II. Hepatic Encephalopathy

II. Hepatic Encephalopathy

This condition is commonly known as hepatic coma. The final clinical manifestation of chronic liver damage often involves hepatic encephalopathy, which is particularly likely to occur in the decompensated stage of cirrhosis under the following circumstances: ① concurrent liver necrosis (chronic severe hepatitis), ② severe upper gastrointestinal bleeding, ③ massive ascites drainage, ④ severe colds or infections, ⑤ renal failure (hepatic renal syndrome), and ⑥ severe electrolyte disturbances.

The primary clinical manifestations of hepatic encephalopathy include mental disorders, agitation, coma, and clonic tremors. The earliest symptoms are irregular sleep patterns—patients may feel drowsy during the day while remaining agitated and restless at night. These symptoms indicate the early stages of hepatic encephalopathy, and clinicians should pay close attention when these signs appear, immediately initiating rescue efforts for hepatic encephalopathy. The biochemical characteristics of this disease can be summarized as three highs and three lows: high blood ammonia levels, elevated levels of false neurotransmitters, and elevated levels of aromatic amino acids; low potassium levels, low serum albumin levels, and low blood glucose levels. The primary goal of clinical rescue for hepatic encephalopathy is to correct the three highs and three lows, ensuring that therapeutic goals are achieved accurately and effectively.

1. Elevated blood ammonia levels: Normal blood ammonia levels range from 13 to 57 µmol/L; when levels exceed this range, blood ammonia is considered elevated, which is a direct cause of hepatic encephalopathy. Clinically, lowering blood ammonia is a top priority. A solution is to administer 23g of lysine in 500ml of 10% glucose intravenously, 25g of arginine in 500ml of 10% glucose intravenously, and 1g of acetylglycine in 500ml of 10% glucose intravenously. While any one of these medications can be used, acetylglycine is generally considered the best choice based on experience. Recently, the new drug Yabosu has also been considered, as it is a compound formulation of ornithine and aspartate, which has a notable ammonia-lowering effect—but it is quite expensive. Potassium magnesium aspartate also has some ammonia-lowering properties and can be used clinically; however, this medication is especially beneficial when potassium and magnesium levels are low, as it helps improve electrolyte imbalances. Lactulose, administered orally, can block the reabsorption of ammonia in the intestines, typically at a dose of 20–40ml, three times a day.

2. Elevated levels of false neurotransmitters: This refers to an increase in hydroxyphenylethanolamine in brain tissue. This substance shares a structural similarity with dopamine and can act as a substitute for dopamine in brain tissue, thereby reducing dopamine levels and accelerating the progression of hepatic encephalopathy. Treatment focuses on replenishing dopamine. However, pure dopamine cannot directly cross the blood-brain barrier; it must be administered in the form of levodopa. Yet, levodopa can damage the liver, so it must be administered in combination with carbidopa to protect the liver. Clinically, 100mg of levodopa combined with 20mg of carbidopa is often administered intravenously in 250–500ml of glucose solution, once or twice daily.

3. Elevated levels of aromatic amino acids: Under normal circumstances, the ratio of branched-chain amino acids like glutamate, arginine, and aspartate to aromatic amino acids like tyrosine, methionine, phenylalanine, and others in human serum remains stable, maintaining a specific proportional relationship. When liver function is severely impaired, the proportion of aromatic amino acids increases, causing changes in the branched-chain-to-aromatic amino acid ratio, which can lead to the development of hepatic encephalopathy. At this point, treatment should focus on supplementing large amounts of branched-chain amino acids. In addition to supplying glutamate, arginine, and acetylglycine, these supplements not only directly reduce blood ammonia levels but also increase the proportion of branched-chain amino acids, helping to restore the balance between branched-chain and aromatic amino acids. The administration of aspartate and ornithine also serves this purpose.

To address the three lows, it is essential to replenish potassium, glucose, and protein. Clinically, 10ml of 10% potassium chloride can be added to 500ml of 10% glucose for intravenous infusion, providing both potassium and glucose supplementation. Serum albumin is available in various concentrations—5g or 10g—and can be administered according to individual needs.

During hepatic encephalopathy, traditional Chinese medicine and herbal remedies also play a role in treatment. I often use the Da Cheng Qi Tang and the Tao Ren Cheng Qi formula. According to the Shanghan Lun, “In cases of diarrhea, accompanied by restlessness and frequent bowel movements, and with blood present in the stool—Da Cheng Qi Tang is prescribed to treat this condition.” “If a patient with a Sunan disease does not recover, and heat accumulates in the bladder, causing delirium, with blood appearing in the stool, then the condition improves once the blood is eliminated. However, if the external symptoms have not yet resolved, treatment should not be initiated until the external symptoms have subsided; when the external symptoms have already improved, but there is still tightness in the lower abdomen, then it is appropriate to use the Huo Ni Cheng Qi Tang.” Both formulas share a common characteristic: they treat fever-related mental symptoms. The “restlessness” mentioned in the former formula and the “delirium” in the latter both resemble mental symptoms associated with hepatic encephalopathy. When treating hepatic encephalopathy with these two formulas, their ability to clear heat and resolve fire aligns with the Yangming Fu Syndrome treatment method in traditional Chinese medicine. By combining these methods with modern Western medicine, we were able to turn the course of hepatic encephalopathy from critical to stable: 10g of rhubarb, 10g of magnesium sulfate (to facilitate the expulsion of toxins), 10g of citrus peel, 6g of magnolia bark, 10g of peach kernel, 6g of licorice, 10g of bupleurum, 10g of white peony, 10g of cinnamon twig, 6g of fresh ginger, 4 jujubes, 10g of scutellaria, 3g of coptis, 10g of wood fragrance, 10g of cardamom, 10g of salvia miltiorrhiza, and other herbs. This formula is decocted in water and taken once daily, administered via nasogastric tube, with each dose ideally around 50–100ml. Once the patient regains consciousness, the medication can be gradually consumed. I believe that the effectiveness of this formula lies in the fact that the large doses of rhubarb and magnesium sulfate promote the elimination of accumulated toxins in the intestines, thereby preventing further absorption of ammonia. Additionally, the large volume of water expelled through bowel movements reduces the progression of cerebral edema.