Severe hepatitis is one of the most severe clinical types of viral hepatitis. Acute severe hepatitis is characterized by acute onset, rapid deepening of jaundice, endotoxemia, different neuropsychiatric disorders (hepatic encephalopathy degree II or higher), significantly prolonged prothrombin time and prothrombin activity below 40%, rapid disease progression, short-term liver and kidney failure, and high morbidity and mortality.
Although subacute and chronic severe hepatitis have a slower onset and differ in etiology, pathogenesis and treatment principles from those of acute severe hepatitis, the complications that arise and the principles of diagnosis and treatment are basically the same.
The typical severe hepatitis has a clinical manifestation of multi-organ failure. Although, the clinical manifestations of different organ failure are different, a vicious circle can be formed between them as a result of the major and interactive effects of severe liver damage. The author knows from the statistics of our hospital in 1995 that the complications of heavy hepatitis are mainly: infection, hepatic encephalopathy, hepatorenal syndrome, gastrointestinal bleeding, cerebral edema, and heart failure.
I. Hepatic encephalopathy and cerebral edema
(A) Hepatic encephalopathy
It is the most prominent and diagnostic early clinical manifestation of acute severe hepatitis, and psychoneurological symptoms usually appear rapidly within 10 days of onset (hepatic encephalopathy of degree II or above). It is characterized by progressive psychoneurological changes, ranging from personality changes, dyscalculia and disorientation, day-night sleep disturbances, followed by delirium, mania, deepening drowsiness, and finally coma. Neurological signs include hyperreflexia of the knee and cone bundle signs of ankle clonus in the early stage, while fluttering tremor is a characteristic manifestation of hepatic encephalopathy, which is caused by altered function of the corticospinal tract. After entering coma, various reflexes weaken or disappear, muscle tone changes from increased to decreased, and pupils are often dilated or significantly reduced. At present, according to the psychoneurological manifestations and EEG examination, there are two kinds of hepatic encephalopathy: four-level classification method and five-level classification iteration.
(B) Brain edema
It is an important extrahepatic injury in acute severe hepatitis, and autopsy can often reveal patients who died from acute severe hepatitis have different degrees of cerebral edema. It has been reported that 13 cases of cerebral edema were found in 16 autopsies, and the autopsy revealed meningeal tension, brain tissue edema with gyrus expansion, and increased brain weight, and about 25%-30% of patients with cerebral edema had cerebral tonsillar herniation or temporal lobe gyrus herniation.
The mechanisms of occurrence may include.
(1) damage to the blood-brain barrier (vasogenic cerebral edema).
(2) Failure of cellular osmoregulation (cytotoxic cerebral edema).
(3) expansion of the extracellular space (interstitial hydrocephalus or hydrocephalus)
(4) associated with cerebrovascular intravascular coagulation. Clinical manifestations of cerebral edema include headache, vomiting, drowsiness, blurred vision, elevated blood pressure, bulbar conjunctival edema, etc. In severe cases, pupil size may vary, respiratory changes, and even respiratory arrest.
(C) principles of treatment of hepatic encephalopathy and cerebral edema
1, the application of amino acids: FISCher et al. found that in hepatic encephalopathy, the serum amino acid balance is out of balance, especially the aromatic amino acids are significantly higher, while the branched chain amino acids change less, causing the branch/aromatic ratio to decrease from the original normal value of 3-3.5 to or <1, and the application of a solution containing branched chain amino acids (referred to as F080), can correct the branch/aromatic ratio, so that patients from coma to awakening. According to the treatment observation results, it is believed that the awakening rate and survival rate of 15~AA on patients with liver coma of cirrhosis are significantly different from those of the control group who applied traditional therapy during the same period, while the efficacy on coma of fulminant liver failure is not satisfactory, (no statistical difference), and the use of 6 amino acids a 400 (or branched chain amino acids) is effective on hepatitis liver coma.
2, levodopa: in the 70s, levodopa was popular for a while, but soon tended to die down, the reason for this is that although levodopa has a positive effect on awakening, it has little effect on survival rate, analyzing the main reason, levodopa is quickly converted into dopamine in the body, which competes with pseudo-neurotransmitters to improve normal impulse transmission between neurons and restore brain function, but it may also have a inhibitory effect, thus causing ischemia and hypoxia in hepatocytes leading to further deterioration of hepatocytes. Usage: Levodopa 200~40Omg added to 10% glucose solution 250ml twice a day, VitB6 should not be given at the same time, or 100mg Levodopa ten 20mg Carbidopa added to 100 glucose solution 250ml IV.
