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TCM and MCM Theory Related to Common Liver Disease Blood Test Markers

Because TCM has no objective diagnostic laboratory testing parameters, using Western medical testing results to gauge use of herbal remedies is a common practice in Modern Chinese Medicine (integrated Chinese and Western medicine).

Based on clinical experiences of many MCM doctors’ practices, the following abnormal markers in liver function tests can be effectively regulated by Chinese herbs and herbal formulas.

1. ALT and AST level

ALT and AST elevation is an indication of liver cell damage or necrosis. The degree of elevation can also represent the severity of the liver inflammation. Generally, ALT and AST are good indicators for liver inflammation. Once inflammation is reduced, the progression of liver fibrosis can be held or even reversed. Thus, anti-inflammation therapy is effective anti-liver fibrosis treatment.

In cases of mild chronic persistent hepatitis, the level of these two enzymes is approximately 50% to 100% above the normal range (range is indicated by the testing facility, usually a number between 0 and 50). If they are elevated to three times or higher than the normal range, the inflammation is considered moderate or severe.
In cases of acute hepatitis or chronic active hepatitis, ALT and AST levels can reach as high as 20 to 30 times the normal range. At those levels, the inflammation in the liver is involved with very active immune reactions and is often seen in autoimmune hepatitis and medication induced hepatitis cases. Because the immune system plays such a major role in the inflammatory process, treatment must not only focus on protecting the liver but also regulate immune reactions.

Sometimes liver enzyme levels are not always parallel with the severity of the liver inflammation. In the cirrhosis stage, when a biopsy indicates piecemeal necrosis (grade III to IV inflammation), enzymes could be in normal range or is only slightly elevated. This phenomenon is caused by the dramatic decrease in the total number of the liver cells. Even if highly inflamed, they are not producing enough enzymes to indicate inflammatory activity.

Anti liver inflammation herbal treatments can prevent liver cell degeneration, necrosis and bring ALT and AST level down to the normal range. The following herbs are commonly used to control liver inflammation and protect liver cells: Wu Wei Zi (Schizandrae Fructus), Gan Cao (Glycyrrhiza uralensis), Shui Fei Ji (Silybum marianum), Ku Shen (Sophorae Radix), Chui Pen Cao (Sedi sarmentosi herba), Chai Hu (Bupleuri Radix). The liver protective effects of these herbs have been tested by animal models and clinically in China. Modern Chinese medicine uses the more potent and stable isolated active ingredient compounds, such as Schisandrin, Glycyrrhizin, Silymarin, Oleanolic acid, Oxymatrine, and Saikosaponin A and D.

If the liver inflammation is quite active with ALT and AST levels three times higher than the normal range, immune regulatory herbs are used to suppress auto-immune reactions. 
 

2. Serum albumin:

The liver is the only place albumin is synthesized. When liver functions are compromised and damage accumulates, the level of albumin drops. Thus, the level of albumin and other laboratory markers can also be used as a predictive indicator in the prognosis of cirrhotic patients. However, a low albumin level alone is not a specific indicator for chronic liver disease. Albumin leakage into extra-vascular, inadequate nutritional intake, poor absorption in the digestion system, over-catalysis of albumin caused by infections, fever, cancer, and abnormal loss from chronic diarrhea and kidney dysfunctions are among some of the other causes. In cirrhosis, the increase of g-globulin can also suppress albumin synthesis. Therefore, it is important to observe the overall “picture” and other lab markers of the patient to choose the correct herbal remedies.

Herbal treatment consists of two routes: direct supplementation of albumin and functional improvement of liver synthesis.

Direct supplement can be done with TCM remedies made from animal sources, such as, Ze He Che (dried placenta) Guong di long (Pheretima aspergillum), LiYu (Cyprinus carpio), Bai Jiang Can (Bcauveria bassiana), Gui Ban (shell of ahinemys reevesii), E Jiao (Skin gelatin made from Equus asinus).

To improve the albumin synthesis: Dong Cuon Xia Cao (Cordyceps sinensis), Dang Gui (Angelicae Radix), Dang Shen (Codonopsis Pilosulae Radix), Huang Qi (Astragali Radix), Ling zhi cao (Ganoderma japonicum), Gou qi zi (Lycium barbarum), Nu Zhen Zi (Ligustrum lucidum Ait), Di Haung (Rehmanniae Radix), Dan Shen (Salviae Miltiorrhziae Radix), Ji Xue Teng (Mucunae Caulis), San Leng (Sparganii Rhizoma), E Zhu (Zedoariae Rhizoma), Xian mao (Curculiginis rhizoma), and Ba Ji Tian (Morindae officinalis radix).

For cirrhotic compensated stage without ascites, aside from regular cirrhosis treatments (see cirrhosis section), low albumin treatment with the above herbs must be used with care. The stomach stimulating and lapactic effects of  Dang Gui and Di Haung. The heat of the following herbs should also be carefully balanced: Dang Shen, Huang Qi, Gou qi zi, Xian mao, and Ba ji tian. Among these herbs, Dang Gui, Huang Qi, and Dan Shen have the best therapeutic effects.

For de-compensated cirrhosis patients, direct supplementation of albumin is recommended. At the same time, diuretic herbs should also be used. The herbs commonly used are Ze He Che, Guong di long, Dang Gui, Huang Qi, and Dan Shen, and formulas such as Wu Ling San (Hoelen Five Herb Combination) and Wu Pi Ying (Decoction Containin Five Kinds of Peel).   

 

3. Blood clotting factors

Liver diseases are the common causes of blood clotting dysfunction. The Liver makes six blood clotting factors: I (fibrinogen), II (Prothrombin), IV, V, VI, and VII. Whenever there is a decrease in any of them, Prothrombin time (PT) will become abnormally prolonged. Therefore, PT can be used as an indication of liver synthesis function or dysfunction. In acute liver cell diseases, if PT prolonged, it usually indicates severe liver cell necrosis and a poor prognosis. In chronic liver diseases, if PT is prolonged to more than five seconds and there is no response to vitamin K injection, this usually suggests extensive liver damage and the long-term prognosis is usually poor. In about 60% of death cases caused by alcoholic liver diseases, PT was prolonged to more than four seconds.

Clinically when we evaluate the result of the PT test, it is important to know whether patient has active bleeding. If there is blood in the stool, the herbal remedies used are Yunan Bai Yao Capsule, Xian He Cao (Herba agremoniae), and Qian Cao (Rubiae radix). If there is black stool and vomiting with blood, Bai Ji (Bletillae rhizoma) and San Qi (Panax notoginseng) should be used.

When treating PT/PA disorder, in MCM terms, treatment is not only focused on preventing and stopping localized bleeding. The TCM theory behind this is to supplement Qi and prevent liver failure. For severe liver inflammation, such as fulminant hepatitis, TCM theory is to treat the “noxious heat and viral qi exhaustion”  with strong herbal formulas such as An Gong Niu Huang Wan (Bolus of Calculus Bovis for Resurrection), Wu Wei Xiao Du Yin (Decoction of Five Ingredients for Antiphologistic), and Zi Xue Dan (Purple-Snow Pellet).  From a conventional medical standpoint, the stoppage of bleeding is the main objective.

Serious bleeding is the most common cause of death in advanced cirrhotic patients. In cases of stable compensated cirrhosis, even small amounts of toxins such as alcohol or other disturbances (including emotional stress) can still trigger bleeding. Thus, patients must pay careful attention to all aspects of diet and stress management.

4. Bile acid metabolism

Bile acid is synthesized in the liver. Its metabolism in the body is mainly controlled by the liver and can therefore reflect its functional status. Everyday, the liver processes more than 18 to 24 grams of bile acid, which is 100 times more than bilirubin. Its serum level elevates to the highest levels in viral hepatitis and extra-liver bile duct stenosis. For chronic hepatitis patients, serum bile acid level usually elevates before the elevation of ALT and AST. After treatment, if the level of serum bile acid continues to elevate even as the histological markers in a liver biopsy improve, the possibility of relapse is still high. In bile retention liver diseases, such as PBC and PSC, serum bile acid level is usually obviously elevated.

In fatty liver or mild chronic hepatitis, bile acid change is usually not as sensitive as changes in ALT and AST markers. But in serious liver diseases, such as cirrhosis, bile acid is more sensitive than the enzymes. The enzymes only reflect the liver cell damage at the moment while bile acid can also reflect the absorption and secretion abilities of the intestines and the liver, and possible existence of portal-systemic circulation bypasses. In predicting liver failure, serum bile acid is a more sensitive indicator than bilirubin.

Clinically, when using Chinese herbal medicine to treat bile acid abnormalities, both Qi and blood should be treated according to TCM theory. When there is bilirubin elevation, it is usually accompanied by ALT and AST elevation. For this condition, the treatment method should be “heat clearing and dampness eliminating.” The commonly used herbal formulas are Yin Chen Wu Ling San (Capillaris and Hoelen Five Formula) and Wu Wei Xiao Du Yin (Decoction of Five Ingredients for Antiphologistic).

When these formulas are used, large doses of Yin Chen Hao (Artemisiae Capillaris), and medium to small doses of Jin Qian Cao (Desmodii Herba) and Da Huang (Rhei Rhizoma) should also be used.

If bilirubin elevation is accompanied by bile acid and GGT elevation, treatment must also focus on improving blood circulation and anti-fibrosis actions. The herbs must have both jaundice clearing and blood activating effects. Examples are: Hu Zhang (Polygoni Cuspidati Rhizoma), Qian Cao (Rubiae radix), Yin Chen Hao (Artemisiae Capillaris), Da Huang (Rhei Rhizoma).

5. Glutamine Transaminase (GGT), or g-Glutamyl Transpeptidase.

Liver cells synthesize GGT and serum GGT mainly originates from the liver. Under the stimulation of inflammation, bile retention, or cancer, the synthesis of GGT in liver cells will increase. Clinically, its significance is similar to that of ALP, but even more sensitive.
GGT elevation could be seen in about 90% of chronic liver and gall bladder disease patients. It is especially obvious in bile retention and cancer patients. In early stages of acute hepatitis, mild chronic hepatitis, and inactive cirrhosis, GGT is usually not elevated. At the peak stage of the acute hepatitis, pre-cirrhotic chronic hepatitis, fatty liver, kidney damage, pancreatitis, diabetes, and heart muscle injuries, GGT it may increase to one to two times above the normal range.

In following conditions, GGT could elevate to two to four times above the normal range: chronic moderate to severe hepatitis, active cirrhosis, alcoholic hepatitis and fatty liver, acute pancreatitis, acute blood stasis in the liver, localized liver cancer damage, acute cardio infarction, and incomplete stenosis of bile ducts. 

In following conditions, it could elevate to five to ten times or higher than the normal range: intra liver bile retention, biliary cirrhosis, and liver cancer.

Although GGT is sensitive, it is not as specific as ALP. Thus, testing with ALP together offers a more complete assessment. When GGT is elevated and ALP is normal, it may be a toxin related. Toxins include alcohol and a number of medications including anti-seizure medications, Coumadin. If both GGT and ALP are elevated, extra-hepatic bile duct stenosis may be the underlying cause.

GGT elevation should also be evaluated together with ALT. If there is slight elevation of both, liver damage is probably light. The severity of the GGT elevation is directly correlated to liver damage.

When GGT is elevated in cases of acute hepatitis or moderate liver disorders, besides using “heat clearing and toxin dissolving” and “heat clearing and dampness eliminating” anti-inflammation herbal treatments, some “blood activating and stasis expelling” herbs should be added: Dan Shen (Salviae Miltiorrhziae Radix), Qing Pi (Citri Immaturi Pericarpium), Chen Pi (Citri Pericarpium), Ze Lan (Lycopi herba), and Yin Xin  Ye (Ginkgo biloba herba).

If there is obvious bile duct stenosis, then following “Li dan tong chang”  (normalizing the secretion and discharge of bile) and “Po xue qu yu” (removing blood stasis with potent medicine) herbs should be used: San Leng (Sparganii Rhizoma), E Zhu (Zedoariae Rhizoma), Bie Jia (Amydae Flos), Da Huang (Rhei Rhizoma), Dan Shen (Salviae Miltiorrhziae Radix), Ji Xue Teng (Mucunae Caulis), and Shui Zhi (Hirudo nipponica, Leech). These herbs should be used together with “heat clearing and toxin dissolving” and “heat and jaundice clearing” herbs.

In summery, GGT elevation is an indication of blood stasis in TCM. Whenever there is elevation of GGT, “blood activation and stasis expelling” herbs should be used in the formulation of the herbal remedies. 

References:

[Liu YL et al., Premary Discusion on the Use of Chinese Medicine According to Blood Tests, CJITWM, Jan 2003, 23(1):54-55]