Hepatic Encephalopathy
Hepatic encephalopathy (also called hepatic coma or por-tosystemic encephalopathy) is a complex neuropsychiatric syn-drome that may complicate advanced liver disease and/or ex-tensive portosystemic collateral formation (shunting). Two major forms of hepatic encephalopathy are recognized: acute and chronic.
Acute hepatic encephalopathy usually occurs in the setting of fulminant hepatic failure. Cerebral edema plays a more im-portant role in this setting: coma is common and mortality is extremely high. Chronic hepatic encephalopathy usually occurs with chronic liver disease, commonly manifests as subtle dis-turbances of neurologic function, and is often reversible.
The pathogenesis of hepatic encephalopathy is thought to involve the inadequate hepatic removal of predominantly ni-trogenous compounds or other toxins ingested or formed in the gastrointestinal tract. Inadequate hepatic removal results from impaired hepatocyte {unction, as well as the extensive shunting of splanchnic blood directly into the systemic circulation by portosystemic collateral vessels. Nitrogenous and other ab-sorbed compounds are thought to gain access to the central ner-vous system and to lead to disturbances in neuronal function. mmonia, derived from both amino acid deamination and bac-terial hydrolysis of nitrogenous compounds in the gut, has been trongly implicated in the pathogenesis of hepatic en-cephalopathy, but its blood levels correlate poorly with the resence or degree of encephalopathy. In vestigators have sug-gested that ammonia generated in the stomach (especially in the presence of hypochloridia) by Helicobacter pylorimay con-tribute to the development of encephalopathy. Other proposed neurotoxins include y-aminobutyric acid, mercaptans, short-chain fatty acids, and benzodiazepine-like compounds. Mer-captans are also thought to produce the characteristic breath odor (fetor hepaticus) of patients with chronic liver failure. Another hypothesis suggests that an imbalance between plasma branched-chain and aromatic amino acids, a common conse-quence of severe liver disease, lead to decreased synthesis of normal neurotransmitters and to increased formation of "false neurotransmitters" from aromatic amino acids in the central nervous system. In addition, altered cerebral metabolism (dis-turbed Na+_K+_ATPase activity), zinc deficiency causing de-creased activity of urea-cycle enzymes, and deposition of man-ganese in the basal ganglia have been implicated as possible mechanisms.
The clinical features of hepatic encephalopathy include disturbances of higher neurologic function E intellectual and personality disorders, dementia, inability to copy simple dia-grams (constructional apraxia), disturbance of consciousness], disturbances of neuromuscular function (asterixis, hyperreflex- ia, myoclonus), and rarely, a Parkinson-like syndrome and progressive, paraplegia. As with other metabolic en-cephalopathies, which may show many of the signs of hepatic encephalopathy, asymmetric neurologic findings are unusual but ca'n occur, and brain stem reflexes (pupillary light, oculovestibular, and oculocephalic responses) are preserved un-til extremely late in the course of the disease. Hepatic en-cephalopathy is usually divided into stages according to its severity. Subtle disorders of psychomotor function may exist in as many as 50 % to 70 % of patients with cirrhosis in whom a conventional neurologic examination is normal. Such subclini-cal encephalopathy (termed stage 0 encephalopathy) is impor-tant in that it may impair work performance. One of the earli-est manifestations is the alteration of the patient's normal sleep-wake cycle. The differential diagnosis of hepatic en-cephalopathy includes hypoglycemia, subdural hematoma, meningitis, and sedative drug overdose, all of which are com-mon in patients with liver disease, particularly patients with alcoholism.
Treatment
Treatment of hepatic encephalopathy is based on four sim-ple principles.
Identify and Treat Precipitating Factors Gastrointesti-nal bleeding and increased protein intake may provide increased substrate for the bacterial or metabolic formation of nitroge-nous compounds that induce encephalopathy. Patients prone to develop hepatic encephalopathy have increased sensitivity to drugs that depress the central nervous system, and the use of these drugs should be avoided in these patients.
Reduce and Eliminate Substrate for the Genera-
tion of Nitrogenous Compounds
Restrict Dietary Protein Patients in coma should re-ceive no protein, whereas those with mild encephalopathy may benefit from restriction of protein intake to 40 to
Cleanse Bowels This recommendation is important mainly in patients with encephalopathy precipitated by acute gastrointestinal bleeding or constipation and is achieved by ad-ministration of enemas.