3, the application of lactulose (Loctulose): its therapeutic effect is more certain, its as the current treatment of hepatic encephalopathy of the basic drugs. Its role ① acidification of the intestinal tract is conducive to the transfer of ammonia from the brain to the intestine and light diarrhea. ②Recently, it is found to provide a substrate for bacteria to use chlorine, so it can inhibit the multiplication of intestinal negative bacteria and the growth of beneficial bacteria and reduce endotoxemia. ③reduce intestinal ammonia absorption, promote ammonia excretion, and make blood ammonia decrease. Recently reported lactitol (Lactitol) is another kind of disaccharide, (β-galactin a sorbitol), the treatment of hepatic encephalopathy effect is similar to lactulose, and the therapeutic effect appears relatively early. Munog pointed out that lactitol is effective for cirrhotic hepatic encephalopathy but not for hepatic coma of hepatitis, at the same time, it is believed that either oral or enema is likely to cause intestinal obstruction and serious lower gastrointestinal bleeding, which should be noted.
4, plasma replacement therapy and the application of biological artificial liver: heavy hepatitis, the patient’s renal blood flow and filtration rate are low, easy to produce renal failure and cause liver and kidney syndrome, aggravate brain damage, and promote death. Polypropylene eye hemodialysis and plasma replacement therapy (2.8~6L of fresh plasma supplementation daily) have good results. The hybrid BLSS consisting of plasma separator, activated carbon, hepatocyte raw reactor, etc. is more reasonable in design and more ideal in effect.
5. It has been reported that zinc acetate 200ng 3 times daily for 7 days, and benzoic acid and phenylacetic acid 10mg daily in 3 oral doses have certain efficacy, but only individual reports have been seen. Recently, it has been reported that the application of benzodiazepine (BZ) receptor antioxidant R015-1788 (Flumazenil) 0.5~lmg injected for 1 minute or 25ms twice a day can have a waking effect, but it has not yet been popularly used, and there is value for further research.
(D) Prevention and treatment of cerebral edema
The management of cerebral edema focuses on prevention, paying attention to the overuse or abuse of sodium-containing drugs. Treatment is more effective when there is hyperreflexia of knee, ankle clonus or positive cone bundle.
1, dehydrating agent: 25% sorbitol or 20% mannitol, each time 250ml fast pressurized static drip in 20-30min, this is very important, and every 4-6h thereafter, such as mental and cerebral edema signs significantly improved can be reduced by half, do not extend the interval to avoid rebound, sorbitol dehydrating effect is slightly inferior to mannitol but no side effect of causing hematuria. In order to reduce rebound, can alternatively use 50% glucose 40ml static push.
2, Dexamethasone: the first dose of 10mg plus an appropriate amount of 10% glucose solution intravenously pushed to every 4-6 hours after 5mg and dehydration agents will be used for 2-3 days. At the same time, inject albumin to strengthen the dehydration effect.
II. Metabolic disorders
(a) clinically early to see hypoglycemia, about 40% of patients with acute heavy hepatitis, hypoglycemic coma regardless of its clinical manifestations and electroencephalogram are very similar to hepatic encephalopathy, patients often have general weakness, limb tremors, mood swings restless; pale face, cold sweat, syncope, dilated pupils, tachycardia, mildly increased blood pressure, tendon reflex active, rely on rapid measurement of blood glucose concentration significantly reduced The diagnosis was made clearly by rapid measurement of blood glucose concentration.
(b) Hyponatremia in severe hepatitis is extremely common clinically and occurs in the later stages.
(1) The patient has severe gastrointestinal symptoms, nausea, vomiting, inadequate sodium intake, and decreased blood sodium concentration.
(2) The application of strong diuretics is not supplemented with care.
(3) ATPase activity is diminished, fluid retention is excessive, and sodium collects in body fluids, creating true hyponatremia.
Persistent hyponatremia is a sign of dying cells and still indicates a serious prognosis. In clinical practice, attention should be paid to whether true hyponatremia or dilute hyponatremia is present. On the one hand, clinicians are often concerned about the aggravation of water and sodium retention and restrict sodium intake and intravenous supplementation, while in clinical practice, both intra- and extra-intestinal sodium supplementation often fails to correct dilutional hyponatremia, but makes symptoms such as abdominal distension and ascites not improve but become severe, so the treatment is quite difficult and must be treated individually.
(c) Hypophosphatemia can be detected early, especially in patients with normal urination.
