Treatment of chronic liver diseases

At the present time are not yet reliable enough and radical methods of treatment of chronic liver diseases. Yet it is possible for chronic hepatitis to achieve long-term stabilization of the disease, and often clinical recovery. In the first two stages of cirrhosis is possible to achieve long-term stabilization process and the satisfactory condition of the patient, and sometimes health; finally, the joint efforts of physicians and surgeons are able to avoid the development of severe complications and considerably prolong the life of the patient. It is extremely important detection of the disease at early stages, because the sooner treatment is started, the greater the likelihood of recovery. In addition, the success of therapy depends on perseverance and pedantry of the doctor and the discipline of the patient.
The essential condition of effectiveness is the need of permanent care: the patient should be treated not only active, but in the inactive phase of the disease, achieving long term and sustainable stabilization of the cirrhotic process.
Schematically, you can highlight the following directions of therapeutic interventions: 1) the removal or neutralization of the existing hepatotropic agent; 2) influence on the basic mechanisms of progression of pathological changes in the liver and other body systems; these impacts are closely aligned with the activities aimed at maintaining and improving liver function, preservation and regeneration of hepatocytes; 3) elimination and prevention of complications such as bleeding, ascites, portosystemic encephalopathy, hypersplenism.
Physical activity in chronic hepatitis and liver cirrhosis should be limited. While there are signs of activity of the process, the patients should be in bed and subsequently pass to the movement gradually. Even after the transition to a stable and compensated by the state, it is reasonable to recommend rest in the middle of the day. Patients with cirrhosis should not engage in activities that cause discomfort.
Dietary treatment of chronic liver diseases should be extended.
At the ratio of proteins, fats and carbohydrates as 1:1:5 daily diet should contain at least 100 grams of protein and bring about 3000 calories (I. I. Loranskaya, 1962). Protein needs are met boiled lean meat, fish, cheese. Fats preferable to eat vegetable.
With cirrhosis of the liver caution should be exercised in the appointment of a large number of proteins. Nitrogen-containing their degradation products can be combined in the bloodstream, bypassing the liver, through out - and intra Porto kavalenya anastomoses and cause encephalopathy and to whom. At the first manifestations of portosystemic encephalopathy should immediately to limit the amount of protein in the diet to a level that did not appear if the symptoms of ammonia poisoning.
Antibiotics may be affecting the bacterial flora of the intestine (oxytetracycline, chloramphenicol and other), can greatly improve the portability of protein.
Vitamins included in the composition of enzyme systems as catalysis mountains, take an active part in exchange processes.
In the active phase of the disease demonstrates the use of ascorbic acid along with bioflavonoids and almost all complex of vitamins Century Wildhirt (1965) and A. S. Loginov (1970) highly appreciated the effectiveness of simultaneous appointment of large doses of vitamin B12 (500-)), and folic acid.
When signs of vitamin a and D (usually with evident violations of bile production) should be appointed and the vitamins. Expressed haemorrhagic syndrome, gipoprotrombinemiey are an indication for the appointment of vitamin K.
In inactive phase of the disease rational to assign inside the complex of b vitamins and ascorbic acid. With this goal can be successfully used drugs are well balanced vitamin complex, such as "Undevit". Also recommended monthly cycles intramuscular vitamin B12 and B6 2-3 times a year.
Lipotropic substances (choline, methionine, lipokain) can bring positive results in those cases when there is a fatty infiltration of the liver; the use of them in its absence makes no sense. Even with fatty infiltration of the liver choline and methionine should be used cautiously. Cornatzer and Sauer (1950) showed that treatment with choline and methionine shown only where single dose of 10 g choline increases content in the blood of phospholipids. The absence of such a reaction indicates that the patient lipotroponoe exchange mechanisms. Introduction of choline and methionine in such cases is not only unnecessary, but may lead to so-called machinenbau intoxication. It should be noted that the described liver damage after applying large doses of methionine (Kinsell, etc., 1948). Many researchers believe that there is no need to enter choline and methionine, as a properly designed diet contains adequate amounts of these substances and provides the necessary lipotropic effect. Thus, the purpose of choline and methionine shown in the presence of fatty liver, and also when there is a risk of the development of fatty infiltration of the liver (associated lesions of the pancreas, diabetes mellitus using a glucocorticoid), and reception of proteins meets difficulties. Dosage of choline - 4-8 g / day 3-4 reception.
