Re: About ursodiol (or Ursodiol)

[Guest guest]

Is liver damage or disease the cause or a side effect of lipodystrophy? For people who want to explore an incredible website, go to http://www.niddk.nih.gov/. I am now hypothesizing that undiagnosed fatty liver and hepatic issues, including inflammation such as hepatitis, are possibly the root cause of lipodystrophy, not to mention a lot of other obvious problems. Take for example, the description of liver cirrhosis at the above referenced site. The explanation of how the liver works and what can go wrong, say if you are taking PIs or other hepatotoxic drugs, is a catalog of every symptom of lipodystrophy I’ve heard of. http://www.niddk.nih.gov/health/digest/pubs/cirrhosi/cirrhosi.htm

This is the first time that I have seen the side effects for ursodiol you have listed. Every reference has possible stomach distress, etc., but not the CNS stuff. When I told my doctor that taking the drug was like having the awake switch turned on all day and night, and that sometimes I got anxious, he said I was having panic attacks unrelated to the ursodiol. Sleeping pills and anti-anxiolytics had little effect. In any case, I took one 300 mg capsule in the morning and one at lunch, always before 6:00 PM so I finally got some more regular sleep. Sometimes I came home at 5:00 and fell into a deep sleep. The drug basically sucks the cholesterol and bile out through your butt, a strange occurrence at first (it’s quite yellowish), and you can rest assured you will have a smooth bowel movement that feels kind of greasy every morning. Taking it with Tricor added to the insomnia effects. But it stripped body fat from around my chest, belly, and hips, and my face started looking normal pretty quickly. I never had severe lipoatrophy of the face, but the gaunt, hollow look left.

I have no idea of what types of drug interactions ursodiol might have. Because it’s a bile salt medical texts say it should not interfere with very many drugs at all. I took it with Tricor and lorazepam for three months and my triglycerides went from 1100 to 140, my bilirubin went to normal, my body fat and belly went away so you could see my lean muscle mass, my TC went from 740 to 110, and my lactate level went to normal. Although I was very careful not to exert myself too much during those three months – after taking Viracept, Zerit and Epivir for several years I developed thyroid problems, pancreatitis, insulin resistance, hemorrhoids, super high TG and TC, and anxiety and sometimes panic related to a very high lactate level. I finally developed lactic acidosis, which they tried to tell me was hysteria (panic attacks and anxiety are probably a symptom of elevated lactate levels) I stopped taking all drugs, including Bactrim, for three months. I actually never started taking the Bactrim again because LA is one of its’ potential side effects, not to mention liver damage. After three months my muscles began to cramp and hurt (possibly myopathy). A month later I started Viread, epivir and nevirapine and have been undetectable and my CD4 have actually doubled after a year. We’ll see what happens.

I’ve been doing research on the drug ursodiol in the last few days to see what new has come out. A couple studies about fatty liver and BMI were presented at the latest DDW 2003 The more that I read about it, the more I think it should work to counteract lipodystrophy, with some exceptions. In people with serious liver disease (as in cirrhosis or bile duct obstruction), the drug is probably not recommended. However, from what I have read recently about Fatty Liver (hepatic steatosis), NASH (non-alcohol related steatohepatitis) and the role of the liver in every process that might lead to lipodystrophy, I’m beginning to think that someone taking HIV meds, or anyone with any liver problems – most notably primary biliary cirrhosis – might be able to prevent or reduce what happens in the liver. Clinical trials would be so great to have to answer these questions. They should all certainly be taking beta carotenoids and vitamin C, drinking lots of water, avoiding alcohol and simple carbohydrates, eating high protein low fat meals or chicken or fish with well cooked vegetables of all types and some whole grains.

Ken

[Guest guest]

HIV, HCV, Lipodystrophy?

I wonder how many people taking atazanavir might develop one of these diseases? An excess of toxic bile acids seems to do some pretty nasty things. This is an unedited version of a ursodiol report I am working on. I have had many requests for more info, so I release it with the caveat that it may contain some errors, and that I am not prescribing anything. Studies have shown that it does prevent the progression of fibrosis to cirrhosis in certain liver diseases. Because of the apparently benign side effect profile – at least in studies of people who did not have HIV – I hope this information does not encourage anyone to place false hopes in it’s use as a lipodystrophy treatment. That is only a hypothesis, an idea that I have that needs to be studied in clinical trials. If you see any mistakes, etc., kindly contact me. Talk with your doctor or a GI or Hepatologist.

Losing Fat and Gall Stones

Ursodiol, or Actigall, is prescribed in the US and Canada and the UK and Africa for several reasons. When people, especially women, lose large amounts of fat very quickly gallstones are very likely to develop. The drug is approved for that purpose, as long as the person losing weight does not dramatically alter their diet withour medical consultation. It also works to dissolve gallstones, as long as the stones are made of bile or cholesterol, do not contain more than 4% calcium, and are very small. The drug is a possible option for people who for whatever reason don’t want to get the stones blasted or cut out. Gallstones are very common in people with HIV. For the actual FDA approval letter which includes the chemical structure, etc. go to <http://www.fda.gov/cder/foi/nda/2000/75-592_Ursodiol.pdf> . A Canadian company sells it in 250 and 500 mg tablets. There are internet pharmacy price wars over the drug. The drug appears to be a useful adjunct with two other drugs for a liver disease called primary sclerosing cholangitis (PSC), although additional studies are required to confirm this.

Primary Biliary Cirrhosis

The drug is also approved for PBC, or Primary Biliary Cirrhosis. This condition can be caused by a lot of different things, although no one is quite sure why it happens. For some reason the liver fails to process bile and bilirubin levels rise. In severe cases, the bilirubin seeps into the skin and causes constant itching, stomach cramps, fatigue. Although ursodiol (Actigall) is not a cure for PBC, it does seem to keep it under control and prevent the development of cirrhosis requiring liver transplant in 2/3 of people taking the drug. . If there is actual bile duct obstruction in the liver, or the gall bladder has been removed the drug is not recommended . It seems to work best at preventing the progression of fibrosis to cirrhosis. PBC might be caused by accumulation of fat in liver cells. Here are two good sites with lots of prescribing information, including when it should not be used, <http://www.medscape.com/viewarticle/429782?WebLogicSession=PtGd9Uf1bSUdgR72ikN6QGa4xXR1IGKDnFYFOT9bg5L8myBh4hKJ|6514660036473353034/184161392/6/7001/7001/7002/7002/7001/-1> and <http://hepatitis-central.com/hcv/drugs/actigall.html>

Is Fatty Liver the obstruction?

According to Liver 411, The term cholestasis refers to stagnation or reduction of normal bile flow from liver cells to the intestine. Bile aids digestion and absorption of food in the intestine and delivers waste products, such as bilirubin, to be eliminated in the bowel movements. The causes of cholestasis can be subdivided into intrahepatic and obstructive. Intrahepatic cholestasis results from impairment of bile formation or secretion by liver cells. In contrast, obstructive cholestasis results from blockage of bile ducts that carry the bile from the live to the intestine. <http://www.liver411.com/education/cholestatis.html> One problem is that the cause of fatty liver, especially in people who do not drink alcohol (when it is called NASH, or non-alcoholic steatohepatitis), is not really known. It could be diet, genetics, exposure to vaccinations, drug use – whatever, but it is alarmingly common in lean young men as demonstrated in a recent study that showed about 21% of them had fatty liver. I don’t think fat laden or iron or copper laden liver cells work well, so something like the production of hormones or the thyroid gets messed up. One of the symptoms of fatty liver appears to be the deposition of cholesterol in clumps under the skin.

Preventing progression of fibrosis to cirrhosis in HCV?

Some hepatologists and gastroenterologists also prescribe the drug off-label. These uses are interesting. It is sometimes prescribed as a “holding drug” to delay fibrosis in people with hepatitis, as it is used in PBC. It does seem to reduce liver enzymes pretty effectively. The other off-label use that is of interest is to prevent liver cell (hepatocyte) apotosis. Apoptosis is basically when a cell commits suicide, possibly due to a chemical cytokine produced in the presence of an infectious agent such as HCV. One small study conducted about a decade ago seems to suggest it does this, but no one has conducted a large study to see what effects long term use of the drug would have. The intriguing finding in people using it, which has never been published but which a GI or hepatologist will tell you is that it does lower the liver enzyme GGT.

GGT is the catchall marker for liver cell death, and is associated more with cholestatic type problems (such as gall stones, hepatitis related liver damage to bile ducts). Think bile or hepatobillary type diseases, on which I am not an expert. So, maybe ursodiol does reduce or prevent liver cell apostosis. I have no idea what the ultimate effect of that would be, unless they were healthy, uninfected healthy liver cells that were being saved. I’d love to see some clinical trials conducted of the drug in different settings, such as lipodystrophy, HCV.

Huntington’s Disease?

The generic drug name for UDCA is ursodiol. Brand names for UDCA include; in the US, Actigall, Urso; in the UK; Destolit, Urdox, Ursofalk, Ursogal; in South Africa, Ursotan. About five years ago Professor Steer was aware of the use of UDCA to treat certain types of liver diseases. He considered that UDCA might prevent liver cell death. His lab work showed that UDCA did indeed protect liver cells and much more. In culture, UDCA protected every type of cell tested from a variety of different agents that produce cell death by apoptosis. Professor Clifford Steer and his colleagues, have developed a safe and effective treatment for Huntington’s Disease in mice and rats, using ursodiol. Seems that toxic bile acids in the brain may be responsible for some aspect of the disease. No human clinical trials have been done, but the professor does a hearty consultation service of the drug in people with HD. For more about that whole story go to <http://hdlighthouse.org/treatment-care/treatment/drugs/tudca/human/updates/0032ursodiol.shtml>

Studies in prevention of colon cancer.

<http://www.annals.org/issues/v134n2/nts/200101160-00003.html> and Several lines of evidence indicate that fecal bile acids are important promoters of colon cancer. Ursodeoxycholic acid (ursodiol) has been shown to inhibit experimental colon carcinogenesis at least partly through decreasing toxic secondary bile acids. Ursodiol is frequently used in primary sclerosing cholangitis (PSC), though it is not clear that it prevents overall progression of disease. However, given the dramatic increase in risk of colorectal cancer in patients with PSC/ulcerative colitis (UC), Tung et al. performed a retrospective analysis from their colonoscopic UC surveillance program to evaluate the relationship between colonic dysplasia, a well-validated intermediate biomarker of colon cancer, and ursodiol use at <http://www-east.elsevier.com/ajg/issues/9606/ajg4004dis.htm>

Subject: Re: About ursodiol (or Ursodiol)

Is liver damage or disease the cause or a side effect of lipodystrophy? For people who want to explore an incredible website, go to http://www.niddk.nih.gov/. I am now hypothesizing that undiagnosed fatty liver and hepatic issues, including inflammation such as hepatitis, are possibly the root cause of lipodystrophy, not to mention a lot of other obvious problems. Take for example, the description of liver cirrhosis at the above referenced site. The explanation of how the liver works and what can go wrong, say if you are taking PIs or other hepatotoxic drugs, is a catalog of every symptom of lipodystrophy I’ve heard of. http://www.niddk.nih.gov/health/digest/pubs/cirrhosi/cirrhosi.htm

This is the first time that I have seen the side effects for ursodiol you have listed. Every reference has possible stomach distress, etc., but not the CNS stuff. When I told my doctor that taking the drug was like having the awake switch turned on all day and night, and that sometimes I got anxious, he said I was having panic attacks unrelated to the ursodiol. Sleeping pills and anti-anxiolytics had little effect. In any case, I took one 300 mg capsule in the morning and one at lunch, always before 6:00 PM so I finally got some more regular sleep. Sometimes I came home at 5:00 and fell into a deep sleep. The drug basically sucks the cholesterol and bile out through your butt, a strange occurrence at first (it’s quite yellowish), and you can rest assured you will have a smooth bowel movement that feels kind of greasy every morning. Taking it with Tricor added to the insomnia effects. But it stripped body fat from around my chest, belly, and hips, and my face started loo king normal pretty quickly. I never had severe lipoatrophy of the face, but the gaunt, hollow look left.

I have no idea of what types of drug interactions ursodiol might have.  Because it’s a bile salt medical texts say it should not interfere with very many drugs at all. I took it with Tricor and lorazepam for three months and my triglycerides went from 1100 to 140, my bilirubin went to normal, my body fat and belly went away so you could see my lean muscle mass, my TC went from 740 to 110, and my lactate level went to normal. Although I was  very careful not to exert myself too much during those three months – after taking Viracept, Zerit and Epivir for several years I developed thyroid problems, pancreatitis, insulin resistance, hemorrhoids, super high TG and TC, and anxiety and sometimes panic related to a very high lactate level. I finally developed lactic acidosis, which they tried to tell me was hysteria (panic attacks and anxiety are probably a symptom of elevated lactate levels) I stopped taking all drugs, including Bactrim, for three months. I act ually never started taking the Bactrim again because LA is one of its’ potential side effects, not to mention liver damage. After three months my muscles began to cramp and hurt (possibly myopathy). A month later I started Viread, epivir and nevirapine and have been undetectable and my CD4 have actually doubled after a year. We’ll see what happens.

   

I’ve been doing research on the drug ursodiol in the last few days to see what new has come out. A couple studies about fatty liver and BMI were presented at the latest DDW 2003 The more that I read about it, the more I think it should work to counteract lipodystrophy, with some exceptions. In people with serious liver disease (as in cirrhosis or bile duct obstruction), the drug is probably not recommended. However, from what I have read recently about Fatty Liver (hepatic steatosis), NASH (non-alcohol related steatohepatitis) and the role of the liver in every process that might lead to lipodystrophy, I’m beginning to think that someone taking HIV meds, or  anyone with any liver problems – most notably primary biliary cirrhosis – might be able to prevent or reduce what happens in the liver. Clinical trials would be so great to have to answer these questions. They should all certainly be taking beta carotenoids and vitamin C, drinking lots of water, avoiding alcohol and simple carbohydrates, eating high protein low fat meals or chicken or fish with well cooked vegetables of all types and some whole grains.

[Guest guest]

I’m beginning to think that someone taking HIV meds, or anyone with any liver problems – most notably primary biliary cirrhosis – might be able to prevent or reduce what happens in the liver. Clinical trials would be so great to have to answer these questions. They should all certainly be taking beta carotenoids and vitamin C, drinking lots of water, avoiding alcohol and simple carbohydrates, eating high protein low fat meals or chicken or fish with well cooked vegetables of all types and some whole grains.

Let's write a letter to the ACTG for them to look at this. Dr Kotler in NY may be interested since he is a GI doc . Dr Dieterich may also be interested. I am going to forward your email to a few docs to see what they think. Thanks for such thought provoking emails.

Vergel

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