(d) Metabolic acidosis is relatively common, mainly due to hepatic insufficiency and impairment of lactate metabolism. It has been shown that many acidoses are associated with tissue hypoxia and accumulation of peripheral lactic acid products, and it is appropriate to give oxygen.
III. Infection
(a) Patients with severe hepatitis are often complicated by various infections, which are associated with immune deficiency, mainly due to impaired neutrophil and blastocyte function and deficiency of conditioners. Mycobacterial infections, mainly Candida, also often occur later in the course of the disease. It has been reported that in 18 years of clinical observation, among 1610 patients hospitalized with severe hepatitis and cirrhosis, there were 95 cases (5.9%) of sepsis with positive blood (bone marrow) cultures, within which there were 6 cases (6.3%) of sepsis with internal plural bacteria. Increasing attention is being paid regarding the role of clostridial cell function in infection, due to its impairment limiting the clearance of endotoxin and facilitating the passage of cells through the gastrointestinal tract to the systemic circulation. A recent study by Camalses et al. confirmed that measurement of galactose clearance in surviving patients with acute liver failure provides insight into the degree of hepatocyte hypofunction and maintains the relevance of early restoration of Kupffer cell function.
(ii) Control of infection
Patients with severe hepatitis presenting with infection do not always have typical clinical and laboratory features; therefore, once a patient is found to have rising body temperature, deepening jaundice, increasing ascites, and hepatic encephalopathy, attention should be paid to.
1, when there are signs of cellular infection, use antibiotics without hepatic or renal toxicity, such as third-generation cephalosporins, which have a certain bactericidal effect on Gram-negative and positive bacteria.
2, anaerobic bacterial infections, can be used metronidazole (methotrexate) 500mg, once a day, IV.
3, mycobacterial infections, can be used to anti-mycobacterial drugs, such as big fukang, gastrointestinal mycobacteria available mycobacteria, dicloxacillin B, and at the same time the application of ecological agents, also known as live agents, the use of harmless or even beneficial to the host can be fixed value of live bacteria to resist foreign or their own overproliferation of bacteria, experimental evidence to exogenous bifidobacteria in the intestine can inhibit Escherichia coli and reduce the level of endotoxin in portal blood.
Fourth, coagulation mechanism disorders
(a) Almost all patients with acute severe hepatitis have severe disorders of coagulation mechanism, significant prolongation of prothrombin time is a characteristic manifestation of patients with acute severe hepatitis in inflammatory patients, which is closely related to the severity of liver injury. half-life of factor V is the shortest, theoretically, it is a more sensitive indicator of impairment of coagulation factor synthesis, in addition, the reduction of coagulation factor synthesis also increases peripheral consumption, as a result of varying degrees of DIC and also quantitative and qualitative defects in platelet function, which not only occurs with thrombocytopenia and increased adhesion and impairment of coagulation. The risk of bleeding is not so much related to the prothrombin time as to the reduction of platelets and the presence of significant DIC. Clinically, patients may present with purple petechiae and petechiae on the skin, bleeding from the gums and oral mucosa, bleeding from the nose and injection sites, and a few patients may have direct symptoms of upper gastrointestinal bleeding.
(B) Prevention and control of bleeding
1, coagulation factor supplementation; most of the coagulation factors have a short half-life, usually only a few hours, can be preserved for a long time under freezing, so fresh frozen plasma should be used, stock plasma supplementation coagulation factor effect is poor, fresh plasma has a variety of coagulation factors and is the only source of factor V, containing regulators and complement.
The effects of plasma in the treatment of severe hepatitis are.
① Enhance the immune regulation ability of patients.
(2) Replenish a variety of coagulation factors to prevent bleeding.
③Replenish blood volume to reduce blood viscosity and improve microcirculation.
④Supplementing protein, increasing plasma osmolarity, promoting diuresis, reducing cerebral edema, eliminating ascites and edema.
⑤Increase the body’s ability to resist infection and improve endotoxemia, plasma needs to be repeatedly input once every other day or 2~3 times a week.
⑥Prothrombinogen complex, also known as polyvalent coagulation factor (PPSB for short) contains four coagulation factors II, V, VII and IX, 300~400U once a day or every other day, twice a week, intravenous drip.
2. H2 receptor orange antagonist: It can prevent bleeding of gastric mucosa due to erosion of excessive gastric acid. Mecamylate 0.2~O.4g/time, three times a day, also available ranitidine 0.15g orally at night before bedtime, acid control agents such as omeprazole 20mg/time.