Injecting a protein hydrolysates and other protein drugs, transfusion of blood and blood plasma is rarely necessary in patients with chronic hepatitis. In patients same cirrhosis testimony to their destination dictated by many circumstances. Direct indication for transfusion of blood and liver cirrhosis is massive blood loss and varicose veins of the esophagus and stomach. Sometimes to replenish blood loss have to enter a very large (up to 6 l) amount of blood. Often transfusion of blood or blood plasma able to stop the rise of hepatic failure and improving patient in the active phase of the disease.
Studies have shown K. A. Dragina (1959), And Magyar (1962), Faloon and others (1949), concerns whether the reduction deaminated liver contraindications to parenteral introduction protein, appeared excessive. Suppose that the function of protein drugs, transfusions of blood or blood plasma is impossible to liquidate the hypoproteinemia or align violated (ascites) colloid-osmotic ratio. Introduction of albumin, plasma and blood can find application in complex therapy of the disease, especially in the presence of ascites. This applies to patients with reduced circulating blood volume, with spasimira veins, frequent heartbeat; patients undergoing re-evacuation of ascites; to cases of postnecrotic cirrhosis, where the first appearance of ascites associated with reduced serum albumin; patients portal cirrhosis, flowing with small or moderate reduction of whey protein (Shinaberger, Golambos, 1964). Positive effect from the introduction of cirrhosis protein drugs such as aminotropin, aminoatil, hydrolysis, is not observed. If there is evidence for parenteral introduction protein is recommended to appoint a transfusion of blood or plasma. The introduction of free human plasma albumin often gives serious complications (pulmonary edema, vomiting, shock) (b Laszlo, 1964). E. M. Tareev (1962, 1970) considers a blood transfusion fully contraindicated in patients prekomatosny and coma condition. Obviously, we should make an exception in cases where coma developed after massive bleeding.
The use of glucocorticoids is considered as one of the methods of pathogenetic treatment. Justification for use of these substances is their ability to regulate immunobiological reactivity, in particular suppress the formation of antibodies to reduce inflammatory response, to oppress kollagenozy (education connective tissue), to suppress the intrahepatic belastes. In addition, they have a tonic effect. Some researchers (N. A. Yudaev, 1963; Feigelson, 1963; X. X. Planelles and A. M. Kharitonov, 1967; A. F. of Bluger and others, 1968) believe that glucocorticoids have the electoral anabolic action on hepatocytes, however diligent research Mistilis, Schiff (1964), X. X. Mansurov al. (1968) refute this position.
As they gain experience an increasing number of researchers come to the conclusion that glucocorticoids is primarily a positive effect on the health of patients, but not substantially change the condition of the liver and no visible impact on the prognosis of the disease (with E. M. Tareev, 1958; E. M. Tareev al., 1970; X. X. Mansurov al., 1968; 3. A. Bondar, 1970; Copenhagen Study Group for Liver Diseases, 1969). Besides the well-known complications, which can lead appointment of glucocorticoids, in patients with chronic liver disease may develop fatty infiltration of the liver (Lindner, 1958; X. X. Mansurov al., 1968), the likelihood of thrombosis varicose modified vessels of the system of portal vein. In exceptional cases, may be a severe hemorrhagic necrosis of the liver parenchyma (Bassler, 1962).
Along with this observation of many researchers (X. X. Mansurov with al., 1968; E. C. Krutskikh, 1968, 1969, and others) and our own experience suggests that with judicious selection of patients for treatment with glucocorticoids and thorough its implementation can achieve positive results. So, Harvald and Madsen (1961), who drove the long-term treatment of patients with cirrhosis prednisolone, reported that by the end of 3 years from treated patients survived 62%of patients not treated with prednisone, - 21%.
Seems reasonable enough opinion O. Kuchel (1963), recommending and liver cirrhosis apply corticosteroids only after testing all other means of treatment, especially if we are not talking about serious condition and prognosis of the disease the patient is relatively favorable.

The appointment of glucocorticoids is shown in the following cases:
1. The initial stages of chronic hepatitis (transition from acute hepatitis), when there continuing active process (E. M. Tareev al., 1970).