Reduce Colonic Bacteria Neomycin administered orally reduces the number of bacteria that are responsible for produc-tion of ammonia and other nitrogenous compounds, but its use may be associated with the development of nephrotoxicity and ototoxicity. Other antibiotics effective in the treatment of hep-atic encephalopathy include metronidazole and rifaximin (a nonabsorbable rifamycin derivative).
Prevent Ammonia Diffusion from the Bowel This is achieved by administration of lactulose, lactitol, and lactose (in lactase:'deficient patients). These are nonabsorbable disac-charities that, when fermented to organic acids by colonic bac-teria, lead to a lower stool pH. This lowered pH traps ammo-nia in the colon as nondiffusible NHa+ ions, but other mecha-nisms such as inhibition of bacterial ammonia production, and the promotion of the growth of non-urease-producing lacto-bacilli may also be important.
Hepatopulmonary Syndrome
Hepatopulmonary syndrome is an increasingly recognized clinical entity (in 10% to 15% of patients with cirrhosis), characterized by abnormalities of arterial oxygenation in pa-tients with chronic liver disease and/or portal hypertension. The pathophysiology of this syndrome involves intrapulmonary vascular dilatation in the absence of architectural damage. These vascular abnormalities consist of precapilary dilatation, direct arteriovenous communications, and dilated pleural ves-sels. Intrapulmonary vascular dilatation is detected by contrast echocardiography, which shows delayed visualization of mi-crobubbles in the left heart chambers. The vascular dilatation leads to impaired oxygen transfer from alveoli to the central stream of red blood cells within capillaries, with a resulting "functional" intrapulmonary right-to-left shunt that improves with 100% oxygen. Clinical features range from subclinical abnormalities in gas exchange to profound hypoxemia causing dyspnea at rest. Patients often require supplemental oxygen and have significant limitations in their performance of usual daily activities. No proven medical therapy exists. As in hepa-torenal syndrome, hepatopulmonary syndrome is a functional disorder that reverses in most patients after liver transplanta-tion.
Hepatic Transplantation Liver transplantation is a high-ly successful procedure in patients with progressive, advanced, and otherwise untreatable liver disease. Advances surgical techniques and supportive care, the use of cyclosporine and tacrolimus for immunosuppression, and careful selection of pa-tients have all contributed to the encouraging results of liver transplantation. From 70 % to 80 % of patients undergoing liv-er transplantation survive at least 3 years, usually with good quality of life. The most common indication for liver trans-plantation in the
The timing of liver transplantation presents a particular challenge. Liver-assist devices for temporary support are cur-rently being evaluated. The survival of ambulatory patients undergoing liver transplantation electively is greater than that of those who are critically ill at the time of the operation. Thus, liver transplantation is usually considered when the pa-tient has refractory ascites and/or spontaneous bacterial peri-tonitis, recurrent variceal hemorrhage, intractable pruritus, or an unacceptable quality of life.
Diagnosis in Traditional Chinese Medicine
In traditional Chinese medicine, hepatocirrhosis is includ-ed in the categories of "gan yu ", " zheng ji ", "pi kuai", "gu zhang", etc.
1. Compensatory Phase: Clinical manifestations include fatigue, loss of appetite, nausea, abdominal fullness and other symptoms of digestive tract. Slight edema and bleeding ten-dency may be present due to reduced liver function. The find-ings of physical examination are mild hepatomegaly with slight hardness, splenomegal, spider nevi and liver palms.
2. Decompensatory Phase :
(1) Portal hypertension syndrome: Splenomegaly with hypersplenism, esophageal and gastric fundal venous varices which may result in hemorrhage of the upper digestive tract.
(2) Impaired liver function syndrome: Fatigue and symp-toms of the digestive tract are aggravated, low fever, jaun-dice, edema and ascites are often present. Patients may have eminent bleeding tendency, darkish complexion and endocrine disorder. In severe cases complications such as hemorrhage of the upper digestive tract and hepatic coma may take their place.
3. Laboratory Examination :
(1)Liver function test: It is found that icteric index has increased, A/G Ratio decreased or reversed, y-globulin in-creased. Flocculation-turbidity test presents a positive; SGPT, transpeptidase and MAO, too elevated. The prothrombin time is often elongated.
(2) Ultrasonography (A and B Mode), liver scan, CT scanning and liver puncture are helpful in confirming the diag-nosis and type of the disease. They are also valuable in differ-entiation from other liver disease such as hepatic carcinoma and liver abscess.