3. Reduce portal pressure: the effect of the heartburn has reduced portal pressure, the dose to slow down the heart rate 25% as the degree, combined with cimetidine, due to the interaction between the two heartburn dose can be reduced from 20mg to 15mg, three times a day. After the above measures can make the bleeding rate decreased significantly, but once the bleeding still need to be actively treated available Sandostatin (Sandostatin) 0.lmg into 25% glucose solution 20ml sedation, after 0.6mg + 10% glucose solution 1000ml maintenance.
4, human albumin can directly supply the body to use, reduce the body’s original protein consumption, thereby reducing the burden on liver cells is conducive to preventing necrosis of liver cells, and prevent hypoproteinemia, maintain normal plasma osmolality, strengthen diuretic and immune and anti-coagulant function. However, the amount should be controlled at 2g a day.
V. Cardiac respiratory complications
(A) heavy hepatitis patients often damaged heart, clinical manifestations of palpitations, shortness of breath, chest tightness, precordial pain, intractable hypotension and shock, physical examination of the heart can be enlarged, heart rate becomes faster, can suddenly die, electrocardiogram changes include atrial fibrillation, atrial flutter, sinus tachycardia, low voltage, bundle branch conduction block and ST segment, T wave abnormalities, hypotension not only reflects the function of the heart and other aspects and produce the brain, heart, liver (1) The hypotension not only reflects the function of the heart and other aspects but also produces a decrease in blood supply to the brain, heart, liver, kidney, causing secondary ischemic damage is very serious.
(b) In the treatment is appropriate to use.
(1) oxygen absorption or rectal perfusion; (2) keep the airway open; (3) change the microcirculation.
①Pansentin has the effect of anti-endotoxemia, active microcirculation, and prevent platelet aggregation. Dosage: 500mg/day.
(1) Scopolamine is effective in relieving microcirculation and arterial spasm, opening the valve between arteries and veins, and relieving arteriovenous short circuit. 40~200mg/day in divided doses intravenously.
③Chuanxiongzin injection has the effect of anti-endotoxic active microcirculation, release platelet aggregation and prevent immune complex formation. It can be used 150~200mg intravenous drip per day.
TAD (Tate) is a precursor of Glutathione (GSH), which is necessary for the body to maintain cellular integrity and physiological functions. Supplementing the reduced GSH in certain diseases with TAD is a reasonable treatment that improves cardiopulmonary function. The dose is 0.6g, qd, for 2 weeks.
VI. Hepatorenal syndrome
(a) Heavy hepatitis can develop into renal failure without clinical and experimental morphological manifestations of nephropathy, which is clinically and conventionally called hepatorenal syndrome (HRS). The clinical manifestations are hepatic failure and oliguria (24-hour urine output <400-500 ml, or even anuria (24-hour urine output <40-50 ml =, significantly reduced renal blood flow and filtration rate, low urine sodium, low blood sodium, elevated blood urea nitrogen and myohepatic values, and β2 microglobulin <200 mg/L. Such complications are serious and difficult to treat.
(B) Management of hepatorenal syndrome: Strict control of intake. The rehydration volume is equivalent to the previous day’s urine volume plus 500~700ml.
(1) Do not use antibiotics that damage liver and kidney function, such as gentamicin, neomycin, kanamycin.
(2) Stop the use of prothrombin complex. Because it can cause intravascular thrombosis of the kidney and clotting, so that the urine volume is reduced.
(3) Application of diuretics: tachyphylaxis, antiseptic.
(4) Dopamine has the effect of dilating renal blood vessels and improving renal blood flow. 20~80mg is added into 500ml of 10% glucose solution.
(5) 654-2 has the effect of improving microcirculation.
(6) Dialysis treatment: Hemodialysis or peritoneal dialysis is ineffective or even dangerous for HSR because it has many disadvantages, such as severe hypotension, infection and bleeding, but it can prolong the survival time for patients with potentially reversible liver disease, such as acute heavy hepatitis caused by drug intoxication is more desirable, and secondly, it can support patients to pass through HRS and wait for liver transplantation. After dialysis, four of them recovered renal function after liver transplantation in l-5 weeks.
Currently, there has been great progress in the diagnosis and treatment of severe hepatitis, but no new breakthroughs have been made. It has been reported that the death rate of acute, subacute and chronic heavy hepatitis complicated by multi-organ failure is 85.7%, 81.80% and 71.79%, respectively, and the most common causes are infection, gastrointestinal haemorrhage and electrolyte disorders. Therefore, striving for early diagnosis and active prevention and treatment of complications is the key to reduce the morbidity and mortality of heavy hepatitis.