2. Active, progressive chronic hepatitis and liver cirrhosis with clear signs of autoimmune reactions (high gamma globulinemia, positive LE-cells in the blood, arthritis etc., plasmocytoma infiltration of the liver and bone marrow).
The question of the rationality of appointment of glucocorticoids can greatly help the study of liver biopsy sample. In cases where the inflammatory changes in the connective tissue formations liver prevail over necrobiotic changes in the parenchyma, in the absence of severe fibrosis discussed medicines can cause a positive effect (Schopper, Kreuzery, 1963; Century, Smagin, O. M. Tatarinov, V. M. Shulman, 1966; X. X. Mansurov al., 1968).
In cases where there necrotic processes in the parenchyma, often reflected on high activity of enzymes, treatment with glucocorticoids are not shown.
3. Hypersplenism or signs of pronounced hemolysis in patients with cirrhosis.
4. Biliary cirrhosis. In these cases, corticosteroids do not cause significant changes of the disease. However, reduction of neuralgia, skin itch, intensity of jaundice occurs faster, and more often in the treatment of corticosteroid than without them.
5. Sometimes glucocorticoids are used for the purpose of suppression of aldosteronism in patients with cirrhosis of the liver with ascites and edema.
Potentiation of diuretics is achieved due to increase in glomerular filtration rate, decreased production of mineralocorticoids (by suppressing the secretion of ACTH) and antidiuretic hormone (b Laszlo, 1964).
In addition to the normal contraindications to the appointment of glucocorticoids (ulcer, diabetes, hypertension, infection, psychosis), from the use of this group of drugs should be avoided in cases of advanced liver failure in severe portal hypertension with varicose veins.
Dosage of steroid hormones is determined depending on individual tolerance, the state of adrenal cortex and the rate of progression of the disease. Usually is sufficient daily intake of 20-40 mg of prednisolone, in some cases, it may be increased to 60-80 mg With the rapid increase in liver failure justified the appointment of higher doses. Glucocorticoids are accepted necessarily a massive vitamin therapy and good saturation of the body potassium. Judicious use of drugs of this group is even possible with the combination of cirrhosis with peptic ulcer disease. In such cases it is necessary parallel antacids and anti-ulcer diet, even in the absence of the symptoms of acute stomach ulcer. The duration of the use of hormonal drugs defined by the patient. Upon the occurrence of improving gradually decrease dose, undoing it is desirable only after the disappearance of signs of disease activity. Dose reduction should be carried out no sooner than 5 mg of prednisone in 6-7 days (or 0.25 mg 3-4 days). With good endurance, and the lack of demonstrated gipokortitizma small dose (5-10 mg / day) can be stored for a long time. With persistent progression of chronic hepatitis and liver cirrhosis should continue taking small doses of steroid drugs for several months, sometimes even several years. In cases continuously progressing chronic hepatitis and cirrhosis, provided careful medical supervision, this method is justified (Harvald, Madsen, 1959, 1961; B., Smagin, 1962, 1966; X. X. Mansurov, 1965).
In recent years accumulated experience of treatment of patients with active chronic hepatitis and liver cirrhosis substances and immunosuppressive antimetabolites actions - 6-mercaptopourina, imuranom (azathioprine). These drugs are deprived of some defects, characteristic of glucocorticoids. They do not cause of ulcer formation, increase blood pressure, diabetes. At the same time, their use can cause leukopenia, aplasia bone marrow, reduce resistance to infection, may lead to disruption of the liver. The appointment of these drugs is indicated for active chronic hepatitis and liver cirrhosis with severe manifestations of immune disorders and in primary biliary cirrhosis, especially in cases where you cannot use glucocorticoids (with concomitant diabetes mellitus, osteoporosis, ulcers).
Initial daily dose of 6-mercaptopurine or azathioprine is based on the rate of 1.5 mg per kg of patient's weight. Almost appoint from 75 to 200 mg, where possible, in combination with low-dose glucocorticoids (5-10 mg prednisolone). After reducing the signs of active disease daily dose is reduced to 20 mg, and in such "support" the dose of the drugs may be given for several months or years (Mackay and others, 1964; Sherlock, 1968). Mackay and Whittingham (1968) And 15 patients with active chronic hepatitis b treated with azathioprine from 1 to 3 years, watched a distinctly positive result. B two cases came exacerbation of the disease after the cancellation of maintenance doses used for 3 years. Terrasse and others (1967) reported some improvement in 10 out of 21 patients with portal cirrhosis who were administered the drug. The same results were obtained by other researchers.
In emerging remission can be used drugs aminobolin series (delagil, plaquenil) as agents maintenance of remission. According to 3. , Prasinoi (1967), the use of plaquenil in the dose of 0.6 and prednisolone 5 mg per day can hold inactive phase of the disease during the year.
Anabolic steroids such as methyltestosterone, metandrostenolon, Durabolin, retabolil shown in cases of severe gipoalbuminemii or in long-term treatment with glucocorticoids. Treatment of anabolic steroids should be done in a few months on the background of rich protein diet and while appointing Pancreatin (Milting, 1965). Remember that anabolic hormones (C17-substituted steroids) may cause intrahepatic cholestasis (Arias 1959; Foulk, 1963, 1968; Iber, 1968). Therefore treatment of them should be under strict control of the level of bilirubin and alkaline phosphatase activity in serum.
Expressed the role of hypoxia (gipotermicescoe and circulatory) damage liver cells (VP Bezugly, 1968; Rossler, 1970) argues oxygen therapy of chronic hepatitis and liver cirrhosis. To do this, use the hyperbolic oxygenotherapy and pharmacokinetics introduction of oxygen through a tube in the form of so-called oxygen foam. C. A. Pilipenko (1967, 1968), B. D. Bratus et al. (1968), and many others have reported a marked positive effect of long-term oxygen therapy.
Intravenous or intramuscular administration eufillina increases the inflow of arterial blood to the liver (A. S. Loginov, 1969) promotes diuresis in patients with cirrhosis.
Attempts to interfere in violation available in the system of cellular oxidative enzymes (see "Pathogenesis"). For this purpose, use kocarboksilazu, coenzyme A, drugs, tioktova acid (Tinjan-s), ATP. Yet it is hard to assess practical results of their application.
Many researchers (Rausch, 1955; Robinson, 1966; A. S. Loginov, etc., 1967, 1969; M. A. Yasinovka and others, 1969) highly evaluate therapeutic efficiency lipoic acid amide lipoic acid. Drugs are synthetic coenzyme involved in the decarboxylation of pyruvic acid, increased activity of cytochrome C oxidase and tissue alkaline phosphatase. Amide lipoic acid is prescribed 25 mg 3 times daily during 25-30 days. When expressed activity of chronic hepatitis (liver cirrhosis) the drug is given in combination with glukokortikoidami in a moderate dose (10-15 me of prednisone per day). In the treatment of 100 patients with chronic hepatitis and liver cirrhosis A. S. Loginov and 3. S. Isakova (1969) not observed improvement in 10 patients.
In cases of severe functional liver failure faster positive effect is achieved by the appointment of L-glutamine from 10.0 to 18.0 per day in one dose of 2.0 to 3.0. Synthesis glutamine leads to ammonia, the emergence of amide groups glutamine. The latter ensures the wide participation of glutamine in many reactions of synthesis, especially of protein synthesis, and may serve as a source of formation of ATP.
In order to reduce dystrophic changes in hepatocytes and alignment of impaired liver function apply deprived of protein extracts of fresh liver - reason, progear, sonepar, GEALAN. It is assumed that these products contain active substances present in a healthy liver. They entered intravenously and intramuscularly from 1 to 5 ml Treatment of liver extracts suitable for chronic hepatitis and liver cirrhosis in a relatively inactive phase. In the active phase of the disease, with severe decompensated cirrhosis these drugs are contraindicated.
Preconceived opinion on the need to abstain for liver from antibiotics should be discarded. Causes concern the violation of antibiotics and vitamin balance may provide sufficient fortification of patients.
Intercurrent infections and related primary diagnosis of inflammatory lesions of the biliary tract are the absolute indication for the use of broad-spectrum antibiotics - oxytetracycline, levomitsetina, monomitsina, neomycin and other
Sherlock (1968) strongly recommends the use of a specified group of antibiotics for the treatment of portosystemic encephalopathy. Us (C. M RISS Century and, Smagin, 1958) received information that indicates that antibiotic therapy increases the relative duration of remission in patients with cirrhosis. All this justifies the inclusion of antibiotics in the complex therapy of chronic hepatitis and liver cirrhosis.