Tuberculosis and liver disease

Disturbances in liver function and structure in patients with tuberculosis can be a consequence of the effect of tuberculosis intoxication, hypoxemia, antituberculous drugs, concomitant diseases, tuberculosis lesion of the hepatobiliary system.

The effect of tuberculosis intoxication affects the enzymatic, protein-synthetic, coagulation, excretory functions of the liver, causes a decrease in the volume flow in the organ and a slowing of the elimination of drug substances. Common forms of tuberculosis can be accompanied by hepato- and splenomegaly. With a general amyloidosis that develops against the background of tuberculosis, liver damage is noted in 70-85% of cases.

At the cellular level, hypoxia leads to switching the work of the respiratory chain to a shorter and energetically favorable pathway for oxidizing succinic acid, inhibiting the monooxidase system, which leads to damage to the structure of the endoplasmic reticulum and disruption of cellular transport.

The sequence of liver function loss during hypoxia is established: protein synthesis; formation of pigments; formation of prothrombin; synthesis of carbohydrates; excretion; urea formation; formation of fibrinogen; esterification of cholesterol; enzymatic function. In the first place, the excretory function suffers; Absorption is disturbed only with respiratory insufficiency III degree. There is also an inverse relationship: the attachment of the liver pathology to pulmonary disease exacerbates the violation of ventilation and gas exchange, which is caused by damage to the cells of the reticuloendothelial, cardiovascular systems, a violation of the function of hepatocytes.

Combination of tuberculosis with liver damage

The defeat of the liver is one of the main causes of the development of drug intolerance in tuberculosis due to the leading role of this organ in the system of detoxification. The frequency of toxic medicinal hepatitis is 4-16% of complications of drug therapy, it increases with the duration of drug intake. Medicinal hepatitis is characterized by a dyspeptic, painful abdominal syndrome, hepatomegaly, sometimes there are icterism of the mucous membranes and sclera, skin itching; the prodrome is uncharacteristic. Inflammatory and cytolytic syndromes predominate with moderately expressed cholestatic syndromes. Laboratory reveals an increase in the level of transaminases, alkaline phosphatase, cholinesterases, less often - bilirubin. With the use of anti-TB drugs, it is possible to develop lightning-fast hepatitis, the mechanism of development is immunoallergic and toxic. Developed violations of liver function persist for 2-4 months after the disappearance of clinical manifestations. The relationship between the tolerability of treatment and the patient's age was noted. In elderly patients, a change in the treatment regimen due to adverse events is necessary, and in the old age, a reduction in the doses of drugs. Data on the hepatotoxicity of antituberculosis drugs are quite contradictory, since this property is associated not only with the chemical structure of the drug, but also with the peculiarities of the liver metabolic capabilities of each patient, the magnitude of the hepatic blood flow, the level of development of portocaval anastomoses, the degree of binding of preparations by plasma proteins,

The increased incidence of combined pathology (tuberculosis and chronic nonspecific lung diseases, digestive tract diseases, hepatobiliary system, diabetes mellitus) leads to increased liver damage. Over the past decades, the number of cases of a combination of pulmonary tuberculosis and liver diseases has increased 23-fold and among newly diagnosed tuberculosis patients it was 16-22%, chronicle media - 38-42%. In phthisiopulmonologic patients, independent liver diseases are diagnosed in 1% of cases, secondary hepatitis accounts for 10-15% of all complications of drug therapy. Structure of secondary hepatitis: 36-54% - nonspecific reactive hepatitis. 16-28% - medicinal. 3-8% - specific tubercular. 2% alcoholic. The combination of pulmonary tuberculosis with liver disease of non-viral etiology is unfavorable, with a tendency towards progression.

With the combination of viral hepatitis B and tuberculosis, the jaundice period is more severe, more frequent liver enlargement and biochemical indications, hemograms, inactivation of isonicotinic acid hydrazide (GINC), hepatotoxicity of rifampicin and pyrazinamide are more frequent, prolonged hepatitis . Among patients with pulmonary tuberculosis who are carriers of hepatitis B markers, hepatotoxic reactions to tuberculostatics are baked in 85% of cases, the disease is characterized by a more acute onset, a pronounced clinical picture and a low effectiveness of treatment. Excretory liver function in such patients is disrupted even before the start of treatment and does not normalize in the process of antituberculous therapy. Hepatitis C is most common in patients with chronic pulmonary tuberculosis. A positive reaction to antibodies to hepatitis C is attributed to risk factors for the development of hepatotoxic reactions when prescribing anti-tuberculosis drugs.

