Tests of liver function

Liver function tests (LFTs or LFs), which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver.

Tests of liver function include:

• albumin (Alb) – This protein is made specifically by the liver, and is the main constituent of total protein. Albumin levels are decreased in chronic liver disease such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. Poor nutrition or states of protein catabolism may also lead to low levels. The half-life of albumin is approximately 20 days. Albumin is not considered to be an especially useful marker of liver synthetic function; coagulation factors are much more sensitive.
• alanine transaminase (ALT) – Also called Serum Glutamic Pyruvate Transaminase (SGPT) or Alanine aminotransferase (ALAT), ALT is an enzyme present in hepatocytes (liver cells). When a cell is damaged, it leaks this enzyme into the blood, where it is measured. ALT rises dramatically in acute liver damage, such as viral hepatitis or acetaminophen overdose.
• aspartate transaminase (AST) – Also called Serum Glutamic Oxaloacetic Transaminase (SGOT) or aspartate aminotransferase (ASAT), AST is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage, but is also present in red blood cells, and cardiac and skeletal muscle and is therefore not specific to the liver.
• alkaline phosphatase (ALP) – ALP is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma will rise with large bile duct obstruction, intrahepatic cholestasis or infiltrative diseases of the liver. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled) and elderly patients with Paget's disease.
• total bilirubin (TBIL) – Bilirubin is a breakdown product of heme (a part of haemoglobin in red blood cells).
• gamma glutamyl transpeptidase (GGT) – Although reasonably specific to the liver and a more sensitive marker for cholestatic (condition where bile cannot flow from the liver to the duodenum) damage than ALP, GGT may be elevated with even minor, sub-clinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP. GGT is raised in alcohol toxicity chronic).

Abnormal liver function measures are expected to be seen in many MP patients because these measures are an indication of an inflammatory response to infection. The experience of Autoimmunity Research FoundationNon-profit foundation dedicated to exploring a pathogenesis and therapy for chronic disease. has, thus far, shows that as long as immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed. is tolerable while liver function remains abnormal, there's no need to make any changes in dosing of the MP medications. However, physicians and patients should always assess if immunopathology is too strong. If this is the case, taking measures to reduce immunopathology is always recommended.

Some of the documented protective effects of ARBs include the ability to:

• inhibit liver fibrosis and aid liver healing¹⁾
• reduce liver fibrosis²⁾

Br J Pharmacol. 2003 Jul;139(6):1085-94. An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells. Kurikawa N, Suga M, Kuroda S, Yamada K, Ishikawa H.

Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd, 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. kurikuri@shina.sankyo.co.jp Abstract 1. We studied the effect of a new angiotensin II type 1 (AT(1)) receptor antagonist, olmesartan medoxomil (olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. ), on the fibrogenic responses in rat hepatic stellate cells (HSCs) and liver fibrogenesis. 2. Olmesartan (1 mg kg(-1) per day) was orally administered to fibrotic rats, induced by bile duct ligation. Liver hydroxyproline content, the mRNA expression of collagen alpha1(I) and alpha-smooth muscle actin (alpha-SMA), and plasma levels of transforming growth factor-beta1 (TGF-beta1) were significantly reduced by olmesartan treatment, suggesting that olmesartan improved liver fibrosis. Interestingly, AT(1) receptors were found to be expressed in alpha-SMA-positive cells in the fibrotic area of livers in bile duct-ligated rats by immunohistochemical analysis. Olmesartan treatment reduced the number of these cells. 3. In vitroA technique of performing a given procedure in a controlled environment outside of a living organism - usually a laboratory. experiments showed that angiotensin II (Ang II) treatment induced proliferation and collagen synthesis, and upregulated the profibrogenic cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system., TGF-beta1 and connective tissue growth factor (CTGF), in rat primary HSCs. Olmesartan blocked all these effects of Ang II. 4. Based on these results, since activated HSCs were found to express AT(1) receptors and Ang II is thought to play an important role in the pathogenesis of liver fibrosis by binding to these receptors, olmesartan may act as a potent antifibrotic drug to suppress the proliferation, collagen synthesis and the expression of profibrogenic cytokines in activated HSCs by blocking these receptors.

PMID: 12871826

Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E227-32. Epub 2004 Apr 13. Angiotensin II type 1 receptor blocker ameliorates overproduction and accumulation of triglyceride in the liver of Zucker fatty rats. Ran J, Hirano T, Adachi M.

First Department of Internal Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan. Abstract The effects of angiotensin II type 1 receptor blocker (ARBA drug which is an angiotensin receptor blocker. One of the ARBs is olmesartan (Benicar). Not all ARBs activate the Vitamin D Receptor.) on triglyceride (TG) metabolism associated with insulin resistance were explored in Zucker fatty (ZF) rats. Olmesartan medoxomil, a newly developed ARB, was given as a 0.01% drinking solution ad libitum to ZF and Zucker lean (ZL) rats for 4 wk. Olmesartan lowered blood pressure in both strains to the same extent. ZF rats had a markedly low insulin sensitivity index (SI) and glucose effectiveness (SG), together with significantly increased glucose levels. Olmesartan treatment substantially elevated both SI and SG. The ZF rats were hyperlipidemic, with plasma TG levels sixfold higher than those of the ZL rats. Olmesartan remarkably decreased the plasma free fatty acid level in the ZF rats, but it did not exert a significant effect on the plasma TG level. The TG secretion rate assessed by the Triton WR-1339 technique was almost six times higher in the ZF than in the ZL rats, and olmesartan treatment suppressed this TG overproduction by one-half. The TG content in the liver was ten times higher in the ZF than in the ZL rats, and olmesartan halved this high hepatic TG content without affecting the cholesterol content. The fatty liver developed in the ZF rats was ameliorated by olmesartan treatment. Olmesartan treatment had no significant effects on TG metabolism or insulin sensitivity in the ZL rats. Taken in sum, ARB improves the overproduction and accumulation of TG in the liver associated with insulin resistance, and it does so through mechanisms independent of its hypotensive action.

PMID: 15082419

Hepatology. 2001 Oct;34(4 Pt 1):745-50. Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Fukui H.

Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan. yoshijih@naramed-u.ac.jp Abstract The renin-angiotensin system (RAS) is frequently activated in patients with chronic liver diseases. Angiotensin-II (AT-II) has been suggested to play an important role in liver fibrogenesis. It induces hepatic stellate cell (HSC) proliferation and up-regulates the transforming growth factor beta(1) (TGF-beta(1)) expression via AT-II type 1 receptor (AT(1)-R) in vitro. The aim of the present study was to examine the in vivoA type of scientific study that analyzes an organism in its natural living environment. effect of candesartan (CA), a clinically used AT(1)-R blocker (ARB), and perindopril (PE), an angiotensin-converting enzyme (ACE) inhibitor (ACE-I), on pig serum-induced liver fibrosis development in rats. The clinically available comparable doses of CA and PE significantly attenuated the fibrosis development. These inhibitory effects of PE and CA were also found in the on-going liver fibrosis model. The hepatic hydroxyproline and serum fibrosis markers were significantly suppressed by CA and PE treatment. Furthermore, the alpha smooth muscle actin (alpha-SMA) positive cells in number were markedly suppressed by CA and PE treatment. Similarly, the hepatic TGF-beta(1) protein and messenger RNA (mRNA) levels were significantly suppressed. Our in vitro study showed that AT-II increased the TGF-beta(1) mRNA expression in the activated HSCs, and this effect was totally blocked by CA. These results suggested that the RAS, especially AT-II and AT(1)-R interaction plays a pivotal role in liver fibrosis development through HSC activation. Because both CA and PE are widely used in clinical practice without serious side effects, these drugs may provide an effective new strategy for anti-liver fibrosis therapy.

PMID: 11584371

Hepatol Res. 2006 Oct;36(2):124-9. Epub 2006 Aug 17. Angiotensin-II and vascular endothelial growth factor interaction plays an important role in rat liver fibrosis development. Yoshiji H, Kuriyama S, Noguchi R, Ikenaka Y, Kitade M, Kaji K, Yoshii J, Yanase K, Yamazaki M, Asada K, Tsujimoto T, Akahane T, Uemura M, Fukui H.

Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan. Abstract Both angiotensin-II (AT-II) and vascular endothelial growth factor (VEGF) have been shown to play important roles in the progression of liver fibrosis. However, the interaction of AT-II with VEGF in the liver fibrosis has not been elucidated yet. The aim of the current study was to elucidate a possible association between these molecules, especially in conjunction with the hepatic stellate cells (HSC). The effect of AT-II type 1 receptor blocker (ARB) was assessed on several indices of choline-deficient l-amino acid-defined (CDAA)-induced liver fibrogenesis. This ARB significantly suppressed liver fibrosis development along with suppression of the VEGF expression and neovascularization in the liver. In the cultured activated HSC, AT-II induced VEGF in a dose- and time-dependent manner. ARB and LY333531, a protein kinase C (PKC) inhibitor, attenuated this augmentation. These results indicated that AT-II and VEGF interaction played an important role in liver fibrosis development, and that in the activated HSC, AT-II utilized type 1 receptor and PKC as an intracellular signaling pathway to induce VEGF.

PMID: 16919500

Prior to beginning the MP, most of my bloodwork results were skewed, including the liver enzymes. The cyst on my liver has remained stable, but the blood levels began to normalize within three to six months after beginning the Protocol.

Carole, MarshallProtocol.com

My liver function test was normal on 11/4/06 after being abnormal in 2004 and 2005. Documented.

Scooker48, Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis..com

TECHREVISE

• Legacy content
  • f200:

A laboratory report of elevated liver enzymes is common. It doesn't indicate a specific disease. Liver enzymes help maintain a variety of chemical and metabolic processes that occur in the liver. Normally, only very small amounts of these enzymes are present in your blood. Treatment of elevated liver enzymes depends on the underlying cause. It is important to tell your doctor about any nutritional or herbal supplements you are taking.

Th1 inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. commonly affects the liver, although it may be subclinical and most liver diseases cause only mild symptoms initially. Patients may be told they have “fatty liver disease” or cirrhosis.

An initial step in detecting liver damage is a simple blood test to determine the presence of certain liver enzymes in the blood. Under normal circumstances, these enzymes reside within the cells of the liver. But when the liver is injured, these enzymes are spilled into the blood stream.

Liver function tests (LFTs or LFs), which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver.

Among the most sensitive and widely used of these liver enzymes are the aminotransferases. They include aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT). These enzymes are normally contained within liver cells. If the liver is injured, the liver cells spill the enzymes into blood, raising the enzyme levels in the blood and signaling the liver damage. AST and ALT are the two most useful liver enzymes.

See What do my lab tests mean?

It not unusual to see liver enzymes elevate while on the MP even if liver disease was not previously suspected because immunopathology is unavoidable during recovery. Your doctor should consider the risk/benefit ratio of treatment with the MP because liver damage will not resolve unless the CWD bacteria are killed.

We cannot define the upper limits of liver enzymes for someone on the MP who needs to recover liver function. The usual scenario that docs see is expected worsening of liver function whereas immunopathology, even if relatively severe, is temporary and probably justified in terms of expected long-term benefit. If this is pointed out to doc, s/he may not be so concerned.

“Any signs of damage to your liver are just that - signs. Any suggestion that there might be liver damage due to any of the MP drugs is totally unfounded in science.”

~Trevor

Angiotensin receptor blocking drugs, such as Benicar, are known to have organ-protective effects. An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells.

NSAIDs (non steroidal anti inflammatory drugs)

These commonly prescribed pain medications can increase liver enzymes. If pain medication is needed, an alternative should be considered. See What should I do for liver or gallbladder pain?

* f202:

Cell death (apoptosis) elevates ALT and resolves fibrotic tissue (filelink)

The sensitive enzyme ALT is elevated when there is liver inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. and cell death (apoptosis). We know that when the immune system is effectively fighting infection, the result is cell death. But this is the road to recovery.

This article about research funded by the Wellcome trust will help you understand that cell death precedes cessation of fibrosis. The article explains that fibrotic damage can/will break down after the liver has regenerated. This research is in line with Dr. Marshall's thinking about fibrotic tissue reversion.

Macrophages, one type of white blood cell, have the duty of killing invaders like bacteria. Macrophages are phagocytes, or “eating cells.” Macrophage are the “big eaters” of the immune system. Take a look at the video clip on this web source by clicking on “time-lapse movie” to see how a white blood cell engulfs an enemy. This is what happens to bacterial invaders.

But engulfing or “eating” the threatening pathogens doesn't finish the job. The macrophage has to die to kill the enemy. Otherwise, bacteria may be able to live and even replicate safely inside the macrophage and the human host will still be ill. This could be serious, considering that the life span of a macrophage may be months or even years. Even slowly-reproducing bacteria might establish a stronghold by living inside macrophages.

The MP supports the immune system macrophages that are holding bacteria they have eaten. Once the antibiotics weaken the intracellular bacteria, the immune system naturally kills them off, and in the process, the infected white blood cells die. Toxic chemicals spill into the host tissue and blood. The host suffers the effects of immunopathology by temporarily feeling worse, even though the cell death will result in better health now that the pathogen is dead.

ABC Australia has a three-part series in their “Great Moments in Science” called “Apoptosis” in this link. It explains the natural process of cell death for the greater good and health of the host.

~Belinda

I also wanted to note that a couple of years ago independent of the MP I had a slightly elevated ALT reading. My doc wasn't too worried because he said typically it was a fairly high reading which caused medical concern but he had no clue why it was just slightly elevated. A couple of months later I decided to google it and found a newly released study from UNC-CH that Tylenol could raise ALT levels slightly even in healthy people. The weird thing was that it didn't take much and the elevation lasted several days after the Tylenol was stopped. I also found that environmental toxins and junk food could raise the values according to some sources.It just sounds like the ALT reading is very sensitive in some of us. Just think what a total bacterial dump would do to something this sensitive.

Mindy, MarshallProtocol.com