrhosis.




The maximum pressure response to phenylephrine was decreased significantly in cirrhosis while chronic naltrexone treatment completely improved it (P <>

PMID: 18465246 [PubMed - indexed for MEDLINE]


[Antipruritic therapy with the oral opioid receptor antagonist naltrexone. Open, non-placebo controlled administration in 133 patients]




CONCLUSIONS: The oral opiate antagonists may well be an effective, well-tolerated therapy for intractable pruritus in many diseases.

PMID: 15517116 [PubMed - indexed for MEDLINE]
Endogenous opioids modulate hepatocyte apoptosis in a rat model of chronic cholestasis: the role of oxidative stress.




CONCLUSION: Our findings demonstrate that the administration of opioid antagonist is protective against hepatic damage in a rat model of chronic cholestasis. We suggest that increased levels of endogenous opioids contribute to hepatocytes apoptosis in cholestasis, possibly through downregulation of liver anti-oxidant defense.

PMID: 17403194 [PubMed - indexed for MEDLINE]

Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhotic rats.


Concurrent administration of naltrexone and L-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to beta-adrenergic stimulation in cirrhosis.

PMID: 16968416 [PubMed - indexed for MEDLINE]