Among people with cirrhosis, the risk of tuberculosis is increased, and patients with acute tuberculosis with liver cirrhosis have a poor prognosis.

With a combination of pulmonary tuberculosis and alcoholism, a poor tolerance of antituberculosis drugs (up to 60%) and liver damage (up to 80%) is likely. Alcohol disrupts lipid metabolism, causing fatty liver infiltration, reduces the intensity of metabolism of biologically active substances, inhibits protein synthesis in hepatocytes, and their ability to regenerate. Perhaps a direct necrobiotic effect of ethanol on the liver. Such patients are characterized by toxic, toxicoallergic and allergic reactions are not characteristic. With a high prevalence of substance abuse and drug addiction, it is possible to predict the increase in the problem of hepatotoxic reactions.

The incidence of tuberculosis in diabetic patients is 5 times higher than the incidence of the population. In patients with hyperglycemia, hyperlipidemia and keto-acidosis in combination with tuberculous intoxication, pathology in the form of protein and fatty dystrophy, inflammatory and cirrhotic changes is revealed in 100% of cases with a puncture biopsy. This prevents effective chemotherapy of pulmonary tuberculosis, being one of the reasons for frequent intolerance of treatment. The combination of pulmonary tuberculosis and diabetes is diagnosed 3 times more often in patients with widespread destructive changes in the lungs than in local forms of tuberculosis without the phenomena of dissemination and destruction.

Tuberculosis of the liver may be the only manifestation of the disease or part of a disseminated process. Morphologically, three main forms of liver damage are distinguished: miliary disseminated, large-node and tumor-like liver tuberculosis. The main way to defeat the liver is hematogenous. With miliary tuberculosis, the liver is almost always involved in acute granulomatous inflammation, liver tuberculosis requires standard systemic antituberculous therapy.

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Treatment of liver diseases in tuberculosis

Prevention of liver damage in tuberculosis and timely correction of violations are vital because they determine the possibility of adequate chemotherapy, manipulation and operations with anesthesia.

The process of lipid peroxidation is more intensive in infiltrative forms of pulmonary tuberculosis than in chronic, widespread destructive forms. This dictates the inclusion in a commonly used set of therapeutic measures of drugs that have antioxidant and antihypoxic activity, protecting the liver parenchyma. They have anti-inflammatory, antifibrotic. Antitoxic properties, restriction of collagen formation and activation of its resorption. To reduce lipid peroxidation and stabilize hepatocyte membranes, hepatoprotectors are recommended. As a corrector of oxidative phosphorylation, metabolites of the Krebs cycle are used. At the expressed toxic reactions removal of specific therapy and intravenous drip infusion of inhibitors of proteases are shown. Glucocorticoids reduce the toxic effect of antibacterial drugs and, when included in complex therapy, significantly reduce the incidence of liver dysfunction. Widespread use for violations of liver function found methods of sorption detoxification and hyperbaric oxygenation.

Of great practical importance is the non-medicamentous correction of liver lesions in tuberculosis. In this case, it is necessary to determine the type of acetylation - the faster its rate, the greater the damaging effect of metabolites of GINC. Selection of the parenteral route of administration, intermittent method of drug administration. Breaks in the appointment of drugs GINK group for 1-2 days significantly reduce its hepatotoxicity. Dystrophic changes in the liver are observed less frequently if the entire daily dose of isoniazid is administered once a day and especially parenterally. Interaction of drugs can be corrected by changing treatment regimens. In the appointment of rifampicin, pyrazinamide and streptomycin 2 times a week, the hepatotoxicity of this combination decreases. With polychemotherapy with the use of 4 to 7 antituberculosis drugs, various schemes are acceptable, but on condition that no more than 3-4 drugs are taken per day, excluding simultaneous reception of rifampicin and isoniazid, protionamide, ethionamide, pyrazinamide.

It should be borne in mind that gastro-and hepatoprotectors themselves can influence the metabolism of drugs. In particular, allohol accelerates the metabolism of isoniazid, increasing its hepatotoxicity and reducing the therapeutic effect, aluminum-containing antacids are able to absorb isoniazid and fluoroquinolones, reducing their absorption and concentration in the blood.

Thus, the state of liver function in tuberculosis depends on many endogenous and exogenous factors that the phthisiatrician must take into account in